DMT paper...

[expandaneum]

yes I have, and I do think its a well written theory. Sometimes making a quick corner to a conclusion.(not that that is a problem or anything)

And I don't have an attitude about it, I just think its important to know what the context and quality of the journal is. How it performs in the field (if there is such a thing on this subject) its not to bash your paper just to place it in context for other members.

I really hope you don't feel offended or bad about my post I did not mean it that way.

take care

 

[laughingcat]

No offence taken. The JSE is one of the leading journals in its field (i.e. Anomalous and under reported science) and has been around since 1987. Authors have included Rupert Sheldrake, David Luke (who referreed the paper), Dean Radin and Michael Winkelman. You won't find it in any journal rankings or impact factor lists as most scientists sadly don't take this kind of work seriously. This is slowly changing though.

 

[Elpo]

I really enjoyed the paper! It comes with some fresh ideas and a great theory. I hope it will get the attention it deserves making it possible to study this further.

Well done Laughingcat!

 

[arcologist]

Well done!

My biggest question is about the timescale of the parallel evolution of the DMT state versus 5-HT state. It is tempting to assume that this coevolution occurred in the recent past (~100,000 years) when our species apparently developed the ability to be creative through art, etc and became functionally human. However, it seems more likely to me that this parallel evolution would have had to occur much longer ago, possibly during the evolution of mammals, since mammals are closely related to humans in biochemistry and general brain morphology. If this is the case, other mammals such as primates, rodents, etc should display similar responses to the presence of DMT. The recent study by Barker et al. which found the presence of DMT in rat pineal glands lends credence to this idea. It would be very interesting to see what effects DMT has on other mammals, especially primates, as this could be used to gauge a timeframe when this parallel evolution occurred.

 

[Rifle]

The one thing I've really been wondering about since this is that salvia users seem to also report visiting other worlds. If strange world building happens under the influence of salvia, it seems to present a problem for the argument laid out in the paper.

 

[laughingcat]

My biggest question is about the timescale of the parallel evolution of the DMT state versus 5-HT state. It is tempting to assume that this coevolution occurred in the recent past (~100,000 years) when our species apparently developed the ability to be creative through art, etc and became functionally human. However, it seems more likely to me that this parallel evolution would have had to occur much longer ago, possibly during the evolution of mammals, since mammals are closely related to humans in biochemistry and general brain morphology.

This is a good question and I agree that the proto-form of this co-evolution has its roots far earlier than 100,000 years or so, when the brain's neurochemical repertoire was developed. However, in the same way that there appears to have been a confluence of factors that triggered the rapid advance in human cognitive evolution (although this largely not understood and something of an assumption), it is possible that a certain degree of cognitive advancement was required before the aberrant patterns of thalamocortical activity caused by DMT levels rising in the brain could be integrated to form a meaningful representation of the alien reality. In other words, just because dogs (for example) have DMT in their pineal doesn't necessarily mean that they will experience the DMT reality or even be capable of doing so. I feel perhaps that humans had to undergo a cognitive evolutionary bifurcation from other mammals in order to develop the ability to interact with other realities by forming meaningful informational representations of them and it is possible that this allowed information to be extracted from these realities that may have played a part in our rapid cognitive development - so it's kind of a mutualistic positive feedback effect.... I hope that makes some sort of sense!

 

[laughingcat]

The one thing I've really been wondering about since this is that salvia users seem to also report visiting other worlds. If strange world building happens under the influence of salvia, it seems to present a problem for the argument laid out in the paper.

This is another good point - one way to think about a "reality" is as a "pattern of information" (perhaps not the most formal term, but makes sense) - this is perhaps hard to imagine, but the world around you must be a pattern of information, otherwise your brain wouldn't be able to represent the structure of the world using sequences and patterns of action potentials ("spikes") in the thalamocortical (TC) system. The way the brain represents the world that appears to your consciousness, is to generate activity (intrinsic activity) that matches the pattern of incoming sensory data as closely as possible, but it must learn to do this. However, when any psychedelic drug enters the brain, the TC system begins generating more chaotic noisy intrinsic activity and there is always the possibility that this may match incoming data from an "alternative reality" (although this is highly controversial) and so it is possible that the intrinsic activity may become kind of phase-locked with the informational structure of this other reality and these strange worlds may enter consciousness. However, this tends to be less reliable than with DMT, where the shift appears reliably and completely, suggesting a well-beaten path. The unique pharmacological peculiarities also support this idea and these are not shared with the salvinorins. However, the model presented in my paper is not meant to be a definitive account of the truth behind what's going on with DMT, but rather a springboard for further discussion - no doubt there is an awful lot more to learn and much of what I'm saying might turn out to be wrong or inaccurate or only partially correct, but that doesn't matter....

