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5-MeO-DiPT neurotoxicity demonstrated

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hamhurricane

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Many have speculated about 5-MeO-DiPT's toxicity, it seems to have been confirmed by this recent journal article:

http://www.jstage.jst.go.jp/article/jphs/106/1/2/_pdf

These results suggest that 5-MeO-DiPT has
potent neurotoxic effect on the serotonergic neurons
(Fig.1), consistent with previous behavioral reports
(34). However, it was reported that 5-MeO-DiPT-
induced cell toxicity for COS-7 cells was independent of
the expression of SERT (24). Additional investigations
will be needed to elucidate the mechanisms underlying
the serotonergic neurotoxic effect of 5-MeO-DiPT.
Click to expand...

I would assume this is a product of the 5-methoxy group and not the DiPT, can anyone speculate if other 5-methyloxated trypts would inhibit SERT mediated uptake, and explain why this SERT blockade produce the potent neurotoxic effects?

it makes me glad i never worked with this one, but n,n-DiPT is my favorite psychedelic so the curiosity is still present.
 
I wouldn't (well, I guess I don't) put much--or any--faith in this paper. First of all, they do not give any indication of the dose levels that they used in any of their assays. I wouldn't be surprised that at a ridiculously high dose (which, concentration wise, might be fatal in humans), 5-MeO-DiPT has non-specific oxidant properties and/or membrane-disrupting detergent-like effects due to the super-high lipophilicity. Second, how did they perform these assays? Since 5-MeO-DiPT is a SERT inhibitor, it makes some sense that it might decrease [3H]citalopram (another SERT inhibitor) binding, either by directly occupying the SERT or by triggering SERT downregulation/internalization. They claim that 5-MeO-DiPT induces potent generalized cytotoxicity in COS-7 cells, yet their reference to this is "fact" is some old (seemingly unrelated) neuro-topology paper from the 1980s. And their claim that this "potent neurotoxic effect" is also supported by behavioral studies is a load of shit. Their reference is to a paper that describes altered motor behavior in rats after giving them 5-MeO-DiPT. How is altered behavior after high-dose administration of a psychedelic proof of "potent neurotoxicity?"

I've read a couple of these papers recently by the Japanese government concerning "new dangerous toxic designer drugs of abuse," such as 2C-B/2C-I/2C-E, DMT/5-MeO-DMT and AMT. Every single paper is written in that same old Reefer Madness!, "Oh Won't Somebody Please Think of The Children?" kind of language. One paper (Nonaka et al, 2007), even says in the abstract: "This assay system was able to designate psychoactive drugs as prohibited substances in accordance with criteria set forth by the Tokyo Metropolitan government." But for most of the compounds, the data just don't show anything evil or dangerous. In all of these papers, the authors interpret interaction with the DAT, SERT or synaptic 5-HT and DA receptors as proof-positive that a compound "is deadly and must be made illegal immediately." Seems like a lot of typical scaremongering and propaganda--more like narc masturbation than objective science (of course, while I am a scientist, I'm hardly objective either).

Edit: Not that I like 5-MeO-DiPT. As a psychedelic compound, I think it sucks ass and I wouldn't be surprised if it was more toxic than a number of other psychedelics (particularly the ergoloids, which are if anything, neuroprotective)--this observation is based upon a very simple piece of data: I tried it and I didn't like it. But what I dislike more is bullshit, such as government claims that if something binds to the DAT, SERT, 5-HT1A or 5-HT2A receptors, it is ipso facto illegal and therefore is also highly toxic.
 
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Riemann Zeta said:
I wouldn't (well, I guess I don't) put much--or any--faith in this paper. First of all, they do not give any indication of the dose levels that they used in any of their assays. I wouldn't be surprised that at a ridiculously high dose (which, concentration wise, might be fatal in humans), 5-MeO-DiPT has non-specific oxidant properties and/or membrane-disrupting detergent-like effects due to the super-high lipophilicity. Second, how did they perform these assays? Since 5-MeO-DiPT is a SERT inhibitor, it makes some sense that it might decrease [3H]citalopram (another SERT inhibitor) binding, either by directly occupying the SERT or by triggering SERT downregulation/internalization. They claim that 5-MeO-DiPT induces potent generalized cytotoxicity in COS-7 cells, yet their reference to this is "fact" is some old (seemingly unrelated) neuro-topology paper from the 1980s. And their claim that this "potent neurotoxic effect" is also supported by behavioral studies is a load of shit. Their reference is to a paper that describes altered motor behavior in rats after giving them 5-MeO-DiPT. How is altered behavior after high-dose administration of a psychedelic proof of "potent neurotoxicity?"

