CANNABINOID RECEPTORS AND THEIR ENDOGENOUS AGONIST, ANANDAMIDE

Cannabinoids are a class of compound found in marijuana which have bee n known for their therapeutic and psychoactive properties for at least 4000 years. Isolation of the active principle in marijuana, Delta 9-T HC, provided the lead structure in the development of highly potent co ngeners which were used to probe for the mechanism of marijuana action . Cannabinoids were shown to bind to selective binding sites in brain tissue thereby regulating second messenger formation. Such studies led to the cloning of three cannabinoid receptor subtypes, CB1, CB2, and CB1A all of which belong to the superfamily of G protein-coupled plasm a membrane receptors. Analogous to the discovery of endogenous opiates , isolation of cannabinoid receptors provided the appropriate tool to isolate an endogenous cannabimimetic eicosanoid, anandamide, from porc ine brain. Recent studies indicate that anandamide is a member of a fa mily of fatty acid ethanolamides that may represent a novel class of l ipid neurotransmitters. This review discusses recent progress in canna binoid research with a focus on the receptors for Delta 9-THC, their c oupling to second messenger responses, and the endogenous lipid cannab imimetic, anandamide.