CB1

Cannabinoid receptor CB1 (CB1R) is a G protein-coupled receptor expressed mainly by neurons in the brain, spinal cord, peripheral nervous system, and enteric nervous system^[1]. Mechanistically, CB1R stimulates Gi/o-dependent signaling and regulates cAMP output, while CB1R-mediated ERK activation in neuronal cells involves receptor tyrosine kinase transactivation, PI3K, Src, PKA, and PP1/PP2A signaling modules^[2][3]. In disease models, CB1R antagonists attenuated doxorubicin-induced oxidative/nitrosative stress, MAPK activation, and cardiomyocyte death, and CB1R antagonism reduced alcohol-induced hippocampal pyroptosis signaling^[4][5]. Compared with CB2, which appears mainly in immune cells, CB1R shows stronger neuronal and enteric distribution and mediates gut motility, intestinal secretion, and cholinergic neurotransmission through peripheral CB1 receptors^[1]. For experimental applications, selective CB1 antagonists or inverse agonists such as SR141716A, AM251, AM281, and rimonabant help test CB1R-dependent signaling, whereas CB1-selective or cannabinoid agonists such as ACEA, HU210, anandamide, and hemopressin support pathway analysis in vascular, cardiac, neuronal, and feeding models^[4][5][6][7].