Cannabinoid receptor family (CBR) (CBR)

The Cannabinoid receptor family comprises a group of G protein-coupled receptors (GPCRs), most notably Cannabinoid receptor 1 (CB1) and Cannabinoid receptor 2 (CB2), which serve as the primary mediators of the endocannabinoid system [1.2.2, 1.3.3]. CB1 is one of the most abundant GPCRs in the central nervous system, where it regulates neurotransmission through retrograde signaling to modulate pain, appetite, and memory [1.2.2, 1.2.4]. In contrast, CB2 is primarily expressed in immune cells and peripheral tissues, playing a critical role in inflammatory responses and immune modulation [1.2.3, 1.3.1]. These receptors are activated by a variety of ligands, including phytocannabinoids like THC and CBD, as well as synthetic agonists and antagonists [1.3.5, 1.4.4]. Therapeutically, the family is targeted for the treatment of chronic pain, epilepsy, and obesity, though central side effects remain a significant hurdle [1.2.4, 1.4.2]. For instance, the CB1 antagonist Rimonabant was withdrawn from the market due to severe psychiatric side effects, highlighting the safety challenges in this space [1.4.4]. Current drug development efforts focus on achieving tissue selectivity or allosteric modulation to improve the therapeutic window [1.4.4]. Additionally, the family is being investigated for roles in cancer and neurodegenerative diseases like Alzheimer's and Huntington's [1.2.4, 1.4.3].

Other names

CBRCNRCannabinoid receptorsCB receptors

Cannabinoid receptors primarily signal through Gi/o-coupled G proteins to inhibit adenylyl cyclase, thereby reducing intracellular cAMP levels [1.3.1, 1.3.4]. They also modulate ion channels, specifically inhibiting voltage-gated calcium channels and activating inwardly rectifying potassium channels, which leads to the suppression of neurotransmitter release in the central nervous system [1.2.1, 1.3.3]. Additionally, they activate mitogen-activated protein kinase (MAPK) pathways to regulate gene expression and cell survival [1.3.1, 1.4.1].