Abstract

The complexity of the endocannabinoid system, and the challenge of developing selective drugs to target its distinct elements

Author(s): Maccarrone Mauro

 Endocannabinoids (eCBs) are endogenous lipids able to activate cannabinoid receptors, the primary molecular targets of the cannabis (Cannabis sativa or Cannabis indica) active principle 9-tetrahydrocannabinol (THC). During the last 25 years, several N-acylethanolamines and acylesters have been shown to act as eCBs, and a complex array of receptors, metabolic enzymes, (transmembrane, intracellular and extracellular) transporters, that altogether form the so-called “eCB system”, has been shown to finely tune the manifold biological activities of eCBs. It appears now urgent to develop selective drugs that allow to dissect the contribution of the distinct components of the eCB system to the overall biological activity of these compounds, thus putting in a better perspective their relevance as key-player of human health and disease conditions. A modern view of the eCBs, the eCB system and of natural or synthetic compounds able to selectively hit its various elements with very limited side effects (if any) is presented here. This information should form the basis for more rationale and effective therapeutic strategies to combat (endo) cannabinoid-related human pathologies. 

 


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