 

[laughingcat]

Another aim of my work is to provide an alternative to the "James Kent - It's just chaotic activity in the TC system and that's all there is to it - Get over it" approach to DMT, which I find deeply unsatisfactory. I am a DMT exceptionalist and I do think that the affective aspects of the experience (e.g. that it FEELS real and FEELS intelligent and powerful) are as important as the content of the experience. To say otherwise is to sell ourselves short IMO. I deal with this in more detail in my next paper, so I won't go into too much detail here, but feel free to ask more questions.

 

[Rifle]

Yes, yes, and a great springboard it is. I must say though, given how different salvia is from DMT (and other psychedelics) pharmacologically, it makes me inclined to think that there is a mechanism or receptor that we are unaware of that is responsible for these effects. Sort of how recent discoveries of trace amine receptors have implicated them in the effects of DMT as well as amphetamines. Still very interested in your idea as well of course, and regardless of how DMT does what it does, you really made a great point of how significant and unique DMT is and how further exploration of it could yield significant discoveries. Also, made me very excited for the day I decide I'm ready to breakthrough.

I also had thought about the fact that DMT was present in rat brains as arcologist did, but I decided it wasn't a big deal since a neurotransmitter often has a myriad of roles in the body. I mean in addition to all it does in the brain serotonin is involved in heart function and I believe is even involved in getting blood to coagulate when we get cut. Plants use DMT for something, we use it for something very different...

 

[laughingcat]

I must say though, given how different salvia is from DMT (and other psychedelics) pharmacologically, it makes me inclined to think that there is a mechanism or receptor that we are unaware of that is responsible for these effects.

Salvinorin is admittedly something of an enigma, in that it has no serotonergic activity - it is in fact a kappa opioid agonist and thus completely different in its mechanism... it shows we still have a lot to learn...

I also had thought about the fact that DMT was present in rat brains as arcologist did, but I decided it wasn't a big deal since a neurotransmitter often has a myriad of roles in the body. I mean in addition to all it does in the brain serotonin is involved in heart function and I believe is even involved in getting blood to coagulate when we get cut. Plants use DMT for something, we use it for something very different...

Indeed - I don't think there's anything inherently special about the DMT molecule - but what is special is the relationship it has developed with the human nervous system, which is nothing short of remarkable...

 

[HeavenlyBlue]

Very well written paper!

A couple of comments:
5-HT has a hydroxyl group at the 5 position that makes it too polar to cross the blood brain barrier. DMT does cross the BBB and that makes it a very poor candidate as a neurotransmitter for the CNS. Are there any organisms that use DMT this way? Perhaps it would be better to think about why it's present in plants?

If it ever was used as a neurotransmitter, it would have been very long ago, long before nervous systems existed as we know them today.

Your background information is fantastic. It is accurate and thorough. However, I don't see how it is pertinent to your argument. You spend zero time on the phylogeny of neurotransmitters or comparing homologous proteins across species. Compare the sequences of transcripts for the enzymes that make DMT with the BLAST database for humans and see what kind of result comes up. You have no choice but to use plants, unless someone has identified them in humans. And no, Rick S. did not identify a pathway for it's production in humans.

If you want to investigate something about the coevolution between DMT producing plants and People, it may be interesting to look at differences in protein expression among cultures that have a long history of DMT use vs. Those that don't. It has been observed that alcohol dehydrogenase has an increased expression in european populations with a long history of alcohol use, while native american and some asian populations produce less. Something similar may happen with DMT. (perhaps with mao?)

 

[laughingcat]

Thanks for your comments - I'll try to answer some quickly...

DMT does cross the BBB and that makes it a very poor candidate as a neurotransmitter for the CNS. Are there any organisms that use DMT this way? Perhaps it would be better to think about why it's present in plants?

I would regard is as a neuromodulator, used for volume transmission over the entire cortex - its ability to cross the BBB is not so much of a concern. And its presence in plants is unsurprising, owing to its facile biosynthesis from tryptophan.

Your background information is fantastic. It is accurate and thorough. However, I don't see how it is pertinent to your argument.

