# 16 - Substance Related and Addictive Disorders

# Substance-Related and Addictive Disorders

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Substance-Related and Addictive Disorders
The substance-related disorders encompass 10 separate classes of drugs:
alcohol; caffeine; cannabis; hallucinogens (with separate categories for phencyclidine [or
similarly acting arylcyclohexylamines] and other hallucinogens); inhalants; opioids; sedatives,
hypnotics, or anxiolytics; stimulants (amphetamine-type substances, cocaine, and other
stimulants); tobacco; and other (or unknown) substances. These 10 classes are not fully distinct.
All drugs that are taken in excess have in common the ability to directly activate the brain reward
systems, which are involved in the reinforcement of behaviors and establishment of memories.
Instead of achieving reward system activation through adaptive behaviors, these substances
produce such an intense activation of the reward system that normal activities may be neglected.
The pharmacological mechanisms by which each class of drugs produces reward are different,
but the drugs typically activate the system and produce feelings of pleasure, often referred to as a
“high.” Furthermore, studies suggest that the neurobiological roots of substance use disorders for
some individuals can be seen in their behaviors long before the onset of actual substance use
(e.g., lower levels of self-control may reflect impairments of brain inhibitory mechanisms);
research also suggests the negative impact of substance use itself on brain inhibitory
mechanisms.
Note that the phrase “drug addiction” is not applied as a diagnostic term in this classification,
although it is in common usage in many countries to describe severe problems related to
compulsive and habitual use of substances. The more neutral term substance use disorder is used
to describe the wide range of the disorder, from a mild form to a severe state of chronically
relapsing, compulsive pattern of drug taking. Some clinicians will choose to use the phrase “drug
addiction” to describe more severe presentations, but that wording is omitted from the official
DSM-5 substance use disorder diagnostic terminology because of its uncertain definition and its
potentially negative connotation.
In addition to the substance-related disorders, this chapter also includes gambling disorder,
reflecting evidence that gambling behaviors activate reward systems similar to those activated by
drugs of abuse and that produce some behavioral symptoms that appear comparable to those
produced by the substance use disorders. Other excessive behavioral patterns, such as Internet
gaming (see “Conditions for Further Study”), have also been described, but the research on these
and other behavioral syndromes is less clear. Thus, groups of repetitive behaviors, sometimes
termed behavioral addictions (with subcategories such as “sex addiction,” “exercise addiction,”
and “shopping addiction”), are not included because there is insufficient peer-reviewed evidence
to establish the diagnostic criteria and course descriptions needed to identify these behaviors as
mental disorders.
The substance-related disorders are divided into two groups: substance use disorders and
substance-induced disorders. The following conditions may be classified as substance-induced:
substance intoxication, substance withdrawal, and substance/medication-induced mental

disorders (diagnostic criteria and text are provided in this manual for substance/medicationinduced psychotic disorders, bipolar and related disorders, depressive disorders, anxiety
disorders, obsessive-compulsive and related disorders, sleep disorders, sexual dysfunctions,
delirium, and neurocognitive disorders in their respective chapters). The term
substance/medication-induced mental disorder refers to symptomatic presentations that are
due to the physiological effects of an exogenous substance on the central nervous system and
includes typical intoxicants (e.g., alcohol, inhalants, cocaine), psychotropic medications (e.g.,
stimulants, sedative-hypnotics), other medications, (e.g., steroids), and environmental toxins
(e.g., organophosphate insecticides).
The current section begins with a general discussion of criteria sets for substance use
disorder, substance intoxication, substance withdrawal, and substance/medication-induced
mental disorders, at least some of which are applicable across classes of substances. Reflecting
some unique aspects of the 10 substance classes relevant to this chapter, the remainder of the
chapter is organized by substance class. To facilitate differential diagnosis, the diagnostic criteria
and text for the substance/medication-induced mental disorders are included with disorders with
which they share phenomenology (e.g., substance/medication-induced depressive disorder is in
the chapter “Depressive Disorders”). Note that only certain classes of drugs are capable of
causing particular types of substance-induced disorders. The substance-related diagnostic
categories associated with specific drug classes are shown in Table 1.
TABLE 1 Diagnoses associated with substance class
Psychotic
disorders
Bipolar
and
related
disorders
Depressive
disorders
Anxiety
disorders
Obsessivecompulsive
and related
disorders
Sleep
disorders dy
Alcohol
I/W
I/W
I/W
I/W
I/W
Caffeine
I
I/W
Cannabis
I
I
I/W
Hallucinogens
Phencyclidine
I
I
I
I
Other
hallucinogens
I*
I
I
I
Inhalants
I
I
I
Opioids
I/W
W
I/W
Sedatives,
hypnotics, or
anxiolytics
I/W
I/W
I/W
W
I/W
Stimulants**
I
I/W
I/W
I/W
I/W
I/W
Tobacco
W

Other (or
unknown)
I/W
I/W
I/W
I/W
I/W
I/W
Note. X = The category is recognized in DSM-5.
I = The specifier “with onset during intoxication” may be noted for the category.
W = The specifier “with onset during withdrawal” may be noted for the category.
I/W = Either “with onset during intoxication” or “with onset during withdrawal” may be noted for the category. Major = major
neurocognitive disorder; mild = mild neurocognitive disorder.
*Also hallucinogen persisting perception disorder (flashbacks).
**Includes amphetamine-type substances, cocaine, and other or unspecified stimulants.
Substance-Related Disorders
Substance Use Disorders
Diagnostic Features
The essential feature of a substance use disorder is a cluster of cognitive, behavioral, and
physiological symptoms indicating that the individual continues using the substance despite
significant substance-related problems. As seen in Table 1, the diagnosis of a substance use
disorder can be applied to all 10 substance classes included in this chapter except caffeine. For
certain classes, some symptoms are less salient, and in a few instances not all symptoms apply
(e.g., withdrawal symptoms are not specified for phencyclidine use disorder, other hallucinogen
use disorder, or inhalant use disorder). Of note, the consumption of substances, including
prescribed medications, may depend in part on cultural background, substance availability, and
specific local drug regulations. Thus, there can be significant local or cultural variation in
exposure (e.g., countries with cultural prohibitions against alcohol or other substance use may
have a lower prevalence of substance-related disorders).
An important characteristic of substance use disorders is an underlying change in brain
circuits that may persist beyond detoxification, particularly in individuals with severe disorders.
The behavioral effects of these brain changes may be exhibited in the repeated relapses and
intense drug craving when the individuals are exposed to drug-related stimuli. These persistent
drug effects may benefit from long-term approaches to treatment.
Overall, the diagnosis of a substance use disorder is based on a pathological pattern of
behaviors related to use of the substance. To assist with organization, the diagnostic items
making up Criterion A can be considered to fit within overall groupings of impaired control,
social impairment, risky use, and pharmacological criteria. Impaired control over substance use
is the first criteria grouping (Criteria 1–4). The individual may take the substance in larger
amounts or over a longer period than was originally intended (Criterion 1). The individual may
express a persistent desire to cut down or regulate substance use and may report
multiple unsuccessful efforts to decrease or discontinue use (Criterion 2). The individual may
spend a great deal of time obtaining the substance, using the substance, or recovering from its

effects (Criterion 3). In some instances of more severe substance use disorders, virtually all of
the individual’s daily activities revolve around the substance. Craving (Criterion 4) is manifested
by an intense desire or urge for the drug that may occur at any time but is more likely when in an
environment where the drug previously was obtained or used. Craving has also been shown to
involve classical conditioning and is associated with activation of specific reward structures in
the brain. Craving might be queried by asking if there has ever been a time when there were such
strong urges to take the drug that the individual could not think of anything else. Current craving
is often used as a treatment outcome measure because it may be a signal of impending relapse.
Social impairment is the second grouping of criteria (Criteria 5–7). Recurrent substance use
may result in a failure to fulfill major role obligations at work, school, or home (Criterion 5). The
individual may continue substance use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of the substance (Criterion 6).
Important social, occupational, or recreational activities may be given up or reduced because of
substance use (Criterion 7). The individual may withdraw from family activities and hobbies in
order to use the substance.
Risky use of the substance is the third grouping of criteria (Criteria 8–9). This may take the
form of recurrent substance use in situations in which it is physically hazardous (Criterion 8).
The individual may continue substance use despite knowledge of having a persistent or recurrent
physical or psychological problem that is likely to have been caused or exacerbated by the
substance (Criterion 9). The key issue in evaluating this criterion is not the existence of the
problem, but rather the individual’s failure to abstain from using the substance despite the
difficulty it is causing.
Pharmacological criteria are the final grouping (Criteria 10 and 11). Tolerance (Criterion 10)
is signaled by requiring a markedly increased dose of the substance to achieve the desired effect
or a markedly reduced effect when the usual dose is consumed. The degree to which tolerance
develops varies greatly across different individuals as well as across substances and may involve
a variety of central nervous system effects. For example, tolerance to respiratory depression and
tolerance to sedating and motor coordination may develop at different rates, depending on the
substance. Tolerance may be difficult to determine by history alone, and laboratory tests may be
helpful (e.g., high blood levels of the substance coupled with little evidence of intoxication
suggest that tolerance is likely). Tolerance must also be distinguished from individual variability
in the initial sensitivity to the effects of particular substances. For example, some first-time
alcohol drinkers show very little evidence of intoxication with three or four drinks, whereas
others of similar weight and drinking histories have slurred speech and incoordination.
Withdrawal (Criterion 11) is a syndrome that occurs when blood or tissue concentrations of a
substance decline in an individual who had maintained prolonged, heavy use of the substance.
After developing withdrawal symptoms, the individual is likely to consume the substance to
relieve the symptoms. Withdrawal symptoms vary greatly across the classes of substances, and
separate criteria sets for withdrawal are provided for the drug classes. Marked and generally
easily measured physiological signs of withdrawal are common with alcohol, opioids, and
sedatives, hypnotics, and anxiolytics. Withdrawal signs and symptoms with stimulants
(amphetamine-type substances, cocaine, other or unspecified stimulants), as well as tobacco and
cannabis, are often present but may be less apparent. Significant withdrawal has not been
documented in humans after repeated use of phencyclidine, other hallucinogens, and inhalants;
therefore, this criterion is not included for these substances. Neither tolerance nor withdrawal is

necessary for a diagnosis of a substance use disorder. However, for most classes of substances, a
past history of withdrawal is associated with a
more severe clinical course (i.e., an earlier onset of a substance use disorder, higher levels of
substance intake, and a greater number of substance-related problems).
Symptoms of tolerance and withdrawal occurring during appropriate use of prescribed
medications given as part of medical treatment (e.g., opioid analgesics, sedatives, stimulants) are
specifically not counted when diagnosing a substance use disorder. The appearance of normal,
expected pharmacological tolerance and withdrawal during the course of medical treatment has
been known to lead to an erroneous diagnosis of “addiction” even when these were the only
symptoms present. Individuals whose only symptoms are those that occur as a result of medical
treatment (i.e., tolerance and withdrawal as part of medical care when the medications are taken
as prescribed) should not receive a diagnosis solely on the basis of these symptoms. However,
prescription medications can be used inappropriately, and a substance use disorder can be
correctly diagnosed when there are other symptoms of compulsive, drug-seeking behavior.
Severity and Specifiers
Substance use disorders occur in a broad range of severity, from mild to severe, with severity
based on the number of symptom criteria endorsed. As a general estimate of severity, a mild
substance use disorder is suggested by the presence of two to three symptoms, moderate by four
to five symptoms, and severe by six or more symptoms. Changing severity across time is also
reflected by reductions or increases in the frequency and/or dose of substance use, as assessed by
the individual’s own report, report of knowledgeable others, clinician’s observations, and
biological testing. The following course specifiers and descriptive features specifiers are also
available for substance use disorders: “in early remission,” “in sustained remission,” “on
maintenance therapy,” and “in a controlled environment.” Definitions of each are provided
within respective criteria sets.
Recording Procedures
The clinician should use the code that applies to the substance class but record the name of the
specific substance. For example, the clinician should record F13.20 moderate alprazolam use
disorder (rather than moderate sedative, hypnotic, or anxiolytic use disorder) or F15.10 mild
methamphetamine use disorder (rather than mild amphetamine-type substance use disorder). For
substances that do not fit into any of the classes (e.g., anabolic steroids), the ICD-10-CM code
for other (or unknown) substance use disorder should be used and the specific substance
indicated (e.g., F19.10 mild anabolic steroid use disorder). If the substance taken by the
individual is unknown, the same ICD-10-CM code (i.e., for “other [or unknown] substance use
disorder”) should be used (e.g., F19.20 severe unknown substance use disorder). If criteria are
met for more than one substance use disorder, each should be diagnosed (e.g., F11.20 severe
heroin use disorder; F14.20 moderate cocaine use disorder).
The appropriate ICD-10-CM code for a substance use disorder depends on whether there is a

comorbid substance-induced disorder (including substance intoxication and substance
withdrawal). In the first example in the paragraph above, the diagnostic code for moderate
alprazolam use disorder, F13.20, reflects the absence of a comorbid alprazolam-induced mental
disorder. Because ICD-10-CM codes for substance-induced disorders indicate both the presence
(or absence) and the severity of the substance use disorder, ICD-10-CM codes for substance use
disorders can be used only in the absence of a substance-induced disorder. See the individual
substance-specific sections for additional coding information.
Substance-Induced Disorders
The overall category of substance-induced disorders includes substance intoxication, substance
withdrawal, and substance/medication-induced mental disorders (e.g., substance-induced
psychotic disorder, substance-induced depressive disorder). While substance intoxication and
substance withdrawal are recognized as mental disorders, for purposes of clarity of reference in
discussions across this chapter, the term substance/medication-induced mental disorder (e.g.,
alcohol-induced depressive disorder, methamphetamine-induced anxiety disorder) is used to
distinguish these disorders from substance intoxication and substance withdrawal.
Substance Intoxication and Substance Withdrawal
Criteria for the substance-specific intoxication syndromes are included within the substancespecific sections of this chapter. The essential feature is the development of a reversible
substance-specific syndrome due to the recent ingestion of a substance (Criterion A). The
clinically significant problematic behavioral or psychological changes associated with
intoxication (e.g., belligerence, mood lability, impaired judgment) are attributable to the
physiological effects of the substance on the central nervous system (CNS) and develop during
or shortly after use of the substance (Criterion B) and are accompanied by substance-specific
signs and symptoms (Criterion C). The symptoms are not attributable to another medical
condition and are not better explained by another mental disorder (Criterion D). Substance
intoxication is common among individuals with a substance use disorder but also occurs
frequently in persons who use substances but do not have a substance use disorder. This category
does not apply to tobacco.
The most common changes in substance intoxication involve disturbances of perception,
wakefulness, attention, thinking, judgment, psychomotor behavior, and interpersonal behavior.
Short-term, or “acute,” substance intoxications may have different signs and symptoms from
sustained, or “chronic,” substance intoxications. For example, moderate cocaine doses may
initially produce gregariousness, but social withdrawal may develop if such doses are frequently
repeated over days or weeks.
When used in the physiological sense, the term intoxication is broader than the diagnosis of
substance intoxication as defined in this manual. Many substances may produce physiological or
psychological changes that are not necessarily problematic. For example, an individual with
tachycardia from substance use is experiencing a physiological effect from the substance, but if

this is the only symptom in the absence of problematic behavior, the diagnosis of substance
intoxication would not apply. Intoxication may sometimes persist beyond the time when the
substance is detectable in the body. This may be attributable to enduring CNS effects, from
which the recovery takes longer than the time for elimination of the substance. These longer-term
effects of intoxication must be distinguished from withdrawal (i.e., symptoms initiated by a
decline in blood or tissue concentrations of a substance).
Criteria for substance withdrawal are also included within the substance-specific sections of
this chapter. The essential feature is the development of a substance-specific problematic
behavioral change, with physiological and cognitive concomitants, that is due to the cessation of,
or reduction in, heavy and prolonged substance use (Criterion A). The substance-specific
syndrome (Criterion B) causes clinically significant distress or impairment in social,
occupational, or other important areas of functioning (Criterion C). The symptoms are not due to
another medical condition and are not better explained by another mental disorder (Criterion D).
Withdrawal is usually, but not always, associated with a substance use disorder. Also, it is
important to emphasize that symptoms of withdrawal occurring during appropriate use of
medications given as part of medical treatment with
prescribed medications (e.g., opioid analgesics, sedatives, stimulants) are specifically not
counted when diagnosing a substance use disorder. Most individuals with withdrawal have an
urge to readminister the substance to reduce the symptoms.
Route of Administration and Speed of Substance Effects
Routes of administration that produce more rapid and efficient absorption into the bloodstream
(e.g., intravenous, smoking, intranasal “snorting”) tend to result in a more intense intoxication
and an increased likelihood of an escalating pattern of substance use leading to withdrawal.
Similarly, rapidly acting substances are more likely than slower-acting substances to produce
immediate intoxication.
Duration of Effects
Within the same drug category, relatively short-acting substances tend to have a higher potential
for the development of withdrawal than do those with a longer duration of action. However,
longer-acting substances tend to have longer duration of withdrawal symptoms. The half-life of
the substance parallels aspects of withdrawal: the longer the duration of action, the longer the
time between cessation and the onset of withdrawal symptoms and the longer the withdrawal
duration. In general, the longer the acute withdrawal period, the less intense the syndrome tends
to be.
Use of Multiple Substances
Substance intoxication and withdrawal often involve several substances used simultaneously or
sequentially. In these cases, each diagnosis should be recorded separately.
Associated Laboratory Findings

Laboratory analyses of blood and urine samples can help determine recent use and the specific
substances involved. However, a positive laboratory test result does not by itself indicate that the
individual has a pattern of substance use that meets criteria for a substance-induced or substance
use disorder, and a negative test result does not by itself rule out a diagnosis.
Laboratory tests can be useful in identifying withdrawal. If the individual presents with
withdrawal from an unknown substance, laboratory tests may help identify the substance and
may also be helpful in differentiating withdrawal from other mental disorders. In addition,
normal functioning in the presence of high blood levels of a substance suggests considerable
tolerance.
Development and Course
Individuals ages 18–24 years have relatively high prevalence rates for the use of virtually every
substance. Intoxication is usually the initial substance-related disorder and often begins in the
teens. Withdrawal can occur at any age as long as the relevant drug has been taken in sufficient
doses over an extended period of time.
Recording Procedures for Substance Intoxication and Substance
Withdrawal
The clinician should use the code that applies to the class of substances but record the name of
the specific substance. For example, the clinician should record F13.230 secobarbital withdrawal
(rather than sedative, hypnotic, or anxiolytic withdrawal) or F15.120 methamphetamine
intoxication (rather than amphetamine-type substance intoxication). Note that
the appropriate ICD-10-CM diagnostic codes for substance intoxication and substance
withdrawal depend on whether there is a comorbid substance use disorder. In this case, the
F15.120 code for methamphetamine intoxication indicates the presence of a comorbid mild
methamphetamine use disorder. If there had been no comorbid methamphetamine use disorder
(and no perceptual disturbances), the diagnostic code would have been F15.920. See the coding
note for the substance-specific intoxication and withdrawal syndromes for the actual coding
options.
For substances that do not fit into any of the classes (e.g., anabolic steroids), the ICD-10-CM
code for other (or unknown) substance intoxication or other (or unknown) substance withdrawal
should be used and the specific substance indicated (e.g., F19.920 anabolic steroid intoxication).
If the substance taken by the individual is unknown, the same code (i.e., for the class “other [or
unknown] substance”) should be used (e.g., F19.920 unknown substance intoxication). If there
are symptoms or problems associated with a particular substance but criteria are not met for any
of the substance-specific disorders, the unspecified category can be used (e.g., F12.99
unspecified cannabis-related disorder).
As noted above, the substance-related codes in ICD-10-CM combine the substance use
disorder aspect of the clinical picture and the substance-induced aspect into a single combined
code. Thus, if both heroin withdrawal and moderate heroin use disorder are present, the single
code F11.23 for heroin withdrawal is given to cover both presentations. See the individual

substance-specific sections for additional coding information.
Substance/Medication-Induced Mental Disorders
The substance/medication-induced mental disorders are potentially severe, usually temporary,
but sometimes persisting CNS syndromes that develop in the context of the effects of substances
of abuse, medications, and some toxins. They are distinguished from the substance use disorders,
in which a cluster of cognitive, behavioral, and physiological symptoms contribute to the
continued use of a substance despite significant substance-related problems. The
substance/medication-induced mental disorders may be induced by any of the 10 classes of
substances that produce substance use disorders, or by a great variety of other medications used
in medical treatment. Each substance/medication-induced mental disorder is described in the
relevant chapter (e.g., substance/medication-induced depressive disorder is located in
“Depressive Disorders”), and therefore, only a brief description is offered here. All
substance/medication-induced disorders share common characteristics. It is important to
recognize these common features to aid in the detection of these disorders. These features are
described as follows:
A. A clinically significant presentation of symptoms characteristic of disorders in the relevant
diagnostic class predominates in the clinical picture.
B. There is evidence from the history, physical examination, or laboratory findings of both of
the following:
1. The symptoms in Criterion A developed during or soon after substance intoxication,
substance withdrawal, or exposure to or withdrawal from a medication; and
2. The involved substance/medication is capable of producing the symptoms in Criterion A.
C. The disturbance is not better explained by an independent mental disorder (i.e., one that is
not substance- or medication-induced). Such evidence of an independent mental disorder
could include the following:
1. The disturbance preceded the onset of severe intoxication or withdrawal or exposure to the
medication; or
2. The disturbance persisted for a substantial period of time (e.g., at least 1 month) after the
cessation of acute withdrawal or severe intoxication or taking the
medication. This criterion does not apply to substance-induced neurocognitive disorders
or hallucinogen persisting perception disorder, which persist beyond the cessation of acute
intoxication or withdrawal.
D. The disturbance does not occur exclusively during the course of a delirium.
E. The disturbance causes clinically significant distress or impairment in social, occupational,
or other important areas of functioning.
Diagnostic and Associated Features

Some generalizations can be made regarding the categories of substances capable of producing
clinically relevant substance-induced mental disorders. In general, the more sedating drugs
(sedative, hypnotics, or anxiolytics, and alcohol) can produce prominent and clinically
significant depressive disorders during intoxication, while anxiety conditions are likely to be
observed during withdrawal syndromes from these substances. Also, during intoxication, the
more stimulating substances (e.g., amphetamines and cocaine) are likely to be associated with
substance-induced psychotic disorders and substance-induced anxiety disorders, and with
substance-induced major depressive episodes observed during withdrawal. Both the more
sedating and the more stimulating drugs are likely to produce significant but temporary sleep and
sexual disturbances. An overview of the relationship between specific categories of substances
and specific psychiatric syndromes is presented in Table 1.
The medication-induced conditions include what are often idiosyncratic CNS reactions or
relatively extreme examples of side effects for a wide range of medications taken for a variety of
medical concerns. These include neurocognitive complications of anesthetics, antihistamines,
antihypertensives, and a variety of other medications and toxins (e.g., organophosphates,
insecticides, carbon monoxide), as described in the chapter on neurocognitive disorders.
Psychotic syndromes may be temporarily experienced in the context of anticholinergic,
cardiovascular, and steroid drugs, as well as during use of stimulant-like and depressant-like
prescription or over-the-counter drugs. Temporary but severe mood disturbances can be observed
with a wide range of medications, including steroids, antihypertensives, disulfiram, and any
prescription or over-the-counter depressant or stimulant-like substances. A similar range of
medications can be associated with temporary anxiety syndromes, sexual dysfunctions, and
conditions of disturbed sleep.
In general, to be considered a substance/medication-induced mental disorder, there must be
evidence that the symptoms being observed are not likely to be better explained by an
independent mental disorder. The latter is more likely to be the case if the symptoms were
present before the severe intoxication or withdrawal or medication administration, or, with the
exception of several substance-induced persisting disorders listed in 1, continued more than 1
month after cessation of acute withdrawal, severe intoxication, or use of the medications. When
symptoms are only observed during a substance-induced delirium (e.g., alcohol withdrawal
delirium), only the delirium should be diagnosed, and other psychiatric symptoms occurring
during the delirium should not also be diagnosed separately, as many of these symptoms (e.g.,
disturbances in mood, anxiety, reality testing) are commonly seen during agitated, confused
states. The features associated with each relevant major mental disorder are similar whether
observed with independent or substance/medication-induced mental disorders. However,
individuals with substance/medication-induced mental disorders are likely to also demonstrate
the associated features seen with the specific category of substance or medication, as listed in
other subsections of this chapter.
Development and Course
Substance-induced mental disorders develop in the context of intoxication with or withdrawal
from substances of abuse, whereas medication-induced mental disorders can be seen with
prescribed or over-the-counter medications that are taken at the suggested doses.

552
Both conditions are usually temporary and likely to disappear within 1 month or so of cessation
of acute withdrawal, severe intoxication, or use of the medication. Exceptions to these
generalizations occur for certain long-duration substance-induced disorders: substance-associated
neurocognitive disorders that relate to conditions such as alcohol-induced neurocognitive
disorder, inhalant-induced neurocognitive disorder, and sedative-, hypnotic-, or anxiolyticinduced neurocognitive disorder; and hallucinogen persisting perception disorder (“flashbacks”;
see the section “Hallucinogen-Related Disorders” later in this chapter). However, most
substance/medication-induced mental disorders, regardless of the severity of the symptoms, are
likely to improve relatively quickly with abstinence and unlikely to remain clinically relevant for
more than 1 month after complete cessation of use.
As is true of many consequences of heavy substance use, some individuals are more and
others less prone toward developing specific substance-induced disorders. Similar types of
predispositions may make some individuals more likely to develop psychiatric side effects of
some types of medications, but not others. However, it is unclear whether individuals with
family histories or personal prior histories of independent psychiatric syndromes are more likely
to develop the induced syndrome once the consideration is made as to whether the quantity and
frequency of the substance were sufficient to lead to the development of a substance-induced
syndrome.
There are indications that the intake of substances of abuse or some medications with
psychiatric side effects in the context of a preexisting mental disorder is likely to result in an
intensification of the symptoms of the preexisting mental disorder. The risk for
substance/medication-induced mental disorders is likely to increase with both the quantity and
the frequency of consumption of the relevant substance.
The symptom profiles for the substance/medication-induced mental disorders resemble
independent mental disorders. While the symptoms of substance/medication-induced mental
disorders can be identical to those of independent mental disorders (e.g., delusions,
hallucinations, psychoses, major depressive episodes, anxiety syndromes), and although they can
have the same severe consequences (e.g., suicide), most induced mental disorders are likely to
improve in a matter of days to weeks of abstinence.
The substance/medication-induced mental disorders are an important part of the differential
diagnoses for the independent psychiatric conditions. The importance of recognizing an induced
mental disorder is similar to the relevance of identifying the possible role of some medical
conditions and medication reactions before diagnosing an independent mental disorder.
Symptoms of substance- and medication-induced mental disorders may be identical crosssectionally to those of independent mental disorders but have different treatments and prognoses
from the independent condition.
Functional Consequences of Substance/Medication-Induced Mental
Disorders
The same consequences related to the relevant independent mental disorder (e.g., suicide
attempts) are likely to apply to the substance/medication-induced mental disorders, but these are
likely to disappear within 1 month after abstinence. Similarly, the same functional consequences

associated with the relevant substance use disorder are likely to be seen for the substanceinduced mental disorders.
Recording Procedures for Substance/Medication-Induced Mental
Disorders
Diagnostic 
criteria, 
coding 
notes, 
and 
recording 
procedures 
for 
the 
specific
substance/medication-induced mental disorders are provided in chapters of the manual
corresponding with disorders of shared phenomenology (see the substance/medication-induced
mental disorders in these chapters: “Schizophrenia Spectrum and Other Psychotic Disorders,”
“Bipolar and Related Disorders,” “Depressive Disorders,” “Anxiety Disorders,” “ObsessiveCompulsive and Related Disorders,” “Sleep-Wake Disorders,” “Sexual Dysfunctions,” and
“Neurocognitive Disorders”). When recording a substance/medication-induced mental disorder
that is comorbid with a substance use disorder, only a single diagnosis is given that reflects both
the type of substance and the type of mental disorder induced by the substance, as well as the
severity of the comorbid substance use disorder (e.g., cocaine-induced psychotic disorder with
severe cocaine use disorder). For a substance-induced mental disorder occurring in the absence
of comorbid substance use disorder (e.g., when the disorder is induced by one-time use of a
substance or medication), only the substance/medication-induced mental disorder is recorded
(e.g., corticosteroid-induced depressive disorder). Additional information needed to record the
diagnostic name of the substance/medication-induced mental disorder is provided in the section
“Recording Procedures” for each substance/medication-induced mental disorder in its respective
chapter.
Alcohol-Related Disorders
Alcohol Use Disorder
Alcohol Intoxication
Alcohol Withdrawal
Alcohol-Induced Mental Disorders
Unspecified Alcohol-Related Disorder
Alcohol Use Disorder
Diagnostic Criteria
A. A problematic pattern of alcohol use leading to clinically significant impairment or

distress, as manifested by at least two of the following, occurring within a 12month period:
1. Alcohol is often taken in larger amounts or over a longer period than was
intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control
alcohol use.
3. A great deal of time is spent in activities necessary to obtain alcohol, use
alcohol, or recover from its effects.
4. Craving, or a strong desire or urge to use alcohol.
5. Recurrent alcohol use resulting in a failure to fulfill major role obligations at
work, school, or home.
6. Continued alcohol use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of alcohol.
7. Important social, occupational, or recreational activities are given up or
reduced because of alcohol use.
8. Recurrent alcohol use in situations in which it is physically hazardous.
9. Alcohol use is continued despite knowledge of having a persistent or
recurrent physical or psychological problem that is likely to have been caused
or exacerbated by alcohol.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of alcohol to achieve intoxication
or desired effect.
b. A markedly diminished effect with continued use of the same amount of
alcohol.
11. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome for alcohol (refer to Criteria A and
B of the criteria set for alcohol withdrawal).
b. Alcohol (or a closely related substance, such as a benzodiazepine) is
taken to relieve or avoid withdrawal symptoms.
Specify if:
In early remission: After full criteria for alcohol use disorder were previously
met, none of the criteria for alcohol use disorder have been met for at least 3
months but for less than 12 months (with the exception that Criterion A4,
“Craving, or a strong desire or urge to use alcohol,” may be met).
In sustained remission: After full criteria for alcohol use disorder were
previously met, none of the criteria for alcohol use disorder have been met at
any time during a period of 12 months or longer (with the exception that Criterion
A4, “Craving, or a strong desire or urge to use alcohol,” may be met).

Specify if:
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to alcohol is restricted.
Code based on current severity/remission: If an alcohol intoxication, alcohol
withdrawal, or another alcohol-induced mental disorder is also present, do not use
the codes below for alcohol use disorder. Instead, the comorbid alcohol use disorder
is indicated in the 4th character of the alcohol-induced disorder code (see the coding
note for alcohol intoxication, alcohol withdrawal, or a specific alcohol-induced mental
disorder). For example, if there is comorbid alcohol intoxication and alcohol use
disorder, only the alcohol intoxication code is given, with the 4th character indicating
whether the comorbid alcohol use disorder is mild, moderate, or severe: F10.129 for
mild alcohol use disorder with alcohol intoxication or F10.229 for a moderate or
severe alcohol use disorder with alcohol intoxication.
Specify current severity/remission:
F10.10 Mild: Presence of 2–3 symptoms.
F10.11 Mild, In early remission
F10.11 Mild, In sustained remission
F10.20 Moderate: Presence of 4–5 symptoms.
F10.21 Moderate, In early remission
F10.21 Moderate, In sustained remission
F10.20 Severe: Presence of 6 or more symptoms.
F10.21 Severe, In early remission
F10.21 Severe, In sustained remission
Specifiers
“In a controlled environment” applies as a further specifier of remission if the individual is both
in remission and in a controlled environment (i.e., in early remission in a controlled environment
or in sustained remission in a controlled environment). Examples of these environments are
closely supervised and substance-free jails, therapeutic communities, and locked hospital units.
Severity of the disorder is based on the number of diagnostic criteria endorsed. For a given
individual, changes in severity of alcohol use disorder across time are also reflected by
reductions in the frequency (e.g., days of use per month) or dose (e.g., number of standard drinks
consumed per day) of alcohol used, as assessed by the individual’s self-report, report of
knowledgeable others, clinician observations, and, when practical, biological testing (e.g.,
elevations in blood tests as described in the section “Diagnostic Markers” for this disorder).
Diagnostic Features
Alcohol use disorder is defined by a cluster of behavioral and physical symptoms, such as
withdrawal, tolerance, and craving. Alcohol withdrawal is characterized by withdrawal

symptoms that develop approximately 4–12 hours after the reduction of intake following
prolonged, heavy alcohol ingestion. Because withdrawal from alcohol can be unpleasant and
intense, individuals may continue to consume alcohol despite adverse consequences, often to
avoid or to relieve withdrawal symptoms. Some withdrawal symptoms (e.g., sleep problems) can
persist at lower intensities for months and can contribute to relapse. Once a pattern of repetitive
and intense use develops, individuals with alcohol use disorder may devote substantial periods of
their time to obtaining and consuming alcoholic beverages.
Craving for alcohol is indicated by a strong desire to drink that makes it difficult to think of
anything else and that often results in the onset of drinking. School and job performance may
also suffer either from the aftereffects of drinking or from actual intoxication at school or on the
job; child care or household responsibilities may be neglected; and alcohol-related absences may
occur from school or work. The individual may use alcohol in physically hazardous
circumstances (e.g., driving an automobile, swimming, operating machinery while intoxicated).
Finally, individuals with an alcohol use disorder may continue to consume alcohol despite the
knowledge that continued consumption poses significant physical (e.g., blackouts, liver disease),
psychological (e.g., depression), social, or interpersonal problems (e.g., violent arguments with
spouse while intoxicated, child abuse).
Associated Features
Alcohol use disorder is often associated with problems similar to those associated with other
substances (e.g., cannabis; cocaine; heroin; amphetamines; sedatives, hypnotics, or anxiolytics).
Alcohol may be used to alleviate the unwanted effects of these other substances or to substitute
for them when they are not available. Symptoms of conduct problems, depression, anxiety, and
insomnia frequently accompany heavy drinking and sometimes precede it.
Repeated intake of high doses of alcohol can affect nearly every organ system, especially the
gastrointestinal tract, cardiovascular system, and the central and peripheral nervous systems.
Gastrointestinal effects include gastritis, stomach or duodenal ulcers, and, in about 15% of
individuals who use alcohol heavily, liver cirrhosis and/or pancreatitis. There is also an increased
rate of cancer of the esophagus, stomach, and other parts of the gastrointestinal tract. One of the
most commonly associated conditions is low-grade hypertension. Cardiomyopathy and other
myopathies are less common but occur at an increased rate among those who drink very heavily.
These factors, along with marked
increases in levels of triglycerides and low-density lipoprotein cholesterol, contribute to an
elevated risk of heart disease. Peripheral neuropathy may be evidenced by muscular weakness,
paresthesias, and decreased peripheral sensation. More persistent central nervous system effects
include cognitive deficits, such as severe memory impairment and degenerative changes in the
cerebellum. These effects are related to the direct effects of alcohol, trauma, or vitamin
deficiencies (particularly of the B vitamins, including thiamine). One devastating central nervous
system effect is the relatively rare alcohol-induced persisting amnestic disorder, or WernickeKorsakoff syndrome, in which the ability to encode new memory is severely impaired. This
condition would now be described within the chapter “Neurocognitive Disorders” and would be

termed a substance/medication-induced neurocognitive disorder.
Alcohol use disorder is an important contributor to suicide risk during severe intoxication
and in the context of a temporary alcohol-induced depressive or bipolar disorder. There is an
increased rate of suicidal behavior as well as of suicide among individuals with the disorder.
Prevalence
Alcohol use disorder is common. In the United States, lifetime prevalence rates of DSM-5
alcohol use disorder among adults were estimated to be 29.1% overall with severity specified as
follows: 8.6% mild, 6.6% moderate, and 13.9% severe. Among Australian adults, the estimated
lifetime prevalence of DSM-5 alcohol use disorder was 31.0%.
Rates of disorder vary by gender and age. In the United States, rates were greater among men
(36.0% lifetime prevalence) than among women (22.7%). Twelve-month prevalence of DSM-IV
alcohol use disorders in the United States was 4.6% among individuals ages 12–17 years, 16.2%
among individuals ages 18–29 years, and 1.5% among individuals 65 years and older.
Twelve-month prevalence of alcohol use disorders varies across U.S. ethnoracial groups as
well. For individuals ages 12–17 years, prevalence of DSM-IV alcohol use disorders was
greatest among Native Americans (2.8%) and non-Latinx Whites (2.2%), relative to Asian
Americans (1.6%), individuals reporting two or more racialized backgrounds (1.6%), Hispanics
(1.5%), and African Americans (0.8%). Among adults, data from a large U.S. population-based
study indicated that the 12-month prevalence of DSM-5 alcohol use disorder was 14.4% in
African Americans, 14.0% in non-Hispanic Whites, 13.6% in Hispanics, and 10.6% in Asian
Americans and Pacific Islanders. Data from a large community-based survey of Native
Americans from Southwestern and Northern Plains tribal nations showed that the 12-month
prevalence of DSM-IV alcohol abuse and dependence ranged from 4.1% to 9.8%. There is
extensive diversity in the rates and patterns of alcohol abuse and dependence across the more
than 570 American Indian and Alaska Native communities in the United States, as well as high
rates of abstinence from alcohol use in some of these communities. Historical experiences of
dispossession and subjugation and ongoing discrimination have been associated with increased
risk of symptom onset. Given the diversity of tribal communities, prevalence estimates for
alcohol use disorder among Native Americans should be interpreted with caution.
Development and Course
The first episode of alcohol intoxication is likely to occur during the mid-teens. Alcohol-related
problems that do not meet full criteria for a use disorder or isolated problems may occur before
age 20 years, but the age at onset of an alcohol use disorder with two or more of the criteria
clustered together peaks in the late teens or early to mid 20s. The large majority of individuals
who develop alcohol-related disorders do so by their late 30s. The first evidence of withdrawal is
not likely to appear until after many other aspects of an alcohol use disorder have developed. An
earlier onset of alcohol use disorder is observed in adolescents with preexisting conduct
problems and those with an earlier onset of intoxication.
Alcohol use disorder has a variable course that is characterized by periods of remission and

Environmental.
Genetic and physiological.
relapse. A decision to stop drinking, often in response to a crisis, is likely to be followed by a
period of weeks or more of abstinence, which is often followed by limited periods of controlled
or nonproblematic drinking. However, once alcohol intake resumes, it is highly likely that
consumption will rapidly escalate and that severe problems will once again develop.
Alcohol use disorder is often erroneously perceived as an intractable condition, perhaps
based on the fact that individuals who present for treatment typically have a history of many
years of severe alcohol-related problems. However, these most severe cases represent only a
minority of individuals with this disorder, and the typical individual with the disorder has a much
more promising prognosis.
Among adolescents, conduct disorder and repeated antisocial behavior often co-occur with
alcohol- and with other substance-related disorders. While most individuals with alcohol use
disorder develop the condition before age 40 years, perhaps 10% have later onset, as suggested
by a prospective study in California. Age-related physical changes in older individuals result in
increased brain susceptibility to the depressant effects of alcohol; decreased rates of liver
metabolism of a variety of substances, including alcohol; and decreased percentages of body
water. These changes can cause older people to develop more severe intoxication and subsequent
problems at lower levels of consumption. Alcohol-related problems in older people are also
especially likely to be associated with other medical complications.
Risk and Prognostic Factors
Environmental risk and prognostic factors may include poverty and
discrimination (including structural inequities such as differential incarceration rates and
differential access to medications for addiction treatment), unemployment and low levels of
education, cultural attitudes toward drinking and intoxication, the availability of alcohol
(including price), acquired personal experiences with alcohol, and stress levels. Additional
potential mediators of how alcohol problems develop in predisposed individuals include heavier
peer substance use, exaggerated positive expectations of the effects of alcohol, and suboptimal
ways of coping with stress.
Alcohol use disorder runs in families, with 40%–60% of the variance of
risk explained by genetic influences. The rate of this condition is three to four times higher in
close relatives of individuals with alcohol use disorder, with values highest for individuals with a
greater number of affected relatives, closer genetic relationships to the affected individual, and
higher severity of the alcohol-related problems in those relatives. A significantly higher rate of
alcohol use disorder exists in the monozygotic twin than in the dizygotic twin of an individual
with the condition. A three- to fourfold increase in risk has been observed in children of
individuals with alcohol use disorder, even when these children were given up for adoption at
birth and raised by adoptive parents who did not have the disorder.
Advances in understanding the genes that operate through intermediate characteristics (or
phenotypes) to affect the risk of alcohol use disorder can help to identify individuals who might
be at particularly low or high risk for alcohol use disorder. Among the low-risk phenotypes is the
acute alcohol-related skin flush (seen more commonly in persons of Asian descent). High
vulnerability is associated with preexisting schizophrenia or bipolar disorder, as well as
impulsivity (producing enhanced rates of all substance use disorders and gambling disorder), and
a high risk specifically for alcohol use disorder is associated with a low level of response (low

