Progress in cannabis research from a pharmaceutical chemist's point of view

Preparations of hemp, Cannabis sativa, have been used for thousands of years as recreational and therapeutic drugs. The most important constituents are the psychoactive (-)-trans-(9)-tetrahydrocannabinol (THC), apartial agonist at cannabinoid (CB) receptors CB1 and CB2, and the non-psychoactive pleiotropic cannabidiol (CBD). Both compounds are highly lipophilic, like the endogenous CB receptor agonists, the arachidonic acid derivatives anandamide and arachidonoyl glycerol. The CB receptors belong to the family of Gprotein-coupled receptors, and the first X-ray crystal structures of both CB receptors subtypes have recently been obtained, which will facilitate the rational design of novel synthetic ligands. Besides the already largely established indications such as chronic pain, chemotherapy-induced vomiting, multiple sclerosis-associated spasms, and cachexia, there is preliminary evidence for several further cannabinoid effects, which will have to be confirmed by clinical studies.