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Blowing Blue Boogers- In Vivo Evidence for Psilacetin Hydrolysis?

R

reformer

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Oct 2, 2010
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Hi,

Yes, this is a serious, ADD-worthy post. Or so I think, at least. <3

Please read before judging.

So, I have been witnessing a reproducible, quite pronounced phenomena upon insufflating 4-Aco-DMT (O-Acetylpsilocin): The next day the nostrils will blow seriously bright/navy blue boogers.

These Blue Stain Boogers are undoubtedly the same color as the Blue Stain of cubensis that has been bruised... a beautiful International Klein Blue straight out of 1962 (see image): Since Blue Stain in Psilocybe mushrooms is due to the oxidative coupling of 4-HO-DMT (psilocin), it is my supposition that the Blue Stain Boogers are a result of oxidative coupling of 4-HO-DMT that was produced by intra-nasal hydrolysis of 4-AcO-DMT.

In this vein, 4-AcO-DMT should not produce Blue Stain color itself, as it's phenolic (indolic) hydroxyl group is blocked by the acetyl group, disabling electron delocalization into the ring of deprotonated phenolate ion (indolate ion), and thus disabling carbon-carbon coupling thought to be responsible for the production of polymeric Blue Stain species.

465pxikb191.jpg


It is hard to gauge whether this intra-nasal hydrolysis is enzymatic, e.g. mediated by enzymes on the epithelial surface or from resident microbes present in any nasal tract, or if it is due to non-enzymatic hydrolysis in the mildly basic and moist environment of the nasal tract.

I know there is much discussion of the effects of 4-AcO-DMT versus 4-HO-DMT, especially as to whether 4-AcO-DMT actually has any biological effect itself or whether the biological activity of 4-AcO-DMT is solely due to it's hydrolysis product 4-HO-DMT. In fact, many researchers report a "Two-Stage" effect via multiple ROA. It is unknown whether this Two Stage effect is due to the differing pharmacodynamics of 4-AcO-DMT versus 4-HO-DMT, or if its due to pharmacokinetics of 4-AcO-DMT hydrolysis.

Even Alexander Shulgin dedicates a fairly large amount of real estate in his TiHKAL to the speculations of activity for 4-AcO-DMT versus 4-PO4-DMT (psilocybin) versus 4-HO-DMT... and ends up admitting defeat: He cannot tell if 4-AcO-DMT has activity itself.

My proposal, or hypothesis, is that 4-AcO-DMT is being hydrolyzed partially at least in the nasal passages, and then the 4-HO-DMT is being absorbed and having an effect. This implies that the insufflation ROA enables an additional mechanism of 4-AcO-DMT hydrolysis that is not available through other ROA...

Though other ROA are thought to result in hydrolysis, there is no real evidence for such a process from what I understand. I don't know of any study that has measured blood levels of 4-HO-DMT after 4-AcO-DMT administration- If you do, please post and let us know. So, then, are my Blue Boogers the first REAL evidence for in vivo conversion of 4-AcO-DMT to 4-HO-DMT??

Surely the 4-AcO-DMT is also bio-available, but the intra-nasal conversion to 4-HO-DMT might play a significant role in the production of biological effect specifically via this ROA.

Has anyone else experienced this phenomena, and if so, do you also experience the "Two-Stage" effect phenomena that many 4-AcO-DMT researchers report?

Could the intra-nasal hydrolysis account for the often reported second wave of effects?

I welcome your advanced discussion of my boogers.
 
To my knowledge, 4-AcO-DMT, like other aryl esters, will hydrolyse in a cup of distilled water left standing at room temperature: it's prima facie assumed that it hydrolyses, but this does not answer the question of the activity of psilacetin, which can only be determined by a binding study.

The two drugs still have differing pharmacokinetics, which some argue changes the nature of the experience, e.g. morphine vs. heroin (though someone will surely point out that heroin is not a true prodrug as it DOES have its own action).
 
I thought it was well-documented that psilacetin, like psilocybin, is mostly just a more stable, easily-handled prodrug for for psilocin. You're not the first one to think of this - Shulgin did, I think, in TiHKAL.

The acetoxy group is rapidly cleaved in blood and tissue, probably by some combination of simple equilibrium and esterases. The acetyl ester results in a more dragged-out and slightly lower peak than a comparable dose of the parent tryptamine (psilocin) See: fospropofol vs propofol, etc.

The proportion that gets hydrolized would be expected to be greatest in oral administration, less in rectal or nasal admin, lower still in SC or IM injection, and lowest in IV admin. So no, I don't think that psilacetin is responsilbe for psilacetin's effects. I feel psilocin is the major active component. See also: 4-meo-tryptamines and their corresponding lack of activity.
 
yeah but why is the high very different from mushrooms? its not just the onset, the whole nature of the trip feels different, the visuals are different to mushrooms and the emotional component is also different as is the much lower level of confusion.

lots of people i have given 4acodmt to have said it does not feel like mushrooms

you may say this is subjective but then again so is your opinion. i think it has been hyposthesised by shulgin, but not proven to happen in the human body...
 
pofacedhoe said:
yeah but why is the high very different from mushrooms? its not just the onset, the whole nature of the trip feels different, the visuals are different to mushrooms and the emotional component is also different as is the much lower level of confusion.

lots of people i have given 4acodmt to have said it does not feel like mushrooms

you may say this is subjective but then again so is your opinion. i think it has been hyposthesised by shulgin, but not proven to happen in the human body...
Click to expand...