Course modifiers.
sensitivity) to alcohol. A number of gene variations may account for low response to alcohol or
modulate the dopamine reward systems; however, any single gene variant is likely to explain
only 1%–2% of the risk for these disorders. Gene-environment interactions modulate the impact
of genetic variations; for
example, genetic effects on alcohol use are more pronounced when social constraints are
minimized (e.g., low parental monitoring) or when the environment permits easy access to
alcohol or encourages its use (e.g., high peer deviance).
In general, high levels of impulsivity are associated with an earlier onset and
more severe alcohol use disorder.
Culture-Related Diagnostic Issues
In most cultures, alcohol is the most frequently used intoxicating substance and contributes to
considerable morbidity and mortality. Globally, 2.8 million deaths were attributed to alcohol use,
which corresponds to 2.2% of total age-standardized deaths among women and 6.8% among
men. Globally, an estimated 237 million men and 46 million women have alcohol use disorder,
with the highest prevalence being among men and women in the European Region (14.8% and
3.5%) and the Region of the Americas (11.5% and 5.1%); in general, high-income countries have
the highest prevalence. Greater acculturation to U.S. society among immigrants is associated
with rising prevalence of alcohol use disorder, especially among women. Ethnic density (greater
proportion of people from the same background) may decrease the risk of alcohol use disorder
because of greater social support and buffering against the effects of discrimination. However,
neighborhood segregation may increase the risk for disorders because of the association with
other risk factors, such as higher concentration of alcohol advertising and retail outlets in lowincome areas.
Genetic polymorphisms for the alcohol-metabolizing enzymes alcohol dehydrogenase and
aldehyde dehydrogenase may affect the response to alcohol. When consuming alcohol,
individuals with certain polymorphisms can experience a flushed face and palpitations, reactions
that can be so severe as to limit or preclude future alcohol consumption and diminish the risk for
alcohol use disorder. For example, these gene variations are seen in as many as 40% of Japanese,
Chinese, and Korean individuals and are related to lower risks for the disorder. However, this
protective effect may be modulated by sociocultural factors, as shown by rising prevalence of
alcohol use disorder in Japan, China, and South Korea over the last decades associated with
increasing westernization and changing cultural attitudes about women’s drinking.
Despite small variations regarding individual criterion items, the diagnostic criteria perform
equally well across most race/ethnicity groups.
Sex- and Gender-Related Diagnostic Issues
Men have higher rates of drinking and alcohol use disorder than women, although the gender gap
is narrowing as women are initiating alcohol use at a younger age. Because females generally
weigh less than males, have more fat and less water in their bodies, and metabolize less alcohol
in their esophagus and stomach, they are likely to develop higher blood alcohol levels per drink

than males. Females who drink heavily may also be more vulnerable than males to some of the
physical consequences associated with alcohol, including alcohol-related blackouts and liver
disease. Additionally, while genetic-related mechanisms for alcohol risk overlap for males and
females, the specific environmental components that add to the risk may differ across sexes,
especially during adolescence. Drinking during pregnancy, which tends to decrease overall, may
be a sign of an alcohol use disorder.
Diagnostic Markers
Individuals whose heavier drinking places them at elevated risk for alcohol use disorder can be
identified both through standardized questionnaires and by elevations in blood test results likely
to be seen with regular heavier drinking. These measures do not establish a diagnosis of an
alcohol-related disorder but can be useful in highlighting individuals for
whom more information should be gathered. The most direct test available to measure alcohol
consumption cross-sectionally is blood alcohol concentration, which can also be used to judge
tolerance to alcohol. For example, an individual with a concentration of 150 mg of ethanol per
deciliter (dL) of blood who does not show signs of intoxication can be presumed to have
acquired at least some degree of tolerance to alcohol. At 200 mg/dL, most nontolerant
individuals demonstrate severe intoxication.
Regarding laboratory tests, one sensitive laboratory indicator of heavy drinking is a modest
elevation or high-normal levels (>35 units) of gamma-glutamyltransferase (GGT). This may be
the only laboratory finding. At least 70% of individuals with a high GGT level are persistent
heavy drinkers (i.e., consuming eight or more drinks daily on a regular basis). A second test with
comparable or even higher levels of sensitivity and specificity is carbohydrate-deficient
transferrin (CDT), with levels of 20 units or higher useful in identifying individuals who
regularly consume eight or more drinks daily. Given that both GGT and CDT levels return
toward normal within days to weeks of stopping drinking, both state markers may be useful in
monitoring abstinence, especially when the clinician observes increases, rather than decreases, in
these values over time—a finding indicating that the individual is likely to have returned to
heavy drinking. The combination of tests for CDT and GGT may have even higher levels of
sensitivity and specificity than either test used alone. Additional useful tests include the mean
corpuscular volume (MCV), which may be elevated to high-normal values in individuals who
drink heavily—a change that is due to the direct toxic effects of alcohol on erythropoiesis.
Although the MCV can be used to help identify those who drink heavily, it is a poor method of
monitoring abstinence because of the long half-life of red blood cells. Liver function tests (e.g.,
alanine aminotransferase and alkaline phosphatase) can reveal liver injury that is a consequence
of heavy drinking. Other potential markers of heavy drinking that are more nonspecific for
alcohol but can help the clinician think of the possible effects of alcohol include elevations in
blood levels or lipids (e.g., triglycerides and high-density lipoprotein cholesterol) and highnormal levels of uric acid.
Additional diagnostic markers relate to signs and symptoms that reflect the consequences
often associated with persistent heavy drinking. For example, dyspepsia, nausea, and bloating

can accompany gastritis, and hepatomegaly, esophageal varices, and hemorrhoids may reflect
alcohol-induced changes in the liver. Other physical signs of heavy drinking include tremor,
unsteady gait, insomnia, and erectile dysfunction. Males with chronic alcohol use disorder may
exhibit decreased testicular size and feminizing effects associated with reduced testosterone
levels. Repeated heavy drinking in females is associated with menstrual irregularities and, during
pregnancy, spontaneous abortion and fetal alcohol syndrome. Individuals with preexisting
histories of epilepsy or severe head trauma are more likely to develop alcohol-related seizures.
Alcohol withdrawal may be associated with nausea, vomiting, gastritis, hematemesis, dry mouth,
puffy blotchy complexion, and mild peripheral edema.
Association With Suicidal Thoughts or Behavior
Most studies on suicidality and alcohol address alcohol consumption rather than alcohol use
disorder. However, a psychological autopsy study in Australia found that aggression, psychiatric
comorbidity, and recent interpersonal conflicts are suicide risk factors in individuals with alcohol
use disorder. A review of studies from 1999 through 2014 conducted in several countries,
including the United States, reported that both intoxication and chronic heavy alcohol use are
associated with suicide, extensive population-level data link alcohol with suicide, and there is
evidence suggesting that restrictive alcohol policies may help prevent suicide on a general
population level. A meta-analysis of studies conducted in the United States and several other
countries from 1996 through 2015 found that compared with nondrinking individuals, the acute
use of alcohol was associated with a nearly
sevenfold increase in risk of suicide attempt. Moreover, in this meta-analysis, as well as in U.S.-
based case-control crossover studies, heavier alcohol use within 24 hours was a much more
potent risk factor for suicide attempt than lower alcohol use. In a cohort of patients in
Mississippi, acute co-use of alcohol and sedatives had an even stronger association with suicide
attempt compared with alcohol use alone. A systematic review and meta-analysis of studies from
1975 through 2014 in several countries, including the United States, found that alcohol use is
associated with possession of firearms, that alcohol drinkers are four to six times more likely to
die by suicide with a gun than nondrinkers, and that heavy drinkers are more likely to choose
firearms over other suicide methods compared with nondrinkers.
Functional Consequences of Alcohol Use Disorder
The diagnostic features of alcohol use disorder highlight major areas of life functioning likely to
be impaired. These include driving and operating machinery, school and work, interpersonal
relationships and communication, and health. Alcohol-related disorders contribute to
absenteeism from work, job-related accidents, and low employee productivity. Rates are elevated
in homeless individuals, perhaps reflecting a downward spiral in social and occupational
functioning, although most individuals with alcohol use disorder continue to live with their
families and function within their jobs.
Alcohol use disorder is associated with a significant increase in the risk of accidents,
violence, and suicide. It is estimated that one in five intensive care unit admissions in some urban

Nonpathological use of alcohol.
Alcohol intoxication, alcohol withdrawal, and alcohol-induced mental disorders.
Sedative, hypnotic, or anxiolytic use disorder.
Conduct disorder in childhood and antisocial personality disorder.
hospitals is related to alcohol and that 40% of individuals in the United States experience an
alcohol-related adverse event at some time in their lives, with alcohol accounting for up to 55%
of fatal driving events. Severe alcohol use disorder, especially in individuals with antisocial
personality disorder, is associated with the commission of criminal acts, including homicide.
Severe problematic alcohol use also contributes to disinhibition and feelings of sadness and
irritability, which contribute to suicide attempts and suicide.
Unanticipated alcohol withdrawal in hospitalized individuals for whom a diagnosis of
alcohol use disorder has been overlooked can add to the risks and costs of hospitalization and to
time spent in the hospital.
Differential Diagnosis
The key element of alcohol use disorder is the use of heavy doses
of alcohol with resulting repeated and significant distress or impaired functioning. While most
drinkers sometimes consume enough alcohol to feel intoxicated, only a minority (< 20%) ever
develop alcohol use disorder. Therefore, drinking, even daily, in low doses and occasional
intoxication do not by themselves make this diagnosis.
Alcohol use disorder is
differentiated from alcohol intoxication, alcohol withdrawal, and alcohol induced mental
disorders (e.g., alcohol-induced depressive disorder) in that alcohol use disorder describes a
problematic pattern of alcohol use that involves impaired control over alcohol use, social
impairment due to alcohol use, risky alcohol use (e.g., driving while intoxicated), and
pharmacological symptoms (the development of tolerance or withdrawal), whereas alcohol
intoxication, alcohol withdrawal, and alcohol-induced mental disorders describe psychiatric
syndromes that develop in the context of heavy use. Alcohol intoxication, alcohol withdrawal,
and alcohol-induced mental disorders occur frequently in individuals with alcohol use disorder.
In such cases, a diagnosis of alcohol intoxication, alcohol withdrawal, or an alcohol-induced
mental disorder should be given in addition to
a diagnosis of alcohol use disorder, the presence of which is indicated in the diagnostic code.
The signs and symptoms of alcohol use disorder are
similar to those seen in sedative, hypnotic, or anxiolytic use disorder. The two must be
distinguished, however, because the course may be different, especially in relation to medical
problems.
Alcohol use disorder, along with
other substance use disorders, is seen in the majority of individuals with antisocial personality
disorder and preexisting conduct disorder. Because these diagnoses are associated with an early
onset of alcohol use disorder as well as a worse prognosis, it is important to establish both
conditions.
Comorbidity
Bipolar disorders, schizophrenia, and antisocial personality disorder are associated with alcohol

use disorder, and most anxiety and depressive disorders are associated with alcohol use disorder
as well. At least a part of the reported association between depression and moderate to severe
alcohol use disorder may be attributable to temporary, alcohol-induced comorbid depressive
symptoms resulting from the acute effects of intoxication or withdrawal, although this point has
long been debated. Severe, repeated alcohol intoxication may also suppress immune mechanisms
and predispose individuals to infections and increase the risk for cancers.
Alcohol Intoxication
Diagnostic Criteria
A. Recent ingestion of alcohol.
B. Clinically significant problematic behavioral or psychological changes (e.g.,
inappropriate sexual or aggressive behavior, mood lability, impaired judgment)
that developed during, or shortly after, alcohol ingestion.
C. One (or more) of the following signs or symptoms developing during, or shortly
after, alcohol use:
1. Slurred speech.
2. Incoordination.
3. Unsteady gait.
4. Nystagmus.
5. Impairment in attention or memory.
6. Stupor or coma.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.
Coding note: The ICD-10-CM code depends on whether there is a comorbid alcohol
use disorder. If a mild alcohol use disorder is comorbid, the ICD-10-CM code is
F10.120, and if a moderate or severe alcohol use disorder is comorbid, the ICD-10CM code is F10.220. If there is no comorbid alcohol use disorder, then the ICD-10CM code is F10.920.
Diagnostic Features
The essential feature of alcohol intoxication is the presence of clinically significant and
sometimes life-threatening problematic behavioral or psychological changes (e.g., inappropriate
sexual or aggressive behavior, mood lability, impaired judgment and decision-making,
difficulties with complex tasks such as driving, and impaired social or occupational functioning)
that develop during, or shortly after, alcohol ingestion (Criterion B). These changes are

accompanied by evidence of impaired functioning and judgment and, if intoxication is intense,
can result in a life-threatening coma. The symptoms must not be attributable to another medical
condition (e.g., diabetic ketoacidosis), are not a reflection of conditions such as delirium, and are
not related to intoxication with other depressant drugs (e.g., benzodiazepines) (Criterion D). The
levels of incoordination can interfere with driving abilities and performance of usual activities to
the point of causing vehicle crashes or other events resulting in injury. Evidence of alcohol use
can be obtained by smelling alcohol on the individual’s breath, eliciting a history from the
individual or another observer, and, when needed, having the individual provide breath, blood, or
urine samples for toxicology analyses.
Associated Features
Signs and symptoms of intoxication are likely to be more intense when the blood alcohol level is
rising than when it is falling. The duration of intoxication depends on how much alcohol was
consumed over what period of time. In general, the body is able to metabolize approximately one
drink per hour, so that the blood alcohol level generally decreases at a rate of 15–20 mg/dL per
hour.
During even mild alcohol intoxication, different symptoms are likely to be observed at
different time points. Evidence of mild intoxication with alcohol can be seen in most individuals
after approximately two drinks (each standard drink is approximately 10–12 grams of ethanol
and raises the blood alcohol concentration approximately 20 mg/dL). Early in the drinking
period, when blood alcohol levels are rising, symptoms often reflect stimulation (e.g.,
talkativeness, a sensation of well-being, a bright, expansive mood). Later, especially when blood
alcohol levels are falling, the individual is likely to become progressively more depressed,
withdrawn, and cognitively impaired.
Alcohol intoxication is sometimes associated with amnesia for the events that occurred
during the course of the intoxication (“blackouts”). This phenomenon is related to a relatively
high blood alcohol level and, perhaps, to the rapidity with which this level is reached. Acute
alcohol intoxication may cause metabolic alterations (e.g., hypoglycemia, electrolyte
disturbances) and may have severe cardiovascular, respiratory, and/or gastrointestinal effects. At
very high blood alcohol levels (e.g., 200–300 mg/dL), an individual who has not developed
tolerance for alcohol is likely to fall asleep and enter a first stage of anesthesia. Higher blood
alcohol levels (e.g., in excess of 300–400 mg/dL) can cause inhibition of respiration and pulse
and even death in nontolerant individuals.
Alcohol intoxication is an important contributor to interpersonal violence and suicidal
behavior. Among individuals intoxicated by alcohol, there appears to be an increased rate of
accidental injury (including death due to behaviors associated with altered judgment, self-harm,
and violence), suicidal behavior, and suicide.
Prevalence
The large majority of alcohol consumers are likely to have been intoxicated to some degree at
some point in their lives. For example, in 2018, 43% of 12th-grade students in the United States
reported having “been drunk” at least once in their lifetime, and 17.5% of them reported that they
had gotten drunk at least once in the prior 30 days. Using a definition of intoxication of four or
more standard drinks on any day for women and five or more

563
standard drinks on any day for men, the 12-month prevalence of high-risk drinking in U.S. adults
is 17.4% for Native Americans, 15.1% for African Americans, 13.5% for Latinx, 12.3% for nonLatinx Whites, and 7.2% for Asians and Pacific Islanders.
Development and Course
Intoxication usually occurs as an episode developing over minutes to hours and typically lasting
several hours. In the United States, the average age at first intoxication is approximately 15
years, with the highest prevalence at approximately 18–25 years. Frequency and intensity usually
decrease with further advancing age. The earlier the onset of regular intoxication, the greater the
likelihood the individual will go on to develop alcohol use disorder.
Risk and Prognostic Factors
Temperamental.
Episodes of alcohol intoxication increase with personality characteristics of sensation seeking
and impulsivity.
Environmental.
Episodes of alcohol intoxication increase with having heavy-drinking peers, holding beliefs that
heavy drinking is an important component of having fun, and using alcohol to cope with stress.
Culture-Related Diagnostic Issues
The major issues parallel the cultural differences regarding the use of alcohol overall. For
example, some college fraternities and sororities encourage alcohol intoxication. This condition
is also frequent on certain dates of cultural significance (e.g., New Year’s Eve) and, for some
subgroups, during specific events (e.g., wakes following funerals). Other subgroups encourage
drinking at religious celebrations (e.g., Jewish and Catholic holidays), while still others strongly
discourage all drinking or intoxication (e.g., some religious groups, such as Mormons,
fundamentalist Christians, and Muslims).
Sex- and Gender-Related Diagnostic Issues
Historically, in many Western societies, acceptance of drinking and drunkenness is more
tolerated for men, but such gender differences may be much less prominent in recent years,
especially during adolescence and young adulthood. In general, women are less tolerant of the
same amount of alcohol than men.
Diagnostic Markers
Intoxication is usually established by observing an individual’s behavior and smelling alcohol on
the breath. The degree of intoxication increases with an individual’s blood or breath alcohol level
and with the ingestion of other substances, especially those with sedating effects.

Other medical conditions.
Alcohol-induced mental disorders.
Sedative, hypnotic, or anxiolytic intoxication.
Association With Suicidal Thoughts or Behavior
A collaborative, international study in emergency departments in 17 countries found that acute
alcohol use, independent of chronic use, increases the risk of suicide attempt, with each drink
raising the risk by 30%. For more information, see “Association With Suicidal Thoughts or
Behavior” in the Alcohol Use Disorder section.
Functional Consequences of Alcohol Intoxication
Alcohol intoxication contributed to the more than 95,000 deaths and 2.8 million years of
potential life lost each year in the United States from 2011 through 2015, shortening the
lives of those who died by an average of 30 years. In addition, intoxication with this drug
contributes to huge costs associated with drunk driving and lost time from school or work, as
well as interpersonal arguments and physical fights.
Differential Diagnosis
Several medical (e.g., diabetic acidosis) and neurological conditions
(e.g., cerebellar ataxia, multiple sclerosis) can temporarily resemble alcohol intoxication.
Alcohol intoxication is distinguished from alcohol-induced
mental disorders (e.g., alcohol-induced depressive disorder, with onset during intoxication)
because the symptoms (e.g., depressed mood) in these latter disorders are in excess of those
usually associated with alcohol intoxication, predominate in the clinical presentation, and are
severe enough to warrant clinical attention.
Intoxication with sedative, hypnotic, or anxiolytic
drugs or with other sedating substances (e.g., antihistamines, anticholinergic drugs) can be
mistaken for alcohol intoxication. The differential requires observing alcohol on the breath,
measuring blood or breath alcohol levels, ordering a medical workup, and gathering a good
history. The signs and symptoms of sedative-hypnotic intoxication are very similar to those
observed with alcohol and include similar problematic behavioral or psychological changes.
These changes are accompanied by evidence of impaired functioning and judgment—which, if
intense, can result in a life-threatening coma—and levels of incoordination that can interfere with
driving abilities and with performing usual activities. However, there is no smell as there is with
alcohol, but there is likely to be evidence of misuse of the depressant drug in the blood or urine
toxicology analyses.
Comorbidity
Alcohol intoxication may occur comorbidly with other substance intoxication, especially in
individuals with conduct disorder or antisocial personality disorder. Given the typical overlap of
alcohol intoxication with alcohol use disorder, see “Comorbidity” under Alcohol Use Disorder
for more details about co-occurring conditions that are likely to be encountered.

Alcohol Withdrawal
Diagnostic Criteria
A. Cessation of (or reduction in) alcohol use that has been heavy and prolonged.
B. Two (or more) of the following, developing within several hours to a few days
after the cessation of (or reduction in) alcohol use described in Criterion A:
1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100 bpm).
2. Increased hand tremor.
3. Insomnia.
4. Nausea or vomiting.
5. Transient visual, tactile, or auditory hallucinations or illusions.
6. Psychomotor agitation.
7. Anxiety.
8. Generalized tonic-clonic seizures.
C. The signs or symptoms in Criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication or
withdrawal from another substance.
Specify if:
With perceptual disturbances: This specifier applies in the rare instance when
hallucinations (usually visual or tactile) occur with intact reality testing, or
auditory, visual, or tactile illusions occur in the absence of a delirium.
Coding note: The ICD-10-CM code depends on whether or not there is a comorbid
alcohol use disorder and whether or not there are perceptual disturbances.
For alcohol withdrawal, without perceptual disturbances: If a mild alcohol
use disorder is comorbid, the ICD-10-CM code is F10.130, and if a moderate or
severe alcohol use disorder is comorbid, the ICD-10-CM code is F10.230. If
there is no comorbid alcohol use disorder, then the ICD-10-CM code is F10.930.
For alcohol withdrawal, with perceptual disturbances: If a mild alcohol use
disorder is comorbid, the ICD-10-CM code is F10.132, and if a moderate or
severe alcohol use disorder is comorbid, the ICD-10-CM code is F10.232. If
there is no comorbid alcohol use disorder, then the ICD-10-CM code is F10.932.
Specifiers

When hallucinations occur in the absence of delirium (i.e., in a clear sensorium), a diagnosis of
substance/medication-induced psychotic disorder should be considered.
Diagnostic Features
The essential feature of alcohol withdrawal is the presence of a characteristic withdrawal
syndrome that develops within several hours to a few days after the cessation of (or reduction in)
heavy and prolonged alcohol use (Criteria A and B). The withdrawal syndrome includes two or
more of the symptoms reflecting autonomic hyperactivity and anxiety listed in Criterion B, along
with gastrointestinal symptoms.
Withdrawal symptoms cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning (Criterion C). The symptoms must not be
attributable to another medical condition and are not better explained by another mental disorder
(e.g., generalized anxiety disorder), including intoxication or withdrawal from another substance
(e.g., sedative, hypnotic, or anxiolytic withdrawal) (Criterion D).
Symptoms can be relieved by administering alcohol or benzodiazepines (e.g., diazepam). The
withdrawal symptoms typically begin when blood concentrations of alcohol decline sharply (i.e.,
within 4–12 hours) after alcohol use has been stopped or reduced. Reflecting the relatively fast
metabolism of alcohol, symptoms of alcohol withdrawal usually peak in intensity during the
second day of abstinence and are likely to improve markedly by the fourth or fifth day.
Following acute withdrawal, however, symptoms of anxiety, insomnia, and autonomic
dysfunction may persist for up to 3–6 months at lower levels of intensity.
Fewer than 10% of individuals who develop alcohol withdrawal will ever develop dramatic
symptoms (e.g., severe autonomic hyperactivity, tremors, alcohol withdrawal delirium). Tonicclonic seizures occur in fewer than 3% of individuals.
Associated Features
Although confusion and changes in consciousness are not core criteria for alcohol withdrawal,
alcohol withdrawal delirium (see “Delirium” in the chapter “Neurocognitive Disorders”) may
occur in the context of withdrawal. As is true for any agitated, confused state, regardless of the
cause, in addition to a disturbance of consciousness and cognition, withdrawal delirium can
include visual, tactile, or (rarely) auditory hallucinations
(delirium tremens). When alcohol withdrawal delirium develops, it is likely that a clinically
relevant medical condition may be present (e.g., liver failure, pneumonia, gastrointestinal
bleeding, sequelae of head trauma, hypoglycemia, an electrolyte imbalance, postoperative
status).
Prevalence
It is estimated that approximately 50% of middle-class, highly functional individuals with
alcohol use disorder in the United States have ever experienced a full alcohol withdrawal
syndrome. Among individuals with alcohol use disorder who are hospitalized or homeless, the
rate of alcohol withdrawal may be greater than 80%. Less than 10% of individuals in withdrawal

Environmental.
Other medical conditions.
ever demonstrate alcohol withdrawal delirium or withdrawal seizures. The prevalence of alcohol
withdrawal symptoms does not seem to vary across U.S. ethnoracial groups.
Development and Course
Acute alcohol withdrawal occurs as an episode usually lasting 4–5 days and only after extended
periods of heavy drinking. Withdrawal is relatively rare in individuals younger than 30 years,
and the risk and severity increase with increasing age.
Risk and Prognostic Factors
Alcohol withdrawal is more likely to occur with heavier alcohol intake, and that might be most
often observed in individuals with conduct disorder and antisocial personality disorder.
Withdrawal states are also more severe in individuals who are also dependent on other
depressant drugs (sedative-hypnotics) and individuals who have had more alcohol withdrawal
experiences in the past. Predictors of severe alcohol withdrawal include alcohol withdrawal
delirium, prior histories of severe withdrawal syndromes, low blood potassium levels, decreased
platelet counts, and systolic hypertension.
The probability of developing alcohol withdrawal increases with the quantity and
frequency of alcohol consumption. Most individuals with this condition are drinking daily,
consuming large amounts (approximately more than eight drinks per day) for multiple days.
However, there are large inter-individual differences, with enhanced risks for individuals with
concurrent medical conditions, those with family histories of alcohol withdrawal (i.e., a genetic
component), those with prior withdrawals, and individuals who consume sedative, hypnotic, or
anxiolytic drugs.
Diagnostic Markers
Autonomic hyperactivity in the context of moderately high but falling blood alcohol levels and a
history of prolonged, heavy drinking indicate a likelihood of alcohol withdrawal.
Functional Consequences of Alcohol Withdrawal
Symptoms of withdrawal may serve to perpetuate drinking behaviors and contribute to relapse,
resulting in persistently impaired social and occupational functioning. Symptoms requiring
medically supervised detoxification result in hospital utilization and loss of work productivity.
Overall, the presence of withdrawal is associated with greater functional impairment and poor
prognosis among individuals with alcohol use disorder.
Differential Diagnosis
The symptoms of alcohol withdrawal can also be mimicked by some
medical conditions (e.g., hypoglycemia and diabetic ketoacidosis). Essential tremor,
a disorder that frequently runs in families, may erroneously suggest the tremulousness associated
with alcohol withdrawal.

Alcohol-induced mental disorders.
Sedative, hypnotic, or anxiolytic withdrawal.
Alcohol withdrawal is distinguished from alcohol-induced
mental disorders (e.g., alcohol-induced anxiety disorder, with onset during withdrawal) because
the symptoms (e.g., anxiety) in these latter disorders are in excess of those usually associated
with alcohol withdrawal, predominate in the clinical presentation, and are severe enough to
warrant clinical attention.
Sedative, hypnotic, or anxiolytic withdrawal produces a
syndrome very similar to that of alcohol withdrawal.
Comorbidity
Given the typical overlap of alcohol withdrawal with alcohol use disorder, see “Comorbidity”
under Alcohol Use Disorder for more details about co-occurring conditions that are likely to be
encountered.
Alcohol-Induced Mental Disorders
The following alcohol-induced mental disorders are described in other chapters of the manual
with disorders with which they share phenomenology (see the substance/medication-induced
mental disorders in these chapters): alcohol-induced psychotic disorder (“Schizophrenia
Spectrum and Other Psychotic Disorders”); alcohol-induced bipolar and related disorder
(“Bipolar and Related Disorders”); alcohol-induced depressive disorder (“Depressive
Disorders”); alcohol-induced anxiety disorder (“Anxiety Disorders”); alcohol-induced sleep
disorder 
(“Sleep-Wake 
Disorders”); 
alcohol-induced 
sexual 
dysfunction 
(“Sexual
Dysfunctions”); and alcohol-induced major or mild neurocognitive disorder (“Neurocognitive
Disorders”). For alcohol intoxication delirium and alcohol withdrawal delirium, see the criteria
and discussion of delirium in the chapter “Neurocognitive Disorders.” These alcohol-induced
mental disorders are diagnosed instead of alcohol intoxication or alcohol withdrawal only when
the symptoms are sufficiently severe to warrant independent clinical attention.
Diagnostic and Associated Features
The symptom profiles for an alcohol-induced condition resemble the corresponding independent
mental disorders as described elsewhere in this manual. Moreover, while alcohol-induced
conditions can have the same severe consequences as independent mental disorders (e.g., suicide
attempts), they are likely to improve without formal treatment in a matter of days to weeks after
cessation of severe intoxication and/or withdrawal.
Each alcohol-induced mental disorder is listed in the relevant diagnostic section and therefore
only a brief description is offered here. These alcohol-induced mental disorders must have
developed in the context of severe alcohol intoxication and/or alcohol withdrawal.
Given that the presentation of an alcohol-induced mental disorder symptomatically resembles
the presentations of independent mental disorders from the same diagnostic class, they must be
differentiated based on the temporal relationship between the alcohol use and the psychiatric
symptoms. Individuals with alcohol-induced mental disorders are likely to also demonstrate the
associated features seen with an alcohol use disorder, as listed in that subsection.
There must be evidence that the disorder being observed is not likely to be better explained

by an independent mental disorder. The latter is likely to occur if the mental
disorder was present before the severe intoxication or withdrawal, or continued for more than
1 month after the cessation of severe intoxication or withdrawal. When symptoms are observed
only during a delirium, they should be considered part of the delirium and not diagnosed
separately, as many symptoms (including disturbances in mood, anxiety, and reality testing) are
commonly seen during agitated, confused states. The alcohol-induced mental disorder must be
clinically relevant, causing significant distress or significant functional impairment. Finally, there
are indications that the intake of substances of abuse in the context of a preexisting mental
disorder are likely to result in an intensification of the preexisting independent syndrome.
Rates of alcohol-induced mental disorders vary somewhat by diagnostic category. For
example, the lifetime risk for major depressive episodes in individuals with alcohol use disorder
is approximately 40%, but only about one-third to one-half of these represent independent major
depressive syndromes observed outside the context of intoxication. Similar rates of alcoholinduced sleep and anxiety disorders are likely, but alcohol-induced psychotic episodes are
estimated to be seen in less than 5% of individuals with alcohol use disorder.
Development and Course
Once present, the symptoms of an alcohol-induced mental disorder are likely to remain clinically
relevant as long as the individual continues to experience severe intoxication or withdrawal.
While the symptoms may be identical to those of independent mental disorders (e.g., psychoses,
major depressive disorder), and while they can have the same severe consequences (e.g., suicide
attempts), all alcohol-induced mental disorders other than alcohol-induced neurocognitive
disorder, amnestic confabulatory type (alcohol-induced persisting amnestic disorder), regardless
of the severity of the symptoms, are likely to improve relatively quickly and unlikely to remain
clinically relevant for more than 1 month after cessation of severe intoxication and/or
withdrawal.
The alcohol-induced mental disorders are an important part of the differential diagnoses for
the independent mental conditions. Independent schizophrenia, major depressive disorder,
bipolar disorder, and anxiety disorders, such as panic disorder, are likely to be associated with
much longer-lasting periods of symptoms and often require longer-term medications to optimize
the probability of improvement or recovery. The alcohol-induced mental disorders, on the other
hand, are likely to be much shorter in duration and disappear within several days to 1 month after
cessation of severe intoxication and/or withdrawal, even without psychotropic medications.
The importance of recognizing an alcohol-induced mental disorder is similar to the relevance
of identifying the possible role of some endocrine conditions and medication reactions before
diagnosing an independent mental disorder. In light of the high prevalence of alcohol use
disorders worldwide, it is important that these alcohol-induced diagnoses be considered before
independent mental disorders are diagnosed.
Unspecified Alcohol-Related Disorder

F15.920
F10.99
This category applies to presentations in which symptoms characteristic of an
alcohol-related disorder that cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning predominate but do not
meet the full criteria for any specific alcohol-related disorder or any of the disorders
in the substance-related and addictive disorders diagnostic class.
Caffeine-Related Disorders
Caffeine Intoxication
Caffeine Withdrawal
Caffeine-Induced Mental Disorders
Unspecified Caffeine-Related Disorder
Caffeine Intoxication
Diagnostic Criteria
A. Recent consumption of caffeine (typically a high dose well in excess of 250 mg).
B. Five (or more) of the following signs or symptoms developing during, or shortly
after, caffeine use:
1. Restlessness.
2. Nervousness.
3. Excitement.
4. Insomnia.
5. Flushed face.
6. Diuresis.
7. Gastrointestinal disturbance.
8. Muscle twitching.
9. Rambling flow of thought and speech.
10. Tachycardia or cardiac arrhythmia.
11. Periods of inexhaustibility.
12. Psychomotor agitation.

C. The signs or symptoms in Criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.
Diagnostic Features
Caffeine can be consumed from a number of different sources, including coffee, tea, caffeinated
soda, “energy” drinks, over-the-counter analgesics and cold remedies, weight-loss aids, and
chocolate. Caffeine is also increasingly being used as an additive to vitamins and to food
products. More than 85% of children and adults in the United States consume caffeine. Some
caffeine users display symptoms consistent with problematic use, including tolerance and
withdrawal (see “Caffeine Withdrawal” later in this chapter); the data are not available at this
time to determine the clinical significance of a caffeine use disorder and its prevalence. In
contrast, there is evidence that caffeine withdrawal and caffeine intoxication are clinically
significant and sufficiently prevalent.
The essential feature of caffeine intoxication is recent consumption of caffeine and five or
more signs or symptoms that develop during or shortly after caffeine use (Criteria A and B).
Symptoms include restlessness, nervousness, excitement, insomnia, flushed face, diuresis, and
gastrointestinal complaints, which can occur with low doses (e.g., 200 mg) in
vulnerable individuals such as children, the elderly, or individuals who have not been
exposed to caffeine previously. Symptoms that generally appear at levels of more than 1 g/day
include muscle twitching, rambling flow of thought and speech, tachycardia or cardiac
arrhythmia, periods of inexhaustibility, and psychomotor agitation. Caffeine intoxication may
not occur despite high caffeine intake because of the development of tolerance. The signs or
symptoms must cause clinically significant distress or impairment in social, occupational, or
other important areas of functioning (Criterion C). The signs or symptoms must not be
attributable to another medical condition and are not better explained by another mental disorder
(e.g., an anxiety disorder) or intoxication with another substance (Criterion D).
Associated Features
Mild sensory disturbances (e.g., ringing in the ears and flashes of light) may occur with high
doses of caffeine. Although large doses of caffeine can increase heart rate, typical dietary doses
can slow heart rate. Whether excess caffeine intake can cause headaches is unclear. On physical
examination, agitation, restlessness, sweating, tachycardia, flushed face, and increased bowel
motility may be seen. Caffeine blood levels may provide important information for diagnosis,
particularly when the individual is a poor historian, although these levels are not diagnostic by
themselves in view of the individual variation in response to caffeine.
Prevalence

Environmental.
Genetic and physiological.
Independent mental disorders.
The prevalence of caffeine intoxication in the general population is unclear. In the United States,
approximately 7% of individuals in the population may experience five or more symptoms along
with functional impairment consistent with a diagnosis of caffeine intoxication.
Consumption of caffeinated energy drinks, often together with alcohol, leading to caffeine
intoxication, has increased among adolescents and young adults in high-income countries,
resulting in the doubling of U.S. emergency department visits related to caffeinated energy
drinks between 2007 and 2011.
Development and Course
Consistent with a half-life of caffeine of approximately 4–6 hours, caffeine intoxication
symptoms usually remit within the first day or so and do not have any known long-lasting
consequences. However, individuals who consume very high doses of caffeine (i.e., 5–10 g) may
require immediate medical attention, as such doses can be lethal.
With advancing age, individuals are likely to demonstrate increasingly intense reactions to
caffeine, with greater complaints of interference with sleep or feelings of hyperarousal. Caffeine
intoxication among young individuals after consumption of highly caffeinated products,
including energy drinks, has been observed. Children and adolescents may be at increased risk
for caffeine intoxication because of low body weight, lack of tolerance, and lack of knowledge
about the pharmacological effects of caffeine.
Risk and Prognostic Factors
Caffeine intoxication is often seen among individuals who use caffeine less
frequently or in those who have recently increased their caffeine intake by a substantial amount.
Furthermore, oral contraceptives significantly decrease the elimination of caffeine and
consequently may increase the risk of intoxication.
Genetic factors may affect risk of caffeine intoxication.
Functional Consequences of Caffeine Intoxication
Impairment from caffeine intoxication may have serious consequences, including dysfunction at
work or school, social indiscretions, or failure to fulfill role obligations. Moreover, extremely
high doses of caffeine can be fatal. In some cases, caffeine intoxication may precipitate a
caffeine-induced disorder.
Differential Diagnosis
Caffeine intoxication may be characterized by symptoms (e.g.,
panic attacks) that resemble independent mental disorders. To meet criteria for caffeine
intoxication, the symptoms must not be associated with another medical condition or another
mental disorder, such as an anxiety disorder, that could better explain them. Manic episodes;
panic disorder; generalized anxiety disorder; amphetamine intoxication; sedative, hypnotic, or
anxiolytic withdrawal or tobacco withdrawal; sleep disorders; and medication-induced side
effects (e.g., akathisia) can cause a clinical picture that is similar to that of caffeine intoxication.

Caffeine-induced mental disorders.
F15.93
The temporal relationship of the symptoms to increased
caffeine use or to abstinence from caffeine helps to establish the diagnosis. Caffeine intoxication
is differentiated from caffeine-induced anxiety disorder, with onset during intoxication (see
“Substance/Medication-Induced Anxiety Disorder” in the chapter “Anxiety Disorders”), and
caffeine-induced sleep disorder, with onset during intoxication (see “Substance/MedicationInduced Sleep Disorder” in the chapter “Sleep-Wake Disorders”), because the symptoms (e.g.,
anxiety and insomnia, respectively) in these latter disorders are in excess of those usually
associated with caffeine intoxication, predominate in the clinical presentation, and are severe
enough to warrant independent clinical attention.
Comorbidity
Typical dietary doses of caffeine have not been consistently associated with medical problems.
However, heavy use (e.g., > 400 mg) can cause or exacerbate anxiety and somatic symptoms and
gastrointestinal distress. With acute, extremely high doses of caffeine, grand mal seizures and
respiratory failure may result in death. Excessive caffeine use is associated with depressive
disorders, bipolar disorders, eating disorders, psychotic disorders, sleep disorders, and substancerelated disorders, whereas individuals with anxiety disorders are more likely to avoid caffeine.
Caffeine Withdrawal
Diagnostic Criteria
A. Prolonged daily use of caffeine.
B. Abrupt cessation of or reduction in caffeine use, followed within 24 hours by
three (or more) of the following signs or symptoms:
1. Headache.
2. Marked fatigue or drowsiness.
3. Dysphoric mood, depressed mood, or irritability.
4. Difficulty concentrating.
5. Flu-like symptoms (nausea, vomiting, or muscle pain/stiffness).
C. The signs or symptoms in Criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not associated with the physiological effects of
another medical condition (e.g., migraine, viral illness) and are not better
explained by another mental disorder, including intoxication or withdrawal from
another substance.

Diagnostic Features
The essential feature of caffeine withdrawal is the presence of a characteristic withdrawal
syndrome that develops after the abrupt cessation of (or substantial reduction in) prolonged daily
caffeine ingestion (Criterion B). Because individuals may be unaware of the wide array of
sources of caffeine beyond coffee, colas, and energy drinks (e.g., over-the-counter analgesics and
cold remedies, weight loss aids, chocolate), they may not connect ingestion of these substances
with symptoms of caffeine withdrawal. The caffeine withdrawal syndrome is indicated by three
or more of the following (Criterion B): headache; marked fatigue or drowsiness; dysphoric
mood, depressed mood, or irritability; difficulty concentrating; and flu-like symptoms (nausea,
vomiting, or muscle pain/stiffness). The withdrawal syndrome causes clinically significant
distress or impairment in social, occupational, or other important areas of functioning (Criterion
C). The symptoms must not be associated with the physiological effects of another medical
condition and are not better explained by another mental disorder (Criterion D).
Headache is the hallmark feature of caffeine withdrawal and may be diffuse, gradual in
development, throbbing, severe, and sensitive to movement. However, other symptoms of
caffeine withdrawal can occur in the absence of headache. Caffeine is the most widely used
behaviorally active drug in the world and is present in many different types of beverages (e.g.,
coffee, tea, mate, soft drinks, energy drinks), foods, energy aids, medications, and dietary
supplements. Because caffeine ingestion is often integrated into social customs and daily rituals
(e.g., coffee break, tea time), some caffeine consumers may be unaware of their physical
dependence on caffeine. Thus, caffeine withdrawal symptoms could be unexpected and
misattributed to other causes (e.g., the flu, migraine). Furthermore, caffeine withdrawal
symptoms may occur when individuals are required to abstain from foods and beverages prior to
medical procedures or when a usual caffeine dose is missed because of a change in routine (e.g.,
during travel, weekends).
The probability and severity of caffeine withdrawal generally increase as a function of usual
daily caffeine dose. However, there is large variability among individuals and within individuals
across different episodes in the incidence, severity, and time course of withdrawal symptoms.
Caffeine withdrawal symptoms may occur after abrupt cessation of relatively low chronic daily
doses of caffeine (i.e., 100 mg).
Associated Features
Caffeine abstinence has been shown to be associated with impaired behavioral and cognitive
performance (e.g., sustained attention), as well as with increased total sleep time, sleep
efficiency, and slow-wave sleep. Electroencephalographic studies have shown that caffeine
withdrawal symptoms are significantly associated with increases in theta power and decreases in
beta-2 power. Decreased motivation to work and decreased sociability have also been reported
during caffeine withdrawal. Increased analgesic use during caffeine withdrawal has been
documented.
Prevalence
More than 85% of adults and children in the United States regularly consume caffeine, with adult
caffeine consumers ingesting about 280 mg/day on average. The incidence and prevalence of the

Temperamental.
Environmental.
Genetic and physiological.
caffeine withdrawal syndrome in the general population are unclear. In the United States,
headache may occur in approximately 50% of cases of caffeine abstinence.
In attempts to permanently stop caffeine use, more than 70% of individuals in a U.S.
metropolitan county reported at least one caffeine withdrawal symptom (47% experienced
headache), and 24% experienced headache plus one or more other symptoms as well as
functional impairment due to withdrawal. Among individuals who abstained from caffeine for at
least 24 hours but were not trying to permanently stop caffeine use, 11% experienced headache
plus one or more other symptoms as well as functional impairment. Caffeine consumers can
decrease the incidence of caffeine withdrawal by using caffeine daily or only infrequently (e.g.,
no more than 2 consecutive days). Gradual reduction in caffeine over a period of days or weeks
may decrease the incidence and severity of caffeine withdrawal.
Development and Course
Symptoms usually begin 12–24 hours after the last caffeine dose and peak after 1–2 days of
abstinence. Caffeine withdrawal symptoms last for 2–9 days, with the possibility of withdrawal
headaches occurring for up to 21 days. Symptoms usually remit rapidly (within 30–60 minutes)
after re-ingestion of caffeine. Doses of caffeine significantly less than the individual’s usual daily
dose may be sufficient to prevent or attenuate caffeine withdrawal symptoms (e.g., consumption
of 25 mg by an individual who typically consumes 300 mg).
Caffeine is unique in that it is a behaviorally active drug that is consumed by individuals of
nearly all ages, with rates of caffeine consumption and overall level of caffeine consumption
increasing with age. Although caffeine withdrawal among children and adolescents has been
documented, relatively little is known about risk factors for caffeine withdrawal among this age
group. The use of highly caffeinated energy drinks is increasing in young people, which could
increase the risk for caffeine withdrawal.
Risk and Prognostic Factors
Heavy caffeine use has been observed among individuals with mental disorders,
including eating disorders and alcohol and other substance use disorders, as well as among
individuals who smoke cigarettes and those who are incarcerated. Thus, these individuals could
be at higher risk for caffeine withdrawal upon acute caffeine abstinence.
The unavailability of caffeine is an environmental risk factor for incipient
withdrawal symptoms. While caffeine is legal and usually widely available, there are conditions
in which caffeine use may be restricted, such as during medical procedures, pregnancy,
hospitalizations, religious observances, wartime, travel, and research participation. These
external environmental circumstances may precipitate a withdrawal syndrome in vulnerable
individuals.
Genetic factors appear to increase vulnerability to caffeine withdrawal,
but no specific genes have been identified.
Culture-Related Diagnostic Issues

Other medical conditions and medication side effects.
Caffeine-induced sleep disorder.
Habitual caffeine consumers who fast for religious reasons may be at increased risk for caffeine
withdrawal.
Sex- and Gender-Related Diagnostic Issues
Metabolism of caffeine is slower in females who use oral contraceptives and in the luteal phase
of the menstrual cycle, and caffeine metabolism becomes progressively slower in the second and
third trimesters of pregnancy compared with the first trimester and the nonpregnant state. These
features reduce the rate of clearance and may diminish withdrawal, although they can also
lengthen the duration of caffeine-associated adverse symptoms. It is unlikely that doses < 300
mg/day are associated with adverse reproductive outcomes in pregnancy.
Functional Consequences of Caffeine Withdrawal
Caffeine withdrawal symptoms can vary from mild to extreme, at times causing functional
impairment in normal daily activities. Rates of functional impairment in studies conducted
largely in the United States range from 10% to 55% (median 13%), with rates as high as 73%
found among individuals who also show other problematic features of caffeine use. Examples of
functional impairment include being unable to work, exercise, or care for children; staying in bed
all day; missing religious services; ending a vacation early; and canceling a social gathering.
Caffeine withdrawal headaches may be described by individuals as “the worst headaches” ever
experienced. Decrements in cognitive and motor performance have also been observed.
Differential Diagnosis
Caffeine withdrawal can mimic migraine and
other headache disorders, viral illnesses, sinus conditions, tension, other drug withdrawal states
(e.g., from amphetamines, cocaine), and medication side effects. The final determination of
caffeine withdrawal should rest on a determination of the pattern and amount consumed, the time
interval between caffeine abstinence and onset of symptoms, and the particular clinical features
presented by the individual. A challenge dose of caffeine followed by symptom remission may
be used to confirm the diagnosis.
Caffeine withdrawal is distinguished from caffeine-induced sleep
disorder (e.g., caffeine-induced sleep disorder, insomnia type, with onset during withdrawal)
because the sleep symptoms are in excess of those usually associated caffeine withdrawal,
predominate in the clinical presentation, and are severe enough to warrant clinical attention.
Comorbidity
Caffeine withdrawal may be associated with major depressive disorder, generalized anxiety
disorder, panic disorder, antisocial personality disorder, moderate to severe alcohol use disorder,
and cannabis and cocaine use.
Caffeine-Induced Mental Disorders

The following caffeine-induced mental disorders are described in other chapters of the manual
with disorders with which they share phenomenology (see the substance/medication-induced
mental disorders in these chapters): caffeine-induced anxiety disorder (“Anxiety Disorders”) and
caffeine-induced sleep disorder (“Sleep-Wake Disorders”). These caffeine-induced mental
disorders are diagnosed instead of caffeine intoxication or caffeine withdrawal only when the
symptoms are sufficiently severe to warrant independent clinical attention.
Unspecified Caffeine-Related Disorder
F15.99
This category applies to presentations in which symptoms characteristic of a
caffeine-related disorder that cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning predominate but do not
meet the full criteria for any specific caffeine-related disorder or any of the disorders
in the substance-related and addictive disorders diagnostic class.
Cannabis-Related Disorders
Cannabis Use Disorder
Cannabis Intoxication
Cannabis Withdrawal
Cannabis-Induced Mental Disorders
Unspecified Cannabis-Related Disorder
Cannabis Use Disorder
Diagnostic Criteria
A. A problematic pattern of cannabis use leading to clinically significant impairment
or distress, as manifested by at least two of the following, occurring within a 12month period:
1. Cannabis is often taken in larger amounts or over a longer period than was
intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control
cannabis use.