Please explain - what information isn't pertinent to my argument? The background information on how the brain represents the informational structure of reality? This is the main thrust of the paper and central to my argument. My interest in DMT, and the main thrust of the paper, is in its relationship to the human brain and trying to explain how it has such spectacularly bizarre effects - you seem to be very plant-oriented, which is fine, but I think you might have missed the point of the paper a little....

You spend zero time on the phylogeny of neurotransmitters or comparing homologous proteins across species. Compare the sequences of transcripts for the enzymes that make DMT with the BLAST database for humans and see what kind of result comes up.

This is certainly something to look at, but again, this was not the main aim of the paper, which was already ~50 pages long. I wanted to focus on the neurological mechanisms rather than plant gene sequences - why don't you look at this?

If you want to investigate something about the coevolution between DMT producing plants and People, it may be interesting to look at differences in protein expression among cultures that have a long history of DMT use vs. Those that don't. It has been observed that alcohol dehydrogenase has an increased expression in european populations with a long history of alcohol use, while native american and some asian populations produce less. Something similar may happen with DMT. (perhaps with mao?)

Again, all interesting ideas and work that can be done, but I'm not sure that it would be relevant to my argument and would only show, for example, upregulation of specific enzymes in DMT users - not that interesting or surprising or relevant to whether DMT is an ancestral neuromodulator...

 

[HeavenlyBlue]

Its ability to cross the BBB IS of concern. That means that it's acting on the periphery, so you must consider its function there too. You have focused only on the brain.

I am not a plant guy, but I am giving you ideas to develop a Testable hypothesis.

Your argument is this:

DMT is the best, cleanest, and most profound psychedelic experience. Therefore, it used to be a neurotransmitter. Telling me HOW psychedelics work in the brain does nothing to support your argument. It tells me a lot about DMT's pharmacology, which is very very cool BTW.

Why isn't psilocin a vestigial neurotransmitter? DET? DPT? MET? 5-MEO DMT? 4-ACO-DMT? 5-MEO-DIPT? 4-HO-MIPT?

Really, with your logic, we could argue that Methamphetamine used to be a neurotransmitter.

File:Methamphetamine.svg - Wikipedia

en.wikipedia.org

For epinephrine

File:Epinephrine structure.svg - Wikipedia

en.wikipedia.org

I do not mean to bash your hard work. It's very good. I just want to make sure people that are not well versed in neuroscience don't become mislead if they read your paper.

The molecule is sacred because of the experience. That alone is more than enough to give it some respect.

 

[Infundibulum]

HeavenlyBlue, you'd seriously make a really bad reviewer of scientific articles, pretty much the one almost all (published) scientists tend to avoid like hell . Obviously almost every scientific article can be criticised to death and people who like to find holes to point fingers at will always be finding holes - but it is impossible to fill all holes to every reviewer's satisfaction. And of course, every single topic covered can be expanded ad infinitum. After all, the paper is published in the Journal of Scientific Exploration and as it stands it complies fully with the scopes of the journal.

So for instance...

Why isn't psilocin a vestigial neurotransmitter? DET? DPT? MET? 5-MEO DMT? 4-ACO-DMT? 5-MEO-DIPT? 4-HO-MIPT?

Really, with your logic, we could argue that Methamphetamine used to be a neurotransmitter.

File:Methamphetamine.svg - Wikipedia

en.wikipedia.org

For epinephrine

File:Epinephrine structure.svg - Wikipedia

en.wikipedia.org

Definitely all these molecules could theoretically have been neurotransmitters, but this is already side-tracking from the focus of the paper, which is dmt. One could have considered what else could and couldn't have been, but then you're looking at filling tomes, not an article in a journal.

But I guess that you are concerned putting things into context more clearly (which I think the author did to a fair extent)

to make sure people that are not well versed in neuroscience don't become mislead if they read your paper.

Yet no matter how many warnings you give, people will always let themselves get misled - albeit a hypothesis, it is a matter of time until you see people quoting said paper as a "scientific proof" that dmt was an ancestral neurotransmitter.

 

[laughingcat]

Your argument is this:

DMT is the best, cleanest, and most profound psychedelic experience. Therefore, it used to be a neurotransmitter. Telling me HOW psychedelics work in the brain does nothing to support your argument.

