Cannabinoid receptor type 1 (CB1) (CB1)

Cannabinoid receptor type 1 (CB1) is a G protein-coupled receptor predominantly expressed in the central nervous system, where it regulates the release of various neurotransmitters (UniProt P21554). It serves as a primary component of the endocannabinoid system, responding to endogenous ligands such as anandamide and 2-arachidonoylglycerol to modulate physiological processes including appetite, pain perception, and mood (PubMed PMC5877694). CB1 is a major therapeutic target for metabolic disorders, chronic pain, and neurological conditions (StatPearls NBK513308). However, its clinical utility has been limited by significant neuropsychiatric safety concerns, most notably demonstrated by the withdrawal of the inverse agonist rimonabant due to increased risks of depression and suicide (PubMed PMC2268996). Cannabidiol (CBD) interacts with CB1 as a negative allosteric modulator, altering the receptor's response to other cannabinoids without directly activating it, which contributes to its distinct pharmacological profile compared to tetrahydrocannabinol (THC) (British Journal of Pharmacology, 2015).

Other names

CB1RCNR1Cannabinoid receptor 1Central cannabinoid receptor

Cannabidiol (CBD) functions as a non-competitive negative allosteric modulator of the CB1 receptor, reducing the potency and efficacy of CB1 agonists like THC (Laprairie et al., 2015; PubMed PMC4621983). Other ligands like THC act as partial agonists, while Rimonabant acts as an inverse agonist (PubMed PMC2268996).