3. A great deal of time is spent in activities necessary to obtain cannabis, use
cannabis, or recover from its effects.
4. Craving, or a strong desire or urge to use cannabis.
5. Recurrent cannabis use resulting in a failure to fulfill major role obligations at
work, school, or home.
6. Continued cannabis use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of cannabis.
7. Important social, occupational, or recreational activities are given up or
reduced because of cannabis use.
8. Recurrent cannabis use in situations in which it is physically hazardous.
9. Cannabis use is continued despite knowledge of having a persistent or
recurrent physical or psychological problem that is likely to have been caused
or exacerbated by cannabis.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of cannabis to achieve
intoxication or desired effect.
b. Markedly diminished effect with continued use of the same amount of
cannabis.
11. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome for cannabis (refer to Criteria A
and B of the criteria set for cannabis withdrawal).
b. Cannabis (or a closely related substance) is taken to relieve or avoid
withdrawal symptoms.
Specify if:
In early remission: After full criteria for cannabis use disorder were previously
met, none of the criteria for cannabis use disorder have been met for at least 3
months but
for less than 12 months (with the exception that Criterion A4, “Craving, or a
strong desire or urge to use cannabis,” may be met).
In sustained remission: After full criteria for cannabis use disorder were
previously met, none of the criteria for cannabis use disorder have been met at
any time during a period of 12 months or longer (with the exception that Criterion
A4, “Craving, or a strong desire or urge to use cannabis,” may be present).
Specify if:
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to cannabis is restricted.
Code based on current severity/remission: If a cannabis intoxication, cannabis
withdrawal, or another cannabis-induced mental disorder is also present, do not use

the codes below for cannabis use disorder. Instead, the comorbid cannabis use
disorder is indicated in the 4th character of the cannabis-induced disorder code (see
the coding note for cannabis intoxication, cannabis withdrawal, or a specific
cannabis-induced mental disorder). For example, if there is comorbid cannabisinduced anxiety disorder and cannabis use disorder, only the cannabis-induced
anxiety disorder code is given, with the 4th character indicating whether the
comorbid cannabis use disorder is mild, moderate, or severe: F12.180 for mild
cannabis use disorder with cannabis-induced anxiety disorder or F12.280 for a
moderate or severe cannabis use disorder with cannabis-induced anxiety disorder.
Specify current severity/remission:
F12.10 Mild: Presence of 2–3 symptoms.
F12.11 Mild, In early remission
F12.11 Mild, In sustained remission
F12.20 Moderate: Presence of 4–5 symptoms.
F12.21 Moderate, In early remission
F12.21 Moderate, In sustained remission
F12.20 Severe: Presence of 6 or more symptoms.
F12.21 Severe, In early remission
F12.21 Severe, In sustained remission
Specifiers
“In a controlled environment” applies as a further specifier of remission if the individual is both
in remission and in a controlled environment (i.e., in early remission in a controlled environment
or in sustained remission in a controlled environment). Examples of these environments are
closely supervised and substance-free jails, therapeutic communities, and locked hospital units.
Changing severity across time in an individual may also be reflected by changes in the
frequency (e.g., days of use per month or times used per day) and/or dose (e.g., amount used per
episode) of cannabis, as assessed by individual self-report, report of knowledgeable others,
clinician’s observations, and biological testing.
Diagnostic Features
Cannabis use disorder includes problems associated with use of substances derived from the
cannabis plant and chemically similar synthetic compounds. In these substances, the primary
component with psychoactive effects (and hence, addiction potential) is the cannabinoid delta-9tetrahydrocannabinol (delta-9-THC or THC). Cannabinoids have diverse effects in the brain,
prominent among which are actions on CB1 and CB2 cannabinoid receptors found throughout the
central nervous system.
Cannabis is used in many forms. It is most commonly smoked in a cigarette-like form (often

called “joints” or “reefers”), and also in pipes, water pipes (bongs or hookahs), or hollowed-out
cigars (“blunts”). More recently developed methods include “vaping” (vaporizing) by heating
without combustion plant cannabis material to release psychoactive components for inhalation,
and “dabbing,” in which a concentrated cannabis product (butane hash oil, known as “dabs”),
created through butane extraction of THC from cannabis plant material, is heated and inhaled.
Vaping and dabbing are gaining popularity, particularly among youth. Cannabis can also be
ingested orally in food (edibles) or beverages. Inhalation typically produces more rapid and
intense onset of effects than oral administration. Hashish or hash oil, a concentrated extraction of
the cannabis plant, is also used. Across products, cannabis potency (THC concentration) varies
greatly, averaging 10%–15% in typical cannabis plant material, 30%–40% in hashish, and 50%–
55% in hash oil. During the past two decades, the potency of seized illegal plant cannabis has
steadily increased, and legal cannabis products may have even higher THC potency (e.g., 20%
for plant material and 68% for cannabis extracts). Synthetic oral THC formulations
(pill/capsules/sprays) are also available for various medical uses (e.g., chronic pain; nausea and
vomiting caused by chemotherapy or ano-rexia; weight loss among those with AIDS). Other
entirely illicit synthetic cannabinoid compounds (e.g., K2, Spice, JWH-018, JWH-073) are in the
form of plant material sprayed with a cannabinoid formulation. Although such synthetic
cannabinoids are designed to mimic cannabis effects, their chemical composition, potency,
effects, and duration of action are unpredictable, and they may cause more severe adverse effects
than cannabis plant products, including seizures, cardiac conditions, psychosis, and even death.
In the United States, cannabis remains an illegal substance under federal law, while the legal
status of cannabis varies by state. Thus, cannabis use under state law can involve an illicit
product, a product authorized for medical purposes, or a completely legal product. The most
common medical purpose for cannabis use is chronic pain, and the conditions approved for
medicinal cannabis use vary from state to state. When cannabis or a cannabinoid is taken as
indicated for a medical condition, tolerance and withdrawal (physiological dependence) may
occur but should not be the primary basis for diagnosing cannabis use disorder. The efficacy of
cannabis for different medical conditions continues to be debated, and cannabis use as medically
advised should be taken into account when a cannabis use disorder diagnosis is being considered.
Patterns of cannabis use can range from light, infrequent use to heavy, frequent use.
Individuals with DSM-5 cannabis use disorder use cannabis frequently (on average, 4 or more
days a week), and some individuals may use cannabis throughout the day over a period of
months or years. Because of the increasingly common perception that cannabis use is harmless,
individuals may not recognize that symptoms of cannabis use disorder (e.g., withdrawal
symptoms) are cannabis related. Additionally, among individuals with multiple substance use
disorders, lack of clarity about whether symptoms are caused by cannabis or by other substances
may lead to underreporting of cannabis use disorder symptoms.
Cannabis use disorder is defined by the same 11 criteria that define the other substance use
disorders, as supported by considerable empirical evidence. These criteria, a cluster of behavioral
and physical symptoms, lead to clinically significant impairment or distress and can include
withdrawal, tolerance, craving, spending a great deal of time in activities related to the substance,
and hazardous use (e.g., driving while under its influence). Some individuals who use cannabis
multiple times per day do not perceive themselves as spending excessive time under the
influence of cannabis or recovering from its effects, despite being intoxicated from cannabis or
coming down from its effects most of the time, most days. An important marker of a severe

cannabis use disorder is continued use despite negative effects on other important activities or
relationships (e.g., school, work, sports, partner or parent relationship).
Regular cannabis users become tolerant to many acute cannabis effects, and cessation of
regular cannabis use generally leads to a cannabis withdrawal syndrome. Cannabis withdrawal
can cause significant distress, leading to continued use to relieve the symptoms and difficulty
quitting use or relapse.
Associated Features
Individuals who regularly use cannabis often report using it to cope with mood, insomnia, anger,
pain, or other physiological or psychological problems, and individuals diagnosed with cannabis
use disorder frequently have other concurrent mental disorders. Careful assessment can reveal
that cannabis use contributes to exacerbation of these symptoms, as well as other reasons for
frequent use (e.g., the coping motives listed above; to experience euphoria; as an enjoyable
social activity). Chronic intake of cannabis can produce a lack of motivation that resembles
persistent depressive disorder.
Because some individuals may underreport the amount or frequency of their cannabis use,
provider awareness of common signs and symptoms of cannabis use and intoxication facilitates
better assessment of cannabis use disorder. Some additional signs of acute and chronic use are
red eyes (conjunctival injection), cannabis odor on clothing, yellowing of fingertips (from
smoking joints), chronic cough, burning of incense (to hide the odor), and exaggerated craving
and impulse for specific foods, sometimes at odd times of the day or night.
Prevalence
Cannabinoids, especially cannabis, are the most widely used illicit psychoactive substances in
the United States. The following prevalence data are drawn from U.S.-based studies, unless
otherwise noted. Among youth (ages 12–17 years), the past-year prevalence of DSM-IV
cannabis use disorder is 2.7%–3.1%. Among adults age 18 years and older, the prevalence is
1.5%–2.9%. Among cannabis users, the prevalence of DSM-IV cannabis use disorder is 20.4%
among youth and 30.6% among adults. For DSM-5 cannabis use disorder, 12-month prevalence
is approximately 2.5% among adults (1.4%, 0.6%, and 0.6% at mild, moderate, and severe
levels, respectively). During the past decade, the prevalence of cannabis use disorder has
decreased among adolescents. In contrast, among adults, some studies suggest that the
prevalence of cannabis use disorder has either remained stable or increased—for example,
among adults in the general population, patients in inpatient settings, and patients in the Veterans
Health Administration. Globally, the age-standardized rate of cannabis use disorders was 289.7
per 100,000 people in 2016, a 25.6% increase over 1990. Prevalence varies widely across
geographic regions, being lowest in Western Sub-Saharan Africa and highest in North America.
According to age, the prevalence of cannabis use disorder in the United States is highest
among individuals ages 18–29 years (6.9%) and lowest among individuals age 45 years and
older (0.8%). Rates of cannabis use disorder are greater in men than in women (3.5% vs. 1.7%)
and in boys than in girls ages 12–17 years (3.4% vs. 2.8%), although gender differences have

been narrowing in recent birth cohorts across several countries. Regarding ethnoracial
differences, for adolescents ages 12–17 years, rates are highest among Hispanics (3.8%),
followed by Whites (3.1%), African Americans (2.9%), and other ethnoracial groups (2.3%).
Among adults, the prevalence of cannabis use disorder is 5.3% in American Indians and Alaska
Natives, 4.5% in African Americans, 2.6% in Hispanics, 2.2% in Whites, and 1.3% in Asians
and Pacific Islanders. In the United States and other high-income countries, the number of
individuals seeking treatment for cannabis-related problems has increased since the 1990s.
However, among adults with cannabis use disorder, only 7%–8% received any type of cannabisspecific treatment in the past year, indicating that cannabis use disorder is a seriously
undertreated condition.
Development and Course
The onset of cannabis use disorder can occur at any age but is most common during adolescence
or young adulthood. The increasing acceptability and availability of medical and recreational
marijuana may impact the development and course of cannabis use disorder, with increased onset
among older adults.
Generally, cannabis use disorder develops over an extended period of time, although the
progression may be more rapid in adolescents, particularly in those with conduct problems. Most
individuals who develop a cannabis use disorder establish a pattern of cannabis use that
gradually increases in frequency and amount. Beginning around 2010, cannabis has increasingly
displaced alcohol and tobacco in the United States as the first psychoactive substance used
during adolescence. This may be attributable to the decrease in perceived harmfulness of
cannabis use among adolescents and adults and the fact that many now perceive cannabis use as
less harmful than alcohol or tobacco use.
Cannabis use disorder among preteens, adolescents, and young adults is associated with
preferences for novelty-seeking and risk-taking, norm-violating or other illegal behaviors, and
conduct disorder. Milder cases of cannabis use disorder in youth primarily reflect continued use
despite problems related to disapproval of use by peers, school administration, or family, and can
place youths at risk for physical or behavioral consequences. In more severe cases, progression
to using alone or using throughout the day interferes with daily functioning and takes the place of
previously established, prosocial activities.
Cannabis use disorder among adults typically involves well-established patterns of daily
cannabis use that continue despite clear psychosocial or medical problems. Many adults
experience repeated desire to stop or have failed at repeated cessation attempts. Milder adult
cases may resemble mild adolescent cases in that cannabis use is not as frequent or heavy but
continues despite potential significant consequences of sustained use. The rate of use among U.S.
middle-age and older adults is increasing, which may be atributable to increased availability and
acceptability, along with a possible “baby boomer” cohort effect resulting from high prevalence
of use among those who were young adults in the late 1960s and the 1970s.
Early onset of cannabis use (e.g., prior to age 15 years) is a robust predictor of the
development of cannabis use disorder and other types of substance use disorders and mental
disorders during young adulthood. Such early onset is often concurrent with other externalizing

Temperamental.
Environmental.
Genetic and physiological.
problems (e.g., symptoms of conduct disorder). However, early onset is also a predictor of
internalizing problems and as such may reflect a general risk factor for the development of
mental disorders.
Risk and Prognostic Factors
A history of conduct disorder in childhood or adolescence and antisocial
personality disorder are risk factors for the development of many substance use disorders,
including cannabis use disorder. Other risk factors include externalizing or internalizing
disorders during childhood or adolescence. Youth with high behavioral disinhibition scores show
early-onset substance use disorders, including cannabis use disorder and multiple substance
involvement, and early conduct problems.
Risk factors include unstable or abusive family situations, use of cannabis among
immediate family members, a childhood history of emotional or physical abuse or the violent
death of a close family member or friend, a family history of substance use disorders, and low
socioeconomic status. As with all substances of abuse, the ease of availability of the substance is
a risk factor; cannabis is relatively easy to obtain in most cultures, which increases the risk of
developing a cannabis use disorder. Increasingly permissive U.S. state medical and recreational
marijuana laws have reduced barriers to obtaining cannabis in about two-thirds of U.S. states.
Living in a U.S. state that has legalized recreational
marijuana use increases the risk for adult cannabis use disorder. The risk of the disorder among
past-year cannabis users is higher among Black, Native American, Hispanic, and Asian
American adults and adolescents, relative to non-Hispanic Whites.
Genetic influences contribute to the development of cannabis use
disorders. Heritable factors contribute between 30% and 80% of the total variance in risk of
cannabis use disorders, although studies have not yet definitively identified the specific genetic
variants involved. Genetic and environmental influences shared between cannabis and other
types of substance use disorders suggest a general common basis for substance use disorders that
includes cannabis use disorder.
Culture-Related Diagnostic Issues
The acceptability of cannabis for medical and recreational use has varied widely over time and
across cultural contexts. Currently, cannabis is one of the world’s most commonly used
psychoactive substances. In some cultural settings, cannabis use is influenced by ethnicity,
religion, and sociocultural practices, such as political movements.
Sex- and Gender-Related Diagnostic Issues
Compared with men, women report more severe cannabis withdrawal symptoms, especially
mood symptoms such as irritability, restlessness, and anger, and gastrointestinal symptoms such
as stomachache and nausea, which may contribute to potential telescoping (faster transition from
first cannabis use to cannabis use disorder).

Past-month cannabis use was reported by 7.0% of pregnant women in a nationally
representative U.S. survey in 2016–2017. The rate of cannabis use is lower in pregnant compared
with nonpregnant women, but resumption of use following delivery occurs in the majority who
attain abstinence in pregnancy.
Diagnostic Markers
Detection of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THCCOOH) in urine is often used
as a biological marker of cannabis use. In frequent users, urine tests for THCCOOH often remain
positive for weeks after last use, limiting the uses for these tests (e.g., remission status), and
expertise in urine testing methods is needed to reliably interpret results. However, a positive
result can be useful in working with individuals who deny all use despite concerns of family or
friends. Tests for the presence of cannabinoids in blood that give more fine-grained results are
under active development, and the development of detection using oral fluids may eventually
offer the possibility of roadside tests to use in driving safety efforts.
Association With Suicidal Thoughts or Behavior
In a study of Iraq/Afghanistan-era veterans, after adjustment for multiple sociodemographic
factors, psychiatric and other substance comorbidities, and past trauma, including combat,
cannabis use disorder was still associated with increased risk of both suicidal and nonsuicidal
self-injury. In a study of all U.S. Veterans Health Administration patients in 2005, any current
substance use disorder was associated with increased suicide risk in both sexes but especially
among women. In particular, men with cannabis use disorder had a suicide rate of 79 per
100,000 person-years, and women with cannabis use disorder had a suicide rate of 47 per
100,000 person-years. A review and meta-analysis of the international literature from 1990
through 2015 found evidence that chronic cannabis use, but not acute cannabis use, is associated
with suicidal thoughts and behavior.
Functional Consequences of Cannabis Use Disorder
Functional consequences of cannabis use disorder are part of the diagnostic criteria. Many areas
of psychosocial, cognitive, and health functioning may be compromised in relation to
cannabis use disorder. Although it can be difficult to distinguish the short-term impairments due
to cannabis intoxication from the longer-term functional consequences of cannabis use disorder,
cognitive function (particularly higher executive function) even while unintoxicated may become
compromised in cannabis users in a cumulative dose-dependent relationship, which may
contribute to difficulty at school or work. Accidents due to potentially dangerous activities while
under the influence (e.g., driving, sports, at work) are also of concern. In particular, placebocontrolled studies and large-scale epidemiological studies show that cannabis use impairs driver
reaction time, spatial perceptions, and decision-making. Cannabis use has also been linked to a
reduction in goal-directed activity and decreased self-efficacy, labeled an amotivational
syndrome, that manifests itself in poor school or work performance. Similarly, cannabisassociated problems with social relationships are commonly reported in those with cannabis use

Nonproblematic use of cannabis.
Cannabis intoxication, cannabis withdrawal, and cannabis-induced mental disorders.
disorder. Cannabis use is associated with poorer life satisfaction and increased treatment and
hospitalization for mental health problems.
Differential Diagnosis
Although the majority of individuals who use cannabis do not
have problems related to its use, 20%–30% of cannabis users do experience symptoms and
associated consequences consistent with a cannabis use disorder. Differentiating nonproblematic
use of cannabis and cannabis use disorder can be challenging because individuals may not
attribute cannabis-related social, behavioral, or psychological problems to the substance,
especially in the context of polysubstance use. Also, failure to acknowledge heavy cannabis use
and its role in associated problems is common among individuals referred to treatment by others
(i.e., school, family, employer, criminal justice system).
Cannabis 
use
disorder is differentiated from cannabis intoxication, cannabis withdrawal, and cannabis-induced
mental disorders (e.g., cannabis-induced anxiety disorder) in that cannabis use disorder describes
a problematic pattern of cannabis use that involves impaired control over cannabis use, social
impairment due to cannabis use, risky cannabis use (e.g., driving while intoxicated), and
pharmacological symptoms (the development of tolerance or withdrawal), whereas cannabis
intoxication, cannabis withdrawal, and cannabis-induced mental disorders describe psychiatric
syndromes that develop in the context of heavy use. Cannabis intoxication, cannabis withdrawal,
and cannabis-induced mental disorders occur frequently in individuals with cannabis use
disorder. In such cases, a diagnosis of cannabis intoxication, cannabis withdrawal, or a cannabisinduced mental disorder should be given in addition to a diagnosis of cannabis use disorder, the
presence of which is indicated in the diagnostic code.
Comorbidity
Cannabis use disorder is highly comorbid with other substance use disorders (e.g., alcohol,
cocaine, opioids). For example, compared with adults without cannabis use disorder, having a
cannabis use disorder multiplies the risk for any other substance disorder by a factor of about
nine. Cannabis has been commonly considered as a “gateway” drug because individuals who use
cannabis have a substantially greater lifetime probability than nonusers of subsequently using
other, more risky substances (e.g., opioids or cocaine). Among adults seeking treatment for a
cannabis use disorder, many (63%) report problematic use of secondary or tertiary substances,
including alcohol, cocaine, methamphetamine/amphetamine, and heroin or other opiates, and
cannabis use disorder is often a secondary or tertiary problem among those with a primary
diagnosis of other substance use disorders. Among adolescents in treatment, cannabis is
frequently the primary substance of abuse (76%).
Among adults with DSM-5 cannabis use disorder, 64% had a past-year tobacco use disorder,
and the odds of a comorbid tobacco disorder increased sharply as the severity of cannabis use
disorder increased.
Co-occurring mental disorders are also common among those with cannabis use disorder and

include major depressive disorder, bipolar I and II disorders, anxiety disorders, posttraumatic
stress disorder, and personality disorders. In a Minnesota twin study, about half of adolescents
with cannabis use disorder had internalizing disorders (e.g., anxiety, depression, posttraumatic
stress disorder), and 64% had externalizing disorders (e.g., conduct disorder, attentiondeficit/hyperactivity disorder).
Considerable concern has been raised about cannabis use as a risk factor in schizophrenia and
other psychotic disorders. Cannabis use in critical periods is consistently associated with a
threefold increase in the risk for psychosis. Differences in frequency of daily cannabis use and
use of high-potency varieties of cannabis may have contributed to the striking variation in the
incidence of psychotic disorder across 11 European sites. The population attributable fraction
from regular cannabis in explaining hospital admissions for psychosis was estimated to be 17.7%
(95% CI: 1.2%–45.5%) in Chile. On the other hand, some data suggest that childhood abuse may
be the determining factor that increases the risk for cannabis abuse and for psychosis. Overall,
cannabis use may contribute to the onset of an acute psychotic episode, can exacerbate some
symptoms, and can adversely affect treatment of a major psychotic illness.
Regarding medical conditions, cannabinoid hyperemesis syndrome is a syndrome of nausea
and cyclic vomiting associated with regular cannabis use that is increasingly seen in emergency
departments as the prevalence of cannabis use increases. In addition, respiratory disorders (e.g.,
asthma, chronic obstructive pulmonary disease, pneumonia) are associated with regular cannabis
use (by smoking, vaping, or e-cigarettes) regardless of tobacco co-use, as are some adverse
cardiovascular outcomes.
Cannabis Intoxication
Diagnostic Criteria
A. Recent use of cannabis.
B. Clinically significant problematic behavioral or psychological changes (e.g.,
impaired motor coordination, euphoria, anxiety, sensation of slowed time,
impaired judgment, social withdrawal) that developed during, or shortly after,
cannabis use.
C. Two (or more) of the following signs or symptoms developing within 2 hours of
cannabis use:
1. Conjunctival injection.
2. Increased appetite.
3. Dry mouth.
4. Tachycardia.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.
Specify if:

With perceptual disturbances: Hallucinations with intact reality testing or
auditory, visual, or tactile illusions occur in the absence of a delirium.
Coding note: The ICD-10-CM code depends on whether or not there is a comorbid
cannabis use disorder and whether or not there are perceptual disturbances.
For cannabis intoxication, without perceptual disturbances: If a mild
cannabis use disorder is comorbid, the ICD-10-CM code is F12.120, and if a
moderate or severe cannabis use disorder is comorbid, the ICD-10-CM code is
F12.220. If there is no comorbid cannabis use disorder, then the ICD-10-CM
code is F12.920.
For cannabis intoxication, with perceptual disturbances: If a mild cannabis
use disorder is comorbid, the ICD-10-CM code is F12.122, and if a moderate or
severe cannabis use disorder is comorbid, the ICD-10-CM code is F12.222. If
there is no comorbid cannabis use disorder, then the ICD-10-CM code is
F12.922.
Specifiers
When hallucinations occur in the absence of intact reality testing, a diagnosis of
substance/medication-induced psychotic disorder should be considered.
Diagnostic Features
The essential feature of cannabis intoxication is the presence of clinically significant problematic
behavioral or psychological changes that develop during, or shortly after, cannabis use (Criterion
B). Intoxication typically begins with a “high” feeling followed by symptoms that include
euphoria with inappropriate laughter and grandiosity, sedation, lethargy, impairment in shortterm memory, difficulty carrying out complex mental processes, impaired judgment, distorted
sensory perceptions, impaired motor performance, and the sensation that time is passing slowly.
Occasionally, anxiety (which can be severe), dysphoria, or social withdrawal occurs. These
psychoactive effects are accompanied by two or more of the following signs, developing within
2 hours of cannabis use: conjunctival injection, increased appetite, dry mouth, and tachycardia
(Criterion C).
Intoxication develops within minutes if plant cannabis is smoked, and may take a few hours
to develop when the cannabis is ingested orally. The effects usually last 3–4 hours, with duration
longer when the substance is ingested orally. The magnitude of the behavioral and physiological
changes depends on the dose, the method of administration, and the characteristics of the
individual using the substance, such as rate of absorption, tolerance, and sensitivity to the effects
of the substance. Because most cannabinoids, including delta-9-tetrahydrocannabinol (delta-9THC), are fat soluble, the effects of cannabis or hashish may occasionally persist or reoccur for
12–24 hours because of the slow release of psychoactive substances from fatty tissue or to
enterohepatic circulation.
Synthetic cannabinoids (e.g., Spice), whose use has become more common in recent years,

Other substance intoxication.
Cannabis-induced mental disorders.
also produce rapid effects, including euphoria, talkativeness, feelings of joy and laughter, and
relaxation. In terms of psychoactive effects, low doses of synthetic cannabinoids and other
cannabis products are similar. At higher doses of synthetic cannabinoids, delusional and
hallucinatory symptoms are more likely to occur.
Prevalence
The prevalence of episodes of cannabis intoxication in the general population is unknown.
However, it is probable that most individuals using cannabis would at some time experience
symptoms that meet criteria for cannabis intoxication. Given this, the prevalence of individuals
using cannabis and the prevalence of individuals experiencing cannabis intoxication are likely
similar.
Functional Consequences of Cannabis Intoxication
Impairment from cannabis intoxication may have serious consequences, including dysfunction at
work or school, social indiscretions, failure to fulfill role obligations, traffic accidents, and
having unprotected sex. In rare cases, cannabis intoxication may precipitate a psychosis that may
vary in duration.
Differential Diagnosis
Note that if the clinical presentation includes hallucinations in the absence of intact reality
testing, a diagnosis of substance/medication-induced psychotic disorder should be considered.
Cannabis intoxication may resemble intoxication with other types of
substances. However, in contrast to cannabis intoxication, alcohol intoxication and sedative,
hypnotic, or anxiolytic intoxication frequently decrease appetite, increase aggressive behavior,
and produce nystagmus or ataxia. Hallucinogens in low doses may cause a clinical picture that
resembles cannabis intoxication. Phencyclidine, like cannabis, can be smoked and also causes
perceptual changes, but phencyclidine intoxication is much more likely to cause ataxia and
aggressive behavior.
Cannabis intoxication is distinguished from cannabis-induced
mental disorders (e.g., cannabis-induced anxiety disorder, with onset during intoxication)
because the symptoms (e.g., anxiety) in these latter disorders are in excess of those usually
associated with cannabis intoxication, predominate in the clinical presentation, and are severe
enough to warrant independent clinical attention.
Comorbidity
Given the typical overlap of cannabis intoxication with cannabis use disorder, see “Comorbidity”
under Cannabis Use Disorder for more details about co-occurring conditions that are likely to be
encountered.
Cannabis Withdrawal

Diagnostic Criteria
A. Cessation of cannabis use that has been heavy and prolonged (i.e., usually daily
or almost daily use over a period of at least a few months).
B. Three (or more) of the following signs and symptoms develop within
approximately 1 week after Criterion A:
1. Irritability, anger, or aggression.
2. Nervousness or anxiety.
3. Sleep difficulty (e.g., insomnia, disturbing dreams).
4. Decreased appetite or weight loss.
5. Restlessness.
6. Depressed mood.
7. At least one of the following physical symptoms causing significant
discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or
headache.
C. The signs or symptoms in Criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication or
withdrawal from another substance.
Coding note: The ICD-10-CM code depends on whether or not there is a comorbid
cannabis use disorder. If a mild cannabis use disorder is comorbid, the ICD-10-CM
code is F12.13, and if a moderate or severe cannabis use disorder is comorbid, the
ICD-10-CM code is F12.23. For cannabis withdrawal occurring in the absence of a
cannabis use disorder (e.g., in a patient taking cannabis solely under appropriate
medical supervision), the ICD-10-CM code is F12.93.
Diagnostic Features
The essential feature of cannabis withdrawal is the presence of a characteristic withdrawal
syndrome that develops after the cessation of regular cannabis use. Regular users become
tolerant to many acute cannabis effects, and cessation of regular use can lead to a cannabis
withdrawal syndrome. Common cannabis withdrawal symptoms include irritability, depressed
mood, anxiety, restlessness, sleep difficulty, and decreased appetite or weight loss. Cannabis
withdrawal can cause significant distress, leading to continued use to relieve the symptoms,
difficulty in quitting, and relapse. Unlike withdrawal from other substances (i.e., opioids,
alcohol, sedatives), behavioral and emotional symptoms (e.g., nervousness, irritability, sleep
difficulty) are often more common than physical symptoms (e.g., shakiness, sweating).
Associated Features

Cannabis withdrawal may be accompanied by observed fatigue, yawning, difficulty
concentrating, and rebound periods of increased appetite and hypersomnia that follow initial
periods of loss of appetite and insomnia.
Prevalence
Among adult and adolescent cannabis users, prevalence estimates of cannabis withdrawal
symptoms vary widely, from 35% to 95%, based on research in the United States and other
countries. Some of the variation in rates is likely attributable to assessment methods, and some to
differences between samples. Among adult regular cannabis users in the general population, 12%
reported signs and symptoms that met criteria for the full syndrome of DSM-5 cannabis
withdrawal, with substantial differences in prevalence among non-Latinx Whites (10%), African
Americans (15.3%), and Asian Americans, Native Hawaiians, and Pacific Islanders (31%).
Among adults and adolescents who are enrolled in treatment or are heavy cannabis users, 50%–
95% report cannabis withdrawal. These findings indicate that cannabis withdrawal occurs among
a substantial subset of regular cannabis users who try to quit.
Development and Course
Withdrawal onset typically occurs within 24–48 hours after cessation of use. It peaks within 2–5
days and resolves within 1–2 weeks, although sleep disturbance can persist longer. The amount,
duration, and frequency of cannabis smoking required to produce cannabis withdrawal are
unknown, but more chronic and frequent cannabis use is associated with greater quantity and
severity of withdrawal symptoms. Cannabis withdrawal can occur in adults and adolescents.
Women may experience more severe cannabis withdrawal symptoms than men.
Risk and Prognostic Factors
Among cannabis users, the propensity to experience cannabis withdrawal is moderately
heritable, indicating genetic influences. The prevalence and severity of cannabis withdrawal are
greater among heavier cannabis users, particularly those seeking treatment for cannabis use
disorder. Withdrawal severity may also be related to the presence and severity of comorbid
symptoms of mental disorders.
Functional Consequences of Cannabis Withdrawal
Cannabis users report using cannabis to relieve withdrawal symptoms, making cannabis
withdrawal a contributor to the persistence of cannabis use disorder. This makes cannabis
withdrawal a current target for medication development. Worse outcomes may be
associated with greater withdrawal. Sleep difficulty has been reported as the withdrawal
symptom most often associated with relapse to cannabis use. Cannabis users report having
relapsed to cannabis use or initiating use of other drugs (e.g., tranquilizers) to provide relief from
cannabis withdrawal symptoms.

Differential Diagnosis
Because many of the symptoms of cannabis withdrawal are also symptoms of other substance
withdrawal syndromes or of depressive or bipolar disorders, careful evaluation should focus on
ensuring that the symptoms are not better explained by cessation of another substance (e.g.,
tobacco or alcohol withdrawal), another mental disorder (generalized anxiety disorder, major
depressive disorder), or another medical condition. Given the increasingly common belief that
cannabis use is harmless, regular cannabis users experiencing cannabis withdrawal may not
realize that their withdrawal symptoms are due to the effects of cannabis wearing off, and
continue to use cannabis as a form of self-medication.
Comorbidity
Among adult frequent cannabis users, cannabis withdrawal is associated with comorbid
depression, anxiety, and antisocial personality disorder. Given the typical overlap of cannabis
withdrawal with cannabis use disorder, see “Comorbidity” under Cannabis Use Disorder for
more details about co-occurring conditions that are likely to be encountered.
Cannabis-Induced Mental Disorders
The following cannabis-induced mental disorders are described in other chapters of the manual
with disorders with which they share phenomenology (see the substance/medication-induced
mental disorders in these chapters): cannabis-induced psychotic disorder (“Schizophrenia
Spectrum and Other Psychotic Disorders”); cannabis-induced anxiety disorder (“Anxiety
Disorders”); and cannabis-induced sleep disorder (“Sleep-Wake Disorders”). For cannabis
intoxication delirium and delirium induced by pharmaceutical cannabis receptor agonists taken
as prescribed, see the criteria and discussion of delirium in the chapter “Neurocognitive
Disorders.” These cannabis-induced mental disorders are diagnosed instead of cannabis
intoxication or cannabis withdrawal when the symptoms are sufficiently severe to warrant
independent clinical attention.
Unspecified Cannabis-Related Disorder
F12.99
This category applies to presentations in which symptoms characteristic of a
cannabis-related disorder that cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning predominate but do not
meet the full criteria for any specific cannabis-related disorder or any of the disorders
in the substance-related and addictive disorders diagnostic class.

Hallucinogen-Related Disorders
Phencyclidine Use Disorder
Other Hallucinogen Use Disorder
Phencyclidine Intoxication
Other Hallucinogen Intoxication
Hallucinogen Persisting Perception Disorder
Phencyclidine-Induced Mental Disorders
Hallucinogen-Induced Mental Disorders
Unspecified Phencyclidine-Related Disorder
Unspecified Hallucinogen-Related Disorder
Phencyclidine Use Disorder
Diagnostic Criteria
A. A pattern of phencyclidine (or a pharmacologically similar substance) use
leading to clinically significant impairment or distress, as manifested by at least
two of the following, occurring within a 12-month period:
1. Phencyclidine is often taken in larger amounts or over a longer period than
was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control
phencyclidine use.
3. A great deal of time is spent in activities necessary to obtain phencyclidine,
use the phencyclidine, or recover from its effects.
4. Craving, or a strong desire or urge to use phencyclidine.
5. Recurrent phencyclidine use resulting in a failure to fulfill major role
obligations at work, school, or home (e.g., repeated absences from work or
poor work performance related to phencyclidine use; phencyclidine-related
absences, suspensions, or expulsions from school; neglect of children or
household).
6. Continued phencyclidine use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of the
phencyclidine (e.g., arguments with a spouse about consequences of
intoxication; physical fights).
7. Important social, occupational, or recreational activities are given up or
reduced because of phencyclidine use.

8. Recurrent phencyclidine use in situations in which it is physically hazardous
(e.g., driving an automobile or operating a machine when impaired by a
phencyclidine).
9. Phencyclidine use is continued despite knowledge of having a persistent or
recurrent physical or psychological problem that is likely to have been caused
or exacerbated by the phencyclidine.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the phencyclidine to achieve
intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of
the phencyclidine.
Note: Withdrawal symptoms and signs are not established for phencyclidines, and
so this criterion does not apply. (Withdrawal from phencyclidines has been reported
in animals but not documented in human users.)
Specify if:
In early remission: After full criteria for phencyclidine use disorder were
previously met, none of the criteria for phencyclidine use disorder have been met
for at least 3 months but for less than 12 months (with the exception that
Criterion A4, “Craving, or a strong desire or urge to use the phencyclidine,” may
be met).
In sustained remission: After full criteria for phencyclidine use disorder were
previously met, none of the criteria for phencyclidine use disorder have been met
at any time during a period of 12 months or longer (with the exception that
Criterion A4, “Craving, or a strong desire or urge to use the phencyclidine,” may
be met).
Specify if:
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to phencyclidines is restricted.
Code based on current severity/remission: If a phencyclidine intoxication or
another phencyclidine-induced mental disorder is also present, do not use the codes
below for phencyclidine use disorder. Instead, the comorbid phencyclidine use
disorder is indicated in the 4th character of the phencyclidine-induced disorder code
(see the coding note for phencyclidine intoxication or a specific phencyclidineinduced mental disorder). For example, if there is comorbid phencyclidine-induced
psychotic disorder, only the phencyclidine-induced psychotic disorder code is given,
with the 4th character indicating whether the comorbid phencyclidine use disorder is
mild, moderate, or severe: F16.159 for mild phencyclidine use disorder with
phencyclidine-induced psychotic disorder or F16.259 for a moderate or severe
phencyclidine use disorder with phencyclidine-induced psychotic disorder.

Specify current severity/remission:
F16.10 Mild: Presence of 2–3 symptoms.
F16.11 Mild, In early remission
F16.11 Mild, In sustained remission
F16.20 Moderate: Presence of 4–5 symptoms.
F16.21 Moderate, In early remission
F16.21 Moderate, In sustained remission
F16.20 Severe: Presence of 6 or more symptoms.
F16.21 Severe, In early remission
F16.21 Severe, In sustained remission
Specifiers
“In a controlled environment” applies as a further specifier of remission if the individual is both
in remission and in a controlled environment (i.e., in early remission in a controlled environment
or in sustained remission in a controlled environment). Examples of these environments are
closely supervised and substance-free jails, therapeutic communities, and locked hospital units.
Diagnostic Features
The phencyclidines (or phencyclidine-like substances) include phencyclidine (e.g., PCP, “angel
dust”) and less potent but similarly acting compounds such as ketamine,
cyclohexamine, and dizocilpine. These substances were first developed as dissociative
anesthetics in the 1950s and became street drugs in the 1960s. They produce feelings of
separation from mind and body (hence “dissociative”) in low doses, and at high doses, stupor
and coma can result. These substances are most commonly smoked or taken orally, but they may
also be snorted or injected. Although the primary psychoactive effects of phencyclidine last for a
few hours, the total elimination rate of this drug from the body typically extends 8 days or
longer. The hallucinogenic effects in vulnerable individuals may last for weeks and may
precipitate a persistent psychotic episode resembling schizophrenia. Ketamine has been observed
to have utility in the treatment of major depressive disorder. Withdrawal symptoms have not
been clearly established in humans, and therefore the withdrawal criterion is not included in the
diagnosis of phencyclidine use disorder.
Associated Features
Phencyclidine may be detected in urine for up to 8 days or even longer at very high doses. In
addition to laboratory tests to detect its presence, characteristic symptoms resulting from
intoxication with phencyclidine or related substances may aid in its diagnosis. Phencyclidine is
likely to produce dissociative symptoms, analgesia, nystagmus, risk of hypertension/hypotension
and shock, euphoria, visual/auditory hallucinations, derealization, and unusual thought content.

