New developments in the pharmacology of cannabinoids

Abstract

This chapter outlines the new developments in the pharmacology of cannabinoids. Cannabis sativa is the source of a set of more than sixty oxygen-containing aromatic hydrocarbon compounds called cannabinoids and one of these, Δ 9 -tetrahydrocannabinol (Δ 9 -THC), is the main psychotropic constituent of this plant. Δ 9 -THC is also of interest because it is one of just two cannabinoids to be licensed for medical use. Thus, as the oral preparation dronabinol (Marinol), it is available in the USA for the suppression of nausea and vomiting provoked by anticancer drugs and for the reversal, through appetite stimulation, of body weight loss experienced by AIDS patients. The other cannabinoid that it is permissible to use clinically is nabilone (Cesamet), a synthetic analogue of Δ 9 -THC that is also given by mouth and that is licensed for use in the UK, again to suppress nausea and vomiting produced by cancer chemotherapy. Because cannabinoids have high lipid solubility and low water solubility, they were long thought to owe their pharmacological properties to an ability to perturb the phospholipid constituents of biological membranes. However, all this changed in the late 1980's with the discovery of specific cannabinoid receptors. The existence of endogenous ligands for these receptors (“endocannabinoids”) has also been demonstrated, suggesting that cannabinoid receptors have physiological as well as pharmacological significance. Cannabinoid receptors and their endogenous ligands constitute the “endocannabinoid system.”