The evolving science of phytocannabinoids

Abstract

The cannabis plant has had a tumultuous past. Once revered for its medicinal properties, it then became a banned narcotic and now the perceived medical benefits of cannabis see it receiving renewed attention. The active ingredients in cannabis plant extracts — phytocannabinoids — are now being investigated, both as formulations and in isolation, for pharmaceutical applications. The most abundant phytocannabinoid is (−)-trans-Δ9-tetrahydrocannabinol, a compound readily extracted from Cannabis sativa. There are over 100 known phytocannabinoids, some of which are present in such low concentrations that chemical syntheses are necessary to advance their medicinal potential. In this Review, we examine phytocannabinoids in terms of their mode of action, biosynthesis, and various total syntheses and derivatizations. Finally, we describe the policy issues surrounding the possession, use and control of phytocannabinoids. Some plant-derived ligands for the cannabinoid receptors — phytocannabinoids — are promising pharmaceuticals. This Review covers the chemical synthesis of phytocannabinoids and metabolites to enable the study of compounds otherwise inaccessible on a practical scale. Availability of drug candidates is also hindered by policy issues, which we discuss with regard to possession, use and control.