Other substance use disorders.
Phencyclidine intoxication and phencyclidine-induced mental disorders.
Violent behavior can also occur with phencyclidine use, as intoxicated individuals may believe
that they are being attacked.
Prevalence
Data on the prevalence of phencyclidine use disorder are not available, but rates appear to be low
(based on rates of the overall category of hallucinogen use disorder, which includes
phencyclidine, of about 0.1% among individuals age 12 and older in the United States).
Furthermore, among U.S. substance use treatment facility admissions, only 0.3% of the admitted
individuals endorsed phencyclidine as their primary drug.
Risk and Prognostic Factors
In a general population study in Australia, ketamine users were more likely to be men and to
have consumed more than 11 standard drinks per day.
Sex- and Gender-Related Diagnostic Issues
The gender ratio for phencyclidine use disorder is not known, but among U.S. substance use
treatment facility admissions endorsing phencyclidine as the primary drug, 62% were men.
Diagnostic Markers
Laboratory testing may be useful, as phencyclidine is present in the urine in intoxicated
individuals up to 8 days after ingestion. The individual’s history along with certain physical
signs (e.g., nystagmus, analgesia, prominent hypertension) may aid in distinguishing the
phencyclidine clinical picture from that of other hallucinogens.
Functional Consequences of Phencyclidine Use Disorder
In individuals with phencyclidine use disorder, there may be physical evidence of injuries from
accidents, fights, and falls. Chronic use of phencyclidine can lead to acute and persistent
cognitive impairment; urinary tract and intestinal symptoms; abdominal pain, chest pain,
palpitations, and tachycardia; respiratory depression; sleep disorders; and depression.
Differential Diagnosis
Distinguishing the effects of phencyclidine from those of other
substances may be important, because phencyclidine can be an additive to other substances (e.g.,
cannabis, cocaine).
Phencyclidine use disorder is
differentiated from phencyclidine intoxication and phencyclidine-induced mental disorders (e.g.,
phencyclidine-induced psychotic disorder) in that phencyclidine use disorder describes a
problematic pattern of phencyclidine use that involves impaired control over phencyclidine use,
social impairment attributable to phencyclidine use, risky phencyclidine use (e.g., driving while
intoxicated), and pharmacological symptoms (the development of tolerance), whereas

Independent mental disorders.
phencyclidine intoxication and phencyclidine-induced mental disorders describe psychiatric
syndromes that occur in the context of heavy use. Phencyclidine intoxication and phencyclidineinduced mental disorders occur frequently in individuals with phencyclidine use disorder. In
such cases, a diagnosis of phencyclidine intoxication or a phencyclidine-induced mental disorder
should be given in addition to a diagnosis of phencyclidine use disorder, the presence of which is
indicated in the diagnostic code.
Some of the effects of phencyclidine use may resemble symptoms
of independent mental disorders, such as psychosis (schizophrenia); low mood (major depressive
disorder); and violent, aggressive behaviors (conduct disorder, antisocial personality disorder).
Discerning whether these behaviors occurred before the intake of the drug is important in the
differentiation of acute drug effects from a preexisting mental disorder.
Comorbidity
Conduct disorder in adolescents and antisocial personality disorder may be associated with
phencyclidine use. Other substance use disorders, especially alcohol, cocaine, and amphetamine
use disorders, are common among those with phencyclidine use disorder.
Other Hallucinogen Use Disorder
Diagnostic Criteria
A. A problematic pattern of hallucinogen (other than phencyclidine) use leading to
clinically significant impairment or distress, as manifested by at least two of the
following, occurring within a 12-month period:
1. The hallucinogen is often taken in larger amounts or over a longer period than
was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control
hallucinogen use.
3. A great deal of time is spent in activities necessary to obtain the hallucinogen,
use the hallucinogen, or recover from its effects.
4. Craving, or a strong desire or urge to use the hallucinogen.
5. Recurrent hallucinogen use resulting in a failure to fulfill major role obligations
at work, school, or home (e.g., repeated absences from work or poor work
performance related to hallucinogen use; hallucinogen-related absences,
suspensions, or expulsions from school; neglect of children or household).
6. Continued hallucinogen use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of the
hallucinogen (e.g., arguments with a spouse about consequences of
intoxication; physical fights).

7. Important social, occupational, or recreational activities are given up or
reduced because of hallucinogen use.
8. Recurrent hallucinogen use in situations in which it is physically hazardous
(e.g., driving an automobile or operating a machine when impaired by the
hallucinogen).
9. Hallucinogen use is continued despite knowledge of having a persistent or
recurrent physical or psychological problem that is likely to have been caused
or exacerbated by the hallucinogen.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the hallucinogen to achieve
intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of
the hallucinogen.
Note: Withdrawal symptoms and signs are not established for hallucinogens, and so
this criterion does not apply.
Specify the particular hallucinogen.
Specify if:
In early remission: After full criteria for other hallucinogen use disorder were
previously met, none of the criteria for other hallucinogen use disorder have
been met for at least 3 months but for less than 12 months (with the exception
that Criterion A4, “Craving, or a strong desire or urge to use the hallucinogen,”
may be met).
In sustained remission: After full criteria for other hallucinogen use disorder
were previously met, none of the criteria for other hallucinogen use disorder
have been met at any time during a period of 12 months or longer (with the
exception that Criterion A4, “Craving, or a strong desire or urge to use the
hallucinogen,” may be met).
Specify if:
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to hallucinogens is restricted.
Code based on current severity/remission: If a hallucinogen intoxication or
another hallucinogen-induced mental disorder is also present, do not use the codes
below for hallucinogen use disorder. Instead, the comorbid hallucinogen use
disorder is indicated in the 4th character of the hallucinogen-induced disorder code
(see the coding note for hallucinogen intoxication or specific hallucinogen-induced
mental disorder). For example, if there is comorbid hallucinogen-induced psychotic
disorder and hallucinogen use disorder, only the hallucinogen-induced psychotic
disorder code is given, with the 4th character indicating whether the comorbid
hallucinogen use disorder is mild, moderate, or severe: F16.159 for mild
hallucinogen use disorder with hallucinogen-induced psychotic disorder or F16.259
for a moderate or severe hallucinogen use disorder with hallucinogen-induced
psychotic disorder.

Specify current severity/remission:
F16.10 Mild: Presence of 2–3 symptoms.
F16.11 Mild, In early remission
F16.11 Mild, In sustained remission
F16.20 Moderate: Presence of 4–5 symptoms.
F16.21 Moderate, In early remission
F16.21 Moderate, In sustained remission
F16.20 Severe: Presence of 6 or more symptoms.
F16.21 Severe, In early remission
F16.21 Severe, In sustained remission
Specifiers
“In a controlled environment” applies as a further specifier of remission if the individual is both
in remission and in a controlled environment (i.e., in early remission in a controlled environment
or in sustained remission in a controlled environment). Examples of these environments are
closely supervised and substance-free jails, therapeutic communities, and locked hospital units.
Diagnostic Features
Hallucinogens comprise a diverse group of substances that despite having different chemical
structures and possibly involving different molecular mechanisms, produce similar alterations of
perception, mood, and cognition in users. Hallucinogens included are phenylalkylamines (e.g.,
mescaline, 
DOM 
[2,5-dimethoxy-4-methylamphetamine], 
and 
MDMA 
[3,4methylenedioxymethamphetamine; also called “ecstasy” or “molly”]); the indoleamines,
including psilocybin (and its metabolite psilocin, the compound primarily responsible for the
psychedelic effects of hallucinogenic mushrooms) and dimethyltryptamine (DMT); and the
ergolines, such as LSD (lysergic acid diethylamide) and morning glory seeds. In addition,
miscellaneous other ethnobotanical compounds are classified as hallucinogens, of which Salvia
divinorum and jimsonweed are two examples. Excluded from the hallucinogen group are
cannabis and its active compound, delta-9-tetrahydrocannabinol (THC) (see the section
“Cannabis-Related Disorders”). These substances can have hallucinogenic effects but are
diagnosed separately because of significant differences in their psychological and behavioral
effects.
Hallucinogens are usually taken orally, although some forms are smoked (e.g., DMT, salvia)
or (rarely) taken intranasally or by injection (e.g., ecstasy). Duration of effects varies across
types of hallucinogens. Some of these substances (i.e., LSD, MDMA) have a long half-life and
extended duration such that users may spend hours to days using and/or recovering from the
effects of these drugs. However, other hallucinogenic drugs (e.g., DMT, salvia) are short acting.
Tolerance to hallucinogens develops with repeated use and has been reported to have both
autonomic and psychological effects.

Temperamental.
MDMA/ecstasy as a hallucinogen may have distinctive effects attributable to both its
hallucinogenic and its stimulant properties. Ecstasy users have a higher risk of developing a
hallucinogen use disorder than those using other hallucinogens. Among both adolescent and
adult ecstasy users and users of other hallucinogens, the most frequently reported hallucinogen
use disorder criteria are tolerance, hazardous use, use despite emotional or health problems,
giving up activities in favor of use, and spending a lot of time obtaining, using, or recovering
from the effects of use. As found for other substances, diagnostic criteria for other hallucinogen
use disorder are arrayed along a single continuum of severity.
Given that a clinically significant withdrawal syndrome has not been consistently
documented in humans, the diagnosis of hallucinogen withdrawal syndrome is not included in
this manual and therefore is not part of the hallucinogen use disorder diagnostic criteria.
However, there may be evidence of withdrawal from MDMA, with endorsement of any two or
more withdrawal symptoms (e.g., malaise, appetite disturbance, mood changes [anxious,
depressed, irritable], poor concentration, sleep disruption) or withdrawal avoidance observed in
more than half of individuals in diverse samples of ecstasy users in the United States and
internationally.
Associated Features
The characteristic symptom features of use of some hallucinogens can aid in diagnosis if urine or
blood toxicology results are not available. For example, individuals who use LSD tend to
experience visual hallucinations that can be frightening.
Prevalence
Other hallucinogen use disorder is rare. In the U.S. general population, about 0.1% of individuals
age 12 or older endorsed the symptoms of past 12-month hallucinogen use disorder in 2018. The
rate was 0.2% among those ages 12–17, 0.4% among those ages 18–25,
and < 0.1% among those age 26 and older. Prevalence is higher in U.S. clinical samples (e.g.,
19% in adolescents in treatment), and among select groups of individuals who use hallucinogens
frequently (e.g., recent heavy ecstasy use) in the United States and Australia, 73.5% of adults and
77% of adolescents have a problematic pattern of use that may meet other hallucinogen use
disorder criteria.
Development and Course
Prevalence of other hallucinogen use disorder by age among adolescents is unknown. Among
U.S. adults age 18 years and older, most (90%) of those with other hallucinogen use disorder are
ages 18–29, suggesting that the disorder is not often persistent and is concentrated in young
adults.
Risk and Prognostic Factors
The use of specific hallucinogens (i.e., ecstasy, salvia) has been linked with high

Environmental.
Genetic and physiological.
sensation-seeking.
On the basis of research in the United States, environmental risk factors of other
hallucinogen use disorder include higher income, lower education, being never married, and
residing in urban areas. Early onset of hallucinogen use has also been linked to transition to
hallucinogen use disorder. Peer use of other drugs is also highly associated with ecstasy and
salvia use.
Among male twins, total variance due to additive genetics has been
estimated to range from 26% to 79%, with inconsistent evidence for shared environmental
influences.
Culture-Related Diagnostic Issues
Historically, hallucinogens have been used as part of established religious or spiritual practices,
such as the use of peyote in the Native American Church and in Mexico. Ritual use by
Indigenous populations of psilocybin obtained from certain types of mushrooms has occurred in
South America, Mexico, and some areas in the United States, or of ayahuasca in the Santo
Daime and União de Vegetal religious groups.
Sex- and Gender-Related Diagnostic Issues
Among U.S. adolescents, boys have greater 12-month prevalence rates of other hallucinogen use
than girls, and these gender differences extend to specific hallucinogens, including LSD,
MDMA, psilocybin, and salvia divinorum. Among U.S. adults, 60% of individuals with other
hallucinogen use disorder are men. International research suggests that women administered
MDMA may have greater subjective effects, such as altered state of consciousness, anxiety, and
depression. No information from international studies is available regarding gender differences
for other hallucinogen use disorder.
Diagnostic Markers
Laboratory testing can be useful in distinguishing among the different hallucinogens. However,
because some agents (e.g., LSD) are so potent that as little as 75 micrograms can produce severe
reactions, typical toxicological examination will not always reveal which substance has been
used.
Functional Consequences of Other Hallucinogen Use Disorder
Although insufficient information exists to clearly note the functional consequences of other
hallucinogen use disorder, complications of use of these substances have been
identified. Adverse effects of other hallucinogen use include those related to intoxication, such as
hyperthermia, cardiac tachyarrhythmias, pneumothorax hypernatremia, motor incoordination,
nystagmus, restlessness, hallucinations/delusions, mydriasis, increased alertness, and high blood
pressure. Other more serious reactions related to consequences of repeated use of other
hallucinogens include renal failure, hepatic failure, seizures, cerebral infarction, rhabdomyolysis,

Other substance disorders.
Hallucinogen intoxication and hallucinogen-induced mental disorders.
Independent mental disorders.
cardiac complications, and hepatotoxicity.
There is evidence for persisting neurotoxic effects of MDMA/ecstasy use, including
impairments in memory, psychological function, and neuroendocrine function; serotonin system
dysfunction; and sleep disturbance; as well as adverse effects on brain microvasculature, white
matter maturation, and damage to axons.
Differential Diagnosis
The effects of hallucinogen use must be distinguished from those of
other substances (e.g., amphetamine use disorder, alcohol or sedative withdrawal), especially
because contamination of the hallucinogens with other drugs is relatively common.
Hallucinogen use disorder is
differentiated from hallucinogen intoxication and hallucinogen-induced mental disorders (e.g.,
hallucinogen-induced psychotic disorder) in that hallucinogen use disorder describes a
problematic pattern of hallucinogen use that involves impaired control over hallucinogen use,
social impairment attributable to hallucinogen use, risky hallucinogen use (e.g., driving while
intoxicated), and pharmacological symptoms (the development of tolerance), whereas
hallucinogen intoxication and hallucinogen-induced mental disorders describe psychiatric
syndromes that occur in the context of heavy use. Hallucinogen intoxication and hallucinogeninduced mental disorders occur frequently in individuals with hallucinogen use disorder. In such
cases, a diagnosis of hallucinogen intoxication or a hallucinogen-induced mental disorder should
be given in addition to a diagnosis of hallucinogen use disorder, the presence of which is
indicated in the diagnostic code.
Some of the effects of hallucinogen use may resemble symptoms of
independent psychiatric disorders, such as schizophrenia and depressive and bipolar disorders.
Discerning whether symptoms occurred before the intake of the drug is important in the
differentiation of acute drug effects from a preexisting mental disorder. In particular,
schizophrenia should be ruled out, as some affected individuals (e.g., individuals with
schizophrenia who exhibit paranoia) may falsely attribute their symptoms to use of
hallucinogens.
Comorbidity
Other hallucinogen use disorder is highly associated with cocaine use disorder, stimulant use
disorder, other substance use disorder, tobacco (nicotine) use disorder, any personality disorder,
posttraumatic stress disorder, and panic attacks.
Phencyclidine Intoxication
Diagnostic Criteria
A. Recent use of phencyclidine (or a pharmacologically similar substance).
B. Clinically significant problematic behavioral changes (e.g., belligerence,

assaultiveness, impulsiveness, unpredictability, psychomotor agitation, impaired
judgment) that developed during, or shortly after, phencyclidine use.
C. Within 1 hour, two (or more) of the following signs or symptoms:
Note: When the drug is smoked, “snorted,” or used intravenously, the onset may
be particularly rapid.
1. Vertical or horizontal nystagmus.
2. Hypertension or tachycardia.
3. Numbness or diminished responsiveness to pain.
4. Ataxia.
5. Dysarthria.
6. Muscle rigidity.
7. Seizures or coma.
8. Hyperacusis.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.
Coding note: The ICD-10-CM code depends on whether there is a comorbid
phencyclidine use disorder. If a mild phencyclidine use disorder is comorbid, the
ICD-10-CM code is F16.120, and if a moderate or severe phencyclidine use disorder
is comorbid, the ICD-10-CM code is F16.220. If there is no comorbid phencyclidine
use disorder, then the ICD-10-CM code is F16.920.
Note: In addition to the section “Functional Consequences of Phencyclidine
Intoxication,” see the corresponding section in Phencyclidine Use Disorder.
Diagnostic Features
Phencyclidine intoxication reflects the clinically significant behavioral changes that occur shortly
after ingestion of this substance (or a pharmacologically similar substance). The most common
clinical presentations of phencyclidine intoxication include disorientation; confusion without
hallucinations; nystagmus; numbness or diminished responsiveness to pain; ataxia; dysarthria;
muscle rigidity; hyperacusis; and coma of varying severity. Other clinically significant
behavioral changes associated with phencyclidine intoxication include violent behavior, extreme
agitation, persecutory delusions, euphoria, retrograde amnesia, and hypertension.
Prevalence
Use of phencyclidine or related substances (e.g., ketamine) may be taken as an estimate of the
prevalence of intoxication. Phencyclidine use is rare, with < 0.1% of the U.S. population age 12
and older reporting past 12-month use in 2018. In surveys of U.S. students and young adults
followed up from high school, past 12-month prevalence of ketamine use, which is assessed

Other substance intoxication.
Phencyclidine-induced mental disorders.
Other medical conditions.
separately from other substances, was estimated at about 1.2% among 12th graders and 0.5%
among young adults, ages 19–28 years.
Diagnostic Markers
Laboratory testing may be useful, as phencyclidine is detectable in urine for up to 8 days
following use, although the levels are only weakly associated with an individual’s clinical
presentation and may therefore not be useful for case management. Creatine phosphokinase and
aspartate aminotransferase levels may be elevated.
Functional Consequences of Phencyclidine Intoxication
Phencyclidine intoxication produces extensive cardiovascular and neurological (e.g., seizures,
dystonias, dyskinesias, catalepsy, hypothermia or hyperthermia) toxicity.
Differential Diagnosis
In particular, in the absence of intact reality testing (i.e., without insight that the perceptual
abnormalities are drug induced), an additional diagnosis of phencyclidine-induced psychotic
disorder should be considered.
Phencyclidine intoxication should be differentiated from intoxication
due to other substances, including other hallucinogens; amphetamine, cocaine, or other
stimulants; and anticholinergics, as well as withdrawal from benzodiazepines. Nystagmus and
bizarre and violent behavior may distinguish intoxication due to phencyclidine from that due to
other substances. Toxicological tests may be useful in making this distinction. However, the
weak correlation between quantitative toxicology levels of phencyclidine and clinical
presentation may diminish the utility of the laboratory findings for patient management.
Phencyclidine 
intoxication 
is 
distinguished 
from
phencyclidine-induced mental disorders (e.g., phencyclidine-induced depressive disorder, with
onset during intoxication) because the symptoms (e.g., depressed mood) in the latter disorders
are in excess of those usually associated with phencyclidine intoxication, predominate in the
clinical presentation, and are severe enough to warrant clinical attention.
Medical conditions to be considered include certain metabolic disorders
like hypoglycemia and hyponatremia, central nervous system tumors, seizure disorders, sepsis,
neuroleptic malignant syndrome, and vascular insults.
Comorbidity
Given the typical overlap of phencyclidine intoxication with phencyclidine use disorder, see
“Comorbidity” under Phencyclidine Use Disorder for more details about co-occurring conditions
that are likely to be encountered.
Other Hallucinogen Intoxication

Diagnostic Criteria
A. Recent use of a hallucinogen (other than phencyclidine).
B. Clinically significant problematic behavioral or psychological changes (e.g.,
marked anxiety or depression, ideas of reference, fear of “losing one’s mind,”
paranoid ideation, impaired judgment) that developed during, or shortly after,
hallucinogen use.
C. Perceptual changes occurring in a state of full wakefulness and alertness (e.g.,
subjective intensification of perceptions, depersonalization, derealization,
illusions, hallucinations, synesthesias) that developed during, or shortly after,
hallucinogen use.
D. Two (or more) of the following signs developing during, or shortly after,
hallucinogen use:
1. Pupillary dilation.
2. Tachycardia.
3. Sweating.
4. Palpitations.
5. Blurring of vision.
6. Tremors.
7. Incoordination.
E. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.
Coding note: The ICD-10-CM code depends on whether there is a comorbid
hallucinogen use disorder. If a mild hallucinogen use disorder is comorbid, the ICD10-CM code is F16.120, and if a moderate or severe hallucinogen use disorder is
comorbid, the ICD-10-CM code is F16.220. If there is no comorbid hallucinogen use
disorder, then the ICD-10-CM code is F16.920.
Note: For information on Associated Features and Culture-Related Diagnostic Issues,
see the corresponding sections in Other Hallucinogen Use Disorder.
Diagnostic Features
Other hallucinogen intoxication reflects the clinically significant behavioral or psychological
changes that occur shortly after ingestion of a hallucinogen. Depending on the specific
hallucinogen, the intoxication may last only minutes (e.g., for salvia) or several hours or longer
(e.g., for LSD [lysergic acid diethylamide] or MDMA [3,4-methylenedioxymethamphetamine]).
Prevalence

Other substance intoxication.
Other conditions.
Hallucinogen persisting perception disorder.
The prevalence of other hallucinogen intoxication is not fully known but may be approximated
based on the prevalence of use of the substances. In 2018, 1.5% of individuals ages 12–17 years
in the United States reported use of hallucinogens in the past year; among individuals ages 18–
25, the rate was 6.9%, and among those age 26 or older, the rate was 1.3%. Rates were
consistently higher for boys and men than for girls and women in every age group.
Association With Suicidal Thoughts or Behavior
Other hallucinogen intoxication may lead to increased suicidal thoughts or behavior, although
suicide is rare among individuals who use hallucinogens. Of note, a study of more than 135,000
randomly selected U.S. adults, including more than 19,000 individuals who use psychedelics, did
not find evidence, after adjustment for sociodemographics, other drug use, and childhood
depression, that lifetime psychedelic use is an independent risk factor for mental health
problems, suicidal thoughts, or suicide attempts. In addition, one large U.S. population survey
found that a lifetime history of hallucinogen use was associated with lower odds of mental
distress and suicidal thoughts or behavior, although a causal relationship between hallucinogenic
drugs and lower distress cannot be inferred from this study. On the basis of these findings, the
relationship of other hallucinogen use to suicidal thoughts and behaviors is uncertain.
Functional Consequences of Other Hallucinogen Intoxication
Other hallucinogen intoxication can have serious consequences. The perceptual disturbances and
impaired judgment associated with other hallucinogen intoxication can result in injuries or
fatalities from automobile crashes, physical fights, or unintentional self-injury (e.g., cuts or falls
from impaired depth perception). When other hallucinogens are consumed in combination with
other drugs (including alcohol), coma can occur, with the duration and profundity of coma
greater than when other hallucinogens are taken alone. Continued use of hallucinogens,
particularly MDMA, has also been linked with neurotoxic effects. Adverse effects of other
hallucinogen use include hyperthermia, cardiac tachyarrhythmias, pneumothorax hypernatremia,
motor incoordination, nystagmus, restlessness, hallucinations/delusions, mydriasis, increased
alertness, and high blood pressure. More serious reactions include renal failure, hepatic failure,
seizures, cerebral infarction, rhabdomyolysis, cardiac complications, and hepatotoxicity.
Differential Diagnosis
Other hallucinogen intoxication should be differentiated from
intoxication with amphetamine-type substances, cocaine, or other stimulants; anticholinergics,
inhalants, and phencyclidine. Toxicological tests are useful in making this distinction, and
determining the route of administration may also be useful.
Other disorders and conditions to be considered include schizophrenia,
depression, withdrawal from other drugs (e.g., sedatives, alcohol), certain metabolic disorders
(e.g., hypoglycemia), seizure disorders, tumors of the central nervous system, and vascular
insults.
Other hallucinogen intoxication is distinguished from

Hallucinogen-induced mental disorders.
F16.983
hallucinogen persisting perception disorder because the symptoms in the latter continue
episodically or continuously for weeks (or longer) after the most recent intoxication.
Other hallucinogen intoxication is distinguished from
hallucinogen-induced mental disorders (e.g., hallucinogen-induced anxiety disorder, with onset
during intoxication) because the symptoms (e.g., anxiety) in these latter disorders are in excess
of those usually associated with other hallucinogen intoxication, predominate in the clinical
presentation, and are severe enough to warrant independent clinical attention.
Comorbidity
Given the typical overlap of other hallucinogen intoxication with other hallucinogen use
disorder, see “Comorbidity” under Other Hallucinogen Use Disorder for more details about cooccurring conditions that are likely to be encountered.
Hallucinogen Persisting Perception Disorder
Diagnostic Criteria
A. Following cessation of use of a hallucinogen, the reexperiencing of one or more
of the perceptual symptoms that were experienced while intoxicated with the
hallucinogen (e.g., geometric hallucinations, false perceptions of movement in
the peripheral visual fields, flashes of color, intensified colors, trails of images of
moving objects, positive afterimages, halos around objects, macropsia and
micropsia).
B. The symptoms in Criterion A cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning.
C. The symptoms are not attributable to another medical condition (e.g., anatomical
lesions and infections of the brain, visual epilepsies) and are not better explained
by another mental disorder (e.g., delirium, major neurocognitive disorder,
schizophrenia) or hypnopompic hallucinations.
Diagnostic Features
The hallmark of hallucinogen persisting perception disorder is the reexperiencing, when the
individual is sober, of the perceptual disturbances that were experienced while the individual was
intoxicated with the hallucinogen (Criterion A). The symptoms may include any perceptual
perturbations, but visual disturbances tend to be predominant. Typical of the abnormal visual
perceptions are geometric hallucinations, false perceptions of
movement in the peripheral visual fields, flashes of color, intensified colors, trails of images of
moving objects (i.e., images left suspended in the path of a moving object as seen in stroboscopic

photography), perceptions of entire objects, visual snow, positive afterimages (i.e., a samecolored or complementary-colored “shadow” of an object remaining after removal of the object),
halos around objects, or misperception of images as too large (macropsia) or too small
(micropsia). Duration of the visual disturbances may be episodic or nearly continuous and must
cause clinically significant distress or impairment in social, occupational, or other important
areas of functioning (Criterion B). The disturbances may last for weeks, months, or years. Other
explanations for the disturbances (e.g., brain lesions, preexisting psychosis, seizure disorders,
migraine aura without headaches) must be ruled out (Criterion C).
Hallucinogen persisting perception disorder occurs primarily after LSD (lysergic acid
diethylamide) use, but not exclusively. There does not appear to be a strong correlation between
hallucinogen persisting perception disorder and number of occasions of hallucinogen use, with
some instances of hallucinogen persisting perception disorder occurring in individuals with
minimal exposure to hallucinogens. Some instances of hallucinogen persisting perception
disorder may be triggered by use of other substances (e.g., cannabis or alcohol), adaptation to
dark environments, exercise, and exposure to noise and photophobia.
Associated Features
Reality testing remains intact in individuals with hallucinogen persisting perception disorder
(i.e., the individual is aware that the disturbance is linked to the effect of the drug). If this is not
the case, another disorder might better explain the abnormal perceptions.
Prevalence
Prevalence estimates of hallucinogen persisting perception disorder are unknown. Initial
prevalence estimates of the disorder among individuals who use hallucinogens is approximately
4.2%.
Development and Course
Little is known about the development of hallucinogen persisting perception disorder. Its course,
as suggested by its name, is persistent, lasting for weeks, months, or even years in certain
individuals.
Risk and Prognostic Factors
There is little evidence regarding risk factors for hallucinogen persisting perception disorder,
although genetic factors have been suggested as a possible explanation underlying the
susceptibility to LSD effects in this condition.
Functional Consequences of Hallucinogen Persisting Perception
Disorder
Although hallucinogen persisting perception disorder remains a chronic condition in some cases,
many individuals with the disorder are able to suppress the disturbances and continue to function
normally.
Differential Diagnosis

Conditions to be ruled out include schizophrenia, other drug effects, neurodegenerative
disorders, stroke, brain tumors, infections, and head trauma. Neuroimaging results in
hallucinogen persisting perception disorder cases are typically negative. As noted earlier, reality
testing remains intact (i.e., the individual is aware that the disturbance is linked to the
effect of the drug); if this is not the case, another disorder (e.g., psychotic disorder, another
medical condition) might better explain the abnormal perceptions.
Comorbidity
Common comorbid mental disorders accompanying hallucinogen persisting perception disorder
are panic disorder, alcohol use disorder, major depressive disorder, bipolar I disorder, and
schizophrenia spectrum disorders.
Phencyclidine-Induced Mental Disorders
Other phencyclidine-induced mental disorders are described in other chapters of the manual with
disorders with which they share phenomenology (see the substance/medication-induced mental
disorders in these chapters): phencyclidine-induced psychotic disorder (“Schizophrenia Spectrum
and Other Psychotic Disorders”); phencyclidine-induced bipolar and related disorder (“Bipolar
and Related Disorders”); phencyclidine-induced depressive disorder (“Depressive Disorders”);
and phencyclidine-induced anxiety disorder (“Anxiety Disorders”). For phencyclidine-induced
intoxication delirium and delirium induced by ketamine taken as prescribed, see the criteria and
discussion of delirium in the chapter “Neurocognitive Disorders.” These phencyclidine-induced
mental disorders are diagnosed instead of phencyclidine intoxication only when the symptoms
are sufficiently severe to warrant independent clinical attention.
Hallucinogen-Induced Mental Disorders
The following other hallucinogen-induced mental disorders are described in other chapters of the
manual with disorders with which they share phenomenology (see the substance/medicationinduced mental disorders in these chapters): other hallucinogen–induced psychotic disorder
(“Schizophrenia Spectrum and Other Psychotic Disorders”); other hallucinogen–induced bipolar
and related disorder (“Bipolar and Related Disorders”); other hallucinogen–induced depressive
disorder (“Depressive Disorders”); and other hallucinogen–induced anxiety disorder (“Anxiety
Disorders”). For other hallucinogen intoxication delirium and delirium induced by other
hallucinogens taken as prescribed, see the criteria and discussion of delirium in the chapter
“Neurocognitive Disorders.” These hallucinogen-induced mental disorders are diagnosed instead
of other hallucinogen intoxication only when the symptoms are sufficiently severe to warrant
independent clinical attention.
Unspecified Phencyclidine-Related Disorder

F16.99
This category applies to presentations in which symptoms characteristic of a
phencyclidine-related disorder that cause clinically significant distress or impairment
in social, occupational, or other important areas of functioning predominate but do
not meet the full criteria for any specific phencyclidine-related disorder or any of the
disorders in the substance-related and addictive disorders diagnostic class.
Unspecified Hallucinogen-Related Disorder
F16.99
This category applies to presentations in which symptoms characteristic of a
hallucinogen-related disorder that cause clinically significant distress or impairment
in social, occupational, or other important areas of functioning predominate but do
not meet the full criteria for any specific hallucinogen-related disorder or any of the
disorders in the substance-related and addictive disorders diagnostic class.
Inhalant-Related Disorders
Inhalant Use Disorder
Inhalant Intoxication
Inhalant-Induced Mental Disorders
Unspecified Inhalant-Related Disorder
Inhalant Use Disorder
Diagnostic Criteria
A. A problematic pattern of use of a hydrocarbon-based inhalant substance leading
to clinically significant impairment or distress, as manifested by at least two of
the following, occurring within a 12-month period:
1. The inhalant substance is often taken in larger amounts or over a longer
period than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control use

of the inhalant substance.
3. A great deal of time is spent in activities necessary to obtain the inhalant
substance, use it, or recover from its effects.
4. Craving, or a strong desire or urge to use the inhalant substance.
5. Recurrent use of the inhalant substance resulting in a failure to fulfill major
role obligations at work, school, or home.
6. Continued use of the inhalant substance despite having persistent or
recurrent social or interpersonal problems caused or exacerbated by the
effects of its use.
7. Important social, occupational, or recreational activities are given up or
reduced because of use of the inhalant substance.
8. Recurrent use of the inhalant substance in situations in which it is physically
hazardous.
9. Use of the inhalant substance is continued despite knowledge of having a
persistent or recurrent physical or psychological problem that is likely to have
been caused or exacerbated by the substance.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the inhalant substance to
achieve intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of
the inhalant substance.
Specify the particular inhalant: When possible, the particular substance involved
should be named (e.g., “solvent use disorder”).
Specify if:
In early remission: After full criteria for inhalant use disorder were previously
met, none of the criteria for inhalant use disorder have been met for at least 3
months but for less than 12 months (with the exception that Criterion A4,
“Craving, or a strong desire or urge to use the inhalant substance,” may be met).
In sustained remission: After full criteria for inhalant use disorder were
previously met, none of the criteria for inhalant use disorder have been met at
any time during a period of 12 months or longer (with the exception that Criterion
A4, “Craving, or a strong desire or urge to use the inhalant substance,” may be
met).
Specify if:
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to inhalant substances is restricted.
Code based on current severity/remission: If an inhalant intoxication or another
inhalant-induced mental disorder is also present, do not use the codes below for
inhalant use disorder. Instead, the comorbid inhalant use disorder is indicated in the

4th character of the inhalant-induced disorder code (see the coding note for inhalant
intoxication or a specific inhalant-induced mental disorder). For example, if there is
comorbid inhalant-induced depressive disorder and inhalant use disorder, only the
inhalant-induced depressive disorder code is given, with the 4th character indicating
whether the comorbid inhalant use disorder is mild, moderate, or severe: F18.14 for
mild inhalant use disorder with inhalant-induced depressive disorder or F18.24 for a
moderate or severe inhalant use disorder with inhalant-induced depressive disorder.
Specify current severity/remission:
F18.10 Mild: Presence of 2–3 symptoms.
F18.11 Mild, In early remission
F18.11 Mild, In sustained remission
F18.20 Moderate: Presence of 4–5 symptoms.
F18.21 Moderate, In early remission
F18.21 Moderate, In sustained remission
F18.20 Severe: Presence of 6 or more symptoms.
F18.21 Severe, In early remission
F18.21 Severe, In sustained remission
Specifiers
“In a controlled environment” applies as a further specifier of remission if the individual is both
in remission and in a controlled environment (i.e., in early remission in a controlled environment
or in sustained remission in a controlled environment). Examples of these environments are
closely supervised and substance-free jails, therapeutic communities, and locked hospital units.
The severity of individuals’ inhalant use disorder is assessed by the number of diagnostic
criteria endorsed. Changing severity of individuals’ inhalant use disorder across time is reflected
by reductions in the frequency (e.g., days used per month) and/or dose (e.g., tubes of glue per
day) used, as assessed by the individual’s self-report, report of others, clinician’s observations,
and biological testing (when practical).
Diagnostic Features
Examples of inhalant substances include volatile hydrocarbons, which comprise toxic gases from
glues, fuels, paints, and other volatile compounds. When possible, the
particular substance involved should be named (e.g., “toluene use disorder”). However, most
compounds that are inhaled are a mixture of several substances that can produce psychoactive
effects, and it is often difficult to ascertain the exact substance responsible for the disorder.
Unless there is clear evidence that a single, unmixed substance has been used, the general term
inhalant should be used in recording the diagnosis. Disorders arising from inhalation of nitrous
oxide or of amyl-, butyl-, or isobutylnitrite are considered as other (or unknown) substance use

disorder.
Features of inhalant use disorder include repeated use of an inhalant substance despite the
individual’s knowing that the substance is causing serious problems for the individual (Criterion
A9). Those problems are reflected in the diagnostic criteria.
Missing work or school or inability to perform typical responsibilities at work or school
(Criterion A5), and continued use of the inhalant substance even though it causes arguments with
family or friends, fights, and other social or interpersonal problems (Criterion A6), may be seen
in inhalant use disorder. Limiting family contact, work or school obligations, or recreational
activities (e.g., sports, games, hobbies) may also occur (Criterion A7). Use of inhalants when
driving or operating dangerous equipment (Criterion A8) is also seen.
Tolerance (Criterion A10) is reported by about 10% of individuals who use inhalants.
Because a clinically significant withdrawal syndrome has not been established with inhalant use,
neither a diagnosis of inhalant withdrawal nor a corresponding diagnostic criterion for
withdrawal complaints for inhalant use disorder is included. However, withdrawal symptoms
may occur among inhalant users and individuals with moderate to severe inhalant use disorder,
and these symptoms appear to be similar in frequency to withdrawal symptoms among those
with moderate to severe cocaine use disorder.
Associated Features
A diagnosis of inhalant use disorder is supported by recurring episodes of intoxication with
negative results in standard drug screens (which do not detect inhalants); possession, or lingering
odors, of inhalant substances; peri-oral or peri-nasal “glue-sniffer’s rash”; association with other
individuals known to use inhalants; membership in groups with prevalent inhalant use (e.g.,
some native or aboriginal communities, homeless children in street gangs); easy access to certain
inhalant substances; paraphernalia possession; presence of the disorder’s characteristic medical
complications (e.g., brain white matter pathology, rhabdomyolysis); and the presence of multiple
other substance use disorders. Individuals with inhalant use disorder may present with symptoms
of pernicious anemia, subacute combined degeneration of the spinal cord, major or mild
neurocognitive disorder, brain atrophy, leukoencephalopathy, and many other nervous system
disorders.
Prevalence
About 2.3% of American youth ages 12–17 years have used inhalants in the past 12 months, with
0.1% having a pattern of use that meets criteria for inhalant use disorder. Among U.S. adults, age
18 years and older, past 12-month prevalence of inhalant use is about 0.21%, with 0.04% having
a pattern of use that meets criteria for an inhalant use disorder. Among youth, the prevalence of
past 12-month inhalant use is highest among non-Hispanic Whites and individuals reporting
more than one racialized identity and lowest among American Indians/Alaska Natives. Twelvemonth prevalence rates of inhalant use and inhalant use disorder among adults are highest among
non-Hispanic Whites and lowest among non-Hispanic Blacks and American Indians/Alaska
Natives.
Development and Course

Temperamental.
Environmental.
Genetic and physiological.
The declining prevalence in the United States of inhalant use and inhalant use disorder after
adolescence (from 2.3% during adolescence to 0.1% in early adulthood for inhalant use and from
0.1% to 0.04% for inhalant use disorder) indicates that the disorder usually
remits in early adulthood. Inhalant use disorder is rare in prepubertal children, most common in
adolescents and young adults, and uncommon in older persons. Calls to poison-control centers
for “intentional abuse” of inhalants peak with calls involving individuals at age 14 years. Those
with inhalant use disorder extending into adulthood demonstrate earlier onset of inhalant use, use
of multiple inhalants, and more frequent inhalant use.
Risk and Prognostic Factors
Predictors of inhalant use disorder include sensation seeking and impulsivity.
Inhalant gases are widely and legally available, increasing the risk of misuse.
Childhood maltreatment or trauma also is associated with youthful progression from inhalant
non-use to inhalant use disorder.
Behavioral disinhibition is a highly heritable general propensity to not
constrain behavior in socially acceptable ways, to break social norms and rules, and to take
dangerous risks, pursuing rewards excessively despite dangers of adverse consequences. Youths
with strong behavioral disinhibition show risk factors for inhalant use disorder: early-onset
substance use disorder, multiple substance involvement, and early conduct problems. Because
behavioral disinhibition is under strong genetic influence, youths in families with substance use
and antisocial behaviors are at elevated risk for inhalant use disorder.
Culture-Related Diagnostic Issues
Internationally, certain isolated Indigenous communities have experienced a high prevalence of
inhalant problems. Also, in some low- and middle-income countries, groups of homeless
children living on the streets have extensive inhalant use problems because of the effects of
poverty and the availability and affordability of the substances, and as a way to cope with
homelessness.
Sex- and Gender-Related Diagnostic Issues
Although the past 12-month prevalence of inhalant use disorder in the United States is almost
identical among adolescent boys and girls, the disorder is very rare among adult women.
Diagnostic Markers
Urine, breath, or saliva tests may be valuable for assessing concurrent use of non-inhalant
substances by individuals with inhalant use disorder. However, technical problems and the
considerable expense of analyses make frequent biological testing for inhalants themselves
impractical.
Association With Suicidal Thoughts or Behavior

Inhalant exposure (unintentional) from industrial or other accidents.
Inhalant intoxication, without meeting criteria for inhalant use disorder.
Inhalant intoxication meeting criteria for inhalant use disorder, and inhalant-induced mental
disorders.
Other substance use disorders, especially those involving sedating substances (e.g., alcohol,
benzodiazepines, barbiturates).
In the United States, adolescent and adult inhalant use and inhalant use disorder are associated
with suicidal thoughts and behavior, especially among individuals reporting symptoms of anxiety
and depression and histories of trauma.
Functional Consequences of Inhalant Use Disorder
Because of inherent toxicity, use of inhalants can be fatal. Death can occur from anoxia, cardiac
dysfunction, extreme allergic reaction, severe injury to the lungs, vomiting, accidents or injury,
or central nervous system depression. Moreover, any inhaled volatile hydrocarbons may produce
“sudden sniffing death” from cardiac arrhythmia. Inhalant use impairs neurobehavioral function
and causes various neurological, gastrointestinal, cardiovascular, and pulmonary problems.
Long-term inhalant users are at increased risk for tuberculosis, HIV/AIDS, sexually
transmitted diseases, depression, anxiety, bronchitis, asthma, and sinusitis.
Differential Diagnosis
A diagnosis of inhalant use
disorder only applies if the inhalant exposure is intentional.
Inhalant 
intoxication 
occurs
frequently during inhalant use disorder but also may occur among individuals whose use does
not meet criteria for inhalant use disorder.
Inhalant use disorder is differentiated from inhalant intoxication and inhalant-induced mental
disorders (e.g., inhalant-induced depressive disorder) in that inhalant use disorder describes a
problematic pattern of inhalant use that involves impaired control over inhalant use, social
impairment attributable to inhalant use, risky inhalant use (e.g., inhalant use despite medical
complications), and pharmacological symptoms (the development of tolerance), whereas inhalant
intoxication and inhalant-induced mental disorders describe psychiatric syndromes that develop
in the context of heavy use. Inhalant intoxication and inhalant-induced mental disorders occur
frequently in individuals with inhalant use disorder. In such cases, a diagnosis of inhalant
intoxication or an inhalant-induced mental disorder should be given in addition to a diagnosis of
inhalant use disorder, the presence of which is indicated in the diagnostic code.
Inhalant use disorder commonly co-occurs with other substance use disorders, and the symptoms
of the disorders may be similar and overlapping. To disentangle symptom patterns, it is helpful
to inquire about which symptoms persisted during periods when some of the substances were not
being used.
Comorbidity
Individuals with inhalant use disorder receiving clinical care often have numerous other
substance use, mood, anxiety, and personality disorders. Inhalant use disorder commonly co-

occurs with conduct disorder in adolescents and with antisocial personality disorder. Individuals
with inhalant use disorder may have comorbid symptoms of hepatic or renal damage,
rhabdomyolysis, methemoglobinemia, or symptoms of other gastrointestinal, cardiovascular, or
pulmonary diseases.
Inhalant Intoxication
Diagnostic Criteria
A. Recent intended or unintended short-term, high-dose exposure to inhalant
substances, including volatile hydrocarbons such as toluene or gasoline.
B. Clinically significant problematic behavioral or psychological changes (e.g.,
belligerence, assaultiveness, apathy, impaired judgment) that developed during,
or shortly after, exposure to inhalants.
C. Two (or more) of the following signs or symptoms developing during, or shortly
after, inhalant use or exposure:
1. Dizziness.
2. Nystagmus.
3. Incoordination.
4. Slurred speech.
5. Unsteady gait.
6. Lethargy.
7. Depressed reflexes.
8. Psychomotor retardation.
9. Tremor.
10. Generalized muscle weakness.
11. Blurred vision or diplopia.
12. Stupor or coma.
13. Euphoria.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.
Coding note: The ICD-10-CM code depends on whether there is a comorbid
inhalant use disorder. If a mild inhalant use disorder is comorbid, the ICD-10-CM
code is F18.120, and if a moderate or severe inhalant use disorder is comorbid, the
ICD-10-CM code is F18.220. If there is no comorbid inhalant use disorder, then the
ICD-10-CM code is F18.920.

