Gift of the MAGL

A team at The Scripps Research Institute has developed the first specific monoacylglyceride lipase (MAGL) inhibitor, which should help determine whether this enzyme is a better pain target than the closely related fatty acid amide dehydrogenase (FAAH).¹ Although the compound, JZL184, is not yet optimized to be a therapeutic candidate, the researchers think it could be a good research tool for further animal studies of endocannabinoid-mediated analgesia.

FAAH and MAGL are responsible for degrading the two major endocannabinoids: FAAH breaks down anandamide and MAGL catabolizes 2-arachidonylglycerol (2-AG). Compounds that block FAAH and MAGL allow the endocannabinoids to activate the cannabinoid receptors (CB receptors), which can promote analgesia and lower inflammation but can also lead to undesirable effects such as catalepsy and cognitive impairment...