New info about nutmeg's mechanism of action

[polymath]

Looks like there is finally evidence that nutmeg (myristica fragrans) has an effect on the endocannabinoid system (this isn't surprising as many people compare the effects of nutmeg to those of cannabis). I actually liked the nutmeg high when I was younger, but after the first time I binged on it for 3 days the effect of it on me seemed to change completely and it started causing lots of anxiety and depression that lasted for several days after even a singe 20 gram dose.

http://www.ncbi.nlm.nih.gov/pubmed/27296774

Indirect modulation of the endocannabinoid system by specific fractions of nutmeg total extract.

Abstract

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.

As far as I know, there are many examples of different inhibitors of the same enzyme having a synergistic instead of simply additive effect. This made me wonder, could a dose of a FAAH inhibitor like paracetamol combined with nutmeg cause a stronger cannabinoid effect than nutmeg by itself? I might be testing this soon by combining a relative low dose (10 grams) of store-bought nutmeg with 1 gram of paracetamol... The trimyristin fraction in nutmeg might be the reason why it sometimes causes anxiety: http://www.ncbi.nlm.nih.gov/pubmed/11812528

 

[aced126]

Looks like there is finally evidence that nutmeg (myristica fragrans) has an effect on the endocannabinoid system (this isn't surprising as many people compare the effects of nutmeg to those of cannabis). I actually liked the nutmeg high when I was younger, but after the first time I binged on it for 3 days the effect of it on me seemed to change completely and it started causing lots of anxiety and depression that lasted for several days after even a singe 20 gram dose.

http://www.ncbi.nlm.nih.gov/pubmed/27296774


As far as I know, there are many examples of different inhibitors of the same enzyme having a synergistic instead of simply additive effect. This made me wonder, could a dose of a FAAH inhibitor like paracetamol combined with nutmeg cause a stronger cannabinoid effect than nutmeg by itself? I might be testing this soon by combining a relative low dose (10 grams) of store-bought nutmeg with 1 gram of paracetamol... The trimyristin fraction in nutmeg might be the reason why it sometimes causes anxiety: http://www.ncbi.nlm.nih.gov/pubmed/11812528

The cannabinoid effect would probably be slightly stronger simply due to more inhibition of the enzyme. I don't see how they would have a synergistic effect. They should've tried to identify the responsible compounds.

 

[polymath]

The cannabinoid effect would probably be slightly stronger simply due to more inhibition of the enzyme. I don't see how they would have a synergistic effect. They should've tried to identify the responsible compounds.

It's been known for a long time, that for instance, different organophosphorus compounds have a synergistic effect when they inhibit acetylcholinesterase: http://jee.oxfordjournals.org/content/59/1/11

The responsible compounds will probably be known in the near future...