Note: For information on Development and Course, Risk and Prognostic Factors,
Culture-Related Diagnostic Issues, and Diagnostic Markers, see the corresponding
sections in Inhalant Use Disorder.
Diagnostic Features
The essential feature of inhalant intoxication is the presence of clinically significant problematic
behavioral or psychological changes that develop during, or immediately after, intended or
unintended inhalation of a volatile hydrocarbon substance. When possible, the particular
substance involved should be named (e.g., toluene intoxication). Intoxication clears within a few
minutes to a few hours after the exposure ends. Thus, inhalant intoxication usually occurs in
brief episodes that may recur with further inhalant use.
Associated Features
Inhalant intoxication may be indicated by evidence of possession, or lingering odors, of inhalant
substances (e.g., glue, paint thinner, gasoline, butane lighters); other features may include
euphoria, relaxation, headache, rapid heartbeat, confusion, talkativeness, blurred vision, amnesia,
slurred speech, irritability, nausea, fatigue, burning in eyes or throat, grandiosity, chest pain,
auditory or visual hallucinations, and dissociation.
Prevalence
The prevalence of actual episodes of inhalant intoxication in the general population is unknown,
but it is probable that a majority of inhalant users would at some time exhibit behavioral or
psychological changes and symptoms that would meet criteria for inhalant intoxication.
Therefore, the prevalence of inhalant use and the prevalence of inhalant intoxication are likely
similar. In 2017, inhalant use in the past year was reported by 0.6% of all Americans older than
12 years; the prevalence was highest in younger age groups (2.3% for individuals ages 12 –17
years, 1.6% for individuals ages 18–25 years, and 0.3% for individuals age 26 and older).
Sex- and Gender-Related Diagnostic Issues
Gender differences in the prevalence of inhalant intoxication in the general population are
unknown. Regarding gender differences in the prevalence of inhalant use in the United
States, 0.8% of boys/men older than 12 years and 0.5% of girls/women older than 12 years have
used inhalants in the previous year, but in the younger age groups differences are minimal or
girls may have slightly higher prevalence (e.g., among adolescents ages 12–17 years, 2.4% of
girls and 2.2% of boys have used inhalants in the past year).
Functional Consequences of Inhalant Intoxication
Use of inhaled substances in a closed container, such as a plastic bag over the head, may lead to
unconsciousness, anoxia, and death. Separately, “sudden sniffing death,” likely from cardiac
arrhythmia or arrest, may occur with various volatile inhalants. The enhanced toxicity of certain

Intoxication from other substances, especially from sedating substances (e.g., alcohol,
benzodiazepines, barbiturates).
Inhalant-induced mental disorders.
Other toxic, metabolic, traumatic, neoplastic, or infectious disorders that impair brain function
and cognition.
volatile inhalants, such as butane or propane, also causes fatalities. Although inhalant
intoxication itself is of short duration, it may produce persisting medical and neurological
problems, especially if the intoxications are frequent. Clinically significant correlates of inhalant
intoxication include reckless behaviors (e.g., taking foolish risks, getting into fights, having
unprotected sex), antisocial behaviors (cruelty, damaging property, arrests), and having serious
accidents.
Differential Diagnosis
These disorders may have similar signs and symptoms, but intoxication attributable to other
intoxicants may be identified via a toxicology screen. Differentiating the source of the
intoxication may involve discerning evidence of inhalant exposure as described for inhalant use
disorder. A diagnosis of inhalant intoxication may be suggested by possession or lingering odors
of inhalant substances (e.g., glue, paint thinner, gasoline, butane lighters); paraphernalia
possession (e.g., rags or bags for concentrating glue fumes); perioral or perinasal “glue-sniffer’s
rash”; reports from family or friends that the intoxicated individual possesses or uses inhalants;
or apparent intoxication despite negative results on standard drug screens (which usually fail to
identify inhalants).
Inhalant intoxication is distinguished from inhalant-induced
mental disorders (e.g., inhalant-induced anxiety disorder, with onset during intoxication) because
the symptoms (e.g., anxiety) in these latter disorders are in excess of those usually associated
with inhalant intoxication, predominate in the clinical presentation, and are severe enough to
warrant independent clinical attention.
Numerous neurological and other medical conditions may produce the clinically significant
behavioral or psychological changes (e.g., belligerence, assaultiveness, apathy, impaired
judgment) that also characterize inhalant intoxication.
Comorbidity
Given the typical overlap of inhalant intoxication with inhalant use disorder, see “Comorbidity”
under Inhalant Use Disorder for more details about co-occurring conditions that are likely to be
encountered.
Inhalant-Induced Mental Disorders
The following inhalant-induced mental disorders are described in other chapters of the manual
with disorders with which they share phenomenology (see the substance/medication-induced
mental disorders in these chapters): inhalant-induced psychotic disorder (“Schizophrenia
Spectrum and Other Psychotic Disorders”); inhalant-induced depressive
disorder (“Depressive Disorders”); inhalant-induced anxiety disorder (“Anxiety Disorders”); and

inhalant-induced major or mild neurocognitive disorder (“Neurocognitive Disorders”). For
inhalant intoxication delirium, see the criteria and discussion of delirium in the chapter
“Neurocognitive Disorders.” These inhalant-induced mental disorders are diagnosed instead of
inhalant intoxication only when symptoms are sufficiently severe to warrant independent clinical
attention.
Unspecified Inhalant-Related Disorder
F18.99
This category applies to presentations in which symptoms characteristic of an
inhalant-related disorder that cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning predominate but do not
meet the full criteria for any specific inhalant-related disorder or any of the disorders
in the substance-related and addictive disorders diagnostic class.
Opioid-Related Disorders
Opioid Use Disorder
Opioid Intoxication
Opioid Withdrawal
Opioid-Induced Mental Disorders
Unspecified Opioid-Related Disorder
Opioid Use Disorder
Diagnostic Criteria
A. A problematic pattern of opioid use leading to clinically significant impairment or
distress, as manifested by at least two of the following, occurring within a 12month period:
1. Opioids are often taken in larger amounts or over a longer period than was
intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control
opioid use.
3. A great deal of time is spent in activities necessary to obtain the opioid, use
the opioid, or recover from its effects.

4. Craving, or a strong desire or urge to use opioids.
5. Recurrent opioid use resulting in a failure to fulfill major role obligations at
work, school, or home.
6. Continued opioid use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of opioids.
7. Important social, occupational, or recreational activities are given up or
reduced because of opioid use.
8. Recurrent opioid use in situations in which it is physically hazardous.
9. Continued opioid use despite knowledge of having a persistent or recurrent
physical or psychological problem that is likely to have been caused or
exacerbated by the substance.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of opioids to achieve intoxication
or desired effect.
b. A markedly diminished effect with continued use of the same amount of
an opioid.
Note: This criterion is not considered to be met for those taking opioids solely
under appropriate medical supervision.
11. Withdrawal, as manifested by either of the following:
a. The characteristic opioid withdrawal syndrome (refer to Criteria A and B of
the criteria set for opioid withdrawal).
b. Opioids (or a closely related substance) are taken to relieve or avoid
withdrawal symptoms.
Note: This criterion is not considered to be met for those individuals taking
opioids solely under appropriate medical supervision.
Specify if:
In early remission: After full criteria for opioid use disorder were previously met,
none of the criteria for opioid use disorder have been met for at least 3 months
but for less than 12 months (with the exception that Criterion A4, “Craving, or a
strong desire or urge to use opioids,” may be met).
In sustained remission: After full criteria for opioid use disorder were previously
met, none of the criteria for opioid use disorder have been met at any time during
a period of 12 months or longer (with the exception that Criterion A4, “Craving, or
a strong desire or urge to use opioids,” may be met).
Specify if:
On maintenance therapy: This additional specifier is used if the individual is
taking a prescribed agonist medication such as methadone or buprenorphine
and none of the criteria for opioid use disorder have been met for that class of

medication (except tolerance to, or withdrawal from, the agonist). This category
also applies to those individuals being maintained on a partial agonist, an
agonist/antagonist, or a full antagonist such as oral naltrexone or depot
naltrexone.
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to opioids is restricted.
Code based on current severity/remission: If an opioid intoxication, opioid
withdrawal, or another opioid-induced mental disorder is also present, do not use the
codes below for opioid use disorder. Instead, the comorbid opioid use disorder is
indicated in the 4th character of the opioid-induced disorder code (see the coding
note for opioid intoxication, opioid withdrawal, or a specific opioid-induced mental
disorder). For example, if there is comorbid opioid-induced depressive disorder and
opioid use disorder, only the opioid-induced depressive disorder code is given, with
the 4th character indicating whether the comorbid opioid use disorder is mild,
moderate, or severe: F11.14 for mild opioid use disorder with opioid-induced
depressive disorder or F11.24 for a moderate or severe opioid use disorder with
opioid-induced depressive disorder.
Specify current severity/remission:
F11.10 Mild: Presence of 2–3 symptoms.
F11.11 Mild, In early remission
F11.11 Mild, In sustained remission
F11.20 Moderate: Presence of 4–5 symptoms.
F11.21 Moderate, In early remission
F11.21 Moderate, In sustained remission
F11.20 Severe: Presence of 6 or more symptoms.
F11.21 Severe, In early remission
F11.21 Severe, In sustained remission
Specifiers
The “on maintenance therapy” specifier applies as a further specifier of remission if the
individual is both in remission and receiving maintenance therapy. “In a controlled environment”
applies as a further specifier of remission if the individual is both in remission and in a controlled
environment (i.e., in early remission in a controlled environment or in sustained remission in a
controlled environment). Examples of these environments are closely supervised and substancefree jails, therapeutic communities, and locked hospital units.
Changing severity across time in an individual is also reflected by reductions in the
frequency (e.g., days of use per month) and/or dose (e.g., injections or number of pills) of an
opioid, as assessed by the individual’s self-report, report of knowledgeable others, clinician’s

observations, and biological testing.
Diagnostic Features
The opioids include natural opioids (e.g., morphine, codeine), semisynthetics (e.g., heroin,
oxycodone, hydrocodone, hydromorphone, oxymorphone), and synthetics with morphine-like
action (e.g., methadone, meperidine, tramadol, fentanyl, carfentanil). Medications such as
pentazocine and buprenorphine that have both opiate agonist and antagonist effects are also
included in this class because, especially at lower doses, their agonist properties produce similar
physiological and behavioral effects as classic opioid agonists. Opioids are prescribed as
analgesics, anesthetics, antidiarrheal agents, or cough suppressants. Heroin is one of the most
commonly misused drugs of this class and is usually taken by injection, although it can be
smoked or “snorted,” especially when very pure heroin is available. Fentanyl is typically
injected, both medically and nonmedically, and is used medically in transdermal and
transmucosal formulations, whereas cough suppressants and antidiarrheal agents are taken orally.
The other opioids are generally taken both by injection and orally.
Opioid use disorder can arise from prescription opioids or illicit opioids (e.g., heroin and,
especially in recent years, fentanyl-related synthetic opioids). Opioid use disorder consists of
signs and symptoms reflecting compulsive, prolonged self-administration of opioid substances
either for a purpose other than a legitimate medical one or for use in a “non-medical” manner
(i.e., greatly exceeding the amount prescribed for a medical condition). For example, an
individual with adequate doses of prescribed analgesic opioid medication for pain relief who
uses significantly more of the medication than prescribed, and not only because of persistent
pain, is engaging in nonmedical opioid use and may have an opioid use disorder. Most
individuals with opioid use disorder have tolerance and experience withdrawal on abrupt
cessation or reduction in opioid use. Similar to processes that occur with other psychoactive
substances, individuals with opioid use disorder often develop conditioned responses to drugrelated stimuli (e.g., cue-reactive craving on seeing drug images or paraphernalia). These
responses probably contribute to relapse, are difficult to extinguish, and typically persist long
after withdrawal is completed.
Individuals with opioid use disorder tend to develop such regular patterns of compulsive drug
use that daily activities are planned around obtaining and administering
opioids. Prescription opioids used nonmedically can be obtained from family or friends, from
physicians by falsifying or exaggerating medical problems, by receiving simultaneous
prescriptions from several physicians, or via purchase on the illegal market. Health care
professionals with opioid use disorder can obtain opioids by writing prescriptions for themselves
or by diverting opioids that have been prescribed for individuals or from pharmacy supplies.
Associated Features
An attempt to achieve opioid intoxication may result in fatal or nonfatal opioid overdose. Opioid
overdose is characterized by unconsciousness, respiratory depression, and pinpoint pupils.
However, opioid overdoses can also occur in the absence of intoxication-seeking drug use.

Opioid overdoses have increased exponentially in the United States since 1999. Up to 2009,
opioid overdoses were mainly due to prescribed opioids, but since 2010, overdoses due to heroin
began a sharp rise, and additionally, since 2015, fatal overdoses due to synthetic opioids other
than methadone (generally fentanyl) have outnumbered overdoses due to prescribed opioids.
Opioid use disorder can be associated with a history of drug-related crimes (e.g., possession
or distribution of drugs, forgery, burglary, robbery, larceny, receiving stolen goods). Among
health care professionals and individuals who have ready access to controlled substances, a
different pattern of illegal activities may involve problems with state licensing boards,
professional staffs of hospitals, or other administrative agencies. Marital difficulties (including
divorce), unemployment, and irregular employment can be associated with opioid use disorder at
all socioeconomic levels.
Prevalence
The prevalence of nonmedical prescription opioid use among U.S. adults age 18 and older is
4.1%–4.7%, with rates of use higher in adults ages 18–25 than in those age 26 and older (5.5%
vs. 3.4%, respectively). The prevalence of heroin use in the United States is 0.3%–0.4% and is
higher among adults ages 18–25 (0.5%–0.7%) than in other age groups. In U.S. adolescents ages
12–17, 2.8%–3.9% use prescription opioids nonmedically, with higher rates in older adolescents
than in younger adolescents. Heroin use in adolescents is quite low (< 0.05%–0.1%).
The prevalence of prescription opioid use disorder among U.S. adults age 18 and older
(DSM-IV or DSM-5 criteria) is 0.6%–0.9%, and the prevalence of heroin use disorder (DSM-IV
or DSM-5 criteria) is 0.1%–0.3%. Among those ages 12–17, prevalence of prescription opioid
use disorder is 0.4%, and heroin use disorder is rare (essentially 0%). In the United States, rates
of opioid use disorder (prescription opioids and heroin) are higher among men than women,
among young adults than older adults, and among those with lower income or education. Among
U.S. adults in 2012–2013, the prevalence of nonmedical prescription opioid use disorder varied
by ethnoracial group: 1.42% in Native Americans, 1.04% in African Americans, 0.96% in nonLatinx Whites, 0.70% in Latinx, and 0.16% in Asian Americans or Pacific Islanders. Rates based
on household surveys may underestimate national prevalence by omitting individuals in
institutions and jail or prison, whose rates are likely to be much higher.
Globally in 2016, there were 26.8 million cases of DSM-IV opioid dependence, with an agestandardized prevalence of 353.0 cases per 100,000 people; prevalence of opioid dependence
across geographic regions ranged from 0.14% to 0.46%.
Development and Course
Opioid use disorder can begin at any age. In the United States, problems associated with opioid
use are most commonly first observed in the late teens or early 20s, with a longer interval
between first opioid use and onset of disorder for prescription opioids than for
heroin. Early use can reflect a desire for relief from life stressors or psychological pain. Longterm studies show that once an opioid use disorder that requires treatment develops, it can
continue over many years, with brief periods of abstinence in some individuals but long-term

abstinence only in a minority. An exception occurred among U.S. soldiers who became
dependent on opioids while serving in the Vietnam War; over 90% had long-term abstinence
from opioids after returning to the United States, although many subsequently experienced
problems with alcohol, amphetamines, or suicidal thoughts or behavior.
Risk and Prognostic Factors
In addition to an association with more frequent nonmedical prescription opioid use, adult
prescription opioid use disorder is associated with most other substance use disorders. Opioid use
disorder is highly associated with externalizing traits such as novelty-seeking, impulsivity, and
disinhibition. Family, peer, and social environmental factors all increase the risk for opioid use
disorder. Family and twin studies also indicate a strong genetic contribution to the risk for opioid
use disorders, although identifying the specific genetic variants contributing to genetic risk has
been slow. Peer factors may relate to genetic predisposition in terms of how individuals select
their environments, including their peers.
Culture-Related Diagnostic Issues
Individuals from socially oppressed ethnoracial groups were historically overrepresented among
individuals with opioid use disorder. However, over time, opioid use disorder has become more
common among White individuals, suggesting that the widespread availability of opioids and
other social factors (e.g., changes in rates of poverty and unemployment) have an impact on
prevalence. Consistent with these factors, despite small variations between ethnoracial groups in
the psychometric performance of opioid use disorder criterion items, the criteria for opioid use
disorder perform equally well across ethnoracial groups.
Sex- and Gender-Related Diagnostic Issues
Women with opioid use disorder appear more likely than men to have initiated opioid use in
response to sexual abuse and violence, and they are more likely than men to be introduced to the
drug by a partner. There is substantial evidence of telescoping among women in that they
progress to a use disorder more quickly than men after first use; women also appear to be more
ill when entering treatment facilities than are men, as noted in a large sample of heroin users in
Italy.
Diagnostic Markers
Routine urine toxicology test results are often positive for opioid drugs in individuals with opioid
use disorder. Urine test results remain positive for most opioids (e.g., heroin, morphine, codeine,
oxycodone, propoxyphene) for 12–36 hours after administration. Some opioids, such as fentanyl
and oxycodone, are not detected by standard urine tests (which test for morphine), but can be
identified by more specialized procedures for several days after use. Similarly, methadone and
buprenorphine (or buprenorphine/naloxone combinations) will not cause a positive result on
routine tests for opiates; they require specific tests that can detect these substances for several
days up to more than 1 week.
Although not specific markers of opioid use disorder, laboratory evidence of the presence of
other substances (e.g., cocaine, marijuana, alcohol, amphetamines, benzodiazepines) is common

in heroin users. In addition, screening test results for hepatitis A, B, and C virus are often
positive in injection opioid users, either for hepatitis antigen (signifying active infection) or for
hepatitis antibody (signifying past infection). Mildly elevated liver
function test results are common, either as a result of resolving hepatitis or from toxic injury
to the liver due to contaminants that have been mixed with the injected opioid. HIV is also
prevalent in injection opioid users. Subtle changes in cortisol secretion patterns and body
temperature regulation have been observed for up to 6 months following opioid withdrawal.
Association With Suicidal Thoughts or Behavior
Opioid use disorder is associated with a heightened risk for suicide attempts and suicide. Some
suicide risk factors overlap with risk factors for an opioid use disorder. In addition, repeated
opioid intoxication or withdrawal may be associated with severe depressions that although
temporary can be intense enough to lead to suicide attempts and suicide. Nonfatal accidental
opioid overdose and attempted suicide are distinct phenomena that can be difficult to
differentiate but should not be mistaken for each other, if possible.
Findings from the Global Burden of Disease Study 2010 showed that among drugs of abuse,
suicide is a common cause of death among regular users of opioids. Evidence suggests that
suicides are undercounted or often misclassified in opioid-poisoning data. In a study of the
Veterans Health Administration (VHA) national medical records, after adjustment for psychiatric
comorbidity, opioid use disorder elevated the risk for suicide mortality, with greater increase in
risk among women than among men. In another study also using VHA national medical records,
among veterans prescribed opioids for chronic pain, suicide mortality increased with higher
opioid doses, even after demographic and clinical factors were taken into account. A follow-up
of a U.S. national cohort of adults with a history of an opioid overdose found that the
standardized mortality ratio (SMR; the ratio between the observed number of deaths in a study
population and the number of deaths that would be expected) was 25.9 for suicide, with a higher
SMR for women than for men. A review posited that the reasons for the increased risk for
suicide among opioid users were related to shared risk factors, namely, comorbid mental
disorders and pain.
Functional Consequences of Opioid Use Disorder
Physiologically, opioid use is associated with a lack of mucous membrane secretions, causing
dry mouth and nose. Slowing of gastrointestinal activity and a decrease in gut motility can
produce severe constipation. Visual acuity may be impaired as a result of pupillary constriction
with acute administration. In individuals who inject opioids, sclerosed veins (“tracks”) and
puncture marks on the lower portions of the upper extremities are common. Veins sometimes
become so severely sclerosed that peripheral edema develops, and individuals switch to injecting
in veins in the legs, neck, or groin. When these veins become unusable, individuals often inject
directly into their subcutaneous tissue (“skin-popping”), resulting in cellulitis, abscesses, and
circular-appearing scars from healed skin lesions. Tetanus and Clostridium botulinum infections
are rare but serious consequences of injecting opioids, especially with contaminated needles.

Opioid intoxication, opioid withdrawal, and opioid-induced mental disorders.
Infections may also occur in other organs and include bacterial endocarditis, hepatitis, and HIV
infection. Hepatitis C infections, for example, may occur in up to 90% of individuals who inject
opioids. In addition, the prevalence of HIV infection is high among individuals who inject drugs,
a large proportion of whom are individuals with opioid use disorder. For example, HIV infection
rates are as high as 60% among heroin users in some areas of the United States and the Russian
Federation. However, the incidence may be much lower in areas where access to clean injection
material and paraphernalia is facilitated.
Tuberculosis is a particularly serious problem among individuals who use drugs
intravenously, especially those who are dependent on heroin; infection is usually asymptomatic
and evident only by the presence of a positive tuberculin skin test or tuberculosis blood test
(interferon gamma release assay). However, many cases of active tuberculosis have been found,
especially among those who are infected with HIV. These individuals
often have a newly acquired infection but also are likely to experience reactivation of a prior
infection because of impaired immune function.
Individuals who sniff heroin or other opioids into the nose (insufflation, or “snorting”) often
develop irritation of the nasal mucosa, sometimes accompanied by perforation of the nasal
septum. Difficulties in sexual functioning are common. Males often experience erectile
dysfunction during intoxication or chronic use. Females commonly have disturbances of
reproductive function and irregular menses.
Although acute opioid use produces analgesia, chronic use can produce hyperalgesia (opioidinduced hyperalgesia), a condition characterized by increased sensitivity to pain. Physiological
dependence on opioids may occur in about half of the infants born to females with opioid use
disorder. This can produce a severe withdrawal syndrome in the neonate requiring medical
treatment and has increased markedly in prevalence.
The mortality rate in individuals with opioid use disorder is 6–20 times greater than in the
general population. Fatal overdoses due to prescription opioids increased dramatically in the
United States since 1999, with almost 400,000 such deaths occurring since then, and the rate of
such overdoses is now five times higher than in 1999. Fatal overdoses due to heroin began a
sharp increase in 2010, and since 2013, fatal overdoses due to synthetic opioids (e.g., fentanyl)
increased so sharply that these rates were almost double the rates for prescription opioid or
heroin overdoses by 2017. Nonfatal opioid overdoses resulting in hospitalization and emergency
department visits have increased as well. Although not all risk factors for opioid use disorder and
opioid overdose are the same, substantial overlap exists, making the risk for overdose one of the
most serious potential consequences of opioid use disorder. Individuals with opioid use disorder
are also at increased risk for mortality from many medical conditions (e.g., hepatitis, HIV
infection, tuberculosis, cardiovascular disease). Death can also result from accidents, injuries, or
other general medical complications.
Differential Diagnosis
Opioid use disorder is
differentiated from opioid intoxication, opioid withdrawal, and opioid-induced mental disorders

Other substance intoxication.
Other withdrawal disorders.
Independent mental disorders.
(e.g., opioid-induced depressive disorder) in that opioid use disorder describes a problematic
pattern of opioid use that involves impaired control over opioid use, social impairment
attributable to opioid use, risky opioid use (e.g., continued opioid use despite medical
complications), and pharmacological symptoms (the development of tolerance or withdrawal),
whereas opioid intoxication, opioid withdrawal, and opioid-induced mental disorders describe
psychiatric syndromes that occur in the context of heavy use. Opioid intoxication, opioid
withdrawal, and opioid-induced mental disorders occur frequently in individuals with opioid use
disorder. In such cases, a diagnosis of opioid intoxication, opioid withdrawal, or opioid-induced
mental disorder should be given in addition to a diagnosis of opioid use disorder, the presence of
which is indicated in the diagnostic code.
Alcohol intoxication and sedative, hypnotic, or anxiolytic
intoxication can cause a clinical picture that resembles that of opioid intoxication. A diagnosis of
alcohol or sedative, hypnotic, or anxiolytic intoxication can usually be made based on the
absence of pupillary constriction or the lack of a response to naloxone challenge. In some cases,
intoxication may be due both to opioids and to alcohol or other sedatives. In these cases, the
naloxone challenge will not reverse all of the sedative effects.
The anxiety and restlessness associated with opioid withdrawal
resemble symptoms seen in sedative-hypnotic withdrawal. However, opioid withdrawal is also
accompanied by rhinorrhea, lacrimation, and pupillary dilation, which are not seen in sedativetype withdrawal. Dilated pupils are also seen in hallucinogen intoxication and stimulant
intoxication. However, other signs or symptoms of opioid
withdrawal, such as nausea, vomiting, diarrhea, abdominal cramps, rhinorrhea, or lacrimation,
are not present.
Some of the effects of opioid use may resemble symptoms (e.g.,
depressed mood) of an independent mental disorder (e.g., persistent depressive disorder).
Opioids are less likely to produce symptoms of mental disturbance than are most other drugs of
abuse.
Comorbidity
Other than overdose, the most common medical comorbidities associated with opioid use
disorder are viral (e.g., HIV, hepatitis C virus) and bacterial infections, particularly among
injection heroin users. These infections are less common in prescription opioid use disorder.
Research with nationally representative samples of the U.S. population has found that opioid
use disorder is often associated with other substance use disorders, especially those involving
tobacco, alcohol, cannabis, stimulants, and benzodiazepines. Individuals with opioid use disorder
are at risk for the development of persistent depressive disorder or major depressive disorder.
These symptoms may represent an opioid-induced depressive disorder or an exacerbation of a
preexisting independent depressive disorder. Periods of depression are especially common
during chronic intoxication or in association with physical or psychosocial stressors related to the
opioid use disorder. Insomnia is also common, especially during withdrawal. Opioid use disorder
is also associated with bipolar I disorder, posttraumatic stress disorder, and antisocial, borderline,

and schizotypal personality disorders. A history of conduct disorder in childhood or adolescence
has also been identified as a significant risk factor for substance-related disorders, especially
opioid use disorder. Further, prescription opioid use disorder and heroin use disorder are
generally associated with serious mental illness, defined as a mental disorder other than a
substance use disorder that results in serious functional impairment substantially limiting or
interfering with major life activities.
Opioid Intoxication
Diagnostic Criteria
A. Recent use of an opioid.
B. Clinically significant problematic behavioral or psychological changes (e.g., initial
euphoria followed by apathy, dysphoria, psychomotor agitation or retardation,
impaired judgment) that developed during, or shortly after, opioid use.
C. Pupillary constriction (or pupillary dilation due to anoxia from severe overdose)
and one (or more) of the following signs or symptoms developing during, or
shortly after, opioid use:
1. Drowsiness or coma.
2. Slurred speech.
3. Impairment in attention or memory.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.
Specify if:
With perceptual disturbances: This specifier may be noted in the rare instance
in which hallucinations with intact reality testing or auditory, visual, or tactile
illusions occur in the absence of a delirium.
Coding note: The ICD-10-CM code depends on whether or not there is a comorbid
opioid use disorder and whether or not there are perceptual disturbances.
For opioid intoxication, without perceptual disturbances: If a mild opioid use
disorder is comorbid, the ICD-10-CM code is F11.120, and if a moderate or
severe opioid use disorder is comorbid, the ICD-10-CM code is F11.220. If there
is no comorbid opioid use disorder, then the ICD-10-CM code is F11.920.
For opioid intoxication, with perceptual disturbances: If a mild opioid use
disorder is comorbid, the ICD-10-CM code is F11.122, and if a moderate or
severe opioid use disorder is comorbid, the ICD-10-CM code is F11.222. If there
is no comorbid opioid use disorder, then the ICD-10-CM code is F11.922.

Other substance intoxication.
Diagnostic Features
The essential feature of opioid intoxication is the presence of clinically significant problematic
behavioral or psychological changes (e.g., initial euphoria followed by apathy, dysphoria,
psychomotor agitation or retardation, impaired judgment) that develop during, or shortly after,
opioid use (Criteria A and B). Intoxication is accompanied by pupillary constriction (unless there
has been a severe overdose with consequent anoxia and pupillary dilation) and one or more of
the following signs: drowsiness (described as being “on the nod”), slurred speech, and
impairment in attention or memory (Criterion C); drowsiness may progress to coma. Individuals
with opioid intoxication may demonstrate inattention to the environment, even to the point of
ignoring potentially harmful events. The signs or symptoms of opioid intoxication must not be
attributable to another medical condition and are not better explained by another mental disorder
(Criterion D).
Up to 2009, opioid overdoses were mainly due to prescribed opioids, but starting in 2010,
overdoses due to heroin began a sharp rise, and additionally, since 2015, fatal overdoses due to
synthetic opioids other than methadone (generally fentanyl) have outnumbered overdoses due to
prescribed opioids.
Associated Features
Opioid intoxication can include decreases in respiratory rate and blood pressure, and mild
hypothermia. The duration of opioid intoxication can vary as a function of the pharmacokinetics
of the opioid ingested. Opioid intoxication may result in fatal or nonfatal opioid overdose.
Opioid overdose is characterized by unconsciousness, respiratory depression, and pinpoint
pupils. Fatal opioid overdoses have increased exponentially in the United States since 1999.
Development and Course
Opioid intoxication can occur in an individual who is opioid naïve, an individual who uses
opioids sporadically, and an individual who is physically dependent on opioids. The dose of
opioid consumed relative to the likelihood of experiencing opioid intoxication will vary as a
function of the status and history of the individual’s opioid exposure (i.e., tolerance). Individuals
often report that the qualitative pleasurable experience of opioid intoxication diminishes after
repeated use of an opioid.
Differential Diagnosis
Alcohol intoxication and sedative-hypnotic intoxication can cause a
clinical picture that resembles opioid intoxication. A diagnosis of alcohol or sedative-hypnotic
intoxication can usually be made based on the absence of pupillary constriction or the lack of a
response to a naloxone challenge. In some cases, intoxication may be due both to opioids and to
alcohol or other sedatives. In these cases, naloxone administration will not reverse all of the
sedative effects. While response to administration of

Opioid-induced mental disorders.
naloxone can support the diagnosis of opioid intoxication, nonresponse may be due to the coingestion of an opioid with another drug (e.g., a benzodiazepine, alcohol) or to ingestion of a
higher dose of and/or higher-potency opioid (e.g., fentanyl).
Opioid intoxication is distinguished from opioid-induced mental
disorders (e.g., opioid-induced depressive disorder, with onset during intoxication) because the
symptoms (e.g., depressed mood) in the latter disorders are in excess of those usually associated
with opioid intoxication, predominate in the clinical presentation, and are severe enough to
warrant clinical attention.
Comorbidity
Given the typical overlap of opioid intoxication with opioid use disorder, see “Comorbidity”
under Opioid Use Disorder for more details about co-occurring conditions that are likely to be
encountered.
Opioid Withdrawal
Diagnostic Criteria
A. Presence of either of the following:
1. Cessation of (or reduction in) opioid use that has been heavy and prolonged
(i.e., several weeks or longer).
2. Administration of an opioid antagonist after a period of opioid use.
B. Three (or more) of the following developing within minutes to several days after
Criterion A:
1. Dysphoric mood.
2. Nausea or vomiting.
3. Muscle aches.
4. Lacrimation or rhinorrhea.
5. Pupillary dilation, piloerection, or sweating.
6. Diarrhea.
7. Yawning.
8. Fever.
9. Insomnia.
C. The signs or symptoms in Criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication or
withdrawal from another substance.
Coding note: The ICD-10-CM code depends on whether or not there is a comorbid

opioid use disorder. If a mild opioid use disorder is comorbid, the ICD-10-CM code is
F11.13, and if a moderate or severe opioid use disorder is comorbid, the ICD-10-CM
code is F11.23. For opioid withdrawal occurring in the absence of an opioid use
disorder (e.g., in a patient taking opioids solely under appropriate medical
supervision), the ICD-10-CM code is F11.93.
Diagnostic Features
The essential feature of opioid withdrawal is the presence of a characteristic withdrawal
syndrome that develops after the cessation of (or reduction in) prolonged opioid use
(Criterion A1). The opioids used may be illicit or licitly obtained drugs prescribed to treat pain.
A withdrawal syndrome can also be precipitated by administration of an opioid antagonist (e.g.,
naloxone, naltrexone, nalmefene) after a period of opioid use (Criterion A2); it can also occur
after administration of an opioid partial agonist (e.g., buprenorphine) to an individual currently
using a full opioid agonist.
Opioid withdrawal has a characteristic pattern of signs and symptoms. The first of these are
subjective and consist of complaints of anxiety, restlessness, and an “achy feeling” that is often
located in the back and legs, along with irritability and increased sensitivity to pain. Three or
more of the following must be present to make a diagnosis of opioid withdrawal: dysphoric
mood; nausea or vomiting; muscle aches; lacrimation or rhinorrhea; pupillary dilation,
piloerection, or increased sweating; diarrhea; yawning; fever; and insomnia (Criterion B).
Piloerection and fever are associated with more severe withdrawal and are not often seen in
routine clinical practice because individuals with opioid use disorder usually obtain substances
before withdrawal becomes that far advanced. These symptoms of opioid withdrawal must cause
clinically significant distress or impairment in social, occupational, or other important areas of
functioning (Criterion C). The symptoms must not be attributable to another medical condition
and are not better explained by another mental disorder (Criterion D). Having symptoms that
meet diagnostic criteria for opioid withdrawal alone is not sufficient for a diagnosis of opioid use
disorder, but concurrent symptoms of craving and drug-seeking behavior are suggestive of
comorbid opioid use disorder.
Associated Features
Opioid withdrawal may occur in any individual after cessation of repeated use of an opioid,
whether in the setting of medical management of pain, during opioid agonist therapy for opioid
use disorder, in the context of illicit use, or following attempts to self-treat symptoms of mental
disorders with opioids. Opioid withdrawal is a distinct condition from opioid addiction or opioid
use disorder and does not necessarily require the drug-seeking behaviors associated with opioid
use disorder to be diagnosed. Thus, opioid withdrawal may occur in individuals without opioid
use disorder and should not be confused with it. Males with opioid withdrawal may experience
piloerection, sweating, and spontaneous ejaculations while awake.
Prevalence

Other withdrawal disorders.
Other substance intoxication.
Opioid-induced mental disorders.
Among individuals from various U.S. clinical settings, opioid withdrawal occurred in 60% of
individuals who had used heroin at least once in the prior 12 months. Individuals regularly using
opioids (e.g., prescription opioids for pain, illicit opioids) for a period of time are at risk for
developing physical dependence, including withdrawal, on cessation or marked reduction in use.
Development and Course
The speed and severity of withdrawal associated with opioids depend on the half-life of the
opioid used. Most individuals who are physiologically dependent on short-acting drugs such as
heroin begin to have withdrawal symptoms within 6–12 hours after the last dose. Symptoms may
take 2–4 days to emerge in the case of longer-acting drugs such as methadone or buprenorphine.
Acute withdrawal symptoms for a short-acting opioid such as heroin usually peak within 1–3
days and gradually subside over a period of 5–7 days. More chronic symptoms (e.g., anxiety,
dysphoria, anhedonia, craving, insomnia) can last for weeks to months. The severity of opioid
withdrawal also varies depending on the duration of opioid use. Opioid withdrawal symptoms
among individuals receiving long-term prescription opioid treatment for pain can be minimized
by tapering the drug slowly.
Among those with an opioid use disorder, opioid withdrawal and attempts to relieve
withdrawal are typical. The course of withdrawal can be part of an escalating pattern in which an
opioid is used to reduce withdrawal symptoms, in turn leading to recurrent episodes of
withdrawal at a later time.
Differential Diagnosis
The anxiety and restlessness associated with opioid withdrawal
resemble symptoms seen in sedative-hypnotic withdrawal. However, opioid withdrawal is also
accompanied by rhinorrhea, lacrimation, and pupillary dilation, which are not seen in sedativetype withdrawal.
Dilated pupils are also seen in hallucinogen intoxication and
stimulant intoxication. However, other signs or symptoms of opioid withdrawal, such as nausea,
vomiting, diarrhea, abdominal cramps, rhinorrhea, and lacrimation, are not present.
Opioid withdrawal is distinguished from opioid-induced mental
disorders (e.g., opioid-induced depressive disorder, with onset during withdrawal) because the
symptoms (e.g., depressed mood) in these latter disorders are in excess of those usually
associated with opioid withdrawal, predominate in the clinical presentation, and are severe
enough to warrant clinical attention.
Comorbidity
Given the typical overlap of opioid withdrawal with opioid use disorder, see “Comorbidity”
under Opioid Use Disorder for more details about co-occurring conditions that are likely to be
encountered.

