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changing metabolism of nutmeg= different metabolites & effects?

StaySedated

StaySedated

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Aug 21, 2010
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Methylenedioxyphenyl compounds such as myristicin also interact with liver
enzymes (Delaforge et al., 1985). Mixed function oxidation is briefly inhibited,
but this is followed by a period in which cytochrome P450 enzymes are induced.
Both phenobarbital-induced cytochrome P450 and 3-methylcholanthrene-induced
cytochrome P450 can metabolically convert methylenedioxybenzene compounds
to their reactive “carbenes” and then interact with them to produce ligand
complexes. The oxidation of the allylic chain to epoxy- or hydroxy-derivatives
enhances the affinity of these compounds
Click to expand...

-ntp.niehs.nih.gov/chem_backroung/myristicin.pdf

Mother brings 14 y.o. female to emergency room. Initial exam is exceptional for elevated respiration and BP, nausea, moderate perspiration, and child complaining of colorful hallucinations. A typical LSD case, or maybe an exotic hallucinogen? Nope. Kids made a concoction out of the following ingredients: Nutmeg, almonds, raw pistachios, cinnamon, cumin, tarragon, oregano, basil, turmeric, cayenne pepper, black pepper, and Maple Syrup, mixed into a vanilla milkshake. Nice coating for pork chops, but is there anything here that would explain the patient's condition? -- Houston, TX (Houston 2006).

The questioner was advised that nutmeg was the likely culprit. However, given the low levels of nutmeg, other ingredients likely play a synergistic role in the inebriating effect. The author, "Me," declares that the recipe will not work unless all ingredients are included. Black pepper also contains high levels of myristicin, and the Winter 2003 issue of The Entheogen Review commented on how the chemical piperine from black pepper inhibits the metabolism of some drugs/chemicals, leading to an increase in their effects [TER 12(4): 134]. Capsaicin, a chemical found in cayenne pepper, is also a mild inhibitor of cytochrome P450 2E1, which is a mixed-function oxidase involved in metabolism that mediates some drug interactions. It could be that one or both of these peppers is the reason why lower doses of nutmeg seem to have stronger effects when taken via this preparation.
Click to expand...

http://www.erowid.org/plants/nutmeg/nutmeg_article1.shtml

could drugs that affect the metabolism of nutmeg's active compouds change what nutmeg is metabolized into and produce different metabolites with different effects than nutmeg ingested alone?

*black pepper has piperidine and capsaicon, which can affect what the compounds in nutmeg are metabolized into via effects on liver enzymes and changing their metabolic pathways creating different metabolites, according to the above sources.
 
bump.
induced
cytochrome P450 can metabolically convert methylenedioxybenzene compounds
to their reactive “carbenes” and then interact with them to produce ligand
complexes. The oxidation of the allylic chain to epoxy- or hydroxy-derivatives
enhances the affinity of these compounds
Click to expand...

look, nutmeg could possibly be metabolized into more "recreational" compounds. does anybody have more info on this, as i plan on trying this.

also, what compounds would become of adding a P450 inducer like black pepper(piperidine)?
 
Capsaicin, a chemical found in cayenne pepper, is also a mild inhibitor of cytochorome P450 2E1, which is a mixed-function oxidase involved in metabolism that mediates some drug interactions. It could be that one or both of these peppers is the reason why lower doses of nutmeg seem to have stronger effects when taken via this preparation. Black pepper also contains high levels of myristicin
Click to expand...

Page 21 of Vernal Equinox 2008 Entheogen Review "Myristica Fragrans, An Exploration of the Narcotic Spice":

*yet even more info
 
i bet with the right amount of research you could answer these questions yourself. you seem to have quite a bit of free time (no offense, just assuming), so yeah... why not be the one that figures this stuff out? :) all the information is most likely somewhere online already!
 
well i tried nutmeg with some black pepper and it made the effects completely different.
 
being that the effects were different, what could have the nutmeg have metabolized into with the piperidine affecting it's metabolism?

it was much different... resembled a psychedelic even more and didn't feel as much like weed. visuals and weird emotional effects were more apparent.
 
odds are this explanation is wrong... but perhaps the with the addition of the black pepper some of the compounds were aminated instead of oxygenated, since the oxygenating enzymes like p450 were possibly overworked? crappy wording, sorry, can't figure out how to put it better. i hope you get the idea. its probably what you were already thinking though, eh?
 
thenightwatch said:
odds are this explanation is wrong... but perhaps the with the addition of the black pepper some of the compounds were aminated instead of oxygenated, since the oxygenating enzymes like p450 were possibly overworked? crappy wording, sorry, can't figure out how to put it better. i hope you get the idea. its probably what you were already thinking though, eh?
Click to expand...

