# 08 - Addiction pharmacology

# Addiction pharmacology

© SPMM Course 
Addiction pharmacology 
DRUG 
MECHANISM 
Alcohol 
Intercalates into the fluid cell membrane; decreases NMDA sensitivity; increases 
GABA sensitivity; down-regulates calcium channels; up-regulates nicotine receptor 
gated sodium channels. 
Amphetamine 
Acts via releasing stored monoamines especially noradrenaline and dopamine. 
Hence a central sympathomimetic. 
Buprenorphine 
Partial opioid agonist. Lower doses – mild agonism; higher doses – antagonistic 
effects. 
Cannabis 
Acts via cannabinoid receptors. CB1 is central and activated by 11OH tetra hydro 
cannabinoid. This inhibits GABA tone in the substantia nigra and other areas. May 
be related to increased dopamine activity at reward centres. CB2 is peripheral 
immune-related and seen in spleen and thymus. (Endogenous cannabinoids called 
anandamides are derived from arachidonic acid; their function is unclear) 
Clonidine, 
lofexidine 
 Presynaptic alpha 2 agonist – reduces central sympathetic tone. Opioid receptors on 
locus coeruleus projections reduce noradrenergic tone on long-term use. The cellular 
machinery compensates via up-regulation of adenylate cyclase and maintains 
sympathetic tone in a chronic user. Sudden withdrawal leads to increased adrenergic 
firing rate (withdrawal symptoms); hence alpha 2 autoreceptor stimulation which 
reduces central sympathetic tone helps in opioid withdrawal. 
Dexfenfluramine 
& Fenfluramine 
Produce massive serotonin release from nerve endings. [Fen-Phen was an off-label 
combination of fenfluramine and phentermine used for promoting weight loss but 
fenfluramine (and dexfenfluramine) was withdrawn due to irreversible serotonergic 
damage, valvular regurgitation and pulmonary fibrosis]. 
Disulfiram 
Inhibits aldehyde dehydrogenase. Leads to accumulation of acetaldehyde if alcohol 
is consumed producing unpleasant reactions. 
Levomethadyl 
acetate (LAAM) 
Long-acting opioid agonist; potentially similar use as methadone. Withdrawn due to 
prolonged QT and torsades de pointes. Pure mu agonist. 
LSD 
5HT2A partial agonism producing hallucinogenic effect 
MDMA 
Has 2 isomers  R(-) isomers produce LSD-like effects and the S(+) isomers have 
amphetamine-like properties LSD-like action is mediated via serotonin release from 
presynaptic neurons. In the long term, this can damage serotonergic tracts 
irreversibly. 
Methadone 
Opioid receptor agonist. Longer acting than heroin and orally available. Pure mu 
agonist. 
Naloxone 
Short-acting opioid mu antagonist 
Naltrexone 
Longer acting opioid mu antagonist 
Phencyclidine 
Noncompetitive NMDA antagonist similar to ketamine; also binds to sigma 
receptors 
Varenicline 
Varenicline (Champix) is a partial agonist at the α4β2 unit of nicotinic acetylcholine 
receptor. It assists smoking cessation by relieving nicotine withdrawal symptoms 
and reducing the rewarding properties of nicotine.