Just because it was there, how do we know if it was naturally there?
Maybe the people just ate oranges? http://the-nexian.me/hom...ture-huge-amounts-of-dmt *g*

I completely agree with you UC.
Until we'll have a definite response from science it is a good thing to keep looking at our own experiences.

For me personally I can't have a psychedelic experience without having my third eye stimulated in a big way. On my last aya journey I felt the visions coming out of my third eye directly. The same thing happens when I meditate, but with much less power.

This of course does not mean that dmt is produced in the pineal gland, but I do believe there is a correlation between the two.

Again I'm short on time, I'll delve into this topic more deeply over the weekend, but allow me to quickly summarize the documents above.

The first one describes the exact pathways by which melatonin is metabolised into pinoline, bufotenine, N,N-dimethyltryptamine, and 5-hydroxytryptamine. (Check out the illustration at the top of the second page)

The second one describes the pathway by which serotonin is converted into 5-MEO-DMT.

This last one appears to demonstrate the presence of bufotenine in the pineal. Will need to get the full text and follow up.

More later

Without going too deep into semantics, it's simply not factual that DMT is made in the human brain. A fact requires proof otherwise it's just conjecture.

Interesting posts Dreamer, what are we supposed to make of these? They seem to have been around for a long time. Are they factually saying the melatonin in our bodies is being metabolized into DMT? So that explains why we have DMT in our bodies? I'm guessing that's not the case otherwise there would be no debate... I won't even pretend to understand the technical jargon.

Simply that this:

and this:

Are incorrect, said evidence does exist.

Well smoalk my alks and call me Charlie... How the hell did this stay buried all these years ?

I saw this in the caption, but the authors neither proposed a mechanism for this, nor elucidated how 5-demethoxylation (or dehydroxylation, for that matter) could occur. I don't see how any of the Cytochrome P450 complexes could remove the methoxy/hydroxy group. O-demethylation is mentioned, so that would give 5-OH-T following deacetylation. 5-HOIMT then methylates twice to give bufotenine.

afaik, once a hydroxy is added, there's no way of removing it enzymatically (a metabolic pathway with an arrow pointing in one direction indicates it's spontaneous, and irreversible).

Thanks for the input. I'm still working on piecing this all together and attempting to understand the mechanisms at play here. My only contention is that DMT is indeed produced in the body, and there is no shortage of evidence for that. Exactly where and how is what I am looking into now. Here are some more papers regarding the subject.

Guchhait, Ras B., and James E. Grau. "BIOSYNTHESIS OF S‐ADENOSYL‐L‐METHIONINE IN THE RAT PINEAL GLAND." Journal of neurochemistry 31.4 (1978 ): 921-925.
*Attached

Yu, Ai-Ming, et al. "Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase." Pharmacogenetics and Genomics 13.6 (2003): 307-319.
*Attached

Guchhait, Ras B., and Andrew A. Monjan. "Circadian Rhythm in Pineal Methionine S‐Adenosyltransferase." Journal of neurochemistry 36.6 (1981): 2092-2093.
*Attached

Grammenos, Dionysios, and Steven A. Barker. "On the transmethylation hypothesis: stress, N, N-dimethyltryptamine, and positive symptoms of psychosis." Journal of Neural Transmission (2014): 1-7.
*Attached

These are a couple that look useful but I was unable to attain copies of:

Ellis, LeGrande C. "Introduction to the Symposium: Endocrine Role of the Pineal Gland." American Zoologist 16.1 (1976): 3-4.

Patten, Nicole J. "The Role of Endogenous N, N,-Dimethyltryptamine in Positive and Negative Symptoms of Schizophrenia."

These next few aren't really applicable, I'm just uploading them here for easy reference.

Bradley, Sean. "The Pineal Gland's Biochemical Function in the Fighting and Meditative Arts Exemplified in Korean Sinmoo Hapkido." Journal of Asian Martial Arts 19.2 (2010).
*Attached

Kärkkäinen, Jorma, et al. "Urinary excretion of bufotenin (N, N-dimethyl-5-hydroxytryptamine) is increased in suspicious violent offenders: a confirmatory study." Psychiatry research 58.2 (1995): 145-152.
*Attached

Smith, Shaun. "N, N-Dimethyltryptamine and Biological Reductive Accounts for Religious and Spiritual Experiences." (2014).
*Attached

And this one is very promising and applicable:

Gomes, Melissa M., et al. "Biosynthesis of N, N-dimethyltryptamine (DMT) in a melanoma cell line and its metabolization by peroxidases." Biochemical pharmacology 88.3 (2014): 393-401.
*Attached

That Biochem. Pharm. article is very interesting indeed. The whole thing about the metabolic pathway through kynurenine and kynuramine derivatives certainly underlines the importance of considering the metabolic fate of substances.

