Cannabinoid receptor 1 (CB1R) and Cannabinoid receptor 2 (CB2R) (CB1R/CB2R)

Cannabinoid receptor 1 (CB1R) and Cannabinoid receptor 2 (CB2R) are G-protein-coupled receptors that function as the primary signaling nodes of the endocannabinoid system (StatPearls, NBK549915). CB1R is highly expressed in the central nervous system, particularly in the cortex, hippocampus, and cerebellum, where it modulates the release of various neurotransmitters to regulate pain, memory, and appetite (UniProt, P21554). CB2R is primarily localized in peripheral tissues and immune cells, such as B-cells and natural killer cells, playing a critical role in the regulation of inflammatory responses and cytokine production (UniProt, P34972). These receptors are activated by endogenous ligands like anandamide, as well as exogenous phytocannabinoids such as THC and CBD (PubChem, CID 16078). Pharmacological targeting of these receptors has led to the development of drugs for chronic pain, multiple sclerosis-associated spasticity, and chemotherapy-induced nausea (PubMed, PMID 30125301). However, drug development is often complicated by the psychoactive effects of CB1R activation, which can include euphoria or paranoia, and the psychiatric risks associated with its antagonism, such as depression (Nature Reviews Drug Discovery, doi:10.1038/nrd.2017.194). CB2R-selective ligands are currently being explored as a way to achieve anti-inflammatory and analgesic effects without the central nervous system side effects typical of CB1R modulation (PubMed, PMID 21215324). Overall, the CB1R/CB2R system remains a high-priority target for neurological and metabolic disorders despite the narrow therapeutic window for certain compounds.

Other names

CNR1CNR2CB1CB2Cannabinoid receptor type 1Cannabinoid receptor type 2Central cannabinoid receptorPeripheral cannabinoid receptor

Agonism, antagonism, or inverse agonism of G-protein-coupled receptors, typically leading to inhibition of adenylyl cyclase and modulation of ion channels via Gi/o proteins.