Triglycerides with CNS effects?

[polymath]

This thread is about the possible CNS effects of glyceryl esters... The psychoactive effects of nutmeg are usually thought to be caused by myristicin, a component of nutmeg oil. There's even the hypothesis that myristicin, elemicin and safrole are aminated in the liver to the corresponding amphetamines, but this has not been proven true.

In nutmeg, there's about 20% of the triglyceride trimyristin by mass. There have been some experiments in the last 10 years that have shown trimyristin to have both anxiogenic and sedative effects in different species of animals:

http://www.sciencedirect.com/science/article/pii/S0091305701006608

Anxiogenic activity of Myristica fragrans

Abstract

In the present study, the n-hexane extract of Myristica fragrans (MF) seeds, acetone-insoluble part of the n-hexane extract (AIMF) and trimyristin (TM) were assessed for their anxiogenic activity. The MF (10 and 30 mg/kg), AIMF (30, 100, and 300 mg/kg), and TM (10, 30, and 100 mg/kg) administered intraperitoneally exhibited anxiogenic activity in elevated plus-maze (EPM) paradigm. The open-field test and hole-board test were also used to assess anxiogenic activity of AIMF and TM. In the EPM test, MF, AIMF, and TM decreased the time spent by mice in the open arm and the entries in the open arm. Further, the effect of diazepam (1 mg/kg ip), serotonin 5-HT3 receptor antagonist, ondansetron (1 mg/kg ip), and 5-HT1A receptor agonist, buspirone (1 mg/kg ip), on the occupancy in open arm and entries in open arm was significantly reduced by TM. In the open-field test, AIMF as well as TM reduced the number of rearing and locomotion. Both TM and AIMF reduced the number of head pock in the hole-board test. Inhibition of anxiolytic activity of ondansetron (5-HT3 receptor antagonist), buspirone (5-HT1A receptor agonist), and diazepam [acting on γ-aminobutyric acid (GABAA) receptor] suggests a nonspecific anxiogenic activity of TM and also a link between 5-HT and GABA systems in the anxiogenic activity of TM.

http://www.sciencedirect.com/science/article/pii/037887418290071X

The pharmacological effects of a ligroin extract of nutmeg (Myristica fragrans)

Abstract
A ligroin extract of nutmeg (Myristica fragrans) caused a significant increase in the duration of light and deep sleep in the young chicken. The presence of trimyristin tended to increase the effect of the extract. The extract did not contain detectable amounts of myristicin, elemicin, safrole, or eugenol, which either individually or collectively have been suggested to be the active agent of

This looks somewhat weird, because triglycerides don't look like molecules that could cross the BBB easily without being actively transported. There's been little research about the CNS effects of triglycerides. Interestingly, the glyceryl ester 2-Arachidonoylglycerol has endogenous cannabinoid-like effects in the brain but is probably not effective when ingested...

Does anyone know more about the possible psychoactive effects of glyceryl esters?

The psychoactive effects of trimyristin alone could be easily tested by steam distilling the volatile oil components off of about 20g of nutmeg and ingesting only the nonvolatile residue. Unfortunately I don't own a steam distillation apparatus... Would keeping ground nutmeg in boiling water for an hour do the job?

 

[Hammilton]

I'm surprised this hasn't generated more discussion. Given the heavy similarity of the effects nutmeg produces to cannabinoids, this seems very interesting. Is it possible that this is a cannabinoid agonist? Cannabionoids and anxiogenesis are intrinsically linked. It has a very long dose to onset curve which makes me think it's being metabolized or very slowly transported.

This could be a worthwhile area for exploration.

 

[basement_shaman]

All I know is that I fucking LOVE nutmeg, and that it's anxiolytic to me, not anxiogenic. I prepare it as a tea, simmering it for 20 minutes in a pot with a lid on, drinking the liquid and eating the sludge. I greatly enjoy the taste. I use two to five whole nuts that I chop.

 

[polymath]

Given the heavy similarity of the effects nutmeg produces to cannabinoids, this seems very interesting. Is it possible that this is a cannabinoid agonist?

Too bad no one has tested whether a CB antagonist would block some of nutmegs/trimyristins effects...

BTW, is the 3D structure of a 2-AG molecule somehow similar in shape to a THC molecule?

 

[Epsilon Alpha]

Now this is what I like to see in ADD!
I'll add this to the list of threads I'll contribute to when I have time, but it'll be interesting what comes out of this one.

It'd be interesting to see what effects this stuff will have on ion channels, particularly GABA-A, given the documented fatality with a benzo antagonist.