Cannabinoid receptors 1 and 2 (CB1 and CB2)

Cannabinoid receptor 1 (CB1) is a G protein-coupled receptor encoded by the CNR1 gene and is primarily expressed in the central nervous system and peripheral nervous system, where it regulates synaptic transmission through activation by endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol, as well as exogenous ligands including THC from cannabis. CB1 has a classical 7-transmembrane domain structure, mediates retrograde neuronal signaling, and is involved in cognitive, pain, and metabolic functions. Cannabinoid receptor 2 (CB2) is encoded by CNR2, is mostly found in immune cells and peripheral tissues, and modulates inflammation and immune responses. Both receptors are drug targets for a range of conditions, including pain, neurodegeneration, obesity, anxiety, and inflammatory diseases, but are associated with significant safety concerns due to their complex physiological effects and widespread tissue distribution.

Other names

Central cannabinoid receptorCB1RCNR1GPRCB1Peripheral cannabinoid receptorCB2RCNR2GPRCB2

Agonists activate the receptor, triggering intracellular G protein signaling cascades, which affects pain, mood, appetite, and memory regulation. Antagonists and inverse agonists block or reduce receptor activity, and have been explored for obesity and addiction treatment. Allosteric modulators change receptor activity by binding to non-orthosteric sites (e.g., pregnenolone for CB1). Downstream effects include inhibition of adenylyl cyclase, modulation of ion channels, and alteration of neurotransmitter release.