I'm sorry, but this is not the argument at all - if it was, it would never have gotten past the referees as that is not an argument but a leap of faith - I suggest you read the paper again, as you don't understand the argument at present... I'm not trying to be harsh, but I did write the paper and so I know what it says and how the argument is developed. It is simply wrong to state that I make the leap from "best, cleanest, and most profound psychedelic experience" to "DMT used to be a neurotransmitter" - I approach this conclusion over several stages and the mechanism of action of DMT in the brain is ESSENTIAL for this argument. For example, a major part of the paper explains how the brain represents the informational structure of worlds - consensus and alternative realities. I then explain how psychedelics alter this process in the brain and allow novel worlds to be built - this is absolutely central to the model I develop later on. If you don't see this then you don't understand this part of the paper - sorry, but I can't say it any other way. Read it again.

Why isn't psilocin a vestigial neurotransmitter? DET? DPT? MET? 5-MEO DMT? 4-ACO-DMT? 5-MEO-DIPT? 4-HO-MIPT?

Again, this is explained in the paper - read it again carefully with that question in mind...

Really, with your logic, we could argue that Methamphetamine used to be a neurotransmitter.

Again, not correct - I explain in the paper...

I do not mean to bash your hard work. It's very good. I just want to make sure people that are not well versed in neuroscience don't become mislead if they read your paper.

I understand this, but I also don't want people to be misled by your lack of understanding of the paper..

The molecule is sacred because of the experience. That alone is more than enough to give it some respect.

Fine, no argument with that, but I am approaching it from a scientific standpoint, which is also of value...

 

[HeavenlyBlue]

You are not approaching this from a scientific standpoint. This was NOT refereed. It was published in a fringe science journal. It looks like science, it talks like science, but it reeks of something unfounded.

I did read the whole thing and I understood what you said. Every word of it.

If you want to contribute to science, then learn the craft and do it right. What you have done is give fuel to conspiracy and misinformation. I do not approve of this.

 

[laughingcat]

I'm not quite sure why I'm responding to such vitriol, but anyway...

You are not approaching this from a scientific standpoint. This was NOT refereed. It was published in a fringe science journal. It looks like science, it talks like science, but it reeks of something unfounded.

It was refereed - by a Senior Lecturer in Psychology at Greenwich University and a professor (ret.) at Arizona State University and author of one of the major academic treatments of shamanism. The JSE has been publishing for 25+ years and is well-established as a forum for controversial areas of science, which is obviously what this is.

I did read the whole thing and I understood what you said. Every word of it.

This is obviously not the case as you make false assertions about the content of the paper and its conclusions.

If you want to contribute to science, then learn the craft and do it right. What you have done is give fuel to conspiracy and misinformation. I do not approve of this.

It's astounding that someone interested in this field has no respect for new ideas, however speculative. The paper is a theoretical discussion based on well-established scientific concepts and ideas from neuroscience, biochemistry and pharmacology - to call it "conspiracy" or "misinformation" is ludicrous. I learned "the craft" at Cambridge where I did my PhD and do not require, nor desire, your approval. If you want to refute my work then please write a rebuttal paper and get it published - but perhaps that would be too much like hard work. You attitude is quite unbelievable.

 

[HeavenlyBlue]

I do not dislike your ideas at all. I dislike that you call it science. Science is a thing with observations and numbers and models that can do productive things in real world scenarios. You present no data to support your claims. PhD from wherever won't change that.

 

[laughingcat]

Science is a thing with observations and numbers and models that can do productive things in real world scenarios.

This, my friend, is a very limited definition of science - are you telling me that speculation, theorising and hypothesis-generation has no place in science? How do we know what experiments to do without such groundwork?

You present no data to support your claims.

The paper is full of data - not my data, but the point of many theoretical papers (including mine) is to assimilate, criticise and synthesise data from other sources in order to generate new models, hypotheses, etc... I don't claim to have the final word on the subject - I am presenting new ideas that can stimulate further ideas, experiments etc. I really don't see your problem with this as being science - that's exactly what it is... not the experimental stage of science, which you seem to think all science must be, but science all the same...

 

[Infundibulum]

I do not dislike your ideas at all. I dislike that you call it science. Science is a thing with observations and numbers and models that can do productive things in real world scenarios. You present no data to support your claims. PhD from wherever won't change that.

I think you are missing the whole point. A publication in the Journal of Scientific Exploration is really not the place to exercise clenched fist-and-rectum scientific criticism. Theorising, speculatign and presenting hypotheses are always welcome as long as they are based on factual, solid observations. Nothing really wrong with that.