Hi Nexians!

Just watched this great talk by Dr Nicholas Cozzi which postulates, and provides good supporting data for, the hypothesis that DMT may work as a neurotransmitter.



Please watch the video and let me know what you think!

Here are a few related threads you may find of interest.

If DMT would be a neurotransmitter
Newest research on DMT supports its role as a neurotransmitter
Endogenous DMT/5MeO and Pinoline- Where, When, and How Much?

Some info from Erowid too:
https://www.erowid.org/ask/ask.php?ID=3146

DMT may also function as the endogenous ligand for the sigma-1 receptor, giving it further purpose for being a piece of human biochemistry. Though it's function as a neurotransmitter and neuromodulater seems absolutely reasonable.

https://www.ncbi.nlm.nih...pmc/articles/PMC2947205/
The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

-eg

From the above information we know that DMT is taken up by neurons and stored in vesicles just like serotonin and other neurotransmitters. In one study they radiolabeled DMT and found that they could still detect it's presence up to a week later. This is really interesting, it suggests that even upon a single administration of DMT, a portion of it will be taken up through the SERT pathway and stored in the neurons as a neurotransmitter, which will then be used (in addition to? in place of? serotonin) as a neurotransmitter in basic physiological processes. It would appear that in a very real way, taking DMT is tweaking the operating system, if only ever so slightly.

I would go on to speculate that taking DMT with harmalas would facilitate this process even moar since MAO will not be immediately destroying the DMT in the synapse, thus allowing for better reuptake into the presynaptic neurons where it will be stored for later metabolic use.

Fascinating. Thanks dreamer.

6-methoxy-tetrahydro-beta-carboline (pinoline) and N,N-Dimethyltryptamine (as well as 5-hydroxy-N,N-dimethyltryptamine and 5-methoxy-dimethyltryptamine) have held some truly amazing potentials as endogenous compounds. The more we understand the more interesting this situation becomes, generally it's the other way around...

(I also feel that under certain circumstances 3,4,5-trimethoxy-phenethylamine may be produced endogenously, though this is probably straying too far off topic. )

I have always considered the phenethylamine and tryptamine psychedelics to be exogenous or external neurotransmitters, or exogenous/external modified neurotransmitters.

-eg

Thanks for the replies guys, I really enjoy learning about this kind of stuff and considering the implications.



I share the same view eg! When you think about it, this is how most drugs produce their effects. It's most applicable to tryptamines and phenethylamines, but I think it extends to many other compounds. The cannabinoids come to mind.

Dennis Mckenna said it best when he said:"We're made of drugs. That's how drugs work."

There's just too many similarities between these compounds and our higher neurotransmitters, it's more than just chemical structure.

Our higher neurotransmitters would not be possible without plants providing our bodies with the essential precursor compounds, if we did not recieve Phenylalanine (and Tyrosine) provided from plants, our bodies would not be able to produce dopamine, epinephrine or norepinephrine. If we did not receive L-tryptophan from plants, our bodies would not be able to produce serotonin, melatonin, pinoline or DMT. So it's the plants that produce the molecules essential for the production our higher neurotransmitters...

Look at how your neurotransmitters are produced, let's take 5-hydroxy-tryptamine, L-tryptophan enters the system, it is then enzamatically 5-hydroxylated (5-hydroxy-tryptophan) then decarboxalated to give 5-hydroxy-tryptamine, the body also produces DMT from tryptophan, tryptophan enters, is decarboxalated (AADC) giving tryptamine, which is then N methylated twice via SAM with INMT, (SAM Becomes SAH after it donates its methyl group) giving DMT....

