Molecular Pharmacology of Phytocannabinoids

Cannabis sativa has been used for recreational, therapeutic and other uses for thousands of years. The plant contains more than 120 C₂₁ terpenophenolic constituents named phytocannabinoids. The Δ⁹-tetrahydrocannabinol type class of phytocannabinoids comprises the largest proportion of the phytocannabinoid content. Δ⁹-tetrahydrocannabinol was first discovered in 1971. This led to the discovery of the endocannabinoid system in mammals, including the cannabinoid receptors CB₁ and CB₂. Δ⁹-Tetrahydrocannabinol exerts its well-known psychotropic effects through the CB₁ receptor but this effect of Δ⁹-tetrahydrocannabinol has limited the use of cannabis medicinally, despite the therapeutic benefits of this phytocannabinoid. This has driven research into other targets outside the endocannabinoid system and has also driven research into the other non-psychotropic phytocannabinoids present in cannabis. This chapter presents an overview of the molecular pharmacology of the seven most thoroughly investigated phytocannabinoids, namely Δ⁹-tetrahydrocannabinol, Δ⁹-tetrahydrocannabivarin, cannabinol, cannabidiol, cannabidivarin, cannabigerol, and cannabichromene. The targets of these phytocannabinoids are defined both within the endocannabinoid system and beyond. The pharmacological effect of each individual phytocannabinoid is important in the overall therapeutic and recreational effect of cannabis and slight structural differences can elicit diverse and competing physiological effects. The proportion of each phytocannabinoid can be influenced by various factors such as growing conditions and extraction methods. It is therefore important to investigate the pharmacology of these seven phytocannabinoids further, and characterise the large number of other phytocannabinoids in order to better understand their contributions to the therapeutic and recreational effects claimed for the whole cannabis plant and its extracts.