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trucha

Another paper

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Thanks for sharing, that was an interesting read. Ill kick start the discussion by sharing a few thoughts I had while reading the paper.

 

In situ hybridization isn’t the best technique to demonstrate DMT is produced within brain tissues.  In situ hybridization allows for visualization of mRNA. Ok so now we know INMT and AADC mRNA has been detected within these tissues. But do we know if INMT and AADC mRNA completes to process of translation to produce functional enzymes? They make a big deal in this study about being the first time to demonstrate INMT and AADC mRNA co-localise within the same cells. But this isn’t the important factor, the important factor is does translation occur allowing both enzymes to function within the same cell? I feel this paper would have been strengthened by examining the protein/enzyme levels not just the mRNA level.

 

Secondly demonstrating the required enzymes mRNA exist in mice and human brain tissues, but only demonstrating the detection of DMT within mice tissues and not human tissues further weakens this publication. If they have the human brain tissues to perform in situ hybridization on, why not perform HPLC as well? Or maybe they did but didn’t publish the results because it didn’t confirm their hypothesis? This would be important data to publish because without it they are relying upon the assumption that INMT and AADC exclusively function to produce DMT when in reality they could perform their function upon a vast number of additional substrates that do not contribute to the DMT biosynthetic pathway.

 

And finally, its amazing to think they have developed mice without pineal glands, and quite interesting that the mice with and without pineal glands produced statistically similar concentrations of DMT.

 

Regardless of my minor criticisms it’s an interesting read and I hope this group gains additional funding, so they can continue their work in the future.

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The mice were  "pinealectomized rats", not bred as such.

I think it might be unethical to induce cardiac arrests in humans just to detect DMT in the brain,

as was done in the mice.

Change, why don't you write to the research team suggesting your superior method.

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Agreed on all of those points. As far as I can tell no one has actually demonstrated the native presence of DMT in those particular tissues except as something transient and observed under very artificially created conditions.

Sasha made a valuable comment, "Never get attached to your theories." Science moves forward best and farthest by finding what is believed to be factual is actually wrong or somehow skewed from accuracy and not by proving something is right. In fact science can really only PROVE what is wrong with a theory and truth becomes more solidly suggested to be accurate by generating additional support and by the repeated failure to disprove it. That is something subtle many people miss; sadly including too many people in science. (The *applications* of science can be established to be right or wrong of course.)

Some of the people involved in this work have actual motivation to prove themselves right. That mindset often compromises good science whether in design of studies or in the interpretation of the results. Thankfully there ARE some excellent workers involved. And those would almost certainly be open to hearing suggestions and criticisms such as what you have voiced.

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Trucha, the philosophy of science is the first subject that I studied  for undergrad. science, and here in Aust. at least I think that is the norm. so researchers do understand what you are saying. There is really very little room in research for egotism, when peer review is such a constant. Science both proves AND disproves theories, that is how it progresses.

I disagree that this study lacks comparative (to real life clinical situations) value because of "very artificially created conditions". The rat anatomy/physiology is a very good model for human such like. The controlled methods employed in this study are important to account for variables. And after all a heart attack is a heart attack, whether in a rat model or human life.

The point of the study is firstly to establish if DMT is produced at death, and secondly what is the function of that DMT in the brain. For the purposes of this study, the discussion of near death experiences was made, and if the NDE visions have a chemical basis. Very interesting.

 

 

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Thanks for the responses everyone,

 

Maybe I will write them an email, but I should probably spend a little more time reading their previous publications first to gain a greater perspective of their past work. Perhaps a lot of my questions have already been answered in past publications, and I wouldn’t want to waste their time repeating themselves.

 

The whole subject is so fascinating, which gets my brain ticking with a lot of questions.

 

So if the theory is, DMT is produced at death, my focus turns to, how can that be regulated? If it wasn’t regulated people would randomly be experiencing this state of mind all the time and perhaps a small percentage of people already do. But if we understood how it was regulated, maybe we could manipulate this level of regulation to induce this phenomena without the need to induce cardiac arrest.

 

Considering if it (DMT produced at death) exists, it must be regulated, leds to several hypothesis including (1) does some sort of signalling molecule trigger the transcription of these enzymes when near death states are being experienced? Allowing for DMT biosynthesis to occur, Or (2) are these enzymes already present but an inhibitor molecule prevents there action, then in times of near death states, a signalling molecule triggers the breakdown of the inhibitor allowing the enzymes to function.

 

If the first is occurring, then its amazing that our bodies can detect imminent death and have the time to produced enzymes, then time for the enzymes to function, allowing for biosynthesis to occur. For this reason, the second hypothesis makes more sense because I assume transcription and translation would be wasting valuable time when your seconds away from kicking the bucket. However, I am not sure how to determine how long these processes actually take to occur.  

 

Then again, maybe im way off the mark and its regulated by a completely different mechanism, or maybe this phenomena doesn’t even exist.  Either way it’s fun to think about.

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The references are at the end of the paper. Rick Strassman, one of the authors would be a good contact to ask your questions. Let us know his response.

