Rick Strassman's research as published in his book "DMT - The Spirit Molecule" led him to conclude that DMT could not always produce what he called "unitive mystical," "white light," or "near death" experiences. In fact, only a small percentage of his patients did.

Rick also mentioned later that these "white light/near death" experiences were more common on 5-Meo-DMT. However, 5-Meo-DMT is unlikely to be the "spirit molecule" because as far as we know, acetylserotonin O-methyltransferase O-methylates serotonin AFTER it is acetylated into acetylserotonin, and if we expect endogenous 5-Meo-DMT to be biosynthesized by INMT through N-methylation of 5-Meo-T, the 5-Meo-T should theoretically appear in only very low concentrations following deacetylation of melatonin.

The psychoactivity of bufotenine, however, is disputed. According to Wikipedia, recent studies have shown that if bufotenine is psychoactive, it's effects are similar to 5-Meo-DMT in nature. Many who have tried ingesting bufotenine find it to have little activity, however, I believe this is mainly caused by 5-hydoxy tryptamines being unable to cross the blood brain barrier because they are too polar.

http://bitnest.ca/external.php?id=%257DbxUgY%255CC%251A%2505%2506pg%257C%2506%2505RCW%250AM%2540w%257F%2560%2515Hk

according to this paper, bufotenine may have a hard time getting to the brain because of its low chloroform-water partition coefficient. However, 5-Aco-DMT, which metabolizes into bufotenine and has a higher partition coefficient, appears to be very active due to the high percentage of CAR failures (in fact, based on the results, it is not unlikely that 5-Aco-DMT is more active than 5-Meo-DMT!).

If we continue to follow the theory that INMT is responsible for methylation of tryptamine compounds, and that formation of psychoactive chemicals are at least partially responsible for near death/mystical experiences, it makes intuitive sense that bufotenine could be a potential "spirit molecule," since tryptamine and 5-Meo-T concentrations in the brain are low compared to those of serotonin. (INMT can methylate serotonin into bufotenine) & (tryptophan molecules are likely to be hydroxylated before being decarboxylated, as seen in the biosynthesis pathway for serotonin.)

INMT (2.1.1.49) is expressed before hydroxylation, as seen in the KEGG pathway; it's a side-rxn following AADC (4.1.1.28 ). The expression of INMT actually inhibits serotonin production.

ahh. i see it is expressed again as a side rxn, forming n-methylserotonin. analogous to serotonin vs DMT formation, the side rxns forming n-Me-5HT and bufotenine are not favored.

bufotenine may not be orally active, but neither is dmt, or even tryptamine, for that matter.
they're all ligands for CYP2D6.

While bufotenin isn't orally active it is still sublingually active from what I have read on various sites of people using this substance, It's also worth noting that oral and injected bufotenin doesn't have the same activity as when it is vaporised/snuffed/sublingually absorbed. The IV reports i have found only give hint's to very mild if any visual activity.

@Benzyme: yeah I was talking about that side reaction you mentioned forming n-methylserotonin. And yes you are correct the side reaction is not favored, but perhaps that's just to prevent us from tripping out in everyday life, and when someone's having a near death/mystical experience, the INMT path is somehow more favored than normal. (pure speculation)

However, Serotonin O-methyltransferase (2.1.1.-) on serotonin leads to 5-Meo-T which I did not notice; I'm not sure if INMT can be used on 5-Meo-T, but maybe 5-Meo-DMT isn't such a bad candidate after all.



Yeah that's probably because bufotenine is too polar and cant cross the blood brain barrier as mentioned. If you'll notice 5-aco-dmt is very active since it can a little better

Speaking purely from a personal experience point if view - I did a fair amount of yopo, whose primary psychoactive chemical is supposed to be bufotenine. It is hard for me to imagine that experience being closely tied to...IT. Bufotuine in the context of yopo is not really that pleasant or naturally feeling. I would expect the spirit molucule to feel less aggressive.

I've snorted Yopo snuff prepared from pulverised A.Peregrina seeds mixed with lime & water 3 times.
The main ingredient of A.Peregrina, and thus of this snuff is Bufotenine.

