In search of endocannabinoid degradation enzymes inhibitors in nutmeg

Abstract

The inhibition of endocannabinoid metabolizing enzymes offers a novel therapeutic target for treatment of depression and anxiety. Previous studies in our laboratory have established cannabis‐like effects of nutmeg extracts in animal models. However, these effects were not coupled to binding to cannabinoid receptors. The main purpose of our study was to examine the effect of nutmeg extracts on the activity of fatty acid amide hydrolase (FAAH) and monoacylglyceryl lipase (MAGL). Total nutmeg extract (TE) was prepared and successively extracted with solvents of various polarities. The extracts were fingerprinted by HPLC and tested for FAAH and MAGL inhibition against positive controls. The total extract showed a concentration‐dependent inhibition for both FAAH and MAGL with IC50 values of 17.71 and 5.17 mg/mL, respectively. The dichloromethane and ethylacetate fractions showed the highest enzyme inhibition. The IC50 values of FAAH and MAGL inhibition by the ethylacetate fraction were 15.21and 49.42 mg/mL, respectively. The IC50 values of FAAH and MAGL inhibition by the dichloromethane fraction were 32.00 and 32.86 mg/mL, respectively. Inhibition of endocannabinoid metabolizing enzymes by nutmeg extracts explains the cannabis‐like effect exerted by nutmeg. Such inhibition also offers potential utilization of nutmeg compounds for indirect modulation of the endocannabinoid system.