Safrole to MDA in the human body

[The Holy Quadruplty]

Oh, amination occurs. Someone provided me with a couple of papers. But it's at the termnal carbon so it appears aminohydroxylation (ring opening) of the epoxide takes place. I presume the body goes on to oxidize that secondary hydroxyl to a ketone.

But what I noted was that the researcher (in the 1960s) isolated only the basic metabolites found in the urine of the animal models. So it actually removes any epoxides. I don't think it was intentional, I think someone just wanted to see if amines WERE being formed and to characterize those amines. If memory serves both the dimethyl amine and the piperidine homologues were formed. Why those two, I don't know.

It's fine that people research these things as long as they apply the same level of critical analysis to papers that align with their prejudices* as they do to papers that do not so align.

I did note that the various 'trip reports' may be considered as unstrucctured case reports. So evidence, but low quality evidence as these things go. If nothing else, 'survivorship bias' means exactly what it says in the case of unconsidered consumption of such essential oils. Dead people generally don't post onto social media (AFAIK).

@Skorpio I spent ages trying to work out a modern idiom for 'cannabimimetic' but after ages trying variations on CannaB1mimetric, I concluded that just as I always feared, I am just not funny. Well, not 'ha, ha' funny, anyway.


*BTW a lot of people seem to think I'm insulting them if I use the term 'prejudice' but it's something we ALL do to some extent. Show me a researcher who hasn't indulged in 'conformation bias' and I will show you a liar.

Well ive been doing the Alky for atleast a solid 6 months now

 

[Allylbenzene]

Good catch on the whole nut vs essential oil aspect.

Do you have the full text for the trimyristin paper? The abstract makes it seem rather non-mechanistic, but I wonder if there are any gems hidden in there.

I’d still love to see some form of empirical evidence for amphetamine formation beyond “it felt like an amphetamine”.

Here's the paper

Anxiogenic activity of Myristica fragrans seeds | 10.1016/s0091-3057(01)00660-8-Sci_hub

sci-hub.hlgczx.com

To clarify, the people who were exploring this allylbenzene bioactivation phenomena were not aiming for amphetmine formation.
Nutmeg was possibly the original (see Space paste recipie on erowid). The other popularised one is Elemi oil and to a lesser extent Basil oil (ct methyl chavicol).

Safrole has not previously been evaluated by the Joint FAO/WHO Expert Committee on Food Additives.
...
Biotransformation

Basic ninhydrin-positive substances were excreted in the urine of
male rats treated with safrole or isosafrole in doses of 75-300 mg/kg
i.p. These substances were not seen when dihydrosafrole was
administered in similar doses. These substances readily decomposed to
carbonyl-containing compounds. The substances were not identified in
this study (Oswald et al., 1969), but in a later study (Oswald et al.,
1971) the safrole metabolites were identified as tertiary amino
propiophenones, 3-N,N-dimethylamino-1-(3',4'-methylenedioxyphenyl)-1-
propanone (I), 3-piperidyl-1-(3',4'-methylenedioxyphenyl)-1-propanone
(II), 3-pyrrolidinyl-1-(3',4'-methylenedioxyphenyl)-1-propanone (III).

I and III are excreted by the rat and II by both the rat and
guinea-pig. These safrole metabolites are Mannich bases which are
believed to be formed by oxidation of the allyl group to yield a vinyl
ketone which condenses with an available amine (McKinney et al.,
1972). I, II and III were competitive inhibitors of rat liver
mitochondrial monoamine oxidase with benzylamine-HCl as a substrate.
Metabolite III inhibited rat liver, kidney, and brain monoamine
oxidase with tyramine HCl or serotonin as substrates (Bangdiwala &
Oswald, 1976).

From https://www.inchem.org/documents/jecfa/jecmono/v16je22.htm

But what I noted was that the researcher (in the 1960s) isolated only the basic metabolites found in the urine of the animal models. So it actually removes any epoxides. I don't think it was intentional, I think someone just wanted to see if amines WERE being formed and to characterize those amines. If memory serves both the dimethyl amine and the piperidine homologues were formed. Why those two, I don't know.

