4-AcO-xxT: A Prodrug or Not?

[Pfafffed]

Initially, people assumed that 4-AcO-DMT was nothing but a prodrug for 4-HO-DMT. It was my understanding that we subsequently learned that 4-AcO-DMT might neither need to be deacetylated to be active nor was it plausible that enough would be deacetylated fast enough to account for its effects.

I'm sorry, I feel like this has been pretty thoroughly addressed in the past, but I can't seem to find the sources for it. Does anyone know where to look?

In the past, I just explained to people that the speed of onset of 4-AcO-DMT via IV injection meant that it had to be active on its own, as it was bypassing extensive first pass metabolism. Upon reflection, though, heroin is supposedly a prodrug that undergoes deacetylation primarily after crossing the BBB when used intravenously. AFAIK, heroin kicks in plenty fast this way, so I'm less sure that this narrative (about being able to use IV administration to empirically test the theory with IV administration) holds up.

II don't want to promulgate misinformation, so any pointers towards articles on the topic would be super helpful!

 

[Skorpio]

I don't really want to weigh in one way or another (although i would not be surprised if it is active in its own right, and then metabolizes into the also active hydroxyl metabolite.

What i do want to say is that ester bond breakage can often be independant of hepatic metabolism. The carboxyesterase family of enzymes (six in humans) are expressed in the intestine, blood, liver, and brain (different subtypes have prevalance in different tissues, and slightly different substrate selectivity).

That being said, it is not improbable that acetyl ester tryptamines could have more rapid passage through the blood brain barrier before significant metabolism occurs, especially in the case of parenteral administration.

An (arduous) experiment would be to go all med-chem and use a non-hydrolyzable group in place of the ester (like a ketone) and then decorate it so that its electrostatics resemble the ester (and cross your fingers that it works at all). If activity remained one would have a clear cut answer.

 

[Xorkoth]

I would be utterly shocked if I were to be shown beyond the shadow of a doubt that the subjective difference in effects I feel between 4-HO-DMT and 4-AcO-DMT are due to placebo. The two are distinct drugs and I am confident that if I were given one in a double blind and I knew it had to be one or the other, I could tell them apart easily. Could a relatively psychedelic naive person? Probably not, but that doesn't mean there are no differences.

Never tried 4-PrO-DMT, so I couldn't say.

I remember when I first started posting here, a lot of the older members insisted that there were no subjective differences between the effects of any of the 4-substituted tryptamines (ie, 4-HO-MiPT is indistinguishable from, say, 4-AcO-DET), and even that there were no differences besides potency and duration between the 2C-Xs. Which is categorically a nonsensical position.

 

[G_Chem]

I 100% agree I too could discern between 4-AcO and Psilocin/Psilocybin. 4-AcO-DMT to me has always felt closer to DMT.

I’ll say this til I die, I’ve never tried a pro drug that felt identical to the drug it’s supposed to metabolize into.. There is always some difference and often the pro drug has its own effects.

Heroin for example quickly converts to 6-MAM which has effects of its own which is then somewhat quickly to morphine. Sure IV morphine and heroin are similar but that initial rush from the 6-MAM hitting on different receptors is what makes people fall in love with H.

-GC

 

[Pfafffed]

A difference in subjective effects wouldn't be ruled out by it being no more than a prodrug. The change in pharmacokinetics could be responsible.

Again, if it's anything like heroin, would the acetoxy substitution increase its lipiphilicity, decreasing the time it takes to cross the BBB after which it could be deacetylated? That alone could change the subjective effects profile.

 

[sekio]

I think that part of the problem here is very few people have actually taken pure, measured amounts of psilocin/psilocybin, rather they have taken mushrooms that contain psilocin/psilocybin...

 

[Xorkoth]

Yes that's true. I have had the good fortune to take pure synthetic 4-HO-DMT a few times, it made the rounds back in 2006 or 2007, at the same time as 4-AcO-DMT was first making its way into receptors everywhere. I'd love to be able to contribute to a double blind study to see if I could tell the difference reliably, as I am certain I could, they are quite different until post-peak. It would be very difficult to convince me that the differences between them are simply due to placebo.

As for some others, like the 1-subs pf LSD vs LSD... I doubt I could tell the difference in a blind test with those. To me they are for all intents and purposes the same, even though I wouldn't be surprised to find that their binding profiles are slightly different, as I do seem to be able to reliably find small differences, but it's easy for me to believe that those differences are due to placebo.

 

[Pfafffed]

I keep meaning to get around to trying 4-HO-DMT, but it's a hard thing to make time for.

 

[Didgital]

I've been fortunate enough to try extracted 4-HO-DMT-Tartrate (analysis said 98% so there could still be minors of other psilo compounds, For me at least, 4-Aco-DMT is very different. I find it a lot slower for one, and oddly, less visual for most of the experience. 4-AcO is so weird to me. Like, for most of the experience, visually, it just makes my vision crisper, and colors pop, and then a wave will hit me and Ill be watching Aztec type Totems all around me. It does resemble psilocin visually but it also has it own character imo. More mushroomey than DMTey but I do see why people sometimes make the comparison.