Pass the Myristica fragrans, please. Compounds in nutmeg have been found to inhibit the body’s production of Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol lipase (MAGL), the enzymes that break down the endocannabinoids Anandamide and 2-AG. 

Thanks to Dr. Istvan Ujvary for sending along Indirect modulation of the endocannabinoid system by specific fractions of nutmeg total extract, an intriguing paper by researchers at the College of Pharmacy, Chicago State University, just published in Pharmaceutical Biology. Below is the abstract:


Nutmeg [Myristica fragrans Houtt. (Myristicaceae)] has a long-standing reputation of psychoactivity. Anecdotal reports of nutmeg use as a cheap marijuana substitute, coupled to previous studies reporting a cannabimimetic-like action, suggest that nutmeg may interact with the endocannabinoid system.


The study evaluates nutmeg fractions for binding capacity with various CNS receptors and their potential interaction with the endocannabinoid system.


Dichloromethane (DF) and ethyl acetate (EF) fractions were prepared from the methanol extract of powdered whole nutmeg. The HPLC-profiled fractions were assayed by the NIMH Psychoactive Drug Screening Program (PDSP) in a panel of CNS targets at a 10 μg/mL concentration. The fractions were also screened for fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition, initially at a concentration of 500 μg/mL, then by concentration-dependent inhibition studies.


None of the tested fractions showed significant binding to CNS receptors included in the PDSP panel. However, both fractions exerted significant inhibition of the FAAH and MAGL enzymes. The DF fraction inhibited FAAH and MAGL enzymes at IC50 values of 21.06 ± 3.16 and 15.34 ± 1.61 μg/mL, respectively. Similarly, the EF fraction demonstrated FAAH and MAGL inhibition with IC50 values of 15.42 ± 3.09 and 11.37 ± 6.15 μg/mL, respectively.


The study provides the first piece of evidence that nutmeg interacts with the endocannabinoid system via inhibition of the endocannabinoid catabolizing enzymes. This mechanism provides insight into reported cannabis-like action as well as expands the potential therapeutic utility of nutmeg.

[PubMed – as supplied by publisher]