The endocannabinoid system and emotional processing: pathophysiology and therapeutic potential.

Journal articleAlthough the pharmacological and medicinal properties of the plant Cannabis sativa have long been known and appreciated, the discovery of the endocannabinoid system began with the isolation of [delta]9-tetrahydrocannabinol (THC), the major psychoactive component of the plant, in the mid-1960s (Gaoni and Mechoulam, 1964). Extensive pharmacological studies followed, and, by the end of the last century, the endogenous cannabinoid (endocannabinoid) system was known to comprise at least two metabotropic receptors, cannabinoid receptor types 1 and 2 (CB1 and CB2); two endogenous ligands, the ethanolamine of arachidonic acid, also known as anandamide (AEA), and 2-arachidonoyl-glycerol (2-AG); and the enzymes responsible for their synthesis and catabolism. However, in the last decade (2000-2010), our understanding of the endocannabinoid system has experienced a true revolution. Novel lipid molecules with endocannabinoid activity have been identified; endocannabinoids have been reported to activate additional targets, including the Transient Receptor Potential Vanilloid 1 (TRPV1) channel, nuclear peroxisome proliferator activated receptors (PPARs) and the G protein-coupled receptor GPR55. Moreover, novel pathways for endocannabinoid synthesis and degradation have been discovered. In this special issue, Pamplona and Takahashi (2012) review the discovery of the endocannabinoid system and present the most recent advances in our understanding of the physiology of this system.peer-reviewe