A Systematic Review Found CB2 Cannabinoid Receptors Play a Key Role in Regulating Food Intake

CB2 receptors in brain reward areas modulate food intake. Two main experimental strategies confirmed this: (1) administering CB2 agonists/antagonists intraperitoneally or intracerebroventricularly, and (2) CB2 receptor knockout in mice. Both approaches demonstrated that CB2 receptors are necessary for modulating food intake and mediating energy balance.

Systematic review following PRISMA guidelines, searching PubMed, Scopus, and EBSCO databases. 13 studies included. Risk of bias assessed using SYRCLE tool for animal studies.

Most appetite research has focused on CB1 receptors (the target of the withdrawn anti-obesity drug rimonabant). Finding that CB2 receptors also regulate food intake opens a potential path to appetite-modulating drugs without the psychiatric side effects that doomed CB1 antagonists.

The failure of rimonabant (a CB1 antagonist) due to depression and suicidal ideation was a major setback for cannabinoid-based obesity treatment. CB2 receptors, which are less associated with mood regulation, could offer an alternative therapeutic target with a better safety profile.

All included studies are animal models, limiting direct clinical translation. Only 13 studies available, reflecting a young research area. SYRCLE risk of bias tool has limitations. No human data included.