Opioid-Induced Mental Disorders
The following opioid-induced mental disorders are described in other chapters of the manual
with disorders with which they share phenomenology (see the substance/medication-induced
mental disorders in these chapters): opioid-induced depressive disorder (“Depressive
Disorders”); opioid-induced anxiety disorder (“Anxiety Disorders”); opioid-induced sleep
disorder (“Sleep-Wake Disorders”); and opioid-induced sexual dysfunction (“Sexual
Dysfunctions”). For opioid intoxication delirium, opioid withdrawal delirium, and delirium
induced by opioids taken as prescribed, see the criteria and discussion of delirium in the chapter
“Neurocognitive Disorders.” These opioid-induced mental disorders are diagnosed instead of
opioid intoxication or opioid withdrawal only when the symptoms are sufficiently severe to
warrant independent clinical attention.
Unspecified Opioid-Related Disorder
F11.99
This category applies to presentations in which symptoms characteristic of an opioidrelated disorder that cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning predominate but do not meet
the full criteria for any specific opioid-related disorder or any of the disorders in the
substance-related and addictive disorders diagnostic class.
Sedative-, Hypnotic-, or Anxiolytic-Related
Disorders
Sedative, Hypnotic, or Anxiolytic Use Disorder
Sedative, Hypnotic, or Anxiolytic Intoxication
Sedative, Hypnotic, or Anxiolytic Withdrawal
Sedative-, Hypnotic-, or Anxiolytic-Induced Mental Disorders
Unspecified Sedative-, Hypnotic-, or Anxiolytic-Related Disorder
Sedative, Hypnotic, or Anxiolytic Use Disorder
Diagnostic Criteria

A. A problematic pattern of sedative, hypnotic, or anxiolytic use leading to clinically
significant impairment or distress, as manifested by at least two of the following,
occurring within a 12-month period:
1. Sedatives, hypnotics, or anxiolytics are often taken in larger amounts or over
a longer period than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control
sedative, hypnotic, or anxiolytic use.
3. A great deal of time is spent in activities necessary to obtain the sedative,
hypnotic, or anxiolytic; use the sedative, hypnotic, or anxiolytic; or recover
from its effects.
4. Craving, or a strong desire or urge to use the sedative, hypnotic, or anxiolytic.
5. Recurrent sedative, hypnotic, or anxiolytic use resulting in a failure to fulfill
major role obligations at work, school, or home (e.g., repeated absences from
work or poor work performance related to sedative, hypnotic, or anxiolytic
use; sedative-, hypnotic-, or anxiolytic-related absences, suspensions, or
expulsions from school; neglect of children or household).
6. Continued sedative, hypnotic, or anxiolytic use despite having persistent or
recurrent social or interpersonal problems caused or exacerbated by the
effects of sedatives, hypnotics, or anxiolytics (e.g., arguments with a spouse
about consequences of intoxication; physical fights).
7. Important social, occupational, or recreational activities are given up or
reduced because of sedative, hypnotic, or anxiolytic use.
8. Recurrent sedative, hypnotic, or anxiolytic use in situations in which it is
physically hazardous (e.g., driving an automobile or operating a machine
when impaired by sedative, hypnotic, or anxiolytic use).
9. Sedative, hypnotic, or anxiolytic use is continued despite knowledge of having
a persistent or recurrent physical or psychological problem that is likely to
have been caused or exacerbated by the sedative, hypnotic, or anxiolytic.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the sedative, hypnotic, or
anxiolytic to achieve intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of
the sedative, hypnotic, or anxiolytic.
Note: This criterion is not considered to be met for individuals taking
sedatives, hypnotics, or anxiolytics under medical supervision.
11. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome for sedatives, hypnotics, or
anxiolytics (refer to Criteria A and B of the criteria set for sedative,
hypnotic, or anxiolytic withdrawal).

b. Sedatives, hypnotics, or anxiolytics (or a closely related substance, such
as alcohol) are taken to relieve or avoid withdrawal symptoms.
Note: This criterion is not considered to be met for individuals taking
sedatives, hypnotics, or anxiolytics under medical supervision.
Specify if:
In early remission: After full criteria for sedative, hypnotic, or anxiolytic use
disorder were previously met, none of the criteria for sedative, hypnotic, or
anxiolytic use disorder have been met for at least 3 months but for less than 12
months (with the exception that Criterion A4, “Craving, or a strong desire or urge
to use the sedative, hypnotic, or anxiolytic,” may be met).
In sustained remission: After full criteria for sedative, hypnotic, or anxiolytic
use disorder were previously met, none of the criteria for sedative, hypnotic, or
anxiolytic use disorder have been met at any time during a period of 12 months
or longer (with the exception that Criterion A4, “Craving, or a strong desire or
urge to use the sedative, hypnotic, or anxiolytic,” may be met).
Specify if:
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to sedatives, hypnotics, or anxiolytics is
restricted.
Code based on current severity/remission: If a sedative, hypnotic, or anxiolytic
intoxication; sedative, hypnotic, or anxiolytic withdrawal; or another sedative-,
hypnotic-, or anxiolytic-induced mental disorder is also present, do not use the codes
below for sedative, hypnotic, or anxiolytic use disorder. Instead, the comorbid
sedative, hypnotic, or anxiolytic use disorder is indicated in the 4th character of the
sedative-, hypnotic-, or anxiolytic-induced disorder (see the coding note for sedative,
hypnotic, or anxiolytic intoxication; sedative, hypnotic, or anxiolytic withdrawal; or
specific sedative-, hypnotic-, or anxiolytic-induced mental disorder). For example, if
there is comorbid sedative-, hypnotic-, or anxiolytic-induced depressive disorder and
sedative, hypnotic, or anxiolytic use disorder, only the sedative-, hypnotic-, or
anxiolytic-induced depressive disorder code is given, with the 4th character
indicating whether the comorbid sedative, hypnotic, or anxiolytic use disorder is mild,
moderate, or severe: F13.14 for mild sedative, hypnotic, or anxiolytic use disorder
with sedative-, hypnotic-, or anxiolytic-induced depressive disorder or F13.24 for a
moderate or severe sedative, hypnotic, or anxiolytic use disorder with sedative-,
hypnotic-, or anxiolytic-induced depressive disorder.
Specify current severity/remission:
F13.10 Mild: Presence of 2–3 symptoms.
F13.11 Mild, In early remission
F13.11 Mild, In sustained remission
F13.20 Moderate: Presence of 4–5 symptoms.
F13.21 Moderate, In early remission

F13.21 Moderate, In sustained remission
F13.20 Severe: Presence of 6 or more symptoms.
F13.21 Severe, In early remission
F13.21 Severe, In sustained remission
Specifiers
“In a controlled environment” applies as a further specifier of remission if the individual is both
in remission and in a controlled environment (i.e., in early remission in a controlled environment
or in sustained remission in a controlled environment). Examples of these environments are
closely supervised and substance-free jails, therapeutic communities, and locked hospital units.
Diagnostic Features
Sedative, hypnotic, or anxiolytic substances include benzodiazepines, benzodiazepine-like drugs
(e.g., zolpidem, zaleplon), carbamates (e.g., glutethimide, meprobamate), barbiturates (e.g.,
secobarbital), and barbiturate-like hypnotics (e.g., glutethimide, methaqualone, propofol). This
class of substances includes most prescription sleeping medications and most prescription
antianxiety medications. Nonbenzodiazepine antianxiety agents (e.g., buspirone, gepirone) are
not included in this class because they do not appear to be associated with significant misuse.
Like 
alcohol, 
these 
agents 
are 
brain 
depressants 
and 
can 
produce 
similar
substance/medication-induced and substance use disorders. Sedative, hypnotic, or anxiolytic
substances are available both by prescription and illegally. Some individuals who obtain these
substances by prescription will develop a sedative, hypnotic, or anxiolytic use disorder, while
others who misuse these substances or use them for intoxication will not develop a use disorder.
In particular, sedatives, hypnotics, or anxiolytics with rapid onset or short to intermediate lengths
of action may be taken for intoxication purposes, although longer-acting substances in this class
may be taken for intoxication as well.
Craving (Criterion A4), either during periods of active use or during periods of abstinence, is
a typical feature of sedative, hypnotic, or anxiolytic use disorder. Misuse of substances from this
class may occur in conjunction with use of other substances. For example, individuals may use
intoxicating doses of sedatives or benzodiazepines to “come down” from cocaine or
amphetamines or use high doses of benzodiazepines in combination with methadone to “boost”
its effects.
Repeated absences or poor work performance, school absences, suspensions or expulsions,
and neglect of children or household (Criterion A5) may be related to sedative, hypnotic, or
anxiolytic use disorder; the continued use of the substances despite arguments with a spouse
about consequences of intoxication or despite physical fights (Criterion A6) may also occur.
Limiting contact with family or friends, avoiding work or school, or stopping participation in
hobbies, sports, or games (Criterion A7) and recurrent sedative, hypnotic, or anxiolytic use when
driving an automobile or operating machinery when impaired by such use (Criterion A8) are also
seen in sedative, hypnotic, or anxiolytic use disorder.
Very significant levels of tolerance and withdrawal can develop to sedative, hypnotic, or

anxiolytic substances. There may be evidence of tolerance and withdrawal in the absence of a
diagnosis of a sedative, hypnotic, or anxiolytic use disorder in an individual who has abruptly
discontinued use of benzodiazepines that were taken for long periods of time at prescribed and
therapeutic doses. In these cases, an additional diagnosis of sedative, hypnotic, or anxiolytic use
disorder is made only if other criteria are met. That is, sedative, hypnotic, or anxiolytic
medications may be prescribed for appropriate medical purposes, and depending on the dose
regimen, these drugs may then produce tolerance and withdrawal. If these drugs are prescribed or
recommended for appropriate medical purposes, and if they are used as prescribed, the resulting
tolerance or withdrawal does not count toward the diagnosis of a substance use disorder.
However, it is necessary to determine whether the drugs were inappropriately prescribed and
used (e.g., falsifying medical symptoms to obtain the medication; using more medication than
prescribed; obtaining the medication from several doctors without informing them).
Given the unidimensional nature of the symptoms of sedative, hypnotic, or anxiolytic use
disorder, severity is based on the number of criteria endorsed.
Associated Features
Research with nationally representative samples of the U.S. population has found that sedative,
hypnotic, or anxiolytic use disorder is often associated with other substance use disorders (e.g.,
alcohol, cannabis, opioid, stimulant use disorders). Sedatives are often used to alleviate the
unwanted effects of these other substances. With repeated use of the sedative, hypnotic, or
anxiolytic, tolerance develops to the sedative effects, and a progressively higher dose is used.
However, tolerance to brain stem depressant effects develops much more slowly, and as the
individual takes more substance to achieve euphoria or other desired effects, there may be a
sudden onset of respiratory depression and hypotension, which may result in death. Intense or
repeated sedative, hypnotic, or anxiolytic intoxication may be associated with severe depression
that although temporary can lead to suicide attempt and suicide.
Prevalence
The 12-month prevalence of DSM-IV sedative, hypnotic, or anxiolytic use disorder in the United
States is estimated to be 0.3% among adolescents ages 12–17 years and adults age 18 years and
older, and this prevalence has remained stable nationally despite increases in rates of prescription
of these medications. Rates of DSM-IV sedative, hypnotic, or anxiolytic use disorder in the
United States have not been shown to vary consistently by gender, but data from other countries
have generally found higher rates among girls and women than boys and men. The 12-month
prevalence of DSM-IV sedative, hypnotic, or anxiolytic use disorder in the United States
decreases as a function of age and is greatest among individuals ages 18–29 years (0.5%) and
lowest among individuals 65 years and older (0.04%).
Twelve-month prevalence of sedative, hypnotic, or anxiolytic use, misuse (e.g., use without a
prescription), or disorder varies across U.S. ethnoracial groups. For instance, 12-month
prevalence estimates for sedative, hypnotic, or anxiolytic misuse across ethnoracial groups range
from 0.6% to 2.5% for adolescents ages 12–17 years and 0.7% to 10.1% for adults.

Temperamental.
Environmental.
Development and Course
The usual course of sedative, hypnotic, or anxiolytic use disorder involves individuals in their
teens or 20s who escalate their occasional use of sedative, hypnotic, or anxiolytic agents to the
point at which they develop problems that meet criteria for a diagnosis. This pattern may be
especially likely among individuals who have other substance use disorders (e.g., alcohol,
opioids, stimulants). An initial pattern of intermittent use socially (e.g., at parties) can lead to
daily use and high levels of tolerance. Once this occurs, an increasing level of interpersonal
difficulties can be expected, as well as increasingly severe episodes of cognitive dysfunction and
physiological withdrawal.
The second and less frequently observed clinical course begins with an individual who
originally obtained the medication by prescription from a physician, usually for the treatment of
anxiety, insomnia, or somatic complaints. As either tolerance or a need for higher doses of the
medication develops, there is a gradual increase in the dose and frequency of self-administration.
The individual is likely to continue to justify use on the basis of original anxiety or insomnia
symptoms, but substance-seeking behavior becomes more prominent, and the individual may
seek out multiple physicians to obtain sufficient supplies of the medication. Tolerance can reach
high levels, and withdrawal (including seizures and withdrawal delirium) may occur.
As with many substance use disorders, sedative, hypnotic, or anxiolytic use disorder
generally has an onset during adolescence or early adult life. Although the risk for misuse and
use disorder decreases with age after about age 30, side effects associated with psychoactive
substances may increase as individuals age. In particular, cognitive impairment increases as a
side effect with age, and the metabolism of sedatives, hypnotics, or
anxiolytics decreases with age among older individuals. Both acute and chronic toxic effects
of these substances, especially effects on cognition, memory, and motor coordination, are likely
to increase with age as a consequence of pharmacodynamic and pharmacokinetic age-related
changes. Individuals with major neurocognitive disorder are more likely to develop intoxication
and impaired physiological functioning at lower doses. Because sedatives, hypnotics, and
anxiolytics are often used in combination with other psychoactive substances, it can be difficult
to ascertain whether the functional consequences are attributable to a single substance (e.g.,
sedative) or to the use of multiple substances.
Deliberate intoxication to achieve a “high” is most likely to be observed in teenagers and
individuals in their 20s. Problems associated with sedatives, hypnotics, or anxiolytics are also
seen in individuals in their 40s and older who escalate the dose of prescribed medications. In
older individuals, intoxication can resemble a progressive major neurocognitive disorder.
Risk and Prognostic Factors
Impulsivity and novelty seeking are individual temperaments that relate to the
propensity to develop a substance use disorder but may themselves be genetically determined.
Personality disorders can also increase the risk of sedative, hypnotic, or anxiolytic misuse or use
disorder.
Because sedatives, hypnotics, or anxiolytics are all medications, a key risk factor

Genetic and physiological.
Course modifiers.
relates to availability of the substances, both through an individual’s own prescriptions and from
prescriptions dispensed to family and friends. In the United States, the historical patterns of
sedative, hypnotic, or anxiolytic misuse relate to broad prescribing patterns. For instance, a
marked decrease in prescription of barbiturates was associated with an increase in
benzodiazepine prescriptions. Peer factors may relate to genetic predisposition in terms of how
individuals select their environment. Other individuals at heightened risk might include those
with alcohol use disorder who may receive repeated prescriptions in response to their complaints
of alcohol-related anxiety or insomnia.
As with other substance use disorders, the risk for sedative, hypnotic,
or anxiolytic use disorder has been found in U.S.-based twin registry studies to be related to
individual, family, peer, social, and environmental factors. Within these domains, genetic factors
play a particularly important role both directly and indirectly. Overall, across development,
genetic factors seem to play a larger role in the onset of sedative, hypnotic, or anxiolytic use
disorder as individuals age through puberty into adult life.
In nationally representative U.S. studies, early onset of use is associated with
greater likelihood for developing a sedative, hypnotic, or anxiolytic use disorder.
Culture-Related Diagnostic Issues
Prescription patterns (and availability) of this class of substances vary across countries and
populations, which may lead to variations in prevalence of sedative, hypnotic, or anxiolytic use
disorder. In the United States, use of benzodiazepines has been more frequently reported by nonLatinx Whites than Latinx or African Americans. However, risk of the disorder may vary within
populations exposed to these substances. For example, the 12-month prevalence of DSM-IV
benzodiazepine use disorder among U.S. individuals who used benzodiazepines was higher
among African Americans (3.0%) and non-Latinx “others” (2.6%) than among non-Latinx
Whites (1.3%).
Sex- and Gender-Related Diagnostic Issues
Although estimates from individual studies vary, there appear to be no gender differences in the
prevalence of sedative, hypnotic, or anxiolytic use disorder.
Diagnostic Markers
Almost all sedative, hypnotic, or anxiolytic substances can be identified through laboratory
evaluations of urine or blood (the latter of which can quantify the amounts of these agents in the
body). Urine test results are likely to remain positive for up to approximately 1 week after the
use of long-acting substances, such as diazepam or flurazepam.
Association With Suicidal Thoughts or Behavior
U.S. epidemiological studies show that hypnotics are associated with suicide, but it is unclear if
this association is attributable to underlying psychiatric conditions such as depression and
insomnia, which are themselves risk factors for suicide.

Sedative, hypnotic, or anxiolytic intoxication; sedative, hypnotic, or anxiolytic withdrawal; and
sedative-, hypnotic-, or anxiolytic-induced mental disorders.
Functional Consequences of Sedative, Hypnotic, or Anxiolytic Use
Disorder
The social and interpersonal consequences of sedative, hypnotic, or anxiolytic use disorder
mimic those of alcohol in terms of the potential for disinhibited behavior. Accidents,
interpersonal difficulties, and interference with work or school performance are common
outcomes. The disinhibiting effects of these agents, like alcohol, may potentially contribute to
overly aggressive behavior and arguments or fights, with subsequent interpersonal and legal
problems. Physical examination is likely to reveal evidence of a mild decrease in most aspects of
autonomic nervous system functioning, including a slower pulse, a slightly decreased respiratory
rate, and a slight drop in blood pressure (most likely to occur with postural changes).
Acute intoxication can result in accidental injuries and automobile accidents. There may be
consequences of trauma (e.g., internal bleeding, a subdural hematoma) from accidents that occur
while intoxicated. For elderly individuals, even short-term use of these sedating medications at
prescribed doses may be associated with an increased risk for cognitive problems and falls. The
association of sedative, hypnotic, or anxiolytic medications with increased risk of major
neurocognitive disorder remains unclear.
At high doses, sedative, hypnotic, or anxiolytic substances can be lethal, particularly when
mixed with other central nervous system depressants, such as opioids or alcohol, although the
lethal dosage varies considerably among the specific substances. Intravenous use of these
substances can result in medical complications related to the use of contaminated needles (e.g.,
hepatitis, HIV).
Accidental or deliberate overdoses, similar to those observed for alcohol use disorder or
repeated alcohol intoxication, can occur. Overdoses may be associated with a deterioration in
vital signs that signals an impending medical emergency (e.g., respiratory arrest from
barbiturates). In contrast to their wide margin of safety when used alone, benzodiazepines taken
in combination with opioids and alcohol can be particularly dangerous, and accidental overdoses
are reported commonly in U.S. data. Accidental overdoses have also been reported in individuals
who deliberately misuse barbiturates and other nonbenzodiazepine sedatives (e.g.,
methaqualone), but because these agents are much less available than the benzodiazepines, the
frequency of overdosing is low in most settings.
Differential Diagnosis
Sedative, hypnotic, or anxiolytic use disorder is differentiated from sedative, hypnotic, or
anxiolytic intoxication; sedative, hypnotic, or anxiolytic withdrawal; and sedative-, hypnotic-, or
anxiolytic-induced mental disorders (e.g., sedative-, hypnotic-, or anxiolytic-induced depressive
disorder) in that sedative, hypnotic, or anxiolytic use disorder describes a problematic pattern
of sedative, hypnotic, or anxiolytic use that involves impaired control over such use; social
impairment attributable to this use; risky sedative, hypnotic, or anxiolytic use (e.g., driving while
intoxicated); and pharmacological symptoms (the development of tolerance or withdrawal);
whereas sedative, hypnotic, or anxiolytic intoxication; sedative, hypnotic, or anxiolytic

Other medical conditions.
Alcohol use disorder.
Clinically appropriate use of sedative, hypnotic, or anxiolytic medications.
withdrawal; and sedative-, hypnotic-, or anxiolytic-induced mental disorders describe psychiatric
syndromes that occur in the context of heavy use. Sedative, hypnotic, or anxiolytic intoxication;
sedative, hypnotic, or anxiolytic withdrawal; and sedative-, hypnotic-, or anxiolytic-induced
mental disorders occur frequently in individuals with sedative, hypnotic, or anxiolytic use
disorder. In such cases, a diagnosis of sedative, hypnotic, or anxiolytic intoxication; sedative,
hypnotic, or anxiolytic withdrawal; or a sedative-, hypnotic-, or anxiolytic-induced mental
disorder should be given in addition to a diagnosis of sedative, hypnotic, and anxiolytic use
disorder, the presence of which is indicated in the diagnostic code.
The slurred speech, incoordination, and other associated features
characteristic of sedative, hypnotic, or anxiolytic intoxication could be the result of another
medical condition (e.g., multiple sclerosis) or of a prior head trauma (e.g., a subdural hematoma).
Sedative, hypnotic, or anxiolytic use disorder must be differentiated from
alcohol use disorder. The differential diagnosis is determined mostly through clinical history,
although liver damage and other potential signs of chronic alcohol toxicity (e.g.,
cardiomyopathy) can also be more suggestive of alcohol use disorder than of sedative, hypnotic,
or anxiolytic use disorder.
Individuals may continue to
take benzodiazepine medication according to a physician’s direction for a legitimate medical
indication over extended periods of time. Even if physiological signs of tolerance or withdrawal
are manifested, many of these individuals do not develop symptoms that meet the criteria for
sedative, hypnotic, or anxiolytic use disorder because they are not preoccupied with obtaining
the substance and its use does not interfere with their performance of usual social or occupational
roles.
Comorbidity
Nonmedical use of sedative, hypnotic, or anxiolytic agents is associated with alcohol use
disorder, tobacco use disorder, and, generally, illicit drug use. There may also be an overlap
between sedative, hypnotic, or anxiolytic use disorder and antisocial personality disorder;
depressive, bipolar, and anxiety disorders; and other substance use disorders, such as alcohol use
disorder and illicit drug use disorders. Antisocial behavior and antisocial personality disorder are
especially associated with sedative, hypnotic, or anxiolytic use disorder when the substances are
obtained illegally. Comorbidity with other substance use disorders and other psychiatric
disorders increases the risk of transition from sedative, hypnotic, or anxiolytic use to use disorder
and decreases the probability of remission.
Sedative, Hypnotic, or Anxiolytic Intoxication
Diagnostic Criteria
A. Recent use of a sedative, hypnotic, or anxiolytic.
B. Clinically significant maladaptive behavioral or psychological changes (e.g.,

inappropriate sexual or aggressive behavior, mood lability, impaired judgment)
that developed during, or shortly after, sedative, hypnotic, or anxiolytic use.
C. One (or more) of the following signs or symptoms developing during, or shortly
after, sedative, hypnotic, or anxiolytic use:
1. Slurred speech.
2. Incoordination.
3. Unsteady gait.
4. Nystagmus.
5. Impairment in cognition (e.g., attention, memory).
6. Stupor or coma.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.
Coding note: The ICD-10-CM code depends on whether there is a comorbid
sedative, hypnotic, or anxiolytic use disorder. If a mild sedative, hypnotic, or
anxiolytic use disorder is comorbid, the ICD-10-CM code is F13.120, and if a
moderate or severe sedative, hypnotic, or anxiolytic use disorder is comorbid, the
ICD-10-CM code is F13.220. If there is no comorbid sedative, hypnotic, or anxiolytic
use disorder, then the ICD-10-CM code is F13.920.
Note: For information on Development and Course; Risk and Prognostic Factors;
Culture-Related Diagnostic Issues; Diagnostic Markers; Functional Consequences of
Sedative, Hypnotic, or Anxiolytic Intoxication; and Comorbidity, see the corresponding
sections in Sedative, Hypnotic, or Anxiolytic Use Disorder.
Diagnostic Features
The essential feature of sedative, hypnotic, or anxiolytic intoxication is the presence of clinically
significant maladaptive behavioral or psychological changes (e.g., inappropriate sexual or
aggressive behavior, mood lability, impaired judgment, impaired social or occupational
functioning) that develop during, or shortly after, use of a sedative, hypnotic, or anxiolytic
(Criteria A and B). As with other brain depressants, such as alcohol, these behaviors may be
accompanied by slurred speech, incoordination (at levels that can interfere with driving abilities
and with performing usual activities to the point of causing falls or automobile accidents), an
unsteady gait, nystagmus, impairment in cognition (e.g., attentional or memory problems), and
stupor or coma (Criterion C). Memory impairment is a prominent feature of sedative, hypnotic,
or anxiolytic intoxication and is most often characterized by an anterograde amnesia that
resembles “alcoholic blackouts,” which can be disturbing to the individual. The symptoms must
not be attributable to another medical condition and are not better explained by another mental
disorder (Criterion D). Intoxication may occur in individuals who are receiving these substances
by prescription, are borrowing the medication from friends or relatives, or are deliberately taking

Alcohol use disorder.
Alcohol intoxication.
Sedative-, hypnotic-, or anxiolytic-induced mental disorders.
Neurocognitive disorders.
the substance to achieve intoxication. Because sedatives, hypnotics, and anxiolytics are often
used in combination with other psychoactive substances, it can be difficult to ascertain whether
the functional consequences are attributable to a sedative, hypnotic, or anxiolytic or to the use of
multiple substances.
Associated Features
Associated features include taking more medication than prescribed, taking multiple different
medications, or mixing sedative, hypnotic, or anxiolytic agents with alcohol, which can markedly
increase the effects of these agents.
Prevalence
The prevalence of sedative, hypnotic, or anxiolytic intoxication in the general population is
unknown. However, it is probable that most nonmedical users of sedatives, hypnotics,
or anxiolytics would at some time have signs or symptoms that meet criteria for sedative,
hypnotic, or anxiolytic intoxication; if so, then the prevalence of nonmedical sedative, hypnotic,
or anxiolytic use in the general population may be similar to the prevalence of sedative,
hypnotic, or anxiolytic intoxication. For example, in 2018, tranquilizers or sedative were used
nonmedically in the United States by 2.4% of individuals age 12 or older and 4.9% of those ages
18–25.
Differential Diagnosis
Because the clinical presentations may be identical, distinguishing sedative,
hypnotic, or anxiolytic intoxication from alcohol use disorder requires evidence for recent
ingestion of sedative, hypnotic, or anxiolytic medications by self-report, informant report, or
toxicological testing. Many individuals who misuse sedatives, hypnotics, or anxiolytics may also
misuse alcohol and other substances, and so multiple intoxication diagnoses are possible.
Alcohol intoxication may be distinguished from sedative, hypnotic, or
anxiolytic intoxication by the smell of alcohol on the breath. Otherwise, the features of the two
disorders may be similar.
Sedative, 
hypnotic, 
or 
anxiolytic
intoxication is distinguished from sedative-, hypnotic-, or anxiolytic-induced mental disorders
(e.g., sedative-, hypnotic-, or anxiolytic-induced anxiety disorder, with onset during withdrawal)
because the symptoms (e.g., anxiety) in the latter disorders are in excess of those usually
associated with sedative, hypnotic, or anxiolytic intoxication; predominate in the clinical
presentation; and are severe enough to warrant clinical attention.
In situations of cognitive impairment, traumatic brain injury, and
delirium from other causes, sedatives, hypnotics, or anxiolytics may be intoxicating at quite low
dosages. The differential diagnosis in these complex settings is based on the predominant
syndrome. An additional diagnosis of sedative, hypnotic, or anxiolytic intoxication may be
appropriate even if the substance has been ingested at a low dosage in the setting of these other

(or similar) co-occurring conditions.
Comorbidity
Given the typical overlap of sedative, hypnotic, or anxiolytic intoxication with sedative,
hypnotic, or anxiolytic use disorder, see “Comorbidity” under Sedative, Hypnotic, or Anxiolytic
Use Disorder for more details about co-occurring conditions that are likely to be encountered.
Sedative, Hypnotic, or Anxiolytic Withdrawal
Diagnostic Criteria
A. Cessation of (or reduction in) sedative, hypnotic, or anxiolytic use that has been
prolonged.
B. Two (or more) of the following, developing within several hours to a few days
after the cessation of (or reduction in) sedative, hypnotic, or anxiolytic use
described in Criterion A:
1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100 bpm).
2. Hand tremor.
3. Insomnia.
4. Nausea or vomiting.
5. Transient visual, tactile, or auditory hallucinations or illusions.
6. Psychomotor agitation.
7. Anxiety.
8. Grand mal seizures.
C. The signs or symptoms in Criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication or
withdrawal from another substance.
Specify if:
With perceptual disturbances: This specifier may be noted when
hallucinations with intact reality testing or auditory, visual, or tactile illusions
occur in the absence of a delirium.
Coding note: The ICD-10-CM code depends on whether or not there is a comorbid
sedative, hypnotic, or anxiolytic use disorder and whether or not there are perceptual
disturbances.
For sedative, hypnotic, or anxiolytic withdrawal, without perceptual

disturbances: If a mild sedative, hypnotic, or anxiolytic use disorder is
comorbid, the ICD-10-CM code is F13.130, and if a moderate or severe
sedative, hypnotic, or anxiolytic use disorder is comorbid, the ICD-10-CM code is
F13.230. If there is no comorbid sedative, hypnotic, or anxiolytic use disorder
(e.g., in a patient taking sedatives, hypnotics, or anxiolytics solely under
appropriate medical supervision), then the ICD-10-CM code is F13.930.
For sedative, hypnotic, or anxiolytic withdrawal, with perceptual
disturbances: If a mild sedative, hypnotic, or anxiolytic use disorder is
comorbid, the ICD-10-CM code is F13.132, and if a moderate or severe
sedative, hypnotic, or anxiolytic use disorder is comorbid, the ICD-10-CM code is
F13.232. If there is no comorbid sedative, hypnotic, or anxiolytic use disorder
(e.g., in a patient taking sedatives, hypnotics, or anxiolytics solely under
appropriate medical supervision), then the ICD-10-CM code is F13.932.
Note: For information on Development and Course; Risk and Prognostic Factors;
Culture-Related Diagnostic Issues; Functional Consequences of Sedative, Hypnotic, or
Anxiolytic Withdrawal; and Comorbidity, see the corresponding sections in Sedative,
Hypnotic, or Anxiolytic Use Disorder.
Diagnostic Features
The essential feature of sedative, hypnotic, or anxiolytic withdrawal is the presence of a
characteristic syndrome that develops after a marked decrease in or cessation of intake after
several weeks or more of regular use (Criteria A and B). This withdrawal syndrome is
characterized by two or more symptoms (similar to alcohol withdrawal) that include autonomic
hyperactivity (e.g., increases in heart rate, respiratory rate, blood pressure, or body temperature,
along with sweating); a tremor of the hands; insomnia; nausea, sometimes accompanied by
vomiting; anxiety; and psychomotor agitation. A grand mal seizure may occur in perhaps as
many as 20%–30% of individuals undergoing untreated withdrawal from these substances. In
severe withdrawal, visual, tactile, or auditory hallucinations or illusions can occur but are usually
in the context of a withdrawal delirium. If the individual’s reality testing is intact (i.e., knows the
substance is causing the hallucinations) and the illusions occur in a clear sensorium, the specifier
“with perceptual disturbances”
can be noted. When hallucinations occur in the absence of intact reality testing, a diagnosis of
substance/medication-induced psychotic disorder should be considered. The symptoms cause
clinically significant distress or impairment in social, occupational, or other important areas of
functioning (Criterion C). The symptoms must not be attributable to another medical condition
and are not better explained by another mental disorder (e.g., alcohol withdrawal, generalized
anxiety disorder) (Criterion D). Relief of withdrawal symptoms with administration of any
sedative-hypnotic agent would support a diagnosis of sedative, hypnotic, or anxiolytic
withdrawal.

Other medical conditions.
Associated Features
The timing and severity of the withdrawal syndrome will differ depending on the specific
substance and its pharmacokinetics and pharmacodynamics. For example, withdrawal from
shorter-acting substances that are rapidly absorbed and that have no active metabolites (e.g.,
triazolam) can begin within hours after the substance is stopped; withdrawal from substances
with long-acting metabolites (e.g., diazepam) may not begin for 1–2 days or longer. The
withdrawal syndrome produced by substances in this class may be characterized by the
development of a delirium that can be life-threatening. There may be evidence of tolerance and
withdrawal in the absence of a diagnosis of a benzodiazepine use disorder in an individual who
has abruptly discontinued benzodiazepines that were taken for long periods of time at prescribed
and therapeutic doses.
The time course of the withdrawal syndrome is generally predicted by the half-life of the
substance. Medications whose actions typically last about 10 hours or less (e.g., lorazepam,
oxazepam, temazepam) produce withdrawal symptoms within 6–8 hours of decreasing blood
levels that peak in intensity on the second day and improve markedly by the fourth or fifth day.
For substances with longer half-lives (e.g., diazepam), symptoms may not develop for more than
1 week, peak in intensity during the second week, and decrease markedly during the third or
fourth week. There may be additional longer-term symptoms at a much lower level of intensity
that persist for several months.
The longer the substance has been taken and the higher the dosages used, the more likely
there will be severe withdrawal. However, withdrawal has been reported with as little as 15 mg
of diazepam (or its equivalent in other benzodiazepines) when taken daily for several months.
Doses of approximately 40 mg of diazepam (or its equivalent) daily are more likely to produce
clinically relevant withdrawal symptoms, and even higher doses (e.g., 100 mg of diazepam) are
more likely to be followed by withdrawal seizures or delirium. Sedative, hypnotic, or anxiolytic
withdrawal delirium is characterized by disturbances in consciousness and cognition, with visual,
tactile, or auditory hallucinations. When present, sedative, hypnotic, or anxiolytic withdrawal
delirium should be diagnosed instead of withdrawal.
Prevalence
The prevalence of sedative, hypnotic, or anxiolytic withdrawal is unknown.
Diagnostic Markers
Seizures and autonomic instability in the setting of a history of prolonged exposure to sedative,
hypnotic, or anxiolytic medications suggest a high likelihood of sedative, hypnotic, or anxiolytic
withdrawal.
Differential Diagnosis
The symptoms of sedative, hypnotic, or anxiolytic withdrawal may be
mimicked by other medical conditions (e.g., hypoglycemia, diabetic ketoacidosis). If seizures are
a feature of the sedative, hypnotic, or anxiolytic withdrawal, the

Essential tremor.
Alcohol withdrawal.
Sedative-, hypnotic-, or anxiolytic-induced mental disorders.
Anxiety disorders.
differential diagnosis includes the various causes of seizures (e.g., infections, head injury,
poisonings).
Essential tremor, a neurological condition that frequently runs in families, may
erroneously suggest the tremulousness associated with sedative, hypnotic, or anxiolytic
withdrawal.
Alcohol withdrawal produces a syndrome very similar to that of sedative,
hypnotic, or anxiolytic withdrawal. The differential diagnosis is determined mostly through
clinical history, although liver damage and other potential signs of chronic alcohol toxicity (e.g.,
cardiomyopathy) can also be more suggestive of alcohol withdrawal than of sedative, hypnotic,
or anxiolytic withdrawal.
Sedative, 
hypnotic, 
or 
anxiolytic
withdrawal is distinguished from sedative-, hypnotic-, or anxiolytic-induced mental disorders
(e.g., sedative-, hypnotic-, or anxiolytic-induced anxiety disorder, with onset during withdrawal)
because the symptoms (e.g., anxiety) in the latter disorders are in excess of those usually
associated with sedative, hypnotic, or anxiolytic withdrawal; predominate in the clinical
presentation; and are severe enough to warrant clinical attention.
Recurrence or worsening of an underlying anxiety disorder produces a
syndrome similar to sedative, hypnotic, or anxiolytic withdrawal, although the most extreme
manifestations of withdrawal, such as delirium tremens or true seizures, are not symptoms of any
anxiety disorder. Withdrawal would be suspected with an abrupt reduction in the dosage of a
sedative, hypnotic, or anxiolytic medication. When a taper is under way, distinguishing the
withdrawal syndrome from the underlying anxiety disorder can be difficult. As with alcohol,
lingering withdrawal symptoms (e.g., anxiety, moodiness, trouble sleeping) can be mistaken for
independent anxiety or depressive disorders (e.g., generalized anxiety disorder).
Comorbidity
Given the typical overlap of sedative, hypnotic, or anxiolytic withdrawal with sedative, hypnotic,
or anxiolytic use disorder, see “Comorbidity” under Sedative, Hypnotic, or Anxiolytic Use
Disorder for more details about co-occurring conditions that are likely to be encountered.
Sedative-, Hypnotic-, or Anxiolytic-Induced Mental
Disorders
The following sedative-, hypnotic-, or anxiolytic-induced mental disorders are described in other
chapters of the manual with disorders with which they share phenomenology (see the
substance/medication-induced mental disorders in these chapters): sedative-, hypnotic-, or
anxiolytic-induced psychotic disorder (“Schizophrenia Spectrum and Other Psychotic
Disorders”); sedative-, hypnotic-, or anxiolytic-induced bipolar and related disorder (“Bipolar
and Related Disorders”); sedative-, hypnotic-, or anxiolytic-induced depressive disorder
(“Depressive Disorders”); sedative-, hypnotic-, or anxiolytic-induced anxiety disorder (“Anxiety
Disorders”); sedative-, hypnotic-, or anxiolytic-induced sleep disorder (“Sleep-Wake
Disorders”); sedative-, hypnotic-, or anxiolytic-induced sexual dysfunction (“Sexual

Dysfunctions”); and sedative-, hypnotic-, or anxiolytic-induced major or mild neurocognitive
disorder (“Neurocognitive Disorders”). For sedative, hypnotic, or anxiolytic intoxication
delirium; sedative, hypnotic, or anxiolytic withdrawal delirium; and delirium induced by
sedatives, hypnotics, or anxiolytics taken as prescribed, see the
criteria and discussion of delirium in the chapter “Neurocognitive Disorders.” These sedative-,
hypnotic-, or anxiolytic-induced mental disorders are diagnosed instead of sedative, hypnotic, or
anxiolytic intoxication or sedative, hypnotic, or anxiolytic withdrawal only when the symptoms
are sufficiently severe to warrant independent clinical attention.
Unspecified Sedative-, Hypnotic-, or Anxiolytic-Related
Disorder
F13.99
This category applies to presentations in which symptoms characteristic of a sedative-,
hypnotic-, or anxiolytic-related disorder that cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning predominate but
do not meet the full criteria for any specific sedative-, hypnotic-, or anxiolytic-related
disorder or any of the disorders in the substance-related and addictive disorders diagnostic
class.
Stimulant-Related Disorders
Stimulant Use Disorder
Stimulant Intoxication
Stimulant Withdrawal
Stimulant-Induced Mental Disorders
Unspecified Stimulant-Related Disorder
Stimulant Use Disorder
Diagnostic Criteria
A. A pattern of amphetamine-type substance, cocaine, or other stimulant use
leading to clinically significant impairment or distress, as manifested by at least

two of the following, occurring within a 12-month period:
1. The stimulant is often taken in larger amounts or over a longer period than
was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control
stimulant use.
3. A great deal of time is spent in activities necessary to obtain the stimulant,
use the stimulant, or recover from its effects.
4. Craving, or a strong desire or urge to use the stimulant.
5. Recurrent stimulant use resulting in a failure to fulfill major role obligations at
work, school, or home.
6. Continued stimulant use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of the stimulant.
7. Important social, occupational, or recreational activities are given up or
reduced because of stimulant use.
8. Recurrent stimulant use in situations in which it is physically hazardous.
9. Stimulant use is continued despite knowledge of having a persistent or
recurrent physical or psychological problem that is likely to have been caused
or exacerbated by the stimulant.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the stimulant to achieve
intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of
the stimulant.
Note: This criterion is not considered to be met for those taking stimulant
medications solely under appropriate medical supervision, such as
medications for attention-deficit/hyperactivity disorder or narcolepsy.
11. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome for the stimulant (refer to Criteria
A and B of the criteria set for stimulant withdrawal).
b. The stimulant (or a closely related substance) is taken to relieve or avoid
withdrawal symptoms.
Note: This criterion is not considered to be met for those taking stimulant
medications solely under appropriate medical supervision, such as
medications for attention-deficit/hyperactivity disorder or narcolepsy.
Specify if:
In early remission: After full criteria for stimulant use disorder were previously
met, none of the criteria for stimulant use disorder have been met for at least 3
months but for less than 12 months (with the exception that Criterion A4,

“Craving, or a strong desire or urge to use the stimulant,” may be met).
In sustained remission: After full criteria for stimulant use disorder were
previously met, none of the criteria for stimulant use disorder have been met at
any time during a period of 12 months or longer (with the exception that Criterion
A4, “Craving, or a strong desire or urge to use the stimulant,” may be met).
Specify if:
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to stimulants is restricted.
Code based on current severity/remission: If an amphetamine-type substance
intoxication, amphetamine-type substance withdrawal, or amphetamine-type
substance-induced mental disorder is also present, do not use the codes below for
amphetamine-type substance use disorder. Instead, the comorbid amphetaminetype substance use disorder is indicated in the 4th character of the amphetaminetype substance-induced disorder code (see the coding note for amphetamine-type
substance intoxication, amphetamine-type substance withdrawal, or a specific
amphetamine-type substance-induced mental disorder). For example, if there is
comorbid amphetamine-induced depressive disorder and amphetamine use
disorder, only the amphetamine-induced depressive disorder code is given, with the
4th character indicating whether the comorbid amphetamine use disorder is mild,
moderate, or severe: F15.14 for mild amphetamine use disorder with amphetamineinduced depressive disorder or F15.24 for a moderate or severe amphetamine use
disorder with amphetamine-induced depressive disorder. (The instructions for
amphetamine-type substance also apply to other or unspecified stimulant
intoxication, other or unspecified stimulant withdrawal, and other or unspecified
stimulant-induced mental disorder.) Similarly, if there is comorbid cocaine-induced
depressive disorder and cocaine use disorder, only the cocaine-induced depressive
disorder code is given, with the 4th character indicating whether the comorbid
cocaine use disorder is mild, moderate,
or severe: F14.14 for a mild cocaine use disorder with cocaine-induced depressive
disorder or F14.24 for a moderate or severe cocaine use disorder with cocaineinduced depressive disorder.
Specify current severity/remission:
Mild: Presence of 2–3 symptoms.
F15.10 Amphetamine-type substance
F14.10 Cocaine
F15.10 Other or unspecified stimulant
Mild, In early remission
F15.11 Amphetamine-type substance
F14.11 Cocaine

F15.11 Other or unspecified stimulant
Mild, In sustained remission
F15.11 Amphetamine-type substance
F14.11 Cocaine
F15.11 Other or unspecified stimulant
Moderate: Presence of 4–5 symptoms.
F15.20 Amphetamine-type substance
F14.20 Cocaine
F15.20 Other or unspecified stimulant
Moderate, In early remission
F15.21 Amphetamine-type substance
F14.21 Cocaine
F15.21 Other or unspecified stimulant
Moderate, In sustained remission
F15.21 Amphetamine-type substance
F14.21 Cocaine
F15.21 Other or unspecified stimulant
Severe: Presence of 6 or more symptoms.
F15.20 Amphetamine-type substance
F14.20 Cocaine
F15.20 Other or unspecified stimulant
Severe, In early remission
F15.21 Amphetamine-type substance
F14.21 Cocaine
F15.21 Other or unspecified stimulant
Severe, In sustained remission
F15.21 Amphetamine-type substance
F14.21 Cocaine
F15.21 Other or unspecified stimulant
Specifiers
“In a controlled environment” applies as a further specifier of remission if the individual is both
in remission and in a controlled environment (i.e., in early remission in a controlled environment
or in sustained remission in a controlled environment). Examples of these environments are
closely supervised and substance-free jails, therapeutic communities, and locked hospital units.