I also note a parallel route into the phenylpropene metabolism world: the N'-acetyl-5-methoxykynuramine produced by peroxidase mediated oxidation of melatonin is a phenyl vinyl ketone Michael adduct akin to the purported active metabolites of allylbenzenes. PVK derivation from the kynuramine is purely for illustrative purposes, and apologies for the misuse of double-headed arrows!

Please let's not make the mistake of thinking that this is a scientific paper. "Make time fast" and "make time slow" as concepts, however well meant here, are going to raise some scientists' eyebrows. Adstructing these concepts with the popular movie "The Matrix" doesn't not win scientific favors either.

It is perhaps a nice read, and I am even personally interested in some of the concepts described, but considering the confusion and controversy that permeates the subject of this thread, it should maybe not be a prime talking point.

What can we be assured of so far? Is DMT definitely made in the brain or just definitely made in the body or just definitely can be ?

There's too much jargon open to many laymen's interpretation right now and I feel the thread got little inaccessible for many all of a sudden.

Recently I came across an article with some tangential relation to this thread. It is not about DMT and the pineal or DMT and the brain. Instead the author argues that the role of the central nervous system as a regulatory system is overrated. The article describes the regulatory role of the vascular endothelium and, among other hormones, the possible role of DMT in this regulatory system.

I thought that the article might be of interest to some members.

On the physiology of metazoa
A. R. Ameen
Experientia 18. 3. 1996, Volume 52, Issue 3, pp 189-211

Abstract
The problem of integration and control of the various processes of the metazoan organism is a major challenge to the physiologist. The traditional research strategy in dealing with the problem is neuron-oriented and its roots extend back into the last century when knowledge of hormones was lacking. In the present article, the traditional strategy is analyzed in the light of available data and its logical basis is questioned. Different levels of communication are supposed to occur in the animal or human body. Circulating hormones are responsible for the highest level of communication that occurs between organs or tissues. The central concept in the article is that regulation of circulating hormones constitutes a higher level of control relative to regulation of intercellular hormones. This is regardless of whether the latter occurs in the nervous system or elsewhere. The approach is utilized in defining the mechanism that integrates and controls the part processes of the body. The mechanism is defined as endothelial; the vascular endothelial system is the controlling part and the nervous system is one of the subordinate parts. Thanks to the new approach, meaningful biological explanations of major psychiatric disorders are now possible.

http://dx.doi.org/10.1007/BF01920707

A few more somewhat related papers for good measure.

Yu, Ai-Ming, et al. "Regeneration of serotonin from 5-methoxytryptamine by polymorphic human CYP2D6." Pharmacogenetics and Genomics 13.3 (2003): 173-181.

Forsström, J. Tuominen, J. Kärkkäinen, T. "Determination of potentially hallucinogenic N-dimethylated indoleamines in human urine by HPLC/ESI-MS-MS." Scandinavian journal of clinical & laboratory investigation 61.7 (2001): 547-556.

Wallach, J. V. "Endogenous hallucinogens as ligands of the trace amine receptors: a possible role in sensory perception." Medical hypotheses 72.1 (2009): 91-94.

Shen, Hong-Wu, et al. "Psychedelic 5-methoxy-N, N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions." Current drug metabolism 11.8 (2010): 659.

And this one is highly relevant.

Saavedra, Juan M., and Julius Axelrod. "Psychotomimetic N-methylated tryptamines: formation in brain in vivo and in vitro." Science 175.4028 (1972): 1365-1366.

Okay so I've basically been using this thread as a dumping ground for papers that may be of interest to the topic to follow up on when I have time. Now I've had some time to follow up on them so here's the skinny.

These papers are not really relevant to the topic, and while they may be of interest to other conversations, they can be safely ignored in this one.

This paper is pretty much redundant to others posted the only relevant bit of information here is that the pineal generates it's own SAMe in quantities sufficient for biogenic amine transmethylation

This paper is quite an interesting perspective on the possible roles endogenous DMT may play in the body but is not really related to the topic of it's biosynthesis.

This one, albeit an interesting read, contains very poor information and is an example of how misinformation gets spread as fact. The reference cited for DMT being synthesized in the pineal doesn't really have anything to do with DMT or the pineal.

This is the reference from the previous article, and as previously stated, it really has nothing to do with the pineal gland and only mentions DMT peripherally. It does make some interesting proposals about using uninary bufo as a marker for low MAO activity which has previously been correlated with violent/criminal behaviour. Interesting, but not relevant to our discussion or the citation that was made in the previous paper.

Another very interesting read, that is not really relevant to our conversation. It does provide and interesting discussion of why the "DMT is responsible for spontaneous mystical experience" argument falls short, which is somewhat related to the topic.

This one just discusses the methodology used to detect tryptamines in urine, it's not relevant to the brain discussion but is relevant to the fact that these compounds are produced in the body.

