Therapeutic perspectives of inhibitors of endocannabinoid degradation

The study of the cannabinoids can be established in the middle sixties with the elucidation of the structure of the active principle of Cannabis sativa plant, the delta9-tetrahydrocannabinol. However, the existence of an endogenous cannabinoid system (ECS) has not been unequivocally accepted until recently. The last two decades have witnessed an impressive advance in the knowledge about cannabinoids, their chemistry, the enzymes involved in their metabolism, and their physiological and pathological roles. In particular, we have made progress in modifying the activity of the ECS with selective compounds, validating the ECS as a new therapeutic target. Endocannabinoids play a role in physiological and pathological processes, and their levels are affected in several disorders. Therefore, it should be possible to ameliorate these pathologies by correcting their altered levels. This review focuses on the current therapeutic opportunities of endocannabinoid-directed drugs, and pays special attention to the therapeutic possibilities underlying the inhibition of the endocannabinoid inactivation. The strategy of manipulating the ECS might open new avenues in the development of therapeutic approaches for a number of disorders, both central and peripheral, that lack as yet effective treatments.