What we know and do not know about the cannabinoid receptor 2 (CB2)

• CB2 is highly expressed by cells of the immune system and can be immunosuppressive.
• CB2 is a member of the G-protein coupled receptor family and binds eicosanoid ligands.
• Endogenous cannabinoids that bind CB2 are ananamide and 2-arachidonoyl glycerol.
• Cannabinoids have therapeutic potential.
• A CB2 polymorphism is associated with human disease.

It has been well appreciated that the endocannabinoid system can regulate immune responses via the cannabinoid receptor 2 (CB2), which is primarily expressed by cells of the hematopoietic system. The endocannabinoid system is composed of receptors, ligands and enzymes controlling the synthesis and degradation of endocannabinoids. Along with endocannabinoids, both plant-derived and synthetic cannabinoids have been shown to bind to and signal through CB2 via G proteins leading to both inhibitory and stimulatory signals depending on the biological process. Because no cannabinoid ligand has been identified that only binds to CB2, the generation of mice deficient in CB2 has greatly expanded our knowledge of how CB2 contributes to immune cell development and function in health and disease. In regards to humans, genetic studies have associated CB2 with a variety of human diseases. Here, we review the endocannabinoid system with an emphasis on CB2 and its role in the immune system.