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Further Evidence That Endogenous DMT Acts On The Human Brain?

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love_sex_desire

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After a recent post in the PD thread "DMT and the Pineal Gland" I began wondering...
Since research indicates that N,N-DMT is most likely an endogenous sigma-1 receptor regulator, does that provide further evidence that endogenous DMT is either produced or is transported into the human brain?

From the article "The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator" in Science magazine, Feb. 13, 2009:

DMT has been found to be produced endogenously, "in human urine, blood, and cerebrospinal fluid" (Science, 323, pg 934-947), so there is no question whether DMT is produced endogenously in the human body, but there is no proof that endogenous DMT it is either produced in or is transported into the human brain. From the same Science article they suggest, "The binding, boichemical, physiological, and behavioural studies reported here all support the hypothesis that DMT acts as a ligand for the sigma-1 receptor." I know little about receptors, but I am under the impression that their are sigma-1 receptors in the brain, so does this study indicate further evidence that endogenous DMT is either produced in or is transported into the human brain?
 
I gotta bump this one. Any one have any knowledge about the sigma-1 receptor? Does the hypothesis that DMT acts as a ligand for the sigma-1 receptor support the hypothesis that DMT is a neurotransmitter that can be found directly in the human brain?
 
DHEA is also a sigma-1 agonist but I felt no psychoactive. The effects of DMT in my opinion beyond current understanding of science. My guess is that quantum physics is in part the reason for a DMT trip.
 
I'm so curious on HOW is DMT produced in the body....
It seems obvious that it comes from tryptophan which is also responsablefor the synthesis of serotonin and later melatonin, but following the various pathways i can't see how that tryptamine gets methylated and which enzyme is responsable for it.
There are no other N-methylated serotonin analogues that have a specific role in the body.
In the case of dopamine analogues like epinephrine we can se that the body has an enzymatic mechanism for methylating nor-adrenaline into adrenaline which has a notorious function in the body.
250px-Catecholamines_biosynthesis.svg.png


But in the case of serotonin analogue pathways there are no such methylations:

365px-Tryptophan_metabolism.png


( melatonin metabolisms: )
http://www.nutritionandmetabolism.com/content/figures/1743-7075-2-22-1-l.jpg
http://www.jpp.krakow.pl/journal/archive/1106_s5/gfx/rys0201.gif

This sort of methylation cannot really occur spontaneously (in labs this is done by reacting the amine with a halomethane under pretty high temperatures), it needs an enzymatic action, that said it is heavily unlikely that it happends by 'accident'.
So the conclusion is that somehow the body has an enzymatic mechanism to turn small quantities of tryptophan into DMT, meaning that the body is supposed to synthetize DMT even if in ridiculous quantities.

And that quite frankly fascinates me apart from making me wonder 'Why?'.

Please correct me if I'm wrong.
 
love_sex_desire said:
After a recent post in the PD thread "DMT and the Pineal Gland" I began wondering...
Since research indicates that N,N-DMT is most likely an endogenous sigma-1 receptor regulator, does that provide further evidence that endogenous DMT is either produced or is transported into the human brain?

From the article "The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator" in Science magazine, Feb. 13, 2009:

DMT has been found to be produced endogenously, "in human urine, blood, and cerebrospinal fluid" (Science, 323, pg 934-947), so there is no question whether DMT is produced endogenously in the human body, but there is no proof that endogenous DMT it is either produced in or is transported into the human brain. From the same Science article they suggest, "The binding, boichemical, physiological, and behavioural studies reported here all support the hypothesis that DMT acts as a ligand for the sigma-1 receptor." I know little about receptors, but I am under the impression that their are sigma-1 receptors in the brain, so does this study indicate further evidence that endogenous DMT is either produced in or is transported into the human brain?
Click to expand...

