The cannabinoids: Recent Progress in Chemistry, Pharmacology and the Clinic

Raphael Mechoulam, Chemistry, Hebrew University, Jerusalem, Israel

Cannabis sativa has been used for millennia as a medicinal plant, as well as a mood-modifying drug. In the early 1960’s we isolated and elucidated the structures of many of its constituents, including the major psychoactive component, Δ9-tetrahydrocannabinol (THC) as well as the main non-psychoactive compound cannabidiol (CBD). The activity of THC was thoroughly investigated by many groups, but until the late 1980’s and early 1990's, when 2 receptors (CB1 and CB2) were identified, its mechanism of action remained unclear. We assumed that specific receptors are not formed in the brain/periphery just to accommodate a psychoactive plant constituent, but are part of a new physiologic signaling system. Following this line of thought we were able to isolate several novel lipid brain/periphery constituents (endocannabinoids), which bind and activate the cannabinoid receptors. Indeed, anandamide and 2-arachidonoyl glycerol (2-AG), which we identified in 1992 and 1995, in the brain and the periphery respectively, have been shown to play a role in many physiological systems. Research from my laboratory, in collaboration with numerous colleagues, has shown that the endocannabinoids parallel to a large extend the activity of THC and/or CBD.

Recently additional numerous endogenous anandamide-like compounds have been identified. Some of them have biological activities.

I shall discuss the analyses of plant cannabinoids, endocannabinoids and the anandamide-like compounds.

I shall also discuss the use of cannabinoids in the clinic in epilepsy and schizophrenia and preclinical work in neuroprotection, appetite/suckling and inflammation.