Oswalds original intention was to verify Shulgins theory that the allylbenzenes in nutmeg can be metabolised into amphetamines.

From one of the papers:

The presently reported investigations were undertaken to firmly document the biological formation of amphetamines from the compounds of essential oils.
No amphetamine production was detected. Instead, more chemically active tertiary aminoketones were isolated and structurally identified.
...
The present study illustrates that allylbenzene derivatives are converted biologically in vivo in the rat and guinea pig to nitrogen-containing tertiary amino substituted propiophenones.
...
All of the tertiary aminopropiophenones described presently may very likely be the active metabolites which elicit the psychotropic activity of the allylbenzene derivatives of essential oils. We also find that elemicin, eugenol and other substituted allylbenzene derivatives are metabolized to the same type of nitrogen-containing metabolites.

 

[Allylbenzene]

To anyone interested, someone on dmt-nexus made a cleaner feeling drink based on nutmeg, "Space Booze".
oilman:

The thing is, space paste is more like really heavy oral THC than space booze. Space booze, for some reason, is different and reminds me more of a classic psychedelic at a low dose (the closest thing I can think of is shrooms). I don't have any explanation as to why I feel that way. They are both good.

A much simpler approach by downwardsfromzero:

But I've always soaked my freshly ground kernels in ethanol (70+%) for a week or more. I'd test the potency by working up in dropwise increments, then a teaspoon's worth put in coffee or something. Start early in the day, the effects last for a long time.

Nutmeg Liquor tek from 2011

Nutmeg Liquor

“I am going Nuts” introduced a misunderstood gem, the Nutmeg, and mentioned the problem of the nuts being very diverse, as you can see in the picture below, and thus a little difficult to dose. One solution is to produce liquor, or in other words, perform an extraction.Halved nutmeg nuts: Size...

www.science20.com

Some people replace nutmeg seeds with mace arils due to their higher allylbenzene %.

 

[4DQSAR]

Well ive been doing the Alky for atleast a solid 6 months now

I'm uncertain what you think I could possibly do with such information apart ask what the term 'Alky' means. In the UK we generally use the term to describe those who consume too much of a chemical to the point where it's harming them'.

You omitted that detail from what I feel certain will be a tome that will at very list be short-listed by the Booker comittee.

After all, didn't shakespeare himself write 'brevity is the soul of wit' (Hamlet Act 2, Scene 2).

 

[Allylbenzene]

Here's a study on the psychoactive effects of myristicin - an allylbenzene like safrole.

The pharmacologic and toxic effects of myristicin have been examined in laboratory animals in order to estimate its safety in man. Myristicin is assumed to be the principal active ingredient of nutmeg powder. In 400mg doses, myristicin produced mild cerebral stimulation in human subjects. This effect is much less than that produced by 15g of nutmeg powder, which was taken by one of the authors in order to describe its psychopharmacologic action. Removal of the volatile components of nutmeg eliminates the psychic action but not all of the side effects. It appears that myristicin does not reproduce the entire activities of whole nutmeg.

https://www.erowid.org/references/texts/show/7158docid6486

After some animal testing, 10 human subjects were given either 400mg of myristicin or a placebo. The administration was orally in capsules. Out of 10 subjects, 4 had confirmed effects from this does. 2 had doubtful but possible effects from myristicin orally. The other 4 either had placebo or no reaction. To see how this differed from actual nutmeg, one of the authors took 15g of nutmeg himself, and reports on the experience. 3 authors then take 10g of nutmeg with the volatile oils removed - they did not get hallucinogenic effects but some did get either sedation or stimulation (suggesting that the fixed oils - i.e. trimyristin - may have some effects which differ in different subjects).
This is the first study on nutmeg that I can find in the literature.
It's not a new phenomenon. According to the study, published in 1961, myristicin - and possibly all allylbenzenes - are active in only about 40% of the population if administered orally as the sole ingredient in a capsule. No wonder so many people think this is BS. Most people don't get effects orally from straight allylbenzenes. But in nutmeg, which contains about 20% trimyristin by weight as well as a lot of other compounds, it is active in almost everyone.