There are 2 known endogenous cannabinoid receptors—CB1 and CB2. Endogenous ligands shown to bind to these receptors have also been identified. These ligands include anandamide and 2-arachidonyl glycerol (2-AG).
Levels of 2-AG are much higher than anandamide, and 2-AG is thought to be involved in several other metabolic pathways. Anandamide and 2-AG exert their actions by binding to and activating the cannabinoid receptors.
CB1-R and CB2-R activation leads to:
Inhibition of adenylate cyclase
Stimulation of mitogen-activated protein kinase
Inhibition of voltage gated Ca2+ channels (CB1-R only)
Cannabinoid receptors are G-protein coupled receptors consisting of 7 transmembrane-spanning domains
Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptor. Pharmacol Ther. 1997;74:129-180.
De Petrocellis L, Cascio MG, Di Marzo V. The endocannabinoid system: a general view and latest additions. Br J Pharmacol. 2004;141:765-774.
Sugiura T, Kondo S, Sukagawa A, et al. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Commun. 1995;215:89-97.
Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258:1946-1949.
Ameri A. The effects of cannabinoids on the brain. Prog Neurobiol. 1999;58:315-348.
Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 1988;34:605-613.