Actions of delta-9-tetrahydrocannabinol in cannabis: Relation to use, abuse, dependence

Cannabis use disorders have been recently identified as a relevant clinical issue: a subset of cannabis smokers seeks treatment for their cannabis use, yet few succeed in maintaining long-term abstinence. The rewarding and positive reinforcing effects of the primary psychoactive component of smoked cannabis, delta-9-tetrahydrocannabinol (THC) are mediated by the cannabinoid CB1 receptor. The CB1 receptor has also been shown to mediate cannabinoid dependence and expression of withdrawal upon cessation of drug administration, a phenomenon verified across species. This paper will review findings implicating the CB1 receptor in the behavioural effects of exogenous cannabinoids with a focus on cannabinoid dependence and reinforcement, factors that contribute to the maintenance of chronic cannabis smoking despite negative consequences. Opioidergic modulation of these effects is also discussed.