This is essentially meaningless unless you're doing double blind comparisons of 4-Aco-DMT and psilocybin. Way too many possible biases and influences.
 
Fascinating, I remember this year after eating lots of green veggies(I cannot recall what) but lots of lettuce or spinach or spring mix, or dandelion green, my boogers where green like no other.
 
specialspack said:
This is essentially meaningless unless you're doing double blind comparisons of 4-Aco-DMT and psilocybin. Way too many possible biases and influences.
Click to expand...

yeah but also people can tell the difference between drugs as they feel different, MDMA/MDEA/MDA being an example.

the point is there is a difference and if you have taken both drugs its incredibly obvious. i ALWAYS find mushrooms confusing, and 4 ACO DMT while powerfull lacks this confusion plus it just feels more lucid and clear headed

a hypothesis that psilacetin become psilocybin in the body is just that until someone can prove otherwise. I'm not discounting that psilacetion will decompose into psilocybin if you leave it in water for a time, what i do dispute is that it has enough time for that process to occur beofre the trip hits you.

a double blind study would be good, but the lack of one doesn't mean i am going to ignore mine and a large number of other peoples intuitions on a drug they have taken
 
Last edited:
sekio said:
You're not the first one to think of this - Shulgin did, I think, in TiHKAL.
Click to expand...

Erm. Yeah. I know. That was part of the point of the post, and why I said this:

reformer said:
Even Alexander Shulgin dedicates a fairly large amount of real estate in his TiHKAL to the speculations of activity for 4-AcO-DMT versus 4-PO4-DMT (psilocybin) versus 4-HO-DMT... and ends up admitting defeat: He cannot tell if 4-AcO-DMT has activity itself.
Click to expand...

In essence, I agree with pofacedhoe than subjective effects cannot be dismissed so readily with talk of acetylated phenols hydrolyzing in water over extended periods of time, and plasma esterases.

The thrust of my post is that everything written to date has been supposition- My Blue Boogers provide hard (and crusty) evidence of in vivo psilacetin hydrolysis to active psilocin. Is anyone aware of published evidence of psilacetin conversion in vivo to psilocin? Please link if so. Even if psilocin is detected in urine after psilacetin administration.

Sure I'm stirring the pot a bit, and some are gonna argue that this pot has already been stirred to death, but the question is whether the intranasal hydrolysis contributes to the qualitative effects of a psilacetin experience.

I tend to agree with atara that the PK will be drastically different for psilocin versus psilacetin, and wonder if the intranasal production of psilocin alters the experience in a fashion that wouldn't be apparent if the hydrolysis didn't occur. Unfortunately, this isn't testable. so it's moot, dammit. :-/

Binding studies actually won't even answer the question either... what if its a super weak agonist or antagonist, like DOTB appears to be?

We really need some in-vitro cell studies, but the problem is how to account for the hydrolysis?

Atara- I got a dumb question; how was it determined that diacetylmorphine has activity itself, and the activity isn't due to intracerebral hydrolysis and production of morphine? I assume this same experiment could be applied to psilacetin?
 
there is an easy experiment to answer this once and for all, administer 4-acoDMT and look at plasma levels 4-AcODMT and 4-OH DMT. as an phenolic acetate ester assume this stuff is going to be rapidly metabolized, with a half life of minutes. Chewed up by plasma acetyl and butyrylcholinesterases and also hepatic and cns esterases.

If there is very little 4-AcO present when the effects start then it is unlikely that 4-AcO is responsible for effects. double blind it too and ask the subjects to discriminate, I doubt I could I subjectively tell the difference between 4-OH and 4AcO but I can definitely tell the difference between pure 4-OH and psilocybe mushrooms, and mushrooms are better, I can also tell the difference between different species of mushrooms but that is irrelevant. it is really poor thinking to compare a pure(ish) compound with the mixture of true actives and synergistically active compounds in mushrooms and use that to claim that 4-AcO is somehow different to psilocin. Poepacedhoe it is not going to make Psilocybin in vivo which is a phosphate ester, no kinase is going to hit it instead it would be psilocin as the active drug.

heroin is irrelevant because only one ester in heroin is comparable to 4-AcO DMT, heroin is metabolised to the monoacetyl compound 6 MAM which unlike heroin itself has decent in vitro receptor affinity and activity as well as better PK.

the trouble is that either one or both 4-AcO and 4-OH DMT are sch1 controlled drugs in most countries and getting sch1 stuff into human trials is a bureaucratic nightmare. so this sadly study is not very likely to occur and this speculation on teh interwebs will continue ad nauseum.
 
pofacedhoe said:
yeah but why is the high very different from mushrooms? its not just the onset, the whole nature of the trip feels different, the visuals are different to mushrooms and the emotional component is also different as is the much lower level of confusion.

lots of people i have given 4acodmt to have said it does not feel like mushrooms

you may say this is subjective but then again so is your opinion. i think it has been hyposthesised by shulgin, but not proven to happen in the human body...
Click to expand...

Mushrooms have more than just one psychoactive ingredient.

Psilocybin
Psilocin
Baeocystin
and possibly...
Norbaeocystin

4-HO-DMT is psilocin, for the record.
 
ok that has explained it to me. an analogy would be why poppy tea/opium is superior to morphine/codeine in my experience.

friends have said to me that 4aco-dmt is not as good as mushrooms
 
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