I've read a couple of these papers recently by the Japanese government concerning "new dangerous toxic designer drugs of abuse," such as 2C-B/2C-I/2C-E, DMT/5-MeO-DMT and AMT. Every single paper is written in that same old Reefer Madness!, "Oh Won't Somebody Please Think of The Children?" kind of language. One paper (Nonaka et al, 2007), even says in the abstract: "This assay system was able to designate psychoactive drugs as prohibited substances in accordance with criteria set forth by the Tokyo Metropolitan government." But for most of the compounds, the data just don't show anything evil or dangerous. In all of these papers, the authors interpret interaction with the DAT, SERT or synaptic 5-HT and DA receptors as proof-positive that a compound "is deadly and must be made illegal immediately." Seems like a lot of typical scaremongering and propaganda--more like narc masturbation than objective science (of course, while I am a scientist, I'm hardly objective either).

Edit: Not that I like 5-MeO-DiPT. As a psychedelic compound, I think it sucks ass and I wouldn't be surprised if it was more toxic than a number of other psychedelics (particularly the ergoloids, which are if anything, neuroprotective). But what I dislike more is bullshit, such as government claims that if something binds to the DAT, SERT, 5-HT1A or 5-HT2A receptors, it is ipso facto illegal and therefore is also highly toxic.
Click to expand...

A bogus mdma study was used to make mdma illegal, so it makes sense that it would happen with newer RCs.
 
Their 'evidence' in that paper for neurotoxicity was decreased levels of intracellular 5HT, and reduced binding of labelled SSRI (I just forgot which one, citalopram I think) all on chronic exposure.

Thats hardly conclusive proof of neurotoxicity is it?
Receptor downregulation/internalisation would do the exact same thing.
 
But I don't think that should be caused by this, should it?

And SSRIs bind to the SERT, whereas this should be a pretty specific 5HT2a agonist.

Just seems like more evidence saying 'stay away from 5-methoxylated-n,n-dialkyl-T's!

Man, while not one of those, I bet 5-Meo-AMT is way worse.
 
Is 5-MeO-DiPT known to bind to SERT at all? or release serotonin for that matter, AFAIK it was just an agonist, either way, it doesn't sound much worse than the odd dose of MDMA according to that paper, and thats not a drug I do often anyhow.

TBH this one doesn't concern me all that much, I haven't tried it, but I guess I still would, that paper sent my bullshit'o'meter dial off the scale.
 
A lot of highly substituted 5-MeO-tryptamines can have effects on the SERT at high enough concentrations. Look at ibogaine--it acts on the SERT as a non-transportable bulky substrate to lock the transporter in an inward-facing conformation, thus preventing the binding of molecules like citalopram. I would bet that 5-MeO-DiPT has similar effects. But SERT binding (which does often cause SERT internalization) is not the same thing as neurotoxicity. I mean, according to these authors (read their other papers, dating back to 2004), every molecule with an indole or phenethylamine moiety is a "dangerous potent neurotoxin," but that's a load of bullshit.

I wouldn't take 5-MeO-DiPT again, however. It feels kind of nasty (with weird peripheral effects and an unusual "body-feel") and doesn't really have useful or insightful psychedelic/cognitive effects. There are far better tryptamine psychedelics, even 5-methoxylated tryptamines. For example, 5-MeO-DMT, a delightful, heavenly molecule.
 
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I haven't much experience with 5-MeO-DMT, the only time I tried it, it was in the form of a mixture of virola 'epena' resin, yopo extract and lime.

Burnt like a bitch though.
 
if the SERT binding inhibits 5ht uptake and 5ht efflux then what would happen if you mixed 5-MeO-DiPT and MDMA, would the 5-MeO-DiPT block the MDMAs serotonergic effects?
 
No, MDMA works also by blocking the SERT, causing a flood of serotonin, which is part of the high. Taking 5-MeO-DiPT and MDMA together would just mean you would trip balls and have a shit ton of side effects.

In my opinion 5-MeO-MiPT feels great. That is the last drug I would think of to be toxic. It gives me very little side effects. Not that side effects always indicate neurotoxicity, or a lack of them indicates a lack of neurotoxicity, but it is sort of a start.

By the way, can't Bufotenine be lethal? How is the effect accomplished? Is Bufotenine neurotoxic? Just seems odd to me, that a tryptamine like such could be so nasty. It just seems to me that Bufotenine might give some "YOU MUST DIE!" signal to your serotonin receptors. I know Bufotenine can kill cats and dogs, how is it it kills them?
 