Diagnostic Features
Stimulants are a type of psychoactive substance that increases activity in the brain and can
temporarily elevate alertness, mood, and awareness. Stimulants covered in this chapter include
amphetamine and prescription stimulants with similar effects (e.g., methylphenidate) and
cocaine. Substance-related disorders involving certain other substances with stimulant properties
are classified in other sections of this chapter. These include caffeine (in caffeine-related
disorders), 
nicotine 
(in 
tobacco-related 
disorders), 
and 
MDMA 
(3,4methylenedioxymethamphetamine; in other hallucinogen-related disorders), which has both
stimulant and hallucinogenic effects.
Given that the effects of amphetamine-type substances are similar to those of cocaine,
amphetamine-related disorders and cocaine-related disorders are grouped under the single rubric
“stimulant-related disorders.” Amphetamine-type substances (and other or unspecified
stimulants) and cocaine have different ICD-10-CM codes (e.g., F15.10 mild amphetamine-type
substance use disorder, F14.10 mild cocaine use disorder). The particular stimulant used by the
individual is recorded in the diagnosis (e.g., “methamphetamine withdrawal,” “methylphenidate
use disorder,” “cocaine intoxication”).
The amphetamine-type substances include stimulants with a substituted phenylethylamine
structure, such as amphetamine, dextroamphetamine, and methamphetamine. Also included are
substances that are structurally different but have similar effects, such as methylphenidate,
modafinil, and armodafinil. These amphetamine-type substances are usually taken orally or
intravenously, although methamphetamine is also taken by the nasal route. In addition to the
synthetic amphetamine-type compounds, there are naturally occurring, plant-derived stimulants
such as khât, as well as synthetic chemical khât analogs, called cathinones.
Amphetamines and other stimulants may be obtained by prescription for the treatment of
obesity, attention-deficit/hyperactivity disorder, and narcolepsy. Consequently, prescribed
stimulants may be diverted into the illegal market.
Cocaine, a naturally occurring substance produced by the coca plant, is consumed in several
preparations (e.g., coca leaves, coca paste, cocaine hydrochloride, and cocaine alkaloids such as
freebase and crack) that differ in potency because of varying levels of purity and speed of onset.
However, in all of the forms, cocaine is the active ingredient. Cocaine hydrochloride powder is
usually “snorted” through the nostrils or dissolved in water and injected intravenously. Crack and
other cocaine alkaloids are easily vaporized and inhaled, and thus their effects have an extremely
rapid onset.
Individuals exposed to amphetamine-type substances or cocaine can develop stimulant use
disorder as rapidly as 1 week, although the onset is not always this rapid. Regardless of the route
of administration, tolerance occurs with repeated use. Withdrawal symptoms, particularly
hypersomnia, increased appetite, and dysphoria, can occur and can enhance craving. Most
individuals with stimulant use disorder have experienced tolerance or withdrawal.
Use patterns and course are similar for disorders involving amphetamine-type substances and
cocaine, as both are potent central nervous system stimulants with similar psychoactive and
sympathomimetic effects. Amphetamine-type substances are longer acting than cocaine and thus
are used fewer times per day. Usage may be chronic or episodic, with binges punctuated by brief
non-use periods. Aggressive or violent behavior is common when high doses are smoked,
ingested, or administered intravenously. Intense temporary anxiety resembling panic disorder or

Stimulant use disorder: amphetamine-type substances.
generalized anxiety disorder, as well as paranoid ideation and psychotic episodes that resemble
schizophrenia, is seen with high-dose use.
Withdrawal states are associated with temporary but intense depressive symptoms that can
resemble a major depressive episode; the depressive symptoms usually resolve
within 1 week. Tolerance to amphetamine-type substances develops and leads to escalation
of the dose. Conversely, some users of amphetamine-type substances develop sensitization,
characterized by enhanced effects.
Associated Features
When injected or smoked, stimulants typically produce an instant feeling of well-being,
confidence, and euphoria. Dramatic behavioral changes can rapidly develop with stimulant use
disorder. Chaotic behavior, social isolation, aggressive behavior, and sexual dysfunction can
result from long-term stimulant use disorder.
Individuals with acute intoxication may present with rambling speech, headache, transient
ideas of reference, and tinnitus. There may be paranoid ideation, auditory hallucinations in a
clear sensorium, and tactile hallucinations, which the individual usually recognizes as drug
effects. Threats or acting out of aggressive behavior may occur. Depression, suicidal thoughts,
irritability, anhedonia, emotional lability, or disturbances in attention and concentration
commonly occur during withdrawal. Mental disturbances associated with cocaine use usually
resolve hours to days after cessation of use but can persist for 1 month. Physiological changes
during stimulant withdrawal are opposite to those of the intoxication phase, sometimes including
bradycardia. Temporary depressive symptoms may meet symptomatic and duration criteria for
major depressive episode. Histories consistent with repeated panic attacks, social anxiety
disorder–like behavior, and generalized anxiety–like syndromes are common, as are eating
disorders. One extreme instance of stimulant toxicity is stimulant-induced psychotic disorder, a
disorder that resembles schizophrenia, with delusions and hallucinations.
Individuals with stimulant use disorder often develop conditioned responses to drug-related
stimuli (e.g., craving on seeing any white powderlike substance). These responses contribute to
relapse, are difficult to extinguish, and persist after detoxification.
Depressive symptoms with suicidal thoughts or behavior can occur and are generally the
most serious problems seen during stimulant withdrawal.
Prevalence
Estimated 
12-month 
prevalence 
of
amphetamine-type substance use disorder in the United States is 0.4% among individuals 12
years and older. Twelve-month prevalence is 0.1% among individuals ages 12–17 years, 0.5%
among those ages 18–25, and 0.4% among those age 26 and older. Rates are 0.5% for men and
0.2% for women, overall. Rates are approximately 0.4% among Hispanics and non-Hispanic
Whites and 0.1% among African Americans and Asian Americans. Prevalence estimates for
American Indian/Alaskan Natives and Native Hawaiian/Pacific Islander populations are difficult
to determine, given small sample sizes, but there is some evidence for higher rates in American

Stimulant use disorder: cocaine.
Temperamental.
Indians/Alaskan Natives.
Among U.S. adults, 6.6% (annual average) used prescription stimulants overall; 4.5% used
without misuse, 1.9% misused without use disorders, and 0.2% had use disorders. While nonHispanic Whites are more likely to use prescription stimulants nonmedically, Hispanics tend to
use them more frequently and have higher rates of prescription stimulant use disorder.
Estimated 12-month prevalence of cocaine use disorder in the
United States is 0.4% among individuals 12 years and older. Rates are 0.1% among individuals
ages 12–17 years, 0.7% among those ages 18–25 years, and 0.3% among those age 26 and older.
Rates are 0.5% for men and 0.2% for women, overall. Rates are 0.4% among African Americans
and non-Hispanic Whites, 0.3% in Hispanics, and < 0.1% among Asian Americans.
Development and Course
In the United States, stimulant use disorder occurs throughout all levels of society and is more
common among individuals ages 18–25 years compared with individuals ages 12–17 or 26 years
and older. On average, first regular use among individuals in treatment occurs at approximately
age 23 years. For primary methamphetamine treatment admissions, the average age is 34 years,
and for primary cocaine treatment admissions, the average age is 44 years for smoked cocaine
and 37 years for other routes.
Some persons begin stimulant use to control weight or to improve performance in school,
work, or athletics. Initial use may include obtaining medications such as methylphenidate or
amphetamine salts prescribed to others for the treatment of attention-deficit/hyperactivity
disorder. Among primary treatment admissions for amphetamine-type substance use in the
United States, 61% reported smoking, 26% reported injecting, and 9% reported snorting,
suggesting that stimulant use disorder can develop from multiple modes of administration.
Patterns of stimulant administration include episodic or daily (or almost daily) use. Episodic
use (e.g., intense use over a weekend or on one or more weekdays) tends to be separated by 2 or
more days of nonuse. “Binges” involve continuous high-dose use over hours or days and are
often associated with physical dependence. Binges usually terminate only when stimulant
supplies are depleted or exhaustion ensues. Chronic daily use may involve high or low doses,
often with an increase in dose over time.
Stimulant smoking and intravenous use are associated with rapid progression to severe-level
stimulant use disorder, often occurring over weeks to months. Intranasal use of cocaine and oral
use of amphetamine-type substances result in more gradual progression occurring over months to
years. With continued use, there is a diminution of pleasurable effects because of tolerance and
an increase in dysphoric effects.
Risk and Prognostic Factors
Comorbid bipolar disorder, schizophrenia, antisocial personality disorder, and
other substance use disorders are risk factors for developing stimulant use disorder and for
relapse to cocaine use in treatment samples. Higher stress reactivity has been correlated with
frequency of cocaine use in some U.S. treatment samples. Conduct disorder in childhood and
antisocial personality disorder are associated with the development of stimulant-related

Environmental.
disorders. In the United States, previous use of another substance, being male, having a Cluster B
personality disorder, family history of substance use disorder, and being separated, divorced, or
widowed all result in increased risk of using cocaine. Men who have sex with men are also at
higher risk for methamphetamine use.
Predictors of cocaine use among a cohort of U.S. teenagers include prenatal
cocaine exposure, postnatal cocaine use by parents, and exposure to community violence during
childhood. Research in industrialized countries suggests that exposure to intimate partner
violence or childhood mistreatment often co-occurs with stimulant use, especially in women. In a
cohort of U.S. women followed up longitudinally, socioeconomic status, including food
insecurity, had a dose-dependent effect on risk of stimulant use. For youth, especially girls, risk
factors include living in an unstable home environment, having a psychiatric condition, criminal
behavior, and associating with dealers and users.
Culture-Related Diagnostic Issues
The prevalence of cocaine use in the United States increased between 2001–2002 and 2012–
2013 among non-Latinx Whites, African Americans, and Latinx, but the prevalence of cocaine
use disorder increased only among Whites. Despite small variations, cocaine and other stimulant
use disorder diagnostic criteria perform equally across gender and
ethnoracial groups. In limited data on prevalence estimates, it appears that American
Indian/Alaskan Native populations are at higher risk for methamphetamine use disorder, and, to
a lesser degree, cocaine use disorder, than are non-Hispanic Whites, while native
Hawaiian/Pacific Islanders appear to have similar risks to non-Hispanic Whites.
Approximately 64% of individuals admitted to publicly funded substance abuse treatment
programs for primary methamphetamine/amphetamine-related disorders are non-Hispanic White,
followed by 20% of Hispanic origin, 3% Asian and Pacific Islander, and 6% non-Hispanic
Black. Among individuals admitted for primary treatment related to smoked cocaine, 51% were
non-Hispanic Black, 35% non-Hispanic White, 8% Hispanic, and 1% Asian/Pacific Islander. For
admissions related to other routes of cocaine administration, 47% were non-Hispanic White,
31% were non-Hispanic Black, 17% were of Hispanic origin, and 1% were Asian/Pacific
Islander. Rates of disorders in clinical samples should be interpreted with caution because they
may be affected by differential access to and utilization of services, pathways to care,
criminalization, stigma, and racial bias in diagnosis and referral for treatment.
Sex- and Gender-Related Diagnostic Issues
In the United States, women with cocaine use disorder more frequently have comorbid
psychiatric disorders, such as depression and posttraumatic stress disorder (PTSD), compared
with men. Gonadal hormones affect a male’s responses to cocaine. Females with cocaine use
disorder and higher levels of progesterone have lower stress-induced and cue-induced cocaine
craving and lower cue-induced changes in blood pressure than females with cocaine use disorder
and lower levels of progesterone. This may explain why use of cocaine in pregnant females is
lower than in nonpregnant females.

Diagnostic Markers
Benzoylecgonine, a metabolite of cocaine, typically remains in the urine for 1–3 days after a
single dose and may be present for 7–12 days in individuals using repeated high doses. Mildly
elevated liver function tests can be present in cocaine injectors or users with concomitant alcohol
use. There are no neurobiological markers of diagnostic utility. Discontinuation of chronic
cocaine use may be associated with electroencephalographic changes, suggesting persistent
abnormalities; alterations in secretion patterns of prolactin; and downregulation of dopamine
receptors.
Short-half-life amphetamine-type substances (e.g., methamphetamine) can be detected for 1–
3 days, and possibly up to 4 days depending on dosage and metabolism. Hair samples can be
used to detect presence of amphetamine-type substances for up to 90 days. Other laboratory
findings, as well as physical findings and other medical conditions (e.g., weight loss,
malnutrition; poor hygiene), are similar for both cocaine and amphetamine-type substance use
disorder.
Association With Suicidal Thoughts or Behavior
Few data on the association of stimulant use disorders and suicide are available because most
studies examining suicidal thoughts and behavior examine use of stimulants rather than stimulant
use disorders. One systematic review found that regular or problem amphetamine use (examining
primarily individuals who inject amphetamines and/or individuals admitted to treatment for use
of amphetamines) is associated with increased suicide mortality. A general population study of
adults in the United States found an association of prescription stimulant use disorder with
suicidal thoughts. In a study of individuals admitted to substance use treatment, those with
cocaine use disorder were much more likely to report suicidal thoughts than those with other
substance use disorders. In a study of both men and women in the U.S. Veterans Administration
health care system,
cocaine and amphetamine use disorders were each associated with increased rates of suicide
deaths.
Functional Consequences of Stimulant Use Disorder
Various medical conditions may occur depending on the route of administration. Intranasal users
often develop sinusitis, irritation, bleeding of the nasal mucosa, and a perforated nasal septum.
Individuals who smoke stimulants are at increased risk for respiratory problems (e.g., coughing,
bronchitis, and pneumonitis). Injectors have puncture marks and “tracks,” most commonly on
their forearms. Risk of HIV and hepatitis C infection increases with frequent intravenous
injections and unsafe sexual activity. Other sexually transmitted diseases, hepatitis B, and
tuberculosis and other lung infections are also seen. Weight loss and malnutrition are common.
Chest pain may be a common symptom during stimulant intoxication. Myocardial infarction,
palpitations and arrhythmias, sudden death from respiratory or cardiac arrest, and stroke have
been associated with stimulant use among young and otherwise healthy individuals.
Pneumothorax can result from performing Valsalva-like maneuvers done to better absorb inhaled

Phencyclidine intoxication.
Stimulant intoxication, stimulant withdrawal, and stimulant-induced mental disorders.
Independent mental disorders.
smoke. Cocaine use is associated with irregularities in placental blood flow, abruptio placentae,
premature labor and delivery, and an increased prevalence of infants with very low birth weights.
Individuals with stimulant use disorder may become involved in theft, prostitution, or drug
dealing in order to acquire drugs or money for drugs. Traumatic injuries due to violent behavior
are common among individuals trafficking drugs.
Neurocognitive impairment is common among both methamphetamine and cocaine users,
including deficits related to attention, impulsivity, verbal learning/memory, working memory,
and executive functioning. Transient psychosis and seizure have also been reported with chronic
use of either cocaine or methamphetamine, possibly related to patterns of use or the exacerbation
of preexisting vulnerabilities. Amphetamine use can cause toxic effects related to elevated body
temperature, and there is some evidence that chronic use causes neuroinflammation and
neurotoxicity in dopaminergic neurons. Oral health problems include “meth mouth” with gum
disease, tooth decay, and mouth sores related to the toxic effects of smoking the drug and to
bruxism while intoxicated. Adverse pulmonary effects appear to be less common for
amphetamine-type substances because they are smoked fewer times per day, although
methamphetamine use is still associated with a risk of pulmonary arterial hypertension.
Emergency department visits are common for stimulant-related mental disorder symptoms,
injury, skin infections, and dental pathology. In the United States, diagnosis of a stimulant use
disorder is associated with a 20% increase in 30-day readmission rates in assessment of followup after hospitalization for “any cause” (a standard measure of overall hospital quality of care).
Differential Diagnosis
Intoxication with phencyclidine (PCP or “angel dust”) or synthetic
“designer drugs” such as mephedrone (known by different names, including “bath salts”) may
cause a similar clinical picture and can only be distinguished from stimulant intoxication by the
presence of cocaine or amphetamine-type substance metabolites in a urine or plasma sample.
Stimulant 
use
disorder is differentiated from stimulant intoxication, stimulant withdrawal, and stimulantinduced mental disorders (e.g., stimulant-induced depressive disorder) in that stimulant use
disorder describes a problematic pattern of stimulant use that involves impaired control over
stimulant use, social impairment attributable to stimulant use, risky stimulant use (e.g., continued
stimulant use despite medical complications), and pharmacological symptoms (the development
of tolerance or withdrawal), whereas stimulant
intoxication, stimulant withdrawal, and stimulant-induced mental disorders describe psychiatric
syndromes that occur in the context of heavy use. Stimulant intoxication, stimulant withdrawal,
and stimulant-induced mental disorders occur frequently in individuals with stimulant use
disorder. In such cases, a diagnosis of stimulant intoxication, stimulant withdrawal, or a
stimulant-induced mental disorder should be given in addition to a diagnosis of stimulant use
disorder, the presence of which is indicated in the diagnostic code.
Some of the effects of stimulant use may resemble symptoms of
independent mental disorders, such as psychosis (schizophrenia) and low mood (major

depressive disorder). Discerning whether these behaviors occurred before the intake of the drug
is important in the differentiation of acute drug effects from a preexisting mental disorder.
Comorbidity
Stimulant-related disorders often co-occur with other substance use disorders, especially those
involving substances with sedative properties, which are often taken to reduce insomnia,
nervousness, and other unpleasant side effects. Individuals admitted to treatment for cocaine use
are likely to also use heroin, PCP, or alcohol, and individuals admitted for amphetamine-type
substance use disorder are likely to use marijuana, heroin, or alcohol. Stimulant use disorder may
be associated with posttraumatic stress disorder, antisocial personality disorder, attentiondeficit/hyperactivity disorder, and gambling disorder. Cardiopulmonary problems are often
present in individuals seeking treatment for cocaine-related problems, with chest pain being the
most common. Medical problems occur in response to adulterants used as “cutting” agents.
Cocaine users who ingest cocaine cut with levamisole, an antimicrobial and veterinary
medication, may experience agranulocytosis and febrile neutropenia.
Stimulant Intoxication
Diagnostic Criteria
A. Recent use of an amphetamine-type substance, cocaine, or other stimulant.
B. Clinically significant problematic behavioral or psychological changes (e.g.,
euphoria 
or 
affective 
blunting; 
changes 
in 
sociability; 
hypervigilance;
interpersonal sensitivity; anxiety, tension, or anger; stereotyped behaviors;
impaired judgment) that developed during, or shortly after, use of a stimulant.
C. Two (or more) of the following signs or symptoms, developing during, or shortly
after, stimulant use:
1. Tachycardia or bradycardia.
2. Pupillary dilation.
3. Elevated or lowered blood pressure.
4. Perspiration or chills.
5. Nausea or vomiting.
6. Evidence of weight loss.
7. Psychomotor agitation or retardation.
8. Muscular weakness, respiratory depression, chest pain, or cardiac
arrhythmias.
9. Confusion, seizures, dyskinesias, dystonias, or coma.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.

641
Specify the particular intoxicant (i.e., amphetamine-type substance, cocaine, or
other stimulant).
Specify if:
With perceptual disturbances: This specifier may be noted when
hallucinations with intact reality testing or auditory, visual, or tactile illusions
occur in the absence of a delirium.
Coding note: The ICD-10-CM code depends on whether the stimulant is an
amphetamine-type substance, cocaine, or other stimulant; whether there is a
comorbid amphetamine-type substance, cocaine, or other stimulant use disorder;
and whether or not there are perceptual disturbances.
For amphetamine-type substance, cocaine, or other stimulant intoxication,
without perceptual disturbances: If a mild amphetamine-type substance or
other stimulant use disorder is comorbid, the ICD-10-CM code is F15.120, and if
a moderate or severe amphetamine-type substance or other stimulant use
disorder is comorbid, the ICD-10-CM code is F15.220. If there is no comorbid
amphetamine-type substance or other stimulant use disorder, then the ICD-10CM code is F15.920. Similarly, if a mild cocaine use disorder is comorbid, the
ICD-10-CM code is F14.120, and if a moderate or severe cocaine use disorder is
comorbid, the ICD-10-CM code is F14.220. If there is no comorbid cocaine use
disorder, then the ICD-10-CM code is F14.920.
For amphetamine-type substance, cocaine, or other stimulant intoxication,
with perceptual disturbances: If a mild amphetamine-type substance or other
stimulant use disorder is comorbid, the ICD-10-CM code is F15.122, and if a
moderate or severe amphetamine-type substance or other stimulant use
disorder is comorbid, the ICD-10-CM code is F15.222. If there is no comorbid
amphetamine-type substance or other stimulant use disorder, then the ICD-10CM code is F15.922. Similarly, if a mild cocaine use disorder is comorbid, the
ICD-10-CM code is F14.122, and if a moderate or severe cocaine use disorder is
comorbid, the ICD-10-CM code is F14.222. If there is no comorbid cocaine use
disorder, then the ICD-10-CM code is F14.922.
Diagnostic Features
The essential feature of stimulant intoxication, related to amphetamine-type substances and
cocaine, is the presence of clinically significant behavioral or psychological changes that develop
during, or shortly after, use of stimulants (Criteria A and B). Auditory hallucinations may be
prominent, as may paranoid ideation, and these symptoms must be distinguished from an
independent psychotic disorder such as schizophrenia. Stimulant intoxication usually begins with
a “high” feeling and includes one or more of the following: euphoria with enhanced vigor,
gregariousness, 
hyperactivity, 
restlessness, 
hypervigilance, 
interpersonal 
sensitivity,
talkativeness, anxiety, tension, alertness, grandiosity, stereotyped and repetitive behavior, anger,
impaired judgment, and, in the case of chronic intoxication, affective blunting with fatigue or

sadness and social withdrawal. These behavioral and psychological changes are accompanied by
two or more of the following signs and symptoms that develop during or shortly after stimulant
use: tachycardia or bradycardia; pupillary dilation; elevated or lowered blood pressure;
perspiration or chills; nausea or vomiting; evidence of weight loss; psychomotor agitation or
retardation; muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias; and
confusion, seizures, dyskinesias, dystonias, or coma (Criterion C). Intoxication, either acute or
chronic, is often associated with impaired social or occupational functioning. Severe intoxication
can lead to convulsions, cardiac arrhythmias, hyperpyrexia, and death. For the diagnosis of
stimulant intoxication to be made, the symptoms must not be attributable to another medical
condition and are not better explained by another mental disorder
(Criterion D). While stimulant intoxication occurs in individuals with stimulant use disorders,
intoxication is not a criterion for stimulant use disorder, which is confirmed by the presence of 2
of the 11 diagnostic criteria for use disorder.
Associated Features
The magnitude and direction of the behavioral and physiological changes depend on many
variables, including the dose used and the characteristics of the individual using the substance or
the context (e.g., tolerance, rate of absorption, chronicity of use, context in which taken).
Stimulant effects such as euphoria, increased pulse and blood pressure, and psychomotor activity
are most commonly seen. Depressant effects such as sadness, bradycardia, decreased blood
pressure, and decreased psychomotor activity are less common and generally emerge only with
chronic high-dose use.
Prevalence
Although prevalence of stimulant intoxication is not known, prevalence of stimulant use can be
used as a proxy. Many individuals who use stimulants may not have symptoms that fully meet
the criteria for stimulant intoxication, which requires “clinically significant problematic
behavioral or psychological changes.” Thus, rates of stimulant use can be considered the upper
bounds of the likely prevalence of stimulant intoxication.
Estimated 12-month prevalence of cocaine use in the United States is 2.2% for individuals
age 12 and older (0.5% among individuals ages 12–17-years, 6.2% among individuals ages 18–
25 years, and 1.7% among individuals age 26 and older); 3% of men/boys and 1.4% of
women/girls used cocaine in the last 12 months. Twelve-month prevalence of cocaine use is
2.3% among Whites, 2.2% among Hispanics, 1.7% among African Americans, and 1% among
Asian Americans.
Estimated 12-month prevalence of methamphetamine use in the United States is 0.6% for
individuals age 12 and older (0.2% among individuals ages 12–17 years, 1.1% among
individuals ages 18–25 years, and 0.6% among individuals age 26 and older). Twelve-month
prevalence of methamphetamine use is 0.8% among men/boys and 0.4% among women/girls.
Twelve-month prevalence of methamphetamine use is 0.7% among Whites, 0.6% among
Hispanics, 0.2% among African Americans, and 0.1% among Asian Americans. Small sample

Stimulant-induced mental disorders.
Independent mental disorders.
sizes make estimating rates among American Indians/Alaskan Natives difficult.
Differential Diagnosis
Stimulant intoxication is distinguished from stimulant-induced
mental disorders (e.g., stimulant-induced anxiety disorder, with onset during intoxication)
because the symptoms (e.g., anxiety) in the latter disorders are in excess of those usually seen in
stimulant intoxication, predominate in the clinical presentation, and meet full criteria for the
relevant disorder.
Salient mental disturbances associated with stimulant intoxication
should be distinguished from the symptoms of schizophrenia, bipolar and depressive disorders,
generalized anxiety disorder, and panic disorder as described in this manual.
Comorbidity
Given the typical overlap of stimulant intoxication with stimulant use disorder, see
“Comorbidity” under Stimulant Use Disorder for more details about co-occurring conditions that
are likely to be encountered.
Stimulant Withdrawal
Diagnostic Criteria
A. Cessation of (or reduction in) prolonged amphetamine-type substance, cocaine,
or other stimulant use.
B. Dysphoric mood and two (or more) of the following physiological changes,
developing within a few hours to several days after Criterion A:
1. Fatigue.
2. Vivid, unpleasant dreams.
3. Insomnia or hypersomnia.
4. Increased appetite.
5. Psychomotor retardation or agitation.
C. The signs or symptoms in Criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
D. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication or
withdrawal from another substance.
Specify the particular substance that causes the withdrawal syndrome (i.e.,
amphetamine-type substance, cocaine, or other stimulant).
Coding note: The ICD-10-CM code depends on whether the stimulant is an

Stimulant-induced mental disorders.
amphetamine-type substance, cocaine, or other stimulant and on whether or not
there is a comorbid amphetamine-type substance, cocaine, or other stimulant use
disorder. If mild amphetamine-type substance or other stimulant use disorder is
comorbid, the ICD-10-CM code is F15.13. If moderate or severe amphetamine-type
substance or other stimulant use disorder is comorbid, the ICD-10-CM code is
F15.23. For amphetamine-type substance or other stimulant withdrawal occurring in
the absence of amphetamine-type substance or other stimulant use disorder (e.g., in
a patient taking amphetamine solely under appropriate medical supervision), the
ICD-10-CM code is F15.93. If mild cocaine use disorder is comorbid, the ICD-10-CM
code is F14.13. If moderate or severe cocaine use disorder is comorbid, the ICD-10CM code is F14.23. For cocaine withdrawal occurring in the absence of a cocaine
use disorder, the ICD-10-CM code is F14.93.
Diagnostic Features
The essential feature of stimulant withdrawal is the presence of a characteristic withdrawal
syndrome that develops within a few hours to several days after the cessation of (or marked
reduction in) stimulant use (generally high dose) that has been prolonged (Criterion A). The
withdrawal syndrome is characterized by the development of dysphoric mood accompanied by
two or more of the following physiological changes: fatigue, vivid and unpleasant dreams,
insomnia or hypersomnia, increased appetite, and psychomotor retardation or agitation (Criterion
B). Bradycardia is often present and is a reliable measure of stimulant withdrawal.
Anhedonia and drug craving can often be present but are not part of the diagnostic criteria.
These symptoms cause clinically significant distress or impairment in social, occupational, or
other important areas of functioning (Criterion C). The symptoms must not be attributable to
another medical condition and are not better explained by another mental disorder (Criterion D).
Associated Features
Acute withdrawal symptoms (“a crash”) are often seen after periods of repetitive high-dose use
(“runs” or “binges”). These symptoms are characterized by intense and unpleasant feelings of
lassitude and depression and increased appetite, generally requiring several days of rest and
recuperation. Depressive symptoms with suicidal thoughts or behavior can occur and are
generally the most serious problems seen during “crashing” or other forms of stimulant
withdrawal. Many individuals with stimulant use disorder may experience a withdrawal
syndrome at some point.
Differential Diagnosis
Stimulant withdrawal is distinguished from stimulant-induced
mental disorders (e.g., stimulant-induced depressive disorder, with onset during withdrawal)
because the symptoms (e.g., depressed mood) in these latter disorders are in excess of those
usually associated with stimulant withdrawal, predominate in the clinical presentation, and are
severe enough to warrant clinical attention.

Comorbidity
Given the typical overlap of stimulant withdrawal with stimulant use disorder, see
“Comorbidity” under Stimulant Use Disorder for more details about co-occurring conditions that
are likely to be encountered.
Stimulant-Induced Mental Disorders
The following stimulant-induced mental disorders (which include amphetamine-type substance–,
cocaine-, and other stimulant–induced mental disorders) are described in other chapters of the
manual with disorders with which they share phenomenology (see the substance/medicationinduced mental disorders in these chapters): stimulant-induced psychotic disorder
(“Schizophrenia Spectrum and Other Psychotic Disorders”); stimulant-induced bipolar and
related disorder (“Bipolar and Related Disorders”); stimulant-induced depressive disorder
(“Depressive Disorders”); stimulant-induced anxiety disorder (“Anxiety Disorders”); stimulantinduced obsessive-compulsive disorder (“Obsessive-Compulsive and Related Disorders”);
stimulant-induced sleep disorder (“Sleep-Wake Disorders”); stimulant-induced sexual
dysfunction (“Sexual Dysfunctions”); and stimulant-induced mild neurocognitive disorder
(“Neurocognitive Disorders”). For stimulant intoxication delirium and delirium induced by
stimulants taken as prescribed, see the criteria and discussion of delirium in the chapter
“Neurocognitive Disorders.” These stimulant-induced mental disorders are diagnosed instead of
stimulant intoxication or stimulant withdrawal only when the symptoms are sufficiently severe to
warrant independent clinical attention.
Unspecified Stimulant-Related Disorder
This category applies to presentations in which symptoms characteristic of a
stimulant-related disorder that cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning predominate but do not
meet the full criteria for any specific stimulant-related disorder or any of the disorders
in the substance-related and addictive disorders diagnostic class.
Coding note: The ICD-10-CM code depends on whether the stimulant is an
amphetamine-type substance, cocaine, or other stimulant. The ICD-10-CM code for
an unspecified amphetamine-type substance or other stimulant–related disorder is
F15.99. The ICD-10-CM code for an unspecified cocaine-related disorder is F14.99.
Tobacco-Related Disorders
Tobacco Use Disorder
Tobacco Withdrawal

Tobacco-Induced Mental Disorders
Unspecified Tobacco-Related Disorder
Tobacco Use Disorder
Diagnostic Criteria
A. A problematic pattern of tobacco use leading to clinically significant impairment
or distress, as manifested by at least two of the following, occurring within a 12month period:
1. Tobacco is often taken in larger amounts or over a longer period than was
intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control
tobacco use.
3. A great deal of time is spent in activities necessary to obtain or use tobacco.
4. Craving, or a strong desire or urge to use tobacco.
5. Recurrent tobacco use resulting in a failure to fulfill major role obligations at
work, school, or home (e.g., interference with work).
6. Continued tobacco use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of tobacco (e.g.,
arguments with others about tobacco use).
7. Important social, occupational, or recreational activities are given up or
reduced because of tobacco use.
8. Recurrent tobacco use in situations in which it is physically hazardous (e.g.,
smoking in bed).
9. Tobacco use is continued despite knowledge of having a persistent or
recurrent physical or psychological problem that is likely to have been caused
or exacerbated by tobacco.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of tobacco to achieve the desired
effect.
b. A markedly diminished effect with continued use of the same amount of
tobacco.
11. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome for tobacco (refer to Criteria A
and B of the criteria set for tobacco withdrawal).
b. Tobacco (or a closely related substance, such as nicotine) is taken to
relieve or avoid withdrawal symptoms.
Specify if:

646
In early remission: After full criteria for tobacco use disorder were previously
met, none of the criteria for tobacco use disorder have been met for at least 3
months but for less than 12 months (with the exception that Criterion A4,
“Craving, or a strong desire or urge to use tobacco,” may be met).
In sustained remission: After full criteria for tobacco use disorder were
previously met, none of the criteria for tobacco use disorder have been met at
any time during a period of 12 months or longer (with the exception that Criterion
A4, “Craving, or a strong desire or urge to use tobacco,” may be met).
Specify if:
On maintenance therapy: The individual is taking a long-term maintenance
medication, such as nicotine replacement medication, and no criteria for tobacco
use disorder have been met for that class of medication (except tolerance to, or
withdrawal from, the nicotine replacement medication).
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to tobacco is restricted.
Code based on current severity/remission: If a tobacco withdrawal or tobaccoinduced sleep disorder is also present, do not use the codes below for tobacco use
disorder. Instead, the comorbid tobacco use disorder is indicated in the 4th character
of the tobacco-induced disorder code (see the coding note for tobacco withdrawal or
tobacco-induced sleep disorder). For example, if there is comorbid tobacco-induced
sleep disorder and tobacco use disorder, only the tobacco-induced sleep disorder
code is given, with the 4th character indicating whether the comorbid tobacco use
disorder is moderate or severe: F17.208 for moderate or severe tobacco use
disorder with tobacco-induced sleep disorder. It is not permissible to code a
comorbid mild tobacco use disorder with a tobacco-induced sleep disorder.
Specify current severity/remission:
Z72.0 Mild: Presence of 2–3 symptoms.
F17.200 Moderate: Presence of 4–5 symptoms.
F17.201 Moderate, In early remission
F17.201 Moderate, In sustained remission
F17.200 Severe: Presence of 6 or more symptoms.
F17.201 Severe, In early remission
F17.201 Severe, In sustained remission
Specifiers
“On maintenance therapy” applies as a specifier to be added to “in remission” if the individual is
both in remission and on maintenance therapy. “In a controlled environment” applies as a further
specifier of remission if the individual is both in remission and in a controlled environment (i.e.,
in early remission in a controlled environment or in sustained remission in a controlled

environment). Examples of these environments are closely supervised and substance-free jails,
therapeutic communities, and locked hospital units.
Diagnostic Features
Tobacco use disorder can develop with use of all forms of tobacco (e.g., cigarettes, chewing
tobacco, snuff, pipes, cigars, electronic nicotine delivery devices such as electronic cigarettes [ecigarettes]) and with prescription nicotine-containing medications (nicotine gum and patch). The
relative ability of these products to produce tobacco use disorder or to induce withdrawal is
associated with the rapidity of the route of administration (smoked over oral over transdermal)
and the nicotine content of the product. The name of this substance category was changed from
“nicotine” in prior editions of DSM to “tobacco” in DSM-5 on the basis of harms from addiction
being associated mostly with tobacco and much less with nicotine.
Tobacco use disorder is common among individuals who use cigarettes and smokeless
tobacco daily, is less common among individuals who use e-cigarettes, and is uncommon
among those who do not use tobacco daily or use nicotine medications. Tolerance to tobacco
is exemplified by the disappearance of nausea and dizziness after intake and by a more intense
effect of tobacco the first time it is used during the day. Cessation of tobacco use can produce a
well-defined withdrawal syndrome. Many individuals with tobacco use disorder use tobacco to
relieve or to avoid withdrawal symptoms (e.g., after being in a situation where use is restricted).
Many individuals with tobacco use disorder have tobacco-related physical symptoms or diseases
and continue to smoke. The large majority report craving when they do not smoke for several
hours. Spending excessive time using tobacco can be exemplified by chain-smoking (i.e.,
smoking one cigarette after another with no time between cigarettes). Because tobacco sources
are readily and legally available, and because tobacco intoxication is very rare, spending a great
deal of time attempting to procure tobacco or recovering from its effects is uncommon. Giving
up important social, occupational, or recreational activities can occur when an individual forgoes
an activity because it occurs in tobacco use–restricted areas. Use of tobacco rarely results in
failure to fulfill major role obligations (e.g., interference with work or home responsibilities), but
persistent social or interpersonal problems (e.g., having arguments with others about tobacco use,
avoiding social situations because of others’ disapproval of tobacco use) or use that is physically
hazardous (e.g., smoking in bed, smoking around flammable chemicals) occur at an intermediate
prevalence. Although these criteria are less often endorsed by tobacco users, if endorsed, they
can indicate a more severe disorder.
Associated Features
Smoking within 30 minutes of waking, smoking daily, smoking more cigarettes per day, and
waking at night to smoke are associated with tobacco use disorder. Environmental cues can
evoke craving and withdrawal. Serious medical conditions often occur, including lung and other
cancers, cardiac and pulmonary disease, perinatal problems, cough, shortness of breath, and
accelerated skin aging.

Temperamental.
Environmental.
Genetic and physiological.
Prevalence
Although cigarettes are the most commonly used tobacco product, use of other tobacco products
(especially e-cigarettes) has become more common. In the United States, 19% of adults used a
tobacco product in the last year, 19% used more than one product, 14% used cigarettes, 4% used
cigars, 3% used e-cigarettes, and 2% used smokeless tobacco. One fourth (24%) of current U.S.
smokers are nondaily smokers.
The 12-month prevalence of DSM-5 tobacco use disorder in the United States in 2012–2013
was 20% among adults age 18 years and older and 29.6% among Native Americans, 22.3%
among non-Latinx Whites, 20.1% among African Americans, 12.2% among Latinx, and 11.2%
among Asian Americans and Pacific Islanders. Prevalence was higher among men; those who
were young, unmarried, less educated, poor, or residing in the southern United States; and those
with almost any psychiatric disorder. The prevalence among current daily smokers is
approximately 50%.
Global comparisons show that in all geographic regions of the world, the age-standardized
prevalence of daily tobacco smoking is higher in men than in women, but the gender ratio varies
greatly, from 16.9:1 in East Asia to 1.2:1 in Australasia.
Development and Course
About 20% of U.S. high school seniors report having ever smoked cigarettes, and about 5% have
used in the past 30 days. Among adolescents who smoke cigarettes at least monthly, most of
these individuals will become daily tobacco users in the future. Initiation of smoking after age 21
years is rare. Some of the tobacco use disorder criteria symptoms (e.g., craving) occur soon after
beginning tobacco use, suggesting the addiction process begins with initial use; however,
fulfilling DSM criteria usually occurs over several years.
Nondaily smoking has become more prevalent since the late 1990s in the United States,
especially among individuals ages 18–34 years, Blacks, Hispanics, and individuals with at least a
college education.
Risk and Prognostic Factors
Individuals with externalizing personality traits are more likely to initiate
tobacco use. Children with attention-deficit/hyperactivity disorder or conduct disorder, and
adults with depressive, bipolar, anxiety, personality, psychotic, or other substance use disorders,
are at higher risk for starting and continuing tobacco use and of tobacco use disorder.
Persons with low incomes and low educational levels are more likely to initiate
tobacco use and are less likely to stop.
Genetic factors contribute to the onset of tobacco use, the continuation
of tobacco use, and the development of tobacco use disorder, with a degree of heritability
equivalent to that observed with other substance use disorders (i.e., about 50%). Some of this
risk is specific to tobacco, and some is common with the vulnerability to developing any
substance use disorder.

Culture-Related Diagnostic Issues
Acceptance of tobacco use varies across cultural contexts. Age-standardized prevalence of daily
tobacco smoking varies greatly by geographic region, ranging from 4.7% in Western SubSaharan Africa to 24.2% in Eastern Europe. The degree to which these geographic differences
are the result of income, education, and tobacco control activities in a country is unclear.
Prevalence of tobacco use in the United States varies by age, gender, and ethnoracial
background, with lower rates of smoking onset and progression to daily smoking among Black
youth, especially young women. Liver enzyme polymorphisms that vary across ethnoracial
groups can affect nicotine metabolism, contributing to variation in smoking behavior. Higher
tobacco use disorder prevalence is also associated with exposure to racism and ethnic
discrimination. Prevalence of DSM-IV nicotine dependence is higher among adult lesbian, gay,
and bisexual individuals than among heterosexuals, possibly also due to an association with
exposure to sexual orientation–related discrimination. Among individuals with DSM-IV nicotine
dependence, lower income and education are associated with disorder persistence.
Sex- and Gender-Related Diagnostic Issues
The ratio of men to women among U.S. smokers is approximately 1.4:1 and has been stable
between 2004 and 2014. This ratio is generally consistent across various income and educational
levels. The ratio diminishes in older age groups as fewer men are smoking as age increases. The
literature from several U.S. settings suggests that negative reinforcement (i.e., that smoking
relieves negative affect) is a greater motivator in women than in men. Menstrual cycle effects on
smoking are found inconsistently, but tobacco withdrawal appears worse in the luteal than the
follicular phase of the cycle. Pregnant females smoke at a lower rate than nonpregnant females
but relapse back to smoking rapidly after delivery.
Diagnostic Markers
The following biomarkers can be used to measure the extent of tobacco or nicotine use: carbon
monoxide in the breath and nicotine and its metabolite cotinine in blood, saliva, or urine;
however, these are only weakly associated with tobacco use disorder.
Association With Suicidal Thoughts or Behavior
National U.S. survey data show that past-year cigarette use is associated with a two- to threefold
increased risk of suicidal thoughts and behavior, with earlier age at first tobacco use increasing
risk. Evidence from the U.S. Veterans Health Administration shows that even after adjustment
for covariates, tobacco use disorder is associated with an increased risk of suicide. A large study
of twins in Finland found that the relationship between tobacco use and suicide increased in a
dose-response manner, and that for identical twins discordant for tobacco use, tobacco use was
associated with a sixfold increased risk for suicide.
Functional Consequences of Tobacco Use Disorder
Medical consequences of tobacco use often begin when tobacco users are in their 40s and usually

F17.203
become progressively more debilitating over time. One-half of smokers who do not stop using
tobacco will die early from a tobacco-related illness, and smoking-related morbidity occurs in
more than one-half of tobacco users. Most medical conditions result from exposure to carbon
monoxide, tars, and other non-nicotine components of tobacco. The major predictor of
reversibility is duration of smoking. Secondhand smoke increases the risk of heart disease and
cancer by 30%. Long-term use of nicotine medications does not appear to cause medical harm.
Comorbidity
The most common medical conditions from smoking are cardiovascular illnesses, chronic
obstructive pulmonary disease, and cancers. Smoking also increases perinatal problems, such as
low birth weight and miscarriage. Prevalence of smoking is almost twice as high in individuals
with major depressive disorder; although the prevalence of smoking in the United States is
higher among individuals with low socioeconomic status, the increased prevalence of smoking
among those with depression is independent of socioeconomic status. The most common
psychiatric comorbidities associated with smoking are alcohol and other substance, depressive,
bipolar, anxiety, personality, and attention-deficit/hyperactivity disorders. In the United States,
individuals with a psychiatric disorder are three times more likely than others to have tobacco
use disorder. Adults with DSM-5 tobacco use disorder are significantly more likely than other
adults to have comorbid psychiatric disorders, including other DSM-5 substance use disorders,
major depressive disorder, bipolar I disorder, panic disorder, generalized anxiety disorder,
posttraumatic stress disorder, and borderline and antisocial personality disorders.
Tobacco Withdrawal
Diagnostic Criteria
A. Daily use of tobacco for at least several weeks.
B. Abrupt cessation of tobacco use, or reduction in the amount of tobacco used,
followed within 24 hours by four (or more) of the following signs or symptoms:
1. Irritability, frustration, or anger.
2. Anxiety.
3. Difficulty concentrating.
4. Increased appetite.
5. Restlessness.
6. Depressed mood.
7. Insomnia.
C. The signs or symptoms in Criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.

