Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

Cumulative evidence has pointed out cannabinoid CB2 receptors (CB₂r) as a potential therapeutic key target for treating alcohol use disorder (AUD). This review provides the most relevant results obtained from rodent and human studies, including an integrative section focused on the involvement of CB₂r in the neurobiology of alcohol addiction. A literature search was conducted using the electronic databases Medline and Scopus for articles. The search strategy was as follows: "Receptor, Cannabinoid, CB2" AND "Alcohol-Related Disorders" AND "human/or patients"; "Receptor, Cannabinoid, CB2" AND "Alcohol" OR "Ethanol" AND "rodents/or mice/or rats". Pharmacological approaches demonstrated that the activation or blockade of CB₂r modulated different alcohol-addictive behaviors. Rodent models of alcoholism revealed significant alterations of CB₂r in brain areas of the reward system. In addition, mice lacking CB₂r (CB₂KO) show increased alcohol consumption, motivation, and relapse alterations. It has been stressed that the potential neurobiological mechanisms underlying their behavioral effects involve critical elements of the alcohol reward system. Interestingly, recent postmortem studies showed CNR2 alterations in brain areas of alcoholic patients. Moreover, although the number of studies is limited, the results revealed an association between some genetic alterations of the CNR2 and an increased risk for developing AUD. This review provides evidence that CB₂r may play a role in alcohol addiction. Clinical studies are necessary to figure out whether CB₂r ligands may prove useful for the treatment of AUD in humans.