The Big and Dandy Endogenous Psychedelics Thread (mega-merged)!

[fastandbulbous]

Sorry, I cannot see how DMT is a metabolite of melatonin. It would involve removal of the 5-methoxy group and replacing the N-acetyl group with N,N-dimethyl groups.

 

[mad_chemist]

well excuse me... n-acetyl-serotonin (normelatonin), which I've already mentioned. DMT is a metabolite of n-acetyl-serotonin, the precursor to melatonin; I believe Dr. Strassman mentions this in the chapter "What is DMT".

5-MeO-DMT is more closely related to melatonin obviously

 

[mad_chemist]

The question of melatonins function in humans:-

It's inconclusive because you can't sacrifice humans at the end of an experiment, whip their brain out, slice it then measure levels of melatonin, like they do with rats, rabbits etc.;

it was actually inconclusive in this particular study, because the results in rabbits, as well as in humans, varied significantly, therefore no deductions could be made that melatonin had any particular role in regulatory management; they observed the production of melatonin in the absence of light stimuli (which as you already pointed out, has been known for quite some time), but were unable to prove beyond a reasonable doubt that melatonin was the sole neurotransmitter responsible for regulating circadian rhythms..

correct me if I'm wrong (if a new study came up with conclusive results), but this still holds true today.



I'm merely illustrating a point : there's some pretty convincing evidence (though some would allude, there's no proof of it) these endogenous indole-based compounds are the guilty parties responsible for alot of peculiar metaphysical phenomenon

but hey, somebody show me the proof, in terms of chemical mechanics, of astral projection phenomena.

 

[BilZ0r]

God, it's like beating your head against a wall, I'm glad you've championed the voice of reason here FastAndBulbous, hats off to you.

No, melatonin is not the only neurotransmitter for regulating circadian rhythms, but that is far from the point here, still, melatonin is produced in a circadian pattern, blocking its receptors effects sleep, and giving it exogenously induces sleep, and resets circadian patterns...


And chemist, before you ask for proof of astral projection phenomena, how about you show it exists in a controlled environment.

 

[mad_chemist]

that's the point; it's like reality...subjective; and consciousness can be cast independently of "controlled" parameters in a scientific setting.
proving the existence of a spirit molecule (especially its action and metabolism in vivo) is equally daunting, but I don't need concrete scientific proof it exists because I've already experienced it.


*side note* you guys oughtta check out "Waking Life" ...good flick

 

[fastandbulbous]

DMT is a metabolite of n-acetyl-serotonin


No it's not.

Serotonin has a 5-hydroxy group, DMT hasn't, and I can't think of any enzyme found in the human body that will remove a hydroxy group from an aromatic ring.

Give a reference for metabolism of a serotonin (ie a 5-hydroxytryptamine) derivative that ends up with the 5-hydroxy group removed, and I might start taking that sort of idea seriously. The metabolic route for DMT will differ from that of serotonin at the tryptophan stage - after that, they're seperate metabolic pathways.

God, it's like beating your head against a wall

And now I need some paracetamol!

 

[mad_chemist]

DMT is a metabolite of n-acetyl-serotonin


No it's not.

Serotonin has a 5-hydroxy group, DMT hasn't, and I can't think of any enzyme found in the human body that will remove a hydroxy group from an aromatic ring.

*sighs* "DMT has been reported to be in the urine of schizophrenic patients, and so have 5-MeO-DMT, bufotenine, and its demethylated homologue N-methylserotonin. The levels increased with the administration of monoamineoxidase inhibitors. A methylating enzyme has been found in blood, capable of forming DMT in plasma, and it is present in both normal subjects and schizophrenics" (#6 - DMT, p. 420; TIHKAL-The Continuation, A. Shulgin)


and http://www.deoxy.org/dmtpro.htm

i forgot about IAA

And now I need some paracetamol!

you'd probably be better off with pindolol.


I'm surprised you haven't denied altogether the existence of DMT in the human body.

 

[fastandbulbous]

Right. read slowly, because I'm sick of trying to get through:


DMT is a metabolite of n-acetyl-serotonin, the precursor to melatonin

Give a reference for metabolism of a serotonin (ie a 5-hydroxytryptamine) derivative that ends up with the 5-hydroxy group removed, (like DMT) and I might start taking that sort of idea seriously

I never said DMT isn't formed in vivo (tell me where I did, and I'll paint my arse blue and show it in a shop window), I said it isn't formed from serotonin

Sorry, but if you say things like the actylserotonin/DMT statement above, but then don't back it up, don't be surprised if people start treating you like you know very little about the subject

 

[mad_chemist]

another quick search yielded this http://www.acutcmdetox.com/tryptophan2.html

interesting, but probably not the lab rat study you're looking for; so if you can find any conclusive studies you published, I'll be more inclined to follow Dr. Strassman and Shulgin's lead.

I'm not even sure if any studies exist (yet) for any specific mechanism removing that pesky 5-OH group

 

[fastandbulbous]

A scientific journal, not new age bollocks

If they didn't put it in a paper for a scientific journal, it's because they didn't have proof of it (peer review, y'know)

And where did they state unequivocally that serotonin is the starting material for DMT? I doubt they said it as a definitive statement

 

[fastandbulbous]

I'm not even sure if any studies exist (yet) for any specific mechanism removing that pesky 5-OH group

It wouldn't be difficult. get a homogenate of brain tissue, add it to a 5-OH substrate, then extract and whack the products in a GC-MS and look for the peak that corresponds to the compound without the OH group.

They haven't looked for it, because it don't look like it exists.