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Here are some interesting review papers on the topic, for those looking for more reading 


https://www.frontiersin.org/articles/10.3389/fnins.2018.00536/full
https://www.frontiersin.org/articles/10.3389/fnins.2018.00232/full
https://journals.sagepub.com/doi/full/10.1177/0269881117736919?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed

 

Interestingly DMT has been shown to inhibit the function of INMT, which has led to the theory that the biosynthesis of DMT would not be able to achieve concentrations required to activate the required receptors. https://pubs.acs.org/doi/abs/10.1021/bi500175p
 
Ill copy paste the conclusion from the third paper, for those interested in a quick summary.

 

Conclusion
Based on the studies reviewed above, a number of conclusions seem to merit consideration.
1.    DMT is not produced in concentrations significant to activate CNS 5-HT2A receptors, and is rapidly broken down by MAO if it is produced.
2.    There is no evidence to suggest that DMT can accumulate within the brain or within neurons at physiologically relevant concentrations; such inferences are either not supported by direct experimental evidence or are based on flawed experiments.
3.    Endorphins, especially DYN, are released during stress, and DYN has very high affinity for the KOR, which can mediate hallucinations and out of body experiences. Other endorphins can mediate euphoria and analgesia through activation of mu or delta opioid receptors.
4.    Asphyxiation or cardiac arrest paradoxically lead to brain activation and result in marked increases of brain neurotransmitters such as dopamine, norepinephrine, and 5-HT, the latter of which can stimulate 5-HT2A receptors.
5.    Asphyxia induces excessive release of the excitatory amino acid, glutamate. Drugs such as ketamine, which also raise cortical glutamate, can produce out of body experiences.
6.    Although the romantic notion that DMT is released from the pineal gland to produce altered states of consciousness at various times of stress is appealing to some, more well-studied systems provide more sound explanations for out of body experiences.

 

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Steven Barker is a good worker and a really nice guy, I've been a fan of his for many years. His goals in this line of work (in and beyond this one paper) do not seem to be totally overlapping with Rick Strassman's though. 

I am in complete agreement that DMT will be found to play some type of role in mammalian neurochemistry but I'd be happy to enter into a wager that the idea a large release DMT at a psychedelic level occurs at birth and death turns out to be pop science. Similarly the cycle of pineal chemistry he described in The Spirit Molecule is at best implausible. I've talked with Rick Strassman on these topics, starting not long after his first book came out. I like him and I enjoy his thoughts but his weak point is having an attachment to proving his theories. Rick Strassman is a medical doctor who is engaged in some interesting research. He is not an actual research scientist. The mark of good scientist is always being open to both exploring the possibility and even to learning that they are wrong.  

"Proving something" does exist in mathematics and in applied sciences. In pure science, a theory is supposed to be evaluated for having a solid basis of plausibility (which is what Barker has been doing very well) and then rigorous attempts to disprove the actual theory are supposed to be made. (Not the established biochemistry but the package that is also being presented concerning, birth, death, NDE etc.) There are no doubt plenty of people who will disagree with that idea as the alternative path is easier but I'd rather trust the people I learned from as to how good science should be done. If a person sets out to prove a cherished theory, especially if they are attached to having a particular outcome, there is a danger they may stop too soon (sometimes as soon as they see some evidence potentially supporting their ideas) or create approaches that contain sampling biases, and other flaws. A heck of a lot of poorly done science exists right now.  (Not counting the actual wealth of BAD science and bogus results one can find flying past peer reviewers in disturbing numbers but that is a separate subject that merits a book of its own.)

That last reference cited above contains a lot of interesting reading for such a short piece (by both Barker and by Nichols). 
Barker, S. A. (2018). N,N-dimethyltryptamine facts and myths. Journal of Psychopharmacology, 32(7), 820–821. doi:10.1177/0269881118767648 
url to share this paper:
sci-hub.se/10.1177/0269881118767648

 

 

Edited by trucha
typo correction
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But, from the paper in discussion "In our previous report of DMT in the rat brain8, it was unclear whether the detected DMT was from the cerebral cortex, pineal gland, or both, since the microdialysis probe traversed the rat brain through both the cortex as well as the pineal gland (see probe design in24). To determine the contribution of the cortex to DMT secretion, we compared normal rats (panel A) to pineolectomized animals (panel B). DMT in rats without the pineal gland, still detectable under baseline (seen at retention time of 7.5 min; blue tracing in panel Ba), ranged 0.25–2.2 nM with an average of 1.02 nM (blue dots in panel Bb). Cortical levels of DMT did not show significant difference between rats with and without the pineal gland under baseline conditions (panel Ca; p = 0.05, via unpaired t-tests with Welch’s correction)."

Obviously Strassman et al, are moving beyond the DMT is produced by the pineal gland theory, and they have established that with this research.

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Very interesting paper, thread and discussion, good ol sab shit. 

 

I admit that I dont like very much the 'psychedelic theist' point of view of things, and that I am annoyed that lots of ethno-drug people have been saying for years that the "DMT in the brain thing" is a proven scientific fact.  So, I am definately negatively predisposed to a Strassman paper. Go Barker! :)

 

Edited by sagiXsagi

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