Endocannabinoid catabolizing enzymes

Endocannabinoid catabolizing enzymes are a group of proteins responsible for the metabolic breakdown of endogenous cannabinoids, primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG) [PMID: 20505144]. The most prominent members of this class are Fatty acid amide hydrolase (FAAH), which primarily degrades AEA, and Monoacylglycerol lipase (MAGL), which is responsible for the majority of 2-AG hydrolysis [PMID: 21079038]. Other enzymes in this group include N-acylethanolamine-hydrolyzing acid amidase (NAAA) and alpha/beta-hydrolase domain-containing proteins like ABHD6 and ABHD12 [PMID: 22408309]. By regulating the levels of these bioactive lipids, these enzymes play a crucial role in modulating the endocannabinoid system, which influences pain perception, mood, appetite, and inflammation [PMID: 18849979]. Pharmacological inhibition of these enzymes is a major therapeutic strategy aimed at enhancing endocannabinoid signaling indirectly, offering a potentially safer alternative to direct cannabinoid receptor agonists [PMID: 22408309]. This approach is being investigated for the treatment of chronic pain, anxiety disorders, and neurodegenerative conditions [PMID: 26911251]. However, the development of these inhibitors has faced challenges, most notably the severe adverse events observed in the BIA 10-2474 clinical trial [PMID: 27276561]. Despite these setbacks, selective and potent inhibitors continue to be developed as potential treatments for a variety of neurological and inflammatory diseases [PMID: 28539258].

Other names

Endocannabinoid degrading enzymesEndocannabinoid hydrolasesFAAH and MAGLEndocannabinoid metabolic enzymes

Inhibition of enzymes responsible for the hydrolysis of endocannabinoids, thereby increasing the local concentration and duration of action of anandamide and 2-arachidonoylglycerol at cannabinoid receptors CB1 and CB2 [PMID: 20505144].