CB2

CB2, or cannabinoid receptor type 2, is a G protein-coupled receptor that is part of the endocannabinoid system. In humans it is encoded by the CNR2 gene. Unlike CB1, which is abundant in the brain, CB2 is predominantly expressed in peripheral tissues, especially cells of the immune system such as B cells, T cells, macrophages, and dendritic cells, with lower but detectable levels in certain brain cells, particularly microglia, where expression can increase during inflammation.

CB2 is activated by endogenous cannabinoids such as 2-arachidonoylglycerol (2-AG) and anandamide, as well as exogenous cannabinoids from cannabis. Many research compounds selectively target CB2, including HU-308 and JWH-133, which have been used to study its function. The receptor typically signals through Gi/o proteins, leading to inhibition of adenylyl cyclase, reduced cAMP levels, and modulation of ion channels and MAP kinase pathways.

Physiologically, CB2 is involved in regulating immune responses and inflammation. It can modulate cytokine production, lymphocyte activity, and microglial activation, which has spurred interest in CB2 as a therapeutic target for inflammatory and autoimmune diseases, neuropathic pain, and certain neurodegenerative conditions. Unlike CB1-mediated psychoactive effects, CB2 activation is generally not associated with central adverse effects, reflecting its peripheral predominance, although CNS involvement can occur under certain conditions.

Clinical development of CB2-selective therapies has been investigated in preclinical and early clinical trials, but as of the mid-2020s, no CB2-targeted drug had received broad regulatory approval. Research continues to explore selective agonists and allosteric modulators, as well as the receptor's role in bone metabolism, metabolism, and immune system disorders.