The endocannabinoid nervous system: unique opportunities for therapeutic intervention

The active principle in marijuana, Delta (9)-tetrahydrocannabinol (THC), ha s been shown to have wide therapeutic application for a number of important medical conditions, including pain, anxiety, glaucoma, nausea, emesis, mus cle spasms, and wasting diseases. Delta (9)-THC binds to and activates two known cannabinoid receptors found in mammalian tissue, CB1 and CB2. The dev elopment of cannabinoid-based therapeutics has focused predominantly on the CBI receptor, based on its predominant and abundant localization in the CN S. Like most of the known cannabinoid agonists, Delta (9)-THC is lipophilic and relatively nonselective for both receptor subtypes. Clinical studies s how that nonselective cannabinoid agonists are relatively safe and provide therapeutic efficacy, but that they also induce psychotropic side effects. Recent studies of the biosynthesis, release, transport, and disposition of anandamide are beginning to provide an understanding of the role of lipid t ransmitters in the CNS. This review attempts to link current understanding of the basic biology of the endocannabinoid nervous system to novel opportu nities for therapeutic intervention. This new knowledge may facilitate the development of cannabinoid receptor-targeted therapeutics with improved saf ety and efficacy profiles. (C) 2001 Elsevier Science Inc. All rights reserv ed.