Endocannabinoids: New targets for drug development

The possible therapeutic use of marijuana's active principles, thr cannabin oids, is currently being debated. It is now known that these substances exe rt several of their pharmacological actions by activating specific cell mem brane receptors, the CB1 and CB2 cannabinoid receptor subtypes. This knowle dge led to the design of synthetic cannabinoid agonists and antagonists wit h high therapeutic potential. The recent discovery of the endocannabinoids, i.e. endogenous metabolites capable of activating the cannabinoid receptor s, and the understanding of the molecular mechanisms leading to their biosy nthesis and inactivation, opened a new era in research on the pharmaceutica l applications of cannabinoids. Ongoing studies on the pathological and phy siological conditions regulating the tissue levels of endocannabinoids, and on the pharmacological activity of these compounds and their derivatives, may provide a lead for the development of new drugs for the treatment of ne rvous and immune disorders, cardiovascular diseases, pain, inflammation and cancer. These studies are reviewed in this article with special emphasis o n the chemical features that determine the interaction of endocannabinoids with the proteins mediating their activity and degradation.