Now, let's look at how plants and fungi produce these exogenous neurotransmitters:
( Rather than detail these pathways in text I have decided to include their biosynthetic pathways in the images attached to this post. )

Now, let's look at structure, (this is simply illustrating structural differences between the compounds) if you take 5-hydroxy-tryptamine and methylate it's amine nitrogen twice and move it's hydroxy grouping from position 5 to 4 you go from serotonin to psilocin, so we can see how some very minor changes to our neurotransmitters produce psychedelic molecules. Let's look at 3,4-dihydroxy-phenethylamine (dopamine) if you methylate the hydroxyl groups at positions three and four and add a methoxy group to position 5 you go from dopamine to mescaline (3,4,5-trimethoxy-phenethylamine)

Serotonin from outside sources would not be orally active, this is because of the exposed amine grouping which makes the molecule amenable to enzymatic deamination, and because of the free hydroxy grouping at position 5, which is a polar, hydrophilic, "bump" protruding from the side of the molecule preventing passage beyond the blood brain barrier. Now, let's protect our amine grouping by placing a methyl grouping on the alpha carbon of the ethylamine side chain, and let's address that hydrophilic, polar hydroxy grouping at position 5 by placing a methyl grouping there as well, by blocking these two positions of the molecule which prevent it access from the brain, we end up with 5-methoxy-alpha-methyl-tryptamine (alpha,O-dimethyl-serotonin), which is can incredibly potent psychedelic, being active between 2.5mgs to 5mgs

Then there's activity. Which ties this all together.

It's these compounds close structure to our neurotransmitters which is allowing us to explore and understand our endogenous receptor systems as well as the functions of our neurotransmitters and our brain as a whole. Now we can manipulate the alpha helical proteins of the receptor sites using molecules Which have the basic shape of the ligand for the receptor but which also have additional groupings protruding from this basic shape, thus bending the alpha helical proteins into novel shapes producing novel responses...



https://www.ncbi.nlm.nih.gov/pubmed/14761703

I could spend all day discussing the relation between psychedelics and neurotransmitters, and in the above post I feel that I was barely scratching the surface on many facets of this topic...

-eg

offtopic:

When I read mescaline in the second chart of eg, I thought of cacti and bubbled something like... mhmmyamnömnöm



tseuq

Soooooooo...

This leads us to the inevitable question.

Are plants using these compounds for their own individual neurotransmission purposes? Or as transmitters in the larger gaian matrix, some sort of interspecies communication tool?

And what of the variety of neurotransmitter-like alkaloids that are not (psycho)active within a mammalian central nervous system? Many of which seem to be powerful anti-oxidants and/or involved in moderating a variety of biological processes (sexual reproduction, circadian rhythms, cellular metabolism, etc).

I would answer yes to the latter question, although the former could be true as well.

Dennis Mckenna always talks about "messenger molecules" and I certainly agree with that conceptualisation.

I find it more likely, personally, that these compounds have more mundane purposes in plants and that as humans our brains have evolved to make them useful and do new novel things with them, like producing visionary states. Idk though, we're all just speculating here so who know's?

We don't know why plants produce neurotransmitters... as these plants don't have a nervous system, neurons, or a brain, we can conclude that neurotransmission is not the purpose of these compounds.

For a good deal of time it was assumed that these molecules were tertiary, that they were waste products of metabolism and that they were intentionally being produced. However, it has been discovered that these plants and fungi are actually devoting enormous amounts of effort and energy to produce these things...so, why would plants expend so much energy to produce molecules Which are of no use to themselves?

Animals communicate through behavior, plants communicate through chemistry, and when examined in depth we can see how plants use chemicals to manipulate and guide the lifeforms around them.



The above video above details several examples of this, and can help put things into perspective.
-eg

Thanks for sharing that video eg, I really enjoyed watching it.


Dennis Mckenna puts it like this:" Plants substitute biosynthesis for behaviour." I really like that statement.

To me the idea of plants, and fungi being conscious, sentient and intelligent seems obvious. These things are not these dumb, listless entities as some people think of them, they are aware, they are intelligent and they are vital to the very survival of life on this planet. They are the backbone of the biosphere. They are the support structure of life on this planet. I feel that if moar people lived with this mindset, we could actually start to work with Mother Nature instead of against her.

Sorry for the rant guys, it's just that I really feel strongly about this.

The metabolic web is complicated/complex:

N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesis.