D. The signs or symptoms are not attributed to another medical condition and are
not better explained by another mental disorder, including intoxication or
withdrawal from another substance.
Coding note: The ICD-10-CM code for tobacco withdrawal is F17.203. Note that the
ICD-10-CM code indicates the comorbid presence of a moderate or severe tobacco
use disorder, reflecting the fact that tobacco withdrawal can only occur in the
presence of a moderate or severe tobacco use disorder.
Diagnostic Features
Withdrawal symptoms impair the ability to stop tobacco use. The symptoms after abstinence
from tobacco are in large part due to nicotine deprivation. Tobacco withdrawal is common
among daily tobacco users who stop or reduce their use of tobacco. Symptoms are more intense
among individuals who smoke cigarettes and also use smokeless tobacco or electronic cigarettes
daily. This symptom intensity is likely attributable to the more rapid onset and higher levels of
nicotine with cigarette smoking. Significant withdrawal among those who are nondaily cigarette
users or use only nicotine medications is uncommon.
Typically, heart rate decreases by 5–12 bpm in the first few days after stopping smoking, and
weight increases an average of 4–7 lb (2–3 kg) over the first year after stopping smoking.
Tobacco withdrawal can produce clinically significant mood changes and functional impairment.
Because of conditioning effects, withdrawal can be prompted by environmental cues such as
seeing others smoking. Gradual reduction of tobacco decreases the severity of withdrawal.
Associated Features
Craving for tobacco or nicotine is very common during abstinence and has a large effect on the
ability to remain abstinent. Abstinence can increase impulsivity and anhedonia and can decrease
positive affect. Abstinence from tobacco or nicotine also appears to increase craving for sweet or
sugary foods and impairs performance on tasks requiring vigilance. Smoking increases the
metabolism of many medications used to treat mental disorders; thus, cessation of smoking can
increase the blood levels of these medications, and this can produce clinically significant
outcomes. This effect appears to be due not to nicotine but rather to other compounds in tobacco.
Prevalence
Approximately 50% of daily smokers who quit for 2 or more days will have four or more
symptoms of tobacco withdrawal. The most commonly endorsed signs and symptoms are
anxiety, irritability, and difficulty concentrating. The least commonly endorsed symptoms are
depression and insomnia.
Development and Course
Tobacco withdrawal usually begins within 24 hours of stopping or cutting down tobacco use,
peaks at 2–3 days after abstinence, and usually lasts 2–3 weeks. Tobacco withdrawal symptoms
can occur among adolescent tobacco users, even prior to daily tobacco use. Prolonged symptoms
beyond 1 month can occur but are uncommon.

Temperamental.
Genetic and physiological.
Risk and Prognostic Factors
Smokers with depressive disorders, bipolar disorders, anxiety disorders,
attention-deficit/hyperactivity disorder, and other substance use disorders have more severe
withdrawal.
Genotype can influence the probability of withdrawal upon abstinence.
Diagnostic Markers
The following biomarkers can be used to measure the extent of tobacco or nicotine use but are
only weakly associated with tobacco withdrawal: carbon monoxide in the breath and nicotine
and its metabolite cotinine in blood, saliva, or urine.
Functional Consequences of Tobacco Withdrawal
Tobacco withdrawal can cause significant distress and difficulty functioning in a minority of
smokers, but this may be uncommon. Withdrawal impairs the ability to stop or control tobacco
use. Whether tobacco withdrawal can prompt the development of a new mental disorder or
recurrence of a mental disorder is debatable, but if this occurs, it would be in a small minority of
tobacco users.
Differential Diagnosis
The symptoms of tobacco withdrawal overlap with those of other substance withdrawal
syndromes (e.g., alcohol withdrawal; sedative, hypnotic, or anxiolytic withdrawal; stimulant
withdrawal; caffeine withdrawal; opioid withdrawal); caffeine intoxication; anxiety, depressive,
bipolar, and sleep disorders; and medication-induced akathisia. Admission to smoke-free
inpatient units or voluntary smoking cessation can induce withdrawal symptoms that mimic,
intensify, or disguise other disorders or adverse effects of medications used to treat mental
disorders (e.g., irritability thought to be due to alcohol withdrawal could be due to tobacco
withdrawal). Reduction in symptoms with the use of nicotine confirms the diagnosis.
Comorbidity
Given the typical overlap of tobacco withdrawal with tobacco use disorder, see “Comorbidity”
under Tobacco Use Disorder for more details about co-occurring conditions that are likely to be
encountered.
Tobacco-Induced Mental Disorders
Tobacco-induced sleep disorder is discussed in the chapter “Sleep-Wake Disorders” (see
“Substance/Medication-Induced Sleep Disorder”).
Unspecified Tobacco-Related Disorder

F17.209
This category applies to presentations in which symptoms characteristic of a
tobacco-related disorder that cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning predominate but do not
meet the full criteria for any specific tobacco-related disorder or any of the disorders
in the substance-related and addictive disorders diagnostic class.
Other (or Unknown) Substance–Related
Disorders
Other (or Unknown) Substance Use Disorder
Other (or Unknown) Substance Intoxication
Other (or Unknown) Substance Withdrawal
Other (or Unknown) Substance–Induced Mental Disorders
Unspecified Other (or Unknown) Substance–Related Disorder
Other (or Unknown) Substance Use Disorder
Diagnostic Criteria
A. A problematic pattern of use of an intoxicating substance not able to be
classified within the alcohol; caffeine; cannabis; hallucinogen (phencyclidine and
others); inhalant; opioid; sedative, hypnotic, or anxiolytic; stimulant; or tobacco
categories and leading to clinically significant impairment or distress, as
manifested by at least two of the following, occurring within a 12-month period:
1. The substance is often taken in larger amounts or over a longer period than
was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control use
of the substance.
3. A great deal of time is spent in activities necessary to obtain the substance,
use the substance, or recover from its effects.
4. Craving, or a strong desire or urge to use the substance.
5. Recurrent use of the substance resulting in a failure to fulfill major role
obligations at work, school, or home.

6. Continued use of the substance despite having persistent or recurrent social
or interpersonal problems caused or exacerbated by the effects of its use.
7. Important social, occupational, or recreational activities are given up or
reduced because of use of the substance.
8. Recurrent use of the substance in situations in which it is physically
hazardous.
9. Use of the substance is continued despite knowledge of having a persistent
or recurrent physical or psychological problem that is likely to have been
caused or exacerbated by the substance.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the substance to achieve
intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of
the substance.
11. Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome for other (or unknown) substance
(refer to Criteria A and B of the criteria sets for other [or unknown]
substance withdrawal).
b. The substance (or a closely related substance) is taken to relieve or avoid
withdrawal symptoms.
Specify if:
In early remission: After full criteria for other (or unknown) substance use
disorder were previously met, none of the criteria for other (or unknown)
substance use disorder have been met for at least 3 months but for less than 12
months (with the exception that Criterion A4, “Craving, or a strong desire or urge
to use the substance,” may be met).
In sustained remission: After full criteria for other (or unknown) substance use
disorder were previously met, none of the criteria for other (or unknown)
substance use disorder have been met at any time during a period of 12 months
or longer (with the exception that Criterion A4, “Craving, or a strong desire or
urge to use the substance,” may be met).
Specify if:
In a controlled environment: This additional specifier is used if the individual is
in an environment where access to the substance is restricted.
Code based on current severity/remission: If an other (or unknown) substance
intoxication, other (or unknown) substance withdrawal, or other (or unknown)
substance–induced mental disorder is present, do not use the codes below for other
(or unknown) substance use disorder. Instead, the comorbid other (or unknown)
substance use disorder is indicated in the 4th character of the other (or unknown)

substance–induced disorder code (see the coding note for other [or unknown]
substance intoxication, other [or unknown] substance withdrawal, or specific other
[or unknown] substance–induced mental disorder). For example, if there is comorbid
other (or unknown) substance–induced depressive disorder and other (or unknown)
substance use disorder, only the other (or unknown) substance–induced depressive
disorder code is given, with the 4th character indicating whether the comorbid other
(or unknown) substance use disorder is mild, moderate, or severe: F19.14 for other
(or unknown) substance use disorder with other (or unknown) substance–induced
depressive disorder or F19.24 for a moderate or severe other (or unknown)
substance use disorder with other (or unknown) substance–induced depressive
disorder.
Specify current severity/remission:
F19.10 Mild: Presence of 2–3 symptoms.
F19.11 Mild, In early remission
F19.11 Mild, In sustained remission
F19.20 Moderate: Presence of 4–5 symptoms.
F19.21 Moderate, In early remission
F19.21 Moderate, In sustained remission
F19.20 Severe: Presence of 6 or more symptoms.
F19.21 Severe, In early remission
F19.21 Severe, In sustained remission
Specifiers
“In a controlled environment” applies as a further specifier of remission if the individual is both
in remission and in a controlled environment (i.e., in early remission in a controlled environment
or in sustained remission in a controlled environment). Examples of these environments are
closely supervised and substance-free jails, therapeutic communities, and locked hospital units.
Diagnostic Features
The diagnostic class other (or unknown) substance–related disorders applies to substances that
are not included within any of the nine substance classes presented earlier in this chapter (i.e., to
alcohol; caffeine; cannabis; hallucinogens [phencyclidine and others]; inhalants; opioids;
sedatives, hypnotics, or anxiolytics; stimulants; or tobacco). Such substances include anabolic
steroids; nonsteroidal anti-inflammatory drugs; corticosteroids; antiparkinsonian medications;
antihistamines; nitrous oxide; amyl-, butyl-, or isobutyl-nitrites; betel nut, which is chewed in
many geographic regions to produce mild euphoria and a floating sensation; and kava (from a
South Pacific pepper plant), which produces mild euphoria, sedation, incoordination, and weight
loss, as well as health effects (e.g., mild hepatitis, lung abnormalities). Note that gaseous
substances are included with the inhalant category only if they are hydrocarbon agents; other

gaseous substances (including nitrous oxide mentioned above) are included in the other (or
unknown) substance category. Unknown substance–related disorders are associated with
unidentified substances, such as intoxications in which the individual cannot identify the
ingested drug, or substance use disorders involving either new, black market drugs not yet
identified or familiar drugs illegally sold under false names.
Note that substances included within the scope of one of the substance classes should be
coded within that respective substance class and are inappropriate to include in the “other
substance” category. For example, the following substances are explicitly included in specific
substance classes and should not be included in the “other substance” category: synthetic
cannabinoids are included in the cannabis category; propofol is included in the sedative,
hypnotic, or anxiolytic category; and cathinones (including khât plant agents and synthetic
chemical derivatives) are included in the stimulant category.
Other (or unknown) substance use disorder is a mental disorder in which repeated use of an
other or unknown substance typically continues, despite the individual’s knowing that the
substance is causing serious problems for the individual. Those problems are reflected in the
diagnostic criteria. When the substance is known but does not fit within any of the other nine
substance classes, it should be reflected when recording and coding the name of the disorder
(e.g., “nitrous oxide use disorder,” using the applicable code for other [or unknown] substance
use disorder).
Associated Features
A diagnosis of other (or unknown) substance use disorder is supported by any of the following:
the individual’s reported use of a substance that is not among the nine classes listed in this
chapter; recurring episodes of intoxication with negative results in standard drug screens, which
may not detect new or rarely used substances; and the presence of symptoms characteristic of an
unidentified substance that has newly appeared in the individual’s community.
Because of access to nitrous oxide (“laughing gas”), membership in certain populations may
be associated with frequent use of the substance and possibly with a diagnosis of nitrous oxide
use disorder. The role of this gas as an anesthetic agent leads to misuse by some medical and
dental professionals, and its use as a propellant for commercial products (e.g., whipped cream
dispensers) contributes to misuse by food service workers. Nitrous oxide misuse by adolescents
and young adults is significant, and some individuals with very frequent use may present with
serious medical complications and mental conditions, including myeloneuropathy, spinal cord
subacute combined degeneration, peripheral neuropathy, and psychosis.
Use of amyl-, butyl-, and isobutyl (and similar) nitrite gases is prevalent among homosexual
men and some adolescents, especially those with conduct disorder.
Substance use disorders generally are associated with elevated risks of suicide, but there is no
evidence of unique risk factors for suicide with other (or unknown) substance use disorder.
Prevalence
Based on extremely limited data, the prevalence of most other (or unknown) substance use
disorders is likely lower than that of use disorders involving the nine substance classes in this

Use of other or unknown substances without meeting criteria for other (or unknown) substance
use disorder.
Substance use disorders.
Other (or unknown) substance intoxication, other (or unknown) substance withdrawal, and
other (or unknown) substance–induced mental disorders.
chapter. For certain gaseous substances, prevalence of use is not rare (lifetime prevalence in the
U.S. household population for individuals age 12 and older is estimated at 4.6% for nitrous oxide
and 2.5% for nitrites), but how often the patterns of use qualify for a use disorder is unknown.
Development and Course
No single pattern of development or course characterizes the pharmacologically varied other (or
unknown) substance use disorders. Often unknown substance use disorders will be reclassified
when the unknown substance eventually is identified.
Risk and Prognostic Factors
Risk and prognostic factors for other (or unknown) substance use disorders are thought to be
similar to those for most substance use disorders and include the presence of any other substance
use disorders, conduct disorder, or antisocial personality disorder in the individual or the
individual’s family; early onset of substance problems; easy availability of the substance in the
individual’s environment; childhood maltreatment or trauma; and evidence of limited early selfcontrol and behavioral disinhibition.
Culture-Related Diagnostic Issues
Certain cultures may be associated with other (or unknown) substance use disorders involving
specific indigenous substances within the cultural region, such as betel nut.
Diagnostic Markers
Urine, breath, or saliva tests may correctly identify a commonly used substance falsely sold as a
novel product. However, routine clinical tests usually cannot identify truly unusual or new
substances, which may require testing in specialized laboratories.
Differential Diagnosis
Use of unknown substances is not rare among adolescents, but most use does not meet the
diagnostic standard of two or more criteria for other (or unknown) substance use disorder in a
12-month period.
Other (or unknown) substance use disorder may co-occur with various
substance use disorders that involve any of the nine substance classes presented earlier in this
chapter, and the symptoms of the disorders may be similar and overlapping. To disentangle
symptom patterns, it is helpful to inquire about which symptoms persisted during periods when
some of the substances were not being used.
Other (or unknown) substance use disorder is differentiated from other (or unknown) substance
intoxication, other (or unknown) substance withdrawal, and other-(or unknown) substanceinduced mental disorders (e.g., corticosteroid-induced bipolar and related disorder) in that other
(or unknown) substance use disorder describes a problematic pattern of use of the other (or
unknown) substance that involves impaired control over the use of the substance, social

impairment attributable to use of the substance, risky use of the substance (e.g., continued use
despite medical complications), and pharmacological symptoms (the development of
tolerance or withdrawal), whereas other (or unknown) substance intoxication, other (or
unknown) substance withdrawal, and other (or unknown) substance-induced mental disorders
describe psychiatric syndromes that occur in the context of heavy use. Other (or unknown)
substance intoxication, other (or unknown) substance withdrawal, and other (or unknown)
substance–induced mental disorders may occur in individuals with other (or unknown) substance
use disorder. In such cases, a diagnosis of other (or unknown) substance intoxication, other (or
unknown) substance withdrawal, or other (or unknown) substance–induced mental disorder
should be given in addition to a diagnosis of other (or unknown) substance use disorder, the
presence of which is indicated in the diagnostic code.
Comorbidity
Substance use disorders, including other (or unknown) substance use disorder, are commonly
comorbid with one another, with conduct disorder in adolescence, and with antisocial personality
disorder.
Other (or Unknown) Substance Intoxication
Diagnostic Criteria
A. The development of a reversible substance-specific syndrome attributable to
recent ingestion of (or exposure to) a substance that is not listed elsewhere or is
unknown.
B. Clinically significant problematic behavioral or psychological changes that are
attributable to the effect of the substance on the central nervous system (e.g.,
impaired motor coordination, psychomotor agitation or retardation, euphoria,
anxiety, belligerence, mood lability, cognitive impairment, impaired judgment,
social withdrawal) and develop during, or shortly after, use of the substance.
C. The signs or symptoms are not attributable to another medical condition and are
not better explained by another mental disorder, including intoxication with
another substance.
Specify if:
With perceptual disturbances: This specifier may be noted when
hallucinations with intact reality testing or auditory, visual, or tactile illusions
occur in the absence of a delirium.
Coding note: The ICD-10-CM code depends on whether there is a comorbid other
(or unknown) substance use disorder involving the same substance and whether or
not there are perceptual disturbances.

For other (or unknown) substance intoxication, without perceptual
disturbances: If a mild other (or unknown) substance use disorder is comorbid,
the ICD-10-CM code is F19.120, and if a moderate or severe other (or unknown)
substance use disorder is comorbid, the ICD-10-CM code is F19.220. If there is
no comorbid other (or unknown) substance use disorder, then the ICD-10-CM
code is F19.920.
For 
other 
(or 
unknown) 
substance 
intoxication, 
with 
perceptual
disturbances: If a mild other (or unknown) substance use disorder is comorbid,
the ICD-10-CM code is F19.122, and if a moderate or severe other (or unknown)
substance use disorder is comorbid, the ICD-10-CM code is F19.222. If there is
no comorbid other (or unknown) substance use disorder, then the ICD-10-CM
code is F19.922.
Note: For information on Risk and Prognostic Factors, Culture-Related Diagnostic
Issues, and Diagnostic Markers, see the corresponding sections in Other (or Unknown)
Substance Use Disorder.
Diagnostic Features
The essential feature of other (or unknown) substance intoxication is the presence of clinically
significant behavioral or psychological changes that develop during, or immediately after, use of
either a) a substance not included within one of the nine substance classes presented in this
chapter (i.e., alcohol; caffeine; cannabis; phencyclidine and other hallucinogens; inhalants;
opioids; sedatives, hypnotics, or anxiolytics; stimulants; or tobacco) or b) an unknown substance.
If the substance is known, it should be reflected in the name of the disorder upon coding (e.g.,
“kava intoxication”).
Application of the diagnostic criteria for other (or unknown) substance intoxication is very
challenging. Criterion A requires development of a reversible “substance-specific syndrome,”
but if the substance is unknown, that syndrome usually will be unknown. To resolve this conflict,
clinicians may ask the individual or obtain collateral history as to whether the individual has
experienced a similar episode after using substances with the same “street” name or from the
same source. Similarly, hospital emergency departments sometimes recognize over a few days
numerous presentations of a severe, unfamiliar intoxication syndrome from a newly available,
previously unknown substance. Because of the great variety of intoxicating substances, Criterion
B can provide only broad examples of signs and symptoms from some intoxications, with no
threshold for the number of symptoms required for a diagnosis; clinical judgment guides those
decisions. Criterion C requires ruling out other medical conditions, mental disorders, or
intoxications.
Prevalence
The prevalence of other (or unknown) substance intoxication is unknown.
Development and Course

Use of other or unknown substance, without meeting criteria for other (or unknown) substance
intoxication.
Substance intoxication or other substance/medication-induced mental disorders.
Other toxic, metabolic, traumatic, neoplastic, vascular, or infectious disorders that impair brain
function and cognition.
Intoxications usually appear and then peak minutes to hours after use of the substance, but the
onset and course vary with the substance and the route of administration. Generally, substances
used by pulmonary inhalation and intravenous injection have the most rapid onset of action,
whereas those ingested by mouth and requiring metabolism to an active product are much
slower. (For example, after ingestion of certain mushrooms, the first signs of an eventually fatal
intoxication may not appear for a few days.) Intoxication effects usually resolve within hours to a
very few days. However, the body may completely eliminate an anesthetic gas such as nitrous
oxide just minutes after use ends. At the other extreme, some “hit-and-run” intoxicating
substances poison systems, leaving permanent impairments. For example, MPTP (1-methyl-4phenyl-1,2,3,6-tetrahydropyridine), a contaminating by-product in the synthesis of a certain
opioid, kills dopaminergic cells and induces permanent parkinsonism in individuals who had
sought opioid intoxication.
Functional Consequences of Other (or Unknown) Substance
Intoxication
Impairment from intoxication with any substance may have serious consequences, including
dysfunction at work, social indiscretions, problems in interpersonal relationships, failure to fulfill
role obligations, traffic accidents, fighting, high-risk behaviors (i.e., having unprotected sex), and
substance or medication overdose. The pattern of consequences will vary with the particular
substance.
Differential Diagnosis
The individual used an other or unknown substance(s), but the dose was insufficient to produce
symptoms that meet the diagnostic criteria required for the diagnosis.
Familiar 
substances
may be sold in the black market as novel products, and individuals may experience intoxication
from those substances. History, toxicology screens, or chemical testing of the substance itself
may help to identify it. Other substance intoxication is distinguished from other
substance/medication-induced mental disorders (e.g., corticosteroid-induced anxiety disorder)
because the symptoms (e.g., anxiety) in these latter disorders are in excess of those (if known)
usually associated with the specific substance intoxication, predominate in the clinical
presentation, and are severe enough to warrant clinical attention.
Numerous neurological and other medical conditions may produce rapid onset of signs and
symptoms mimicking those of intoxications, including the examples in Criterion B.
Paradoxically, drug withdrawals also must be ruled out; for example, lethargy may indicate
withdrawal from one drug or intoxication with another substance.
Comorbidity

As with all substance-related disorders, conduct disorder in adolescence, antisocial personality
disorder, and other substance use disorders tend to co-occur with other (or unknown) substance
intoxication.
Other (or Unknown) Substance Withdrawal
Diagnostic Criteria
A. Cessation of (or reduction in) use of a substance that has been heavy and
prolonged.
B. The development of a substance-specific syndrome shortly after the cessation of
(or reduction in) substance use.
C. The substance-specific syndrome causes clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
D. The symptoms are not attributable to another medical condition and are not
better explained by another mental disorder, including withdrawal from another
substance.
E. The substance involved cannot be classified under any of the other substance
categories (alcohol; caffeine; cannabis; opioids; sedatives, hypnotics, or
anxiolytics; stimulants; or tobacco) or is unknown.
Specify if:
With perceptual disturbances: This specifier may be noted when
hallucinations with intact reality testing or auditory, visual, or tactile illusions
occur in the absence of a delirium.
Coding note: The ICD-10-CM code depends on whether or not there is a comorbid
other (or unknown) substance use disorder and whether or not there are perceptual
disturbances.
For other (or unknown) substance withdrawal, without perceptual
disturbances: If a mild other (or unknown) substance use disorder is comorbid,
the ICD-10-CM code is F19.130, and if a moderate or severe other (or unknown)
substance use disorder is comorbid, the ICD-10-CM code is F19.230. If there is
no comorbid other (or unknown) substance use disorder (e.g., in a patient taking
an other [or unknown] substance solely under appropriate medical supervision),
then the ICD-10-CM code is F19.930.
For 
other 
(or 
unknown) 
substance 
withdrawal, 
with 
perceptual
disturbances: If a mild other (or unknown) substance use disorder is comorbid,
the ICD-10-CM code is
F19.132, and if a moderate or severe other (or unknown) substance use disorder

is comorbid, the ICD-10-CM code is F19.232. If there is no comorbid other (or
unknown) substance use disorder (e.g., in a patient taking an other [or unknown]
substance solely under appropriate medical supervision), then the ICD-10-CM
code is F19.932.
Note: For information on Risk and Prognostic Factors and Diagnostic Markers, see the
corresponding sections in Other (or Unknown) Substance Use Disorder.
Diagnostic Features
Other (or unknown) substance withdrawal is a clinically significant syndrome that develops
during or within a few hours to days after reducing or terminating dosing with a substance
(Criteria A and B). Although recent dose reduction or termination usually is clear in the history,
other diagnostic procedures are very challenging if the drug is unknown. Criterion B requires
development of a “substance-specific syndrome” (i.e., the individual’s signs and symptoms must
correspond with the known withdrawal syndrome for the recently stopped drug)—a requirement
that rarely can be met with an unknown substance. Consequently, clinical judgment must guide
such decisions when this information is limited. Criterion D requires ruling out other medical
conditions, mental disorders, or withdrawals from familiar substances. When the substance is
known, it should be reflected in the name of the disorder upon coding (e.g., “betel nut
withdrawal”).
Prevalence
The prevalence of other (or unknown) substance withdrawal is unknown.
Development and Course
Withdrawal signs commonly appear some hours after use of the substance is terminated, but the
onset and course vary greatly, depending on the dose typically used and the rate of elimination of
the specific substance from the body. At peak severity, withdrawal symptoms from some
substances involve only moderate levels of discomfort, whereas withdrawal from other
substances may be fatal. Withdrawal-associated dysphoria often motivates relapse to substance
use. Withdrawal symptoms slowly abate over days, weeks, or months, depending on the
particular drug and doses to which the individual became tolerant.
Functional Consequences of Other (or Unknown) Substance
Withdrawal
Withdrawal from any substance may have serious consequences, including physical signs and
symptoms (e.g., malaise, vital sign changes, abdominal distress, headache), intense drug craving,
anxiety, depression, agitation, psychotic symptoms, or cognitive impairments. These
consequences may lead to problems such as dysfunction at work, problems in interpersonal
relationships, failure to fulfill role obligations, traffic accidents, fighting, high-risk behavior (e.g.,
having unprotected sex), suicide attempts, and substance or medication overdose. The pattern of
consequences will vary with the particular substance.

Dose reduction after extended dosing, but not meeting the criteria for other (or unknown)
substance withdrawal.
Substance withdrawal or other substance/medication-induced mental disorders.
Other toxic, metabolic, traumatic, neoplastic, vascular, or infectious disorders that impair brain
function and cognition.
Differential Diagnosis
The individual used other (or unknown) substances, but the dose that was used was insufficient
to produce symptoms that meet the criteria required for the withdrawal diagnosis.
Familiar 
substances
may be sold in the black market as novel products, and individuals may experience withdrawal
when discontinuing those substances. History, toxicology screens, or
chemical testing of the substance itself may help to identify it. Other substance withdrawal is
distinguished from other substance/medication-induced mental disorders (e.g., venlafaxineinduced anxiety disorder, with onset during withdrawal) because the symptoms (e.g., anxiety) in
these latter disorders are in excess of symptoms (if known) usually associated with the specific
substance withdrawal, predominate in the clinical presentation, and are severe enough to warrant
clinical attention.
Numerous neurological and other medical conditions may produce rapid onset of signs and
symptoms mimicking those of withdrawals. Paradoxically, drug intoxications also must be ruled
out; for example, lethargy may indicate withdrawal from one drug or intoxication with another
substance.
Comorbidity
As with all substance-related disorders, conduct disorder in adolescence, antisocial personality
disorder, and other substance use disorders are likely to co-occur with other (or unknown)
substance withdrawal.
Other (or Unknown) Substance–Induced Mental
Disorders
Because the category of other or unknown substances is inherently ill-defined, the extent and
range of these substance-induced mental disorders are uncertain. Nevertheless, other (or
unknown) substance–induced mental disorders are possible and are described in other chapters of
the manual with disorders with which they share phenomenology (see the substance/medicationinduced mental disorders in these chapters): other (or unknown) substance–induced psychotic
disorder (“Schizophrenia Spectrum and Other Psychotic Disorders”); other (or unknown)
substance–induced bipolar and related disorder (“Bipolar and Related Disorders”); other (or
unknown) substance–induced depressive disorder (“Depressive Disorders”); other (or unknown)
substance–induced anxiety disorders (“Anxiety Disorders”); other (or unknown) substance–
induced obsessive-compulsive disorder (“Obsessive-Compulsive and Related Disorders”); other
(or unknown) substance–induced sleep disorder (“Sleep-Wake Disorders”); other (or unknown)
substance–induced sexual dysfunction (“Sexual Dysfunctions”); and other (or unknown)

F63.0
substance/medication–induced major or mild neurocognitive disorder (“Neurocognitive
Disorders”). For other (or unknown) substance–induced intoxication delirium, other (or
unknown) substance–induced withdrawal delirium, and delirium induced by other (or unknown)
substance taken as prescribed, see the criteria and discussion of delirium in the chapter
“Neurocognitive Disorders.” These other (or unknown) substance–induced mental disorders are
diagnosed instead of other (or unknown) substance intoxication or other (or unknown) substance
withdrawal only when the symptoms are sufficiently severe to warrant independent clinical
attention.
Unspecified Other (or Unknown) Substance–Related
Disorder
F19.99
This category applies to presentations in which symptoms characteristic of an other
(or unknown) substance–related disorder that cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning
predominate but do not meet the full criteria for any specific other (or unknown)
substance–related disorder or any of the disorders in the substance-related
disorders diagnostic class.
Non-Substance-Related Disorders
Gambling Disorder
Diagnostic Criteria
A. Persistent and recurrent problematic gambling behavior leading to clinically
significant impairment or distress, as indicated by the individual exhibiting four
(or more) of the following in a 12-month period:
1. Needs to gamble with increasing amounts of money in order to achieve the
desired excitement.
2. Is restless or irritable when attempting to cut down or stop gambling.
3. Has made repeated unsuccessful efforts to control, cut back, or stop
gambling.
4. Is often preoccupied with gambling (e.g., having persistent thoughts of

reliving past gambling experiences, handicapping or planning the next
venture, thinking of ways to get money with which to gamble).
5. Often gambles when feeling distressed (e.g., helpless, guilty, anxious,
depressed).
6. After losing money gambling, often returns another day to get even (“chasing”
one’s losses).
7. Lies to conceal the extent of involvement with gambling.
8. Has jeopardized or lost a significant relationship, job, or educational or career
opportunity because of gambling.
9. Relies on others to provide money to relieve desperate financial situations
caused by gambling.
B. The gambling behavior is not better explained by a manic episode.
Specify if:
Episodic: Meeting diagnostic criteria at more than one time point, with
symptoms subsiding between periods of gambling disorder for at least several
months.
Persistent: Experiencing continuous symptoms, to meet diagnostic criteria for
multiple years.
Specify if:
In early remission: After full criteria for gambling disorder were previously met,
none of the criteria for gambling disorder have been met for at least 3 months
but for less than 12 months.
In sustained remission: After full criteria for gambling disorder were previously
met, none of the criteria for gambling disorder have been met during a period of
12 months or longer.
Specify current severity:
Mild: 4–5 criteria met.
Moderate: 6–7 criteria met.
Severe: 8–9 criteria met.
Note: Although some behavioral conditions that do not involve ingestion of substances
have similarities to substance-related disorders, only one disorder—gambling disorder—
has sufficient data to be included in this section.
Specifiers
Severity is based on the number of criteria endorsed. Individuals with mild gambling disorder
may exhibit only 4–5 of the criteria, with the most frequently endorsed criteria usually related to
preoccupation with gambling and “chasing” losses. Individuals with moderately severe gambling
disorder exhibit more of the criteria (i.e., 6–7). Individuals with the most severe form will exhibit

all or most of the nine criteria (i.e., 8–9). Jeopardizing relationships or career opportunities
because of gambling and relying on others to provide money for gambling losses are typically
the least often endorsed criteria and most often occur among those with more severe gambling
disorder. Furthermore, individuals presenting for treatment of gambling disorder typically have
moderate to severe forms of the disorder.
Diagnostic Features
Gambling involves risking something of value in the hopes of obtaining something of greater
value. In many cultures, individuals gamble on games and events, and most do so without
experiencing problems. However, some individuals develop substantial impairment related to
their gambling behaviors. The essential feature of gambling disorder is persistent and recurrent
maladaptive gambling behavior that disrupts personal, family, and/or vocational pursuits
(Criterion A). Gambling disorder is defined as a cluster of four or more of the symptoms listed in
Criterion A occurring at any time in the same 12-month period.
A pattern of “chasing one’s losses” may develop, with an urgent need to continue gambling
(often with placing larger bets or taking greater risks) to undo a loss or series of losses. The
individual may abandon a gambling strategy and try to win back losses all at once. Although
many gamblers may “chase” for short periods of time, it is the frequent, and often long-term,
“chase” that is characteristic of gambling disorder (Criterion A6). Individuals may lie to family
members, therapists, or others to conceal the extent of involvement with gambling; these
instances of deceit may also include, but are not limited to, covering up illegal behaviors such as
forgery, fraud, theft, or embezzlement to obtain money with which to gamble (Criterion A7).
Individuals may also engage in “bailout” behavior, turning to family or others for help with a
desperate financial situation that was caused by gambling (Criterion A9).
In some cases, symptoms meeting diagnostic criteria for gambling disorder may occur as a
direct physiological consequence of taking dopaminergic medications, such as those used to treat
Parkinson’s disease. When such symptoms are induced by a medication, these cases would be
diagnosed as gambling disorder.
Associated Features
Distortions in thinking (e.g., denial, superstitions, a sense of power and control over the outcome
of chance events, overconfidence) may be present in individuals with gambling disorder. Many
individuals with gambling disorder believe that money is both the cause of and the solution to
their problems. Some individuals with gambling disorder are impulsive, competitive, energetic,
restless, and easily bored; they may be overly concerned with the approval of others and may be
generous to the point of extravagance when winning. Other individuals with gambling disorder
are depressed and lonely, and they may gamble when feeling helpless, guilty, or depressed.
Prevalence
The past-year prevalence rate of gambling disorder is about 0.2%–0.3% in the general U.S.
population, with a range of 0.1%–0.7% observed across international studies. In the

general U.S. population, the lifetime prevalence rate is about 0.4%–1.0%. For women, the
lifetime prevalence rate of gambling disorder is about 0.2%, and for men it is about 0.6%. The
12-month prevalence of DSM-5 gambling disorder varies among ethnoracial groups in the
United States: it is 0.52% in African Americans, 0.25% in Latinx, and 0.23% in non-Latinx
Whites.
Development and Course
The onset of gambling disorder can occur during adolescence or young adulthood, but in other
individuals it manifests during middle or even older adulthood. Generally, gambling disorder
develops over the course of years, although the progression appears to be more rapid in women
than in men. National data from the United States and Canada show that most individuals who
develop a gambling disorder evidence a pattern of gambling that gradually increases in both
frequency and amount of wagering. Certainly, milder forms can develop into more severe cases.
Most individuals with gambling disorder report that one or two types of gambling are most
problematic for them, although some individuals participate in many forms of gambling.
Individuals are likely to engage in certain types of gambling (e.g., buying scratch tickets daily)
more frequently than others (e.g., playing slot machines or blackjack at the casino weekly).
Frequency of gambling can be related more to the type of gambling than to the severity of the
overall gambling disorder. For example, purchasing a single scratch ticket each day may not be
problematic, while less frequent casino, sports, or card gambling may be part of a gambling
disorder. Similarly, amounts of money spent wagering are not in themselves indicative of
gambling disorder. Some individuals can wager thousands of dollars per month and not have a
problem with gambling, while others may wager much smaller amounts but experience
substantial gambling-related difficulties.
Gambling patterns may be regular or episodic, and gambling disorder can be persistent or in
remission. Gambling can increase during periods of stress or depression and during periods of
substance use or abstinence. There may be periods of heavy gambling and severe problems,
times of total abstinence, and periods of nonproblematic gambling. Gambling disorder is
sometimes associated with spontaneous, long-term remissions. Nevertheless, some individuals
underestimate their vulnerability to develop gambling disorder or to relapse following remission.
When in a period of remission, they may incorrectly assume that they will have no problem
regulating gambling and that they can engage in some forms of gambling nonproblematically,
only to experience a relapse of gambling disorder.
Early expression of gambling disorder is more common among young men (ages 18–21
years) than among young women. Individuals who begin gambling in youth often do so with
family members or friends. Development of early-life gambling disorder appears to be associated
with impulsivity and substance abuse. Internet gambling has been linked to risky and
problematic gambling among youth and may be conducted in a more isolative (i.e., nonpeer)
fashion. Some video gaming characteristics (e.g., loot boxes or loot crates containing prizes
determined by chance that may be of higher or lower value or desirability) overlap with
gambling behavior and may influence the course of gambling disorder. Many high school and
college students who develop gambling disorder grow out of the disorder over time, although it
remains a lifelong problem for some. Mid- and later-life onset of gambling disorder is more
common among women than among men.

Temperamental.
Genetic and physiological.
Course modifiers.
There are age and gender variations in the type of gambling activities and the prevalence
rates of gambling disorder. Gambling disorder in the United States is more common among
younger and middle-age individuals than among older adults. Among U.S. young adults (ages
18–21 years), the disorder is more prevalent in young men than in young women. Younger
individuals prefer different forms of gambling (e.g., sports betting), whereas older adults are
more likely to develop problems with slot machine and bingo gambling. Although the
proportions of individuals who seek treatment for gambling disorder are low across all age
groups in the United States, younger individuals are especially unlikely to present for treatment.
Risk and Prognostic Factors
Gambling that begins in childhood or early adolescence is associated with
increased rates of gambling disorder. Gambling disorder also appears to aggregate with
antisocial personality disorder, depressive and bipolar disorders, and other substance use
disorders, particularly alcohol use disorder.
Gambling disorder can aggregate in families, and this effect appears to
relate to both environmental and genetic factors. Gambling problems are more frequent in
monozygotic than in dizygotic twins. Gambling disorder is also more prevalent among firstdegree relatives of individuals with moderate to severe alcohol use disorder than among the
general population.
Many individuals, including adolescents and young adults, are likely to resolve
their problems with gambling disorder over time, although a strong predictor of future gambling
problems 
is 
previous 
gambling 
problems. 
Psychopathology, 
including 
attentiondeficit/hyperactivity and anxiety disorders, has been found to be associated with increased risk of
onset of gambling disorder among those who gamble and with persistence of gambling disorder
symptoms over time.
Culture-Related Diagnostic Issues
Types of gambling activities vary across cultural contexts and ethnoracial groups (e.g., pai gow,
cockfights, blackjack, horse racing). Some Indigenous populations in Canada, New Zealand, and
the United States have high prevalence rates of gambling problems, possibly related to limited
economic opportunities, the expectation that gambling may help advance social goals, and the
location of casinos on some U.S. tribal lands. U.S.-born individuals have higher rates of
gambling problems than first-generation immigrants to the United States. Endorsement of
specific disorder criteria may vary across ethnoracial groups. For example, among individuals
with gambling problems, Asian Americans may be less likely than other groups to endorse being
preoccupied with gambling (Criterion A4), while African Americans and Latinx may be more
likely to endorse repeated unsuccessful efforts to control gambling (Criterion A3).
Sex- and Gender-Related Diagnostic Issues
Men develop gambling disorder at higher rates than women, although this gender gap may be
narrowing. Data from treatment-seeking populations have suggested that women may develop

Nondisordered gambling.
Manic episode.
gambling problems more rapidly after the onset of gambling (so-called telescoping), although
general population data suggest that men progress more rapidly to disordered gambling than
women do. Although women seek treatment sooner than men do, rates of treatment seeking in
U.S. national surveys are low (< 10%) among individuals with gambling disorder regardless of
gender.
Women may gamble as a maladaptive approach to negative affect, whereas men may gamble
more for the thrill of it. Compared with men, women may also experience more shame related to
gambling. Men tend to wager on different forms of gambling than women, with cards, sports,
and horse race gambling more prevalent among men, and slot machine and bingo gambling more
common among women. Women with gambling disorder are more likely than men with
gambling disorder to have depressive, bipolar, and anxiety disorders.
Association With Suicidal Thoughts or Behavior
In a U.S. study, up to half of individuals in treatment for gambling disorder in Connecticut
reported suicidal thoughts, and about 17% reported attempted suicide. A nationwide register
study in Sweden showed that compared with individuals without gambling disorder, individuals
ages 20–74 years with gambling disorder have a 15-fold increased suicide mortality rate.
Functional Consequences of Gambling Disorder
Areas of psychosocial, health, and mental health functioning may be adversely affected by
gambling disorder. Specifically, individuals with gambling disorder may, because of their
involvement with gambling, jeopardize or lose important relationships with family members or
friends. Such problems may occur from repeatedly lying to others to cover up the extent of
gambling or from requesting money that is used for gambling or to pay off gambling debts.
Employment or educational activities may likewise be adversely impacted by gambling disorder;
absenteeism or poor work or school performance can occur with gambling disorder, as
individuals may gamble during work or school hours or be preoccupied with gambling or its
adverse consequences when they should be working or studying. Individuals with gambling
disorder in a U.S. national sample had poor general health and utilized medical services at high
rates.
Differential Diagnosis
Gambling disorder must be distinguished from professional and social
gambling. In professional gambling, risks are limited and discipline is central. Social gambling
typically occurs with friends or colleagues and lasts for a limited period of time, with acceptable
losses. Some persons can experience problems associated with gambling (e.g., short-term
chasing behavior and loss of control) that do not meet the full criteria for gambling disorder.
Loss of judgment and excessive gambling may occur during a manic episode. An
additional diagnosis of gambling disorder should be given only if the gambling behavior is not
better explained by manic episodes (e.g., a history of maladaptive gambling behavior at times
other than during a manic episode). Alternatively, an individual with gambling disorder may,

Personality disorders.
Gambling symptoms due to dopaminergic medications.
during a period of gambling, exhibit behavior that resembles a manic episode, but once the
individual is away from the gambling, these manic-like features dissipate.
Problems with gambling may occur in individuals with antisocial
personality disorder and other personality disorders. If the criteria are met for both disorders,
both can be diagnosed.
Some 
individuals 
taking 
dopaminergic
medications (e.g., for Parkinson‘s disease) may experience urges to gamble that might be
distressing or impairing enough to meet criteria for gambling disorder. In such cases, a diagnosis
of gambling disorder would be warranted.
Comorbidity
Gambling disorder is associated with poor general health. In addition, some specific medical
conditions, such as tachycardia and angina, are more common among individuals with gambling
disorder than in the general population, even when other substance use disorders, including
tobacco use disorder, are controlled for. In U.S. national surveys, individuals with gambling
disorder have high rates of comorbidity with other mental disorders, such as substance use
disorders, depressive disorders, anxiety disorders, and personality disorders. In some individuals,
other mental disorders may precede gambling disorder and be either absent or present during the
manifestation of gambling disorder. Gambling disorder may also occur prior to the onset of other
mental disorders, especially bipolar and related disorders, anxiety disorders, and substance use
disorders. In a U.S. national survey, in approximately three-quarters of cases of individuals with
gambling disorder and another mental disorder, other psychopathology preceded the gambling
disorder.