I can assure you: Wildly psychoactive when snorted. Not only that, but deeply psychedelic.
Yopo snuff gave me profound visions of pastel-colored human beings being all around me.
The 3d and last time I did it I broke through to their realm.
It was before I ever smoalked DMT. Very psychedelic. I reckon the predominanty presence of
5-HO-DMT in the Yopo snuff must be responsible for these wild visions...and the wild nausea too probably.

I've heard of people smoking straight Yopo seeds and
experiencing psychoactive effects. Extremely potent tryptamine.

At the tail-end of his newest podcast, Kevin Pereira's talks about his experience during his last night of a 2 week Ayahuasca retreat in peru, he talks about snorting something called 'vilca (which means sacred and is a mix of dmt/ bufo and something else which I cant remember right now) in which his breathing and heart rate dropped and then was scooped up by something blacker than darkness, lifted miles above his own body, kissed by a cosmic sized human-esque face, and then dropped onto a planet where 10 foot star fish picked him up and passed him around before waking up in the jungle.

Interesting to say the least!

starts around the hour and 21 minute mark here

http://supercreative.tv/pointless_89/

I have done extensive work with bufotenine and I can say with confidence that 90% of the info out there on bufotenine by leading researchers is incorrect. It's psychoactivity is not disputed IMO...just that old data that is wrong is repeated everywhere. Bufotenine does not produce anything like a unitive mystical white light experience..on the contrary, it produces many visions but noting I would call unitive or even expansive in terms of its psychological effect.

Bufotenine is active and very visual...and nothing at all like 5-MeO-DMT. It's hard for me to even really decided weather or not bufotenine is a psychedelic. It's a a visionary substance for sure, but mentally it lacks all the profound spiritual insight of other tryptamines like DMT and psilocybin...and the side effects of bufotenine are extremely unpleasant.

It is extremely visionary but mentally not really all that profouond.

The reports about vilca keep stating it as a DMT experience..it is not. It is a bufotenine experience. There is trace levels of DMT at best..not enough for activity.

Also, bufotenine IS orally active..see how much of the net info from "experts" is bs. Listen to Ott and that's about it. At some point in the near future I am going to write a nice long paper on bufotenine and refute a number of claims made by leading researchers. Ive taken it about 100 times(including cleaned up crystal bufotenine) so I feel confident that I have a good grasp on the subjective activity of this tryptamine, more so than most it seems who have published data on it.

I would not dub it the "spirit molecule". I still think 5-MeO-DMT likely plays a larger role...though bufotenine may be responsible for some visionary phenomenon, but alone it is not really that profound for me and many others I have spoken with. Ive given it to others also and never ounce have I seen a person say they gained deep insight from it, unless it is combined with another deep psychedelic like ayahuasca, mushrooms or san pedro. When combined with other psychedelics it boosts the visionary activity greatly of whatever you pair it with.

There is no dissolution of ego I have observed with bufotenine..there is a very fuzzy spaced out feeling, extreme nausea and you are basically laying there sick as hell mind fully intact seeing visions so concrete that they can replace the room you are in..but the psychological connection to the visions is absent largely IME. It is not a very pleasant tryptamine.

As far as I know, 5-aco-DMT as a bufotenine pro drug is a theory yet to be proven. Ive been waiting on this for years, but as of yet no one seems to working with 5aco.

I did my main bulk of work with bufotenine about 5 years ago and then lost interest. It's definatly an interesting visionary tool. Not something I am drawn to for expansive or healing experiences however. I can see why shamans like it though.

jamie, that was a wonderful response and I would love to read your nice long paper when you do write it.

Perhaps the "spirit molecule" is something we havent discovered yet, or maybe there are many such "spirit molecules" all unleashed during these experiences, we do not know. Based on what you've said I'm beginning to doubt my theory of bufotenine as a "spirit molecule." The fact that 5-Meo-DMT still fits the model relatively well compared to other tryptamines might be evidence for the pineal gland playing a role in all this, since some 5-methoxytryptamine is found in there.

Back to square 1 for me.

Why?

Is this purely an observation, or is there some deeper implication here? CYP2D6 variance among different populations has some kind of overall significance.