Role of neuronal nicotinic acetylcholine receptors in cannabinoid dependence

Cannabis is among the most widely consumed psychoactive drugs around the world and cannabis use disorder (CUD) has no current approved pharmacological treatment. Nicotine and cannabis are commonly co-used which suggests there to be overlapping neurobiological actions supported primarily by the co-distribution of both receptor systems in the brain. There appears to be strong rationale to explore the role that nicotinic receptors play in cannabinoid dependence. Preclinical studies suggest that the alpha 7 nAChR subtype may play a role in modulating the reinforcing and discriminative stimulus effects of cannabinoids, while the alpha 4 beta 2 * nAChR subtype may be involved in modulating the motor and sedative effects of cannabinoids. Preclinical and human genetic studies point towards a potential role of the alpha 5, alpha 3, and beta 4 nAChR subunits in CUD, while human GWAS studies strongly implicate the alpha 2 subunit as playing a role in CUD susceptibility. Clinical studies suggest that current smoking cessation agents, such as varenicline and bupropion, may also be beneficial in treating CUD, although more controlled studies are necessary. Additional behavioral, molecular, and mechanistic studies investigating the role of nAChR in the modulation of the pharmacological effects of cannabinoids are needed.

Automated summary

Cannabis is widely used worldwide and there is no approved treatment for cannabis use disorder (CUD). Co-use of nicotine and cannabis suggests overlapping neurobiological actions, supported by their receptor systems in the brain. Studying nicotinic receptors may help understand cannabinoid dependence, with different subtypes potentially modulating different effects of cannabinoids. Clinical and genetic studies indicate potential involvement of alpha 5, alpha 3, and beta 4 nAChR subunits, while the alpha 2 subunit is strongly implicated in CUD susceptibility. Current smoking cessation agents may also be beneficial in treating CUD, but further controlled studies are needed. Additional research is necessary to investigate the role of nAChR in the pharmacological effects of cannabinoids.