This one is a fascinating read, it's not particularly relevant to the biosynthesis discussion, but it provides some really interesting insight into the role of endogenous tryptamines and differences in whether they act as neurotransmitters or hormones. Highly recommend giving this one a read.

This generally has more to do with the pathways by which DMT is metabolized, however it makes a case for DMT appearing in a wider variety of cells than was previously known which may prove indirectly beneficial to the conversation.

Okay, now for the ones that are actually relevant.

As mentioned previously this one provides some insight into the pathways by which melatonin is converted into other psychoactive tryptamines. This may not well apply to DMT as Benz pointed out (although they do mention it as a metabolite) in any case it's still quite relevant to Bufo and 5-MEO-DMT.

This paper is referenced in the previous paper and provides some insight into the pathways by which the interconversion of serotonin, melatonin, and 5-MEO-Tryptamine takes place. This is also quite relevant to Bufo/5-MEO-DMT/Pinoline interconversion.

This one is very important and highly cited as one of the main papers demonstrating the endogenous biosynthesis of tryptamines by the pineal gland. This is an in vitro study, however it quite clearly demonstrates the ability of brain tissues to synthesize methylated tryptamines.

This one demonstrates the ability of rat pineals to synthesized DMT, 5-MEO-DMT, and Bufo when fortified with SAMe, it also demonstrates that the pineal biosynthesizes it's enough of it's own SAMe to facilitate this process.

This one proposes a mechanism for methylation/demethylation of Bufo/5-MEO-DMT by hydroxyindole O-methyltransferase and CYP2D6. See figure 7 and it's related explanation for the quick overview.

This one contains great information on the pharmacology of 5-MEO-DMT and the exact mechanisms by which it is metabolised into Bufo.

This one shows that Tryptamine is naturally present in the human brain, that Tryptamine adminstration results in the formation of NMT and DMT in the rat brain, and that the necessary enzymes to convert Tryptamine into DMT are present in the human brain.

This one does not discuss tryptamines in particular, but sheds some further insight into the biosynthetic pathways of indoles in the pineal gland.

I would really love it if someone could find this paper please.
According to the way it's cited in another paper, it appears this one found 5-MEO-DMT in the pineal. Most assuredly worth following up on.

So, first and foremost we need to remember it's not just about DMT. The biochemical makeup of the nervous system is incredibly complex and DMT plays an incredibly minuscule part in it's functioning, even if somehow we were able to increase the amount of endogenous DMT produced ten thousand fold it would still not even come close to being present in amounts that would have any kind of psychoactive effect. So at the outset we can lay to rest the theories about dreaming and spontaneous mystical experiences being the sole results of DMT production spikes.

Now social media fed propaganda aside, there is something incredibly interesting happening here. The pineal is pumping out dozens of Tryptamine and Beta-carboline compounds that are most likely psychoactive, and even more likely so in combination, which is how they are produced. There is strong evidence that some kind of endohuasca-type phenomenon is involved with dreaming, mediation, hypnosis and other altered states of consciousness. So, yes it is likely DMT does play some small role in these states, but no it is not soley responsible for them. It's far more complex than any single compound. Even the endohuasca idea is extremely narrow and not taking into account how complex our neurochemical balance is.So let's keep that in mind as well, these compounds play a role in these phenomena, they are not responsible for these phenomena.

So is there "proof" DMT is produced by the pineal gland/in the brain? Technically no, and it's hard to say if such "proof" will ever exist. There is a quite a bit of evidence that is supportive of that hypothesis however. All the necessary enzymes for it's synthesis exist within the brain, the necessary pathways are there. DMT has been detected in cerebrospinal fluid. DMT crosses the blood brain barrier. DMT has been demonstrated to to be taken up and stored by neurons, and fulfils the requirements of being labelled a neurotransmitter. There is quite a bit of evidence that DMT may be an endogenous ligand for sigma 1 receptors which are highly concentrated in the brain and central nervous system. Other methylated and dimethylated tryptamines such as NMT, 5-MEO-DMT, and Bufo appear to be present in/synthesized by the brain/pineal. DMT was found in the pineal of other mammals (rats in particular). So while the "proof" isn't there, the evidence is certainly piling up in support of the hypothesis.

But as alluded to above, if so, so what? It's likely there is more DMT produced in places like the lungs and the retinas than there is in the brain/pineal, and nowhere in the body is any amount produced that would come near being enough to provide a psychedelic experience. In reality this age old discussion is beating a long dead horse. At the end of the day these indole compounds are a part of human metabolism. Rather than focus on how/where they are made, a more relevant question is what are they doing there and what can we do with them?

Big thanks to dr.eamor for taking the time to post these!

bump



Anyone able to get a hold of this?

I'm not sure if this was posted or not, it must have been right?


-eg