W.Mazier , D. Cota et al. dansTrends Endocrinol Metab.
Le Phénix renaît de ses cendres: Le retour du système endocannabinoïde comme cible thérapeutique des maladies métaboliques
The Endocannabinoid System: Pivotal Orchestrator of Obesity and Metabolic Disease. Mazier W, Saucisse N, Gatta-Cherifi B, Cota D.
Trends Endocrinol Metab. 2015 Oct;26(10):524-37. doi: 10.1016/j.tem.2015.07.007. Review.
Daniela Cota: The first reports of increased appetite induced by cannabis (also known as marijuana) in humans were documented in 300 AD.
Pharmacological studies carried out in different animal models between the late seventies and the early nineties had further shown that peripheral or central administration of Δ9-tetrahydrocannabinol (THC), the main psychoactive component of marijuana, or other synthetic cannabinoids increased food intake, especially for palatable food.
However, understanding of the biological mechanisms underlying the “munchies” started only after the discovery of specific, G protein coupled cannabinoid receptors, CB1 and CB2, followed by the identification of endogenous lipid-derived ligands, the endocannabinoids, and elucidation of their biosynthesis and degradation pathways.
Studies carried out over the past 20 years clearly demonstrate that the endocannabinoid system (ECS) works as a “chef d’orchestre” strategically positioned to maximize intake and conservation of energy, likely to increase survival in times of scarcity.
However, in modern society where food is plentiful, excessive ECS activity is a landmark feature of obesity and metabolic disease and targeting the ECS might help tackle these pathological conditions. Indeed rimonabant, an anorectic drug and systemic CB1 receptor inverse agonist, was approved as anti-obesity therapy in Europe in 2006, but in late 2008 it was withdrawn due to its psychiatric side effects.
This event profoundly affected further drug development efforts by the pharmaceutical industry, causing the termination of all clinical programs involving rimonabant-like CB1 receptor antagonists in development.
Nevertheless, studies published during the past 5 years have not only provided information on new physiological roles played by the ECS in the context of energy balance, but have also identified novel mechanisms of action that have rendered the ECS once more a very attractive target for therapy.
In this article Mazier et al. review these recent advances and discuss evidence that brings the ECS back at the center stage for the treatment of obesity and metabolic disease.
Above…the latest cover of Trends in Endocrinology & Metabolism is dedicated to the article of Mazier et al., where the authors review emerging evidence that suggest new physiological roles of the ECS in energy balance regulation, and point to new mechanisms of action, that again make the ECS as an attractive target for therapy. Cover image was created by Charlie Padgett.
Postdoctoral Research Associate
INSERM depuis Mai 2014
Neurocentre Magendie, Bordeaux, France
Group « Pathophysiology of energy balance and Obesity » (Team leader: Dr. Cota)