Cannabinoid receptor 1 (CB1) (CNR1)

Cannabinoid receptor 1 (CB1), encoded by the CNR1 gene, is one of the most abundant G protein-coupled receptors in the mammalian central nervous system, predominantly localized on the presynaptic terminals of neurons [2, 17]. It serves as a primary mediator of the endocannabinoid system, where it responds to endogenous ligands like anandamide and 2-arachidonoylglycerol to regulate the release of neurotransmitters such as GABA and glutamate through retrograde signaling [2, 12, 17]. This regulatory mechanism plays a critical role in various physiological processes, including the modulation of pain, appetite, mood, and cognitive functions [5, 17]. In clinical contexts, CB1 is a significant therapeutic target for metabolic and neurological disorders. Agonists like dronabinol are used to treat chemotherapy-induced nausea and stimulate appetite in wasting syndromes, while CB1 activity is also explored for chronic pain management [8, 10, 15]. Conversely, the development of CB1 antagonists and inverse agonists for treating obesity, such as rimonabant, was famously curtailed by the occurrence of severe neuropsychiatric adverse effects, including depression and suicidal ideation [1, 7, 8]. Current pharmaceutical research focuses on developing peripherally-restricted ligands and biased agonists that can achieve therapeutic efficacy in metabolic or inflammatory conditions without crossing the blood-brain barrier, thereby avoiding central nervous system toxicity [3, 15, 21].

Other names

CB1CB1RCB-RCANN6CB1ACB1BCentral cannabinoid receptor

Drugs targeting this receptor act primarily through orthosteric agonism, antagonism, or inverse agonism, as well as allosteric modulation, to influence Gi/o protein-mediated inhibition of adenylyl cyclase and regulation of ion channels.