Cannabinoid receptor 1 (CB1)

Cannabinoid receptor 1 is a G protein-coupled receptor encoded by the CNR1 gene. It is one of the most abundant GPCRs in the central nervous system but is also found in peripheral tissues. The principal endogenous ligands are endocannabinoids such as anandamide and 2-arachidonoylglycerol; it is also activated by phytocannabinoids like THC from Cannabis sativa. Upon activation, CB1 modulates neurotransmitter release through inhibition of adenylyl cyclase and regulation of ion channel activity. It plays key roles in pain perception, appetite regulation, memory formation, mood stabilization, and motor control. Dysregulation or pharmacological targeting of this receptor has implications for numerous diseases including chronic pain syndromes, obesity/metabolic syndrome, neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis, substance use disorders/addiction medicine applications as well as psychiatric illnesses like schizophrenia or depression. While it remains a promising therapeutic target due to its broad physiological impact—especially within the CNS—therapeutic development faces challenges related to psychoactivity and safety concerns[1][2][3][4][6].

Other names

CB1CNR1 (gene symbol)Central cannabinoid receptorCannabinoid receptor type 1

Agonists activate CB1 to inhibit adenylyl cyclase via Gi/o proteins, reducing cAMP levels. Activation modulates neurotransmitter release by inhibiting voltage-gated Ca²⁺ channels and activating K⁺ currents. Antagonists/inverse agonists block or reverse these effects[2][4].