Regulation of Endocannabinoid Levels under Physiological and Pathological Conditions. A Mini-review

After the discovery of the endogenous ligands of cannabinoid receptors, the “endocannabinoids” anandamide (N-arachidonoyl-ethanolamine) and 2-arachidonoylglycerol, several studies have been carried out to clarify the molecular mechanisms underlying the regulation of the levels of these compounds in animal tissues. More than one biosynthetic pathway has been proposed for anandamide and 2-arachidonoylglycerol, and several routes for the inactivation of these substances have been identified also. Specific inhibitors of anandamide inactivation have been designed. More recently, the levels of these compounds have been correlated to the occurrence of some physiological and pathological situations, such as cell damage, shock, neurological disorders, pain and inflammation, brain development, and drug tolerance. Some of these studies are reviewed briefly here and have led to the proposal of the use of endocannabinoid-derived substances as analgesic and neuroprotective drugs, and to suggest a role for anandamide and 2-arachidonoylglycerol in motor disorders.