^^^
oh maybe i imagined the article said something about blocking 5ht efflux.

would 5-MeO-MiPT not be closer to 5-ht in structure than 5-MeO-DiPT? that considered it seems odd that MiPT is so much friendlier.
 
By the way, can't Bufotenine be lethal? How is the effect accomplished? Is Bufotenine neurotoxic? Just seems odd to me, that a tryptamine like such could be so nasty. It just seems to me that Bufotenine might give some "YOU MUST DIE!" signal to your serotonin receptors. I know Bufotenine can kill cats and dogs, how is it it kills them?
Click to expand...
Bufotenine doesn't damage 5-HT receptors and the potentially deadly effects have little if anything to do with the CNS. Death is due to heart attack--in high concentrations, when introduced directly to the bloodstream, both bufotenine and serotonin can cause cardiovascular and vasoactive problems.
 
Yeah, bufotenine has quite notable cardiac action at 10mg of the base insufflated.

Some definate psychotropic effect though, from working with an alkaloidal isolate of yopo beans.
 
^^^ The way I always heard it was like this: It's bound by SERT, which takes it up into a synaptic vesicle. There, somehow, it causes the vesicle to bind to the membrane and release 5-HT into the synapse. It's still a SERT inhibitor because it competes with 5-HT for binding.
 
Question?

Studying neurotoxicity is a subjective aspect of neuropharm. It shouldn't be but theres really no way to directly measure it. To date, the primary methods are to examine how certain known toxic drugs work (MTPT, [high-doses of] Methamphetamine, etc). Then their mechanisms of action are compared to other drugs. I agree that this article may be a scare tatic (we will see a lot more as the popularity of these compounds increase), however it also may be valid examination. The authors should have reported the dose, but even if it was high, the implications could also apply to 'light' but chronic use as well.
We need to step back from your personal views on these drugs and ask yourself- how can we infer toxicity better?
 
Considering the fact that no methods were reported, the authors' only measure of "toxicity" was [3H]citalopram binding and the reference that they gave supporting their finding of "toxicity" was a red-herring, let's just say that the bullshit detector beeping wildly. The authors' motives as government-employed forensic agents is the icing on the cake.
 
...and reading the article myself now,I strongly second Riemann_Zeta. This is indeed nothing else than governmental anti-drug propaganda with some pseudo-scientific paintwork to justify even more prohibition.

Seriously: Shame on those researches!!! Nothing but officially paid whores!

Edit: Or to put it in more gentle words: I haven't read such a crappy done research paper for long! Normally, a publication contains something like an "Experimental Section" with enough details to enable every other researcher to repeat the work. This piece of sh...(ok ok,"more gentle" I said) this publication doesn't have anything that comes close. Then again I'd like to remind everyone that it is supposed to be a review (!), which normally leave out such details. But I just can't help myself: It's crap.

Edit2: From the "Guidelines for Authors" of the publishing journal, being the "Journal of Pharmacologal Sciences":
4) Materials and Methods - should include explicit, concise descriptions of all new methods or procedures
employed. Commonly used methods require only a citation of the original source. The description should be such that the reader can judge the accuracy, reproducibility, reliability, etc. of the work.
Click to expand...
...which the reader obviously CAN'T!
 
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Willliams MT et al. Effects of 5-MeO-DiPT

Willliams MT et al. Alterations in Body Temperature, Cortiscosterone, and Behavior Following the Administration of 5-Methoxy-Diisopropyltryptamine (foxy) to Adult Rats. Neuropsychopharmacology. 2007, 32, 1404-1420

I was reading this article. I'm focusing on the first experiment, not the behavoiral end now, and this is what I found.
The results are patchy- some effect of corticosterone for 3 days. Slight changes in 5ht/5hiaa levels, definite hypothermia, myclonous, some showed seizure and 1 died.
This is where it gets interesting. They gave four doses over six hours every 2hrs of, get this, 10mg/kg and 20mg/kg, despite knowing standard protocol requiring 0.82mg/kg. They argue that an admittedly small comparative study yielded these results. Their logic, "Nevertheless, the present study doses are not unreasonable considering their are data for 5-Meo-DiPT users that show seizure activity." Or basically, The ends justify the means.
What I take from this, average use of this drug is likely safe considering the vast lack of significant data for treatment riddling the study. Keep in mind, this is data from Adult rats, likely not using a variety of drugs simultaneously.
 
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