Once more. The substrate for DMT will either be tryptophan or tryptamine NOT serotonin

 

[mad_chemist]

hence why I said it was interesting, but not the labrat study you were looking for

screw it...just for the hell of it, I'll email RS and ask him if he has any notes for it; he's certainly more versed in the subject than anyone on the board.

 

[fastandbulbous]

I look forward to seeing the reply

 

[mad_chemist]

Once more. The substrate for DMT will either be tryptophan or tryptamine NOT serotonin

looked back to what I posted initially..that's exactly what I said, about 5-MeO-DMT; DMT also exists parallel to 5-MeO, but somewhere in my replies, i mixed up the two heh curse me for not reading back

5-MeO (not DMT) would have more to do with serotonin. mah bad

still going to email him, and post his response here (regarding the whole metabolic path of tryptophan to DMT/5-MeO...I've emailed him before about a question regarding psilocybin, he does reply)

 

[fastandbulbous]

No you didn't

methylation of n-acetyl-serotonin would give DMT; there are a few psychoactive compounds (including 5-MeO-DMT) that are derived (metabolized) from 5-HT, melatonin, and 5-HIAA

You're going on about tryptophan -> serotonin -> DMT. I'm saying once it becomes serotonin, it will never be metabolized to DMT.

A realistic metabolic route would involve either

tryptophan -> tryptamine -> N-methyltryptamine -> DMT

or

tryptophan -> N-methyltryptophan -> N,N-dimethyltryptophan -> DMT


At no point is serotonin involved

 

[mad_chemist]

yeah I did.

Originally posted by mad_chemist
an actual starting point, technically (if you want to be anal about it) is l-tryptophan

 

[fastandbulbous]

Look at the quote from you that I used in the last post, speceifically the bit in italics.

Tell you what, here it is again

methylation of n-acetyl-serotonin would give DMT; there are a few psychoactive compounds (including 5-MeO-DMT) that are derived (metabolized) from 5-HT, melatonin, and 5-HIAA

also

an actual starting point, technically (if you want to be anal about it) is l-tryptophan....because l-tryptophan eventually metabolizes into 5-HTP, which metabolizes into serotonin, serotonin eventually metabolizes into melatonin

and once more

n-acetyl serotonin/melatonin would be the precursors for 5-meo-dmt, because they're the precursors for DMT

The bits in italics are the bits I'm talking about.


If you'd bothered to look at my previous posts

OK, all of the tryptamines (plant alkaloids included) start with tryptophan

5-methoxy DMT from serotonin - yes
5-methoxy DMT from melatonin - no
DMT from serotonin/melatonin - no


You're talking about

Tryptophan -> serotonin -> DMT which doesn't happen

 

[mad_chemist]

isn't that what I just admitted a few posts ago?

I emailed Dr. RS regarding the whole metabolism of tryptophan with respect to DMT and 5-MeO, and will post his reply as soon as I get it.

 

[fastandbulbous]

No, in fact you've consistantly kept going on about serotonin/N-acetyl serotonin/melatonin being the metabolic precursor of DMT (also that melatonin is the metabolic precursor of 5-methoxy DMT).

I've got no problem with the idea that 5-methoxy DMT is an endogenous compound in man, as we've got plenty of enzymes that tag methyl groups onto oxygen and nitrogen atoms, it's just that through evolution, the metabolic pathways have become very economical, so the idea of hydroxylating (or acetylating) a compound then removing it again, just doesn't ring true.

If Rick Strassman has a ref for said metabolic route (serotonin/melatonin to DMT), I'll be the first to admit that I'm wrong, but I don't think he will.

Notice: a reference, not just a post that starts 'RS said/wrote...'. On that basis, I could say that I've received an e-mail from God saying he designed the metabolism the way I've described - doesn't mean it actually happened

 

[mad_chemist]

looked back to what I posted initially..that's exactly what I said, about 5-MeO-DMT; DMT also exists parallel to 5-MeO, but somewhere in my replies, i mixed up the two heh curse me for not reading back

5-MeO (not DMT) would have more to do with serotonin. mah bad

yeah, I'll request references; and if you could give some references for these supposedly conclusive studies on melatonin's defined role on circadian rhythms (I doubt those exist either, but definitely an interesting subject as well), that'd be great too


here's what he just sent :

Well, I think tryptophan needs to be converted to tryptamine, which isn't
especially difficult, and has been established as a bonafide metabolic
pathway. From there, it requires two methylations onto tryptamine, by
indole-N-methyl transferase. You may want to look over this paper in press,
which discusses some of these issues. Also, if you haven't seen my old rant
about such things in Psychedelic Monographs and Essays, let me know an
address to send a copy of it to you.

Best,

Rick


----- Original Message -----
From: "Ben Martinez" <[email protected]>
To: <[email protected]>
Sent: Tuesday, February 01, 2005 3:03 PM
Subject: question about tryptophan metabolism


> Hi, Dr. Strassman. I'm not sure if you remember me,
> , I emailed you with
> a question regarding chocolate as a weak
> MAOI, and a possible potentiator with psilocybin last
> year.
>
> This time I come to you with a question you may be
> more familiar with...it's regarding tryptophan
> metabolism into DMT and 5-MeO-DMT. Do you know the
> metabolic pathways that convert l-tryptophan into said
> tryptamines, and the enzymes responsible for the
> reactions? Does serotonin metabolize into DMT (and if
> so, what enzyme removes the hydroxy group)?
>
> respectfully,
> Ben M.


he responded rather quickly; I'll certainly look into it further.