And it just so happens that this also intersects with the products of of phenylpropene (as in myristicin, elemicin etc.) metabolism to a certain degree, which I find rather curious.

Kynurenamines as Neural Nitric Oxide Synthase Inhibitors (2005) Journal of Medicinal Chemistry, 2005, Vol. 48, No. 26, 8174 - 8181

One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?

It's also possible for DMT to metabolise to dimethylkynurenamine. Vaguely attempting to veer back on topic

Thanks!

Just skimmed through as of now, but will enjoy further reading.

myristicin and elemicin? Quite curious, this in particular interests me...

Thank you again.

-eg

People forget that the air we breathe, the food we eat, the cloths we wear, the materials we build our homes from, and the neurotransmitters in your body, are all provided by plants.

Are these life forms conscious? Of coarse! Buts it's not consciousness as we would be familiar with it. when it comes to the collective conscious of all life and the species, the consciousness of plants, even concepts like Rupert sheldrake's "morphogenetic fields" we must push our definition of what it means to be conscious...

I offer that video in my posts because I feel.it clearly demonstrates how plants are aware of their surroundings, they are aware of their environment, aware of the lifeforms around them, and that they act with intention to manipulate all of the above.

I have been using these examples on the nexus forever:


Wild tobacco using chemistry to manipulate the lifeforms around it

The dodder vine actively seeks it's prey.

In this thread https://www.dmt-nexus.me...aspx?g=posts&t=73213 I go into greater detail.

However, about those examples above, I came across a research paper on NCBI which uses these exact examples, and while they are naturally taking a skeptical view point, I think they seem to validate some of my claims as well...
https://www.ncbi.nlm.nih...pmc/articles/PMC4152196/

Are Jellyfish conscious? (They do not have a brain, the do not have a nervous system (they have a loose "nerve net" ) )

However, I feel focus on neurotransmitters is more suited to this thread, and debate regarding plant consciousness and plant intention is somewhat off topic.

If we want to be objective, I think we can leave it at "plants produce the precursors to our higher neurotransmitters" as is the case with L-tryptophan for our tryptamine neurotransmitters and Phenylalanine and tyrosine for our phenethylamine neurotransmitters.

-eg

Plants are actually using them to talk to the ants. Us mammals only got caught up in it by chance..

This (about the ants) is claimed in the scientific article titled "Extrafloral-nectar-based partner manipulation in plant–ant relationships". If you are interested, you can find a reference to it in this post, part of a lively discussion thread, also involving highly related topics such as stoned apes, flying saucers from the hollow earth and "semen man".


Not only off topic, but often a generous invitation for sloppy reasoning as well. I don't have the time to point out the insane amount of bollox and wishful thinking that seems to be par for those threads.

Entheogenic-gnosis, we've been down this road before, so before this blows up again, I'll try to suffice by quoting myself quoting your quoting of "authorities on the matter" (in another post in the above referenced thread):

I can only hope that the proponents of plant intelligence/consciousness will take notice of these observations.


These amino acids, among many others, are primarily the building blocks of various proteins. Proteins are essential to life as we know it. In comparison, neurohormones are rather coincidental and insignificant in the bigger picture. Plants produce these amino acids to sustain their own lifeform, rather than to assist in our "conscious evolution".

Let's refrain from reinventing more "stoned ape" nonsense.

I'm pleased to see my little comment has stirred up so much controversy.

The answer is of course, all of the above. For example, we know that melatonin controls circadian processes in plants and even down to algeas and unicellular organisms (1). We also know that serotonin is involved in a variety of physiological processes in plants such as morphogenesis and auxin formation (2).

The study with the harmalas and bees and the ant one pitubo mentioned demonstrate how these compounds are used in interspecies communication processes.

Now why does a poppy make morphine or an acacia DMT? Is it for their own purposes, or for the benefit of their mammalian seed transporters? Or to put it another way, who is cultivating whom?

Calling these a "benefit" is making quite an assumption. It seems to me that in most cases, the appropriate description of the "intent" of the mechanism in these interspecies chemical communications is that of a deterrent rather than an enticement.