so how different would the metabolites be?
 
eh i'm the wrong guy to ask. like i said, odds are what i said was wrong. the wishful-thinker in me wants to believe that with the black pepper involved a molecule ammonia would be added to the end of the allyl chain of myristicin instead of what would happen if cyp450 weren't inhibited, however. but if it sounds too good to be true then it probably is, right?
 
myristicin or 6-allyl-4-methoxy-1,3-benzodioxole is the volitile oil in nutmeg, dill, pasrly, and pepper, it is partially responsible for the odor and taste. Shulgin stated that myristicin could in theory be metabolized to (3-methoxy-4,5-methylenedioxyamphetamine)5-MMDA,
5-methoxy-mda, now i find this hard to believe but in theory all that needs to happen is the clevage of the methyl grouping (CH3) on the oxygen on the aromatic ring, then the CH2(methylene) group must be change to an amine (NH2) and additonal carbon on the carbon chain coming from the ring, now this seems to complex for any enzymatic process to preform.
most likly the route of meta is going to be is 5-allyl-1-methoxy-2,3-dihydroxybenzene, 1-hydroxymyristicin, all in all the 5- allyl grouping is not going to cleave unless it undergoes amination im not sure if it can in the body, thus resulting in a impossible method of metabolsim to 5-methoxy-mda, and all the ring substiutions bla bla bla
 
blessedamines said:
myristicin or 6-allyl-4-methoxy-1,3-benzodioxole is the volitile oil in nutmeg, dill, pasrly, and pepper, it is partially responsible for the odor and taste. Shulgin stated that myristicin could in theory be metabolized to (3-methoxy-4,5-methylenedioxyamphetamine)5-MMDA,
5-methoxy-mda, now i find this hard to believe but in theory all that needs to happen is the clevage of the methyl grouping (CH3) on the oxygen on the aromatic ring, then the CH2(methylene) group must be change to an amine (NH2) and additonal carbon on the carbon chain coming from the ring, now this seems to complex for any enzymatic process to preform.
most likly the route of meta is going to be is 5-allyl-1-methoxy-2,3-dihydroxybenzene, 1-hydroxymyristicin, all in all the 5- allyl grouping is not going to cleave unless it undergoes amination im not sure if it can in the body, thus resulting in a impossible method of metabolsim to 5-methoxy-mda, and all the ring substiutions bla bla bla
Click to expand...

the black pepper should have made the enzymes break the nutmeg down via transamination instead of oxidation.
 
i dont think that piperine could actually change the method of enzymes breaking down the molecule but, it certainly acts as a MAOI and can enhance the break down of myristicin, that would result in further breakdown but not into an amphetamine analoge most likly your bodys not going to produce a secondary amine, with a methoxy or anyother grouping with an amphetamine. Amphetamine and especially mdma, mda, mmda, mde, are all fairly complex pharmacology wise and i think before they reached that stated we would have some toxicty happening in our bodys, us humans are designed to break things down into simply and easly excreted metabolites, and something reducing to an amhpet it would have to then further be metabolized again by the body, would be rough
 
in theory tho it sounds sweet :) and very well could happen.


staysedated> id like to see some literature about the piperine changing the of metabolism as i could not find anything, but seems worth investigating
 
blessedamines said:
in theory tho it sounds sweet :) and very well could happen.


staysedated> id like to see some literature about the piperine changing the of metabolism as i could not find anything, but seems worth investigating
Click to expand...

look at my first posts. :)
 
piperonylic acid, a reaction which also shows the capability of oxidizing olefinic side chains. If this same degenerative process will act on myristicin, or elemicin, then a possible intermediate (a vinyl alcohol) could undergo transamination producing 3,4,5-trimethoxyamphetamine, which is known to have similar effects.
Click to expand...

-erowid nutmeg vault

black pepper has piperonylic acid as a result of piperidine metabolism, could this affect the metabolism of the active compounds in nutmeg?
 
the piperonylic acid in THEORY could oxidize the olefinic chain but that still leaves you with the problem of the methyl groupin on the carbon chain coming from the ring in order to become 3,4,5-trimethoxyamphetamine or TMA-1 plus the total transformation of the methylenedioxy grouping result in a grouping (H3CO) 3 hydrogen atoms bonded to a lone carbon with a electron ready for bonding, no explained method of enzymatic breakdown for that as i know of.
 
also its been speculated that myristicin could potentially be a liver carcinogen due to the 1-sulfoxy metabolite, or 2,3-dihydroxy metabolite
 
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