There are obviously many plants containing small amounts of DMT (it seems that even some types of clovers produce DMT...cool) however from what i've read DMT is normally broken down in the stomach by monoamie oxidase, in fact some south-american cultures feel the 'healing and divinatory' effects of Ayahuasca drinks thanks to the MAOIs content of the recipe.
http://en.wikipedia.org/wiki/Ayahuasca

So unless all the individuals tested for detection of endogenous DMT inconsciously consumed a similar mixture of chemicals, we should deduce that DMT is truly endogenous.
 
I understand that DMT is produced endogenously in the human body, but I am wondering if the article I had quoted, or any other resources indicate evidence that DMT is either produced or has a role in the human brain. I do not have much scientific understanding, so I am unable to interpret what the article is saying. If DMT is somehow created in the human body from tryptophan, would this synthesis have to take place in the brain? I'm wondering if any scientific evidence indicates that endogenous DMT is created, or transported specifically in the brain.
 
From PubMed:

Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.

Jacob MS, Presti DE.

Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA.

The presence of the potent hallucinogenic psychoactive chemical N,N-dimethyltryptamine (DMT) in the human body has puzzled scientists for decades. Endogenous DMT was investigated in the 1960s and 1970s and it was proposed that DMT was involved in psychosis and schizophrenia. This hypothesis developed from comparisons of the blood and urine of schizophrenic and control subjects. However, much of this research proved inconclusive and conventional thinking has since held that trace levels of DMT, and other endogenous psychoactive tryptamines, are insignificant metabolic byproducts. The recent discovery of a G-protein-coupled, human trace amine receptor has triggered a reappraisal of the role of compounds present in limited concentrations in biological systems. Interestingly enough, DMT and other psychoactive tryptamine hallucinogens elicit a robust response at the trace amine receptor. While it is currently accepted that serotonin 5-HT(2A) receptors play a pivotal role in the activity of hallucinogenic/psychedelic compounds, we propose that the effects induced by exogenous DMT administration, especially at low doses, are due in part to activity at the trace amine receptor. Furthermore, we suggest that endogenous DMT interacts with the TA receptor to produce a calm and relaxed mental state, which may suppress, rather than promote, symptoms of psychosis. This hypothesis may help explain the inconsistency in the early analysis of endogenous DMT in humans. Finally, we propose that amphetamine action at the TA receptor may contribute to the calming effects of amphetamine and related drugs, especially at low doses.
 
Fascinating stuff.

We were recently debating whether some drugs like Salvia could indirectly stimulate endogenous psychedelics and be considered a true psychedelic despite lack of strong 5ht2 agonism.
 
/navarone/ said:
This sort of methylation cannot really occur spontaneously (in labs this is done by reacting the amine with a halomethane under pretty high temperatures), it needs an enzymatic action, that said it is heavily unlikely that it happends by 'accident'.
So the conclusion is that somehow the body has an enzymatic mechanism to turn small quantities of tryptophan into DMT, meaning that the body is supposed to synthetize DMT even if in ridiculous quantities.

And that quite frankly fascinates me apart from making me wonder 'Why?'.

Please correct me if I'm wrong.
Click to expand...

The enzyme is tryptamine-N-methyltransferase.
 
I think there is circumstantial evidence that DMT is made by the Pineal Gland such as the required enzymes located at the pineal gland. Also the fact melatonin is not that exciting and cannot be the only use for the pineal!

According to Strassman within the next 6 months we should be able to prove or disprove DMT's relation to the pineal gland
 
Runera46 said:
I think there is circumstantial evidence that DMT is made by the Pineal Gland such as the required enzymes located at the pineal gland. Also the fact melatonin is not that exciting and cannot be the only use for the pineal!

According to Strassman within the next 6 months we should be able to prove or disprove DMT's relation to the pineal gland
Click to expand...

more than 6 months has passed.
do you think strassman is just foolin' around?
 
Considering tryptamines are a class of trace amines and metabolism of trace phenethylamines involves a lot of nonspecific-NMT methylation (as well as phenylethanolamine-NMT methylation) in the brain, I would be shocked if the trace tryptamines weren't substrates for brain NMT.

https://en.wikipedia.org/wiki/Trace_amine
 
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