Cannabinoid receptor 2 (CB2) (CB2)

Cannabinoid receptor 2 (CB2) is a G protein-coupled receptor (GPCR) primarily expressed in the immune system, including cells such as macrophages, B-cells, and T-cells, as well as in peripheral tissues (UniProt P34972). Unlike the CB1 receptor, which is predominantly found in the central nervous system and mediates psychoactive effects, CB2 is largely responsible for modulating inflammatory and immune responses (IUPHAR/BPS Guide to Pharmacology). Delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, acts as a partial agonist at both CB1 and CB2 receptors (PubChem CID 16078). Activation of CB2 by ligands like THC generally leads to the inhibition of adenylyl cyclase and the modulation of various signaling pathways that suppress the release of pro-inflammatory cytokines (PubMed PMC4144593). Because of its localized expression and role in immune regulation, CB2 is a significant therapeutic target for treating chronic pain, neuroinflammation, and autoimmune diseases without the psychotropic side effects associated with CB1 activation (StatPearls NBK549915).

Other names

CNR2CB-2CX5Cannabinoid receptor 2 (macrophage)

Agonism of the CB2 receptor (e.g., by THC) leads to the inhibition of adenylyl cyclase via Gi/o proteins, resulting in decreased intracellular cAMP levels and the modulation of mitogen-activated protein kinase (MAPK) pathways, which ultimately suppresses immune cell activation and the release of pro-inflammatory cytokines.