CANNABINOID RECEPTORS AND THEIR ENDOGENOUS AGONISTS

Marijuana has been in use for over 4000 years as a therapeutic and as a recreational drug. Within the past decade, two cannabinoid receptor types have been identified, their signal transduction characterized, a nd an endogenous lipid agonist isolated from mammalian tissues. The CB 1 cannabinoid receptor is widely distributed in mammalian tissues, wit h the highest concentrations found in brain neurons. CB1 receptors are coupled to modulation of adenylate cyclase and ion channels. The CB2 receptor is found in cells of the immune system and is coupled to inhi bition of adenylate cyclase. Both receptor types selectively bind Delt a(9)-THC, the active principle in marijuana, and anandamide (arachidon ylethanolamide), an endogenous cannabimimetic eicosanoid. Progress is being made in the development of novel agonists and antagonists with r eceptor subtype selectivity, mice with genetic deletion of the cannabi noid receptors, and receptor-specific antibodies, which should help in providing a better understanding of the physiological role of the can nabinoid receptors.