Hi all,

I posted this in the Scientific Articles on DMT/Ayahuasca section but it seemed a bit buried. I moved it here since it is an interesting recent finding about the metabolism of 5-meo. The original research paper can still be found in the Articles section.

"Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-Methoxy-N,N-dimethyltryptamine Metabolism and Pharmacokinetics"

This is a very fresh paper on the metabolism of 5-meo dmt to bufotenine in vivo which is augmented in the presence of MAOIs. 5-meo-dmt is subjected to two types of metabolism. The first and known one is its deactivation by deamination from MAO enzymes. The second type of metabolism that emerges from previous work of teh same group is its O-demethylation by the cytochrome P450 2D6 to produce bufotenine.

This paper describes that in in vitro assays of human liver cells the presence of harmaline or pargyline (another MAOI) not only stops the deaminating deactivation (the reaction MAOs are responsible for) of 5-meo dmt but also causes rapid formation of bufotenine from 5-meo dmt via the cytochrome P450 2D6.

The authors also describe in detail some very elegant in vivo experiments where mice were intraperitoneally injected with 5-meo-dmt. They used 2 types of mice; standard mice and mutant mice that carry the human cytochrome P450 2D6 instead of their mouse one. It appears that the human cytochrome P450 2D6 is 60% better at converting 5-meo-dmt to bufotenine. When either mice were injected intraperitoneally with harmaline prior to the 5-meo, the majority of the 5-meo was converted to bufotenine.

This paper has very important implications for the different ingestion methods of 5-meo. When one smokes based 5-meo, he experiences the 5-meo in the brain. But with sublingual or oral 5-meo, one allows for slower absorption and chance to pass from liver metabolism and bufo formation prior to entering the brain. Sublingual administration is comparable (in effectiveness and absorption duration) to the intraperinoneal administration the mice in the study were subjected to.

The above is important especially when one uses chaliponga for ayahuasca or tries 5-meo with MAOIs. Has anyone tried sublingual 5-meo in the presence of MAOI here in the Nexus? I remember 69ron mentioning that for SWIM sublingual 5-meo is like a low dosage for lsd.

Has anyone tried 5-meo in "other than smoked" route and experienced bufo-like visuals or (for all purposes) any visuals at all?

Interesting study! I just went to grab the fulltext, but apparently it's so new that it's not available (the article's been peer-reviewed and the journal has accepted it, but it hasn't been copy edited and typeset to their format yet)

They did have the abstract up though. It sounds like they specifically found that certain specific CYP2D6 genotypes affect this O-demethylation much more effectively than others. Here's the abstract in full for anyone interested:

This is one intersting article!

Maybe with the SHE this comming Saturday I will take rue extract with chaliponga tea. I'll keep you updated on that.


Kind regards,

The Traveler

Entropy, I posted the original article there. This is the whole paper, with materials, results discussion references etc. It is just not formatted to the standard publication format, it is on submission-type format (double spacing, figures in the end etc)

Thanks, I didn't even see that

I have drank chaliponga in brews many times..and also quidded it a few times..
I have also taken bufotenine many many times..I have never experienced anything from chaliponga admixture brews or quidded chali that resembled bufotenine..bufotenine is extremely visionary..the chaliponga quid was prob the closest to 5meo only..and it felt very warm and euphoric, mentally psychedelic..with almost no visuals at all..any visuals i did have were just sort of faint grey and black oulines with eyes closed, barely noticeable..

I think I posted a review paper about this very topic a few months back?

here is the reference:

indolealkyamines: biotransformations and potential drug drug interactions. 2008 AAPS journal volume 10 by Ai-Ming Yu.

Here they speculated based on in vitro (maybe also some animal data too i forget) data that such interconversions might happen. Good to see the follow up work as been done.

https://www.dmt-nexus.me....aspx?g=posts&t=8859

https://www.dmt-nexus.me....aspx?g=posts&t=8256

Here is where we dabbled in this discussion before.

Well 5-MeO-DMT is slightly similar to 5-HO-DMT when taken orally in terms of its effects on the body. Orally, it causes some very slight nausea sometimes that is similar to 5-HO-DMT when it’s taken orally. Also the body feel in the sense of touch is similar to oral 5-HO-DMT. The mental and visual effects are nothing alike though, no matter how you take it. So if 5-MeO-DMT does convert to 5-HO-DMT, it probably does so very slowly, long after the effects have died down.

Do we even know that when we smoke bufotenine that bufotenine is responciple for the peak visionary effects? It seems that there is a stage after the main peak that is different, more like psilocin..but also there are those first effects of the first few minutes that cause the side effects..then they taper off into the visionary peak..how do we know bufo isntquickly metabolized into something else that casues the visionary effects?

I know, this is the culprit; Given our current knowledge on the effects of 5meo and bufotenine, it is much more likely that 5meo and bufotenine may be interchangeable with regard to the body (peripheral) effects and different to the brain.

I need to add that the mice in the study were administered an amount of 10mg/kg of 5meo. In human terms, this is 700mg! This is not very much in line with the doses people take with regard to 5meo. It is not very elegant for the study either since much smaller amounts of isotope or radioactively labelled 5meo could be used to study its conversion to bufotenine in vivo.

The massive amounts are justified because radiolabeling or isotope labelling are not easy to do in mice accurately. They are very small and taking blood from a mouse is far more difficult than people think.