Abstract

Cannabis has been employed medicinally and recreationally for thousands of years,1,2 but it was not until the 1960s that the structure and pharmacology of its primary phytocannabinoid components, cannabidiol (CBD)3 and tetrahydrocannabinol (THC)4 were identified, and another generation before the nature and function of the endocannabinoid system (ECS) were elucidated (see reference 5 for a comprehensive review). The ECS consists of endogenous cannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), their biosynthetic and catabolic enzymes, and their receptors: CB1, which is psychoactive, analgesic, neuromodulatory and the most abundant G-protein coupled receptor in the brain, and CB2, which is non-psychoactive, immunomodulatory and anti-inflammatory. The ECS may be thought of as a grand homeostatic regulator of chordate physiological functions, whose roles have been summarised as: “relax, eat, sleep, forget and protect”.6 Those actions closely describe the effects of THC and AEA, which are both weak partial agonists at CB1 and CB2.