It is about 99% certain that DMT is produced in the human body endogenously, based on scientific literature.

Where people go wrong is assuming it has to be produced in the pineal gland, when in fact the biosynthesis pathways all point to the lungs as being the primary place it happens. Which also anecdotally explains why many people, myself included, have experienced strong visionary states during various types of breathwork like Pranayama, Wim Hof method, Holotropic breathing, etc.

What is interesting is that there in an inbuilt limiter on the process so as not to cause runaway production.

In the step where SAM is used to methylate tryptamine the first time, you get SAH as a byproduct and that inhibits INMT. Then when the NMT is is methylated again to get DMT, BOTH the DMT and the resulting SAH are INMT inhibitors.

Do you have a reference for this (highlighted in bold) - the wikipedia dizocilpine page could do with updating...

https://www.researchgate...phencyclidinegd-receptor

the full text has figures of various binding affinities, with respect to the common dissociatives, iirc.
I used to (incorrectly) think sigma-1 was the receptor responsible for phencyclidine's dissociative effects; of course, it is common knowledge that its NMDA-antagonism is.

Hi Benzyme, as you are a flask-bearer I wonder if you could kindly tell me if there is any endogenous pathway for converting Serotonin into Tryptamine (especially in the pineal as per the quote below)?

"The pineal also has the ability to convert serotonin to tryptamine, a critical step in DMT formation."

Strassman M.D., Rick. DMT: The Spirit Molecule: A Doctor's Revolutionary Research into the Biology of Near-Death and Mystical Experiences (p. 69). Inner Traditions/Bear & Company. Kindle Edition.

It would seem a relatively simple step as the molecules are so similar, but have not been able to find it, but Strassman states that there is in The Spirit Molecule as per the above quote. I do see that Serotonin can be converted to 5-MethoxyTryptamine via HIOMT, so it can definitely be converted to *a* tryptamine, if not *just* trytamine... or I wonder if he meant to say Tryptophan instead of Serotonin. But if he was right then this would be a huge implication for DMT production in the pineal as there is so much serotonin there.

My sense is that the lungs are the primary endogenous producer of DMT, and perhaps the pineal could be the producer of 5MeoDMT under conditions in which INMT is brought there from the lungs via CSF, etc.

serotonin to tryptamine? probably not.
there is no energetically favorable way to remove a covalently bound O-group on the benzene ring.

I observe the same as you..peripheral tissue production. the likely scenario is gut, lung, heart, adrenal, and muscle expression of INMT, for the most part, certainly more than any region in the brain.

Thanks Benzyme, this saves me a lot of searching as my intuition said there was no such pathway and that he must have been been thinking of tryptophan but wrote serotonin instead.

Today I found a reddit comment by Strassman where he now says the lungs are the primary producer of DMT. Now that is 3 years ago, but I assume he still feels that way:

I am Rick Strassman, author of DMT: The Spirit Molecule; and DMT and the Soul of Prophecy. AMA! by Dr_Rick_Strassman in Psychonaut
[–]Dr_Rick_Strassman[S] 3 points 2 years ago
"I'm not an expert on the flouride-pineal issue. But people live normal lives without pineal glands, at least for all intents and purposes. The lungs are the primary organs that generate endogenous DMT."

Hopefully this can serve to diminish the pineal-centric view around here, given that it came from the horses mouth so to say.

That said, I am now turning my attention to how the pineal might produce pinoline. Looks like the pathway is not fully described in the literature, but could involve either

1. Tryptamine condensing to THBC then being converted to Pinoline or
2. Melatonin being converted to 5MeoT w aryl aclyamidase as a catalyst, then 5MeoTryptamine being converted to Pinoline

Looking at the molecules in step 1 it would seem that this might be the easier pathway.

It would then seem like 5meoDMT could get produced from serotonin in the pineal and preserved there and even have a bit of a runaway reaction.

Pinoline is both a mild MAOI and a serotonin reuptake inhibitor, so the raw material for the serotonin -> 5MeoT -> 5MeoDMT would be in large supply, with the INMT coming from the CSF if needed for the final methylation steps maybe...

apparently, I've posted the KEGG pathway a number of times. here is my initial post
https://www.dmt-nexus.me...ts&m=77783#post77783

so it's been found to be expressed in the rat brain, since I've made that post.
the extent of expression is very questionable and a matter of debate. since a majority of serotonin is produced in the gut, it would seem more plausible that simple tryptamines are also produced there, and/or surrounding tissues.

I had no idea that such a thing as that KEGG resource existed, THANK YOU Benzyme!!!