Indirect modulation of the endocannabinoid system by specific fractions of nutmeg total extract. Pharm Biol 2016 Dec;54(12):2933-2938
Date
06/15/2016Pubmed ID
27296774DOI
10.1080/13880209.2016.1194864Scopus ID
2-s2.0-84974800846 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
CONTEXT: 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.
OBJECTIVE: The study evaluates nutmeg fractions for binding capacity with various CNS receptors and their potential interaction with the endocannabinoid system.
MATERIALS AND METHODS: 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.
RESULTS: 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.
DISCUSSION AND CONCLUSION: 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.
Author List
El-Alfy AT, Joseph S, Brahmbhatt A, Akati S, Abourashed EAAuthors
Ehab A. Abourashed PhD Professor in the School of Pharmacy Administration department at Medical College of WisconsinAbir El-Alfy PhD Assistant Dean, Professor in the School of Pharmacy Administration department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AmidohydrolasesEndocannabinoids
Humans
Plant Extracts
Protein Binding
Receptor, Cannabinoid, CB1
Receptor, Cannabinoid, CB2