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If DMT would be a neurotransmitter. Options
 
polytrip
#1 Posted : 1/11/2011 11:48:51 PM
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I don't want to reboot the pinealgland theory here. I would want to look at DMT in a different way.

My question is: if DMT would be a neurotransmitter instead of some coincidental by-product, what would it's function be then?
I'm not saying it is a neurotransmitter, i don't even think i'm suggesting it is, all i'm asking is..what if it IS a neurotransmitter?

There must be some people here who've got ideas about that.
 

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jamie
#2 Posted : 1/12/2011 12:06:18 AM

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I didnt know there was any dispute about DMT being a neurotransmitter..isnt that was it does?....

I thought the whole dispute about DMT was weather it was used that way endogenousily...cant something exogenous still act as a neurotransmitter when taken in a certain dose even if it doesnt act that way as it occurs endogenousily in the body?
 
benzyme
#3 Posted : 1/12/2011 12:58:28 AM

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oh it's certainly a neurotransmitter, binding metabotropic (G-coupled) receptors, whether endogenous or exogenous; this isn't really disputable. it's a competitive ligand at active binding sites, and thus initiates signal transduction as such.

what is its function?
well, that is a question on par with, "what is the function of consciousness?"
since it is rapidly metabolized by MAO and isn't normally present in any active concentration, it obviously doesn't have any vital function.
dmt production inhibits serotonin production, thus inhibiting melatonin production; dmt is a side-reaction product.
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Infundibulum
#4 Posted : 1/12/2011 1:21:18 AM

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benzyme wrote:
oh it's certainly a neurotransmitter, binding metabotropic (G-coupled) receptors, whether endogenous or exogenous; this isn't really disputable. it's a competitive ligand at active binding sites, and thus initiates signal transduction as such.


But this isn't the definition of neurotransmiter, no?

A "neurotransmitter" has to be released from presynaptic neuron with an aim to bind to an try to depolarise the post-synaptic one. Neurotransmiters are by definition released in the synapses. Norepinephrine is a neurotransmiter but epinephrine is not; epinephrine is an endocrine hormone and not neurotransmitter since it is not released in the synapsis.

Is there a publication that shows dmt to be released in the synapsis?

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actualfactual
#5 Posted : 1/12/2011 1:23:31 AM

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DMTs function is to show you the other side rather then this side.
 
ragabr
#6 Posted : 1/12/2011 1:29:18 AM

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aloneits wrote:
DMTs function is to show you the other side rather then this side.

Not helpful.
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benzyme
#7 Posted : 1/12/2011 1:40:07 AM

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Infundibulum wrote:
benzyme wrote:
oh it's certainly a neurotransmitter, binding metabotropic (G-coupled) receptors, whether endogenous or exogenous; this isn't really disputable. it's a competitive ligand at active binding sites, and thus initiates signal transduction as such.


But this isn't the definition of neurotransmiter, no?

A "neurotransmitter" has to be released from presynaptic neuron with an aim to bind to an try to depolarise the post-synaptic one. Neurotransmiters are by definition released in the synapses. Norepinephrine is a neurotransmiter but epinephrine is not; epinephrine is an endocrine hormone and not neurotransmitter since it is not released in the synapsis.

Is there a publication that shows dmt to be released in the synapsis?


not that i'm aware of; hmm...so what is it, a pseudo-neurotransmitter? it would still be
a secondary messenger
yea, i forgot that neurotransmitters are packed into vesicles, which fuse with the presynaptic-membrane following Ca2+ influx.

if epinephrine is a hormone, that would make it a primary messenger (neurotransmitters are secondary messengers).
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corpus callosum
#8 Posted : 1/12/2011 3:27:39 AM

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I like Infundibulums definition of a neurotransmitter; with this in mind I think the most we can say presently is that DMT is an analogue of certain endogenous neurotransmitters.

The lack of evidence (presently) that DMT is sequestered in vesicles makes it hard to really define DMT as a true neurotransmitter in its own right.
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benzyme
#9 Posted : 1/12/2011 3:29:41 AM

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it's the classic definition of a neurotransmitter
afaik, dmt is produced in the cytoplasm, mostly in epithelial cells. whether or not it ends up in vesicles has yet to be seen; it still hasn't been probed en vivo
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pau
#10 Posted : 1/12/2011 6:25:34 AM

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just thinkin':

as we allow ourselves to evolve, our neruocircuitry rewires itself in new ways, even new biological structures, that can handle the new biochemistry that is evoloving alongside it. So take a hypothetical example, say the Buddha, might he have been simultaneously living both here and in hyperspace? Or perhaps there would be no difference to someone like that between "this world" and hyperspace? Obviously, we aren't able to do that...yet.

This is by no means my original idea, but Nexusizing the last year or so has allowed me to think more deeply about how it might work and the science behind it.
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Infundibulum
#11 Posted : 1/12/2011 2:16:31 PM

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benzyme wrote:


not that i'm aware of; hmm...so what is it, a pseudo-neurotransmitter? it would still be
a secondary messenger
yea, i forgot that neurotransmitters are packed into vesicles, which fuse with the presynaptic-membrane following Ca2+ influx.

if epinephrine is a hormone, that would make it a primary messenger (neurotransmitters are secondary messengers).

I think that it is most likely to act as a hormone. As you say, this would do it a "primary" messenger (message generator) rather than "second" messenger (message conveyor). But that's as far as it's endogenous role(s) and action goes.

Obviously, exogenously administered dmt reaches the synapses and binds to receptors as a "pseudo-neurotransmitter just as all the other psychotropic drugs.



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polytrip
#12 Posted : 1/12/2011 4:12:03 PM
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Based on the responses so far, i would rather ask now: Based on the facts that DMT binds to so many different receptors and that binding to many of those receptors leads to different aspects of the psychedelic experience, is there a connexion between these receptors?

If one receptor leads to seeing coloured patterns and another leads to altered bodily sensation and yet another to a different perception of the self, you would start thinking that it hardly can be coincidence that one molecule has all these different effects, but that so many of them in some way create an altered state of counsiousness.

Are these receptors related in a systematic way, that could be essential for counsiousness?

Or could the brain be wired in such a way that it is bound to generate religious/spiritual/psychedelic experiences?

A question that could help answering these greater question is: what would happen if you'd inject a person a substance that blocks the effects of DMT? Does that change anything in how a human being functions or perceives things?
 
benzyme
#13 Posted : 1/12/2011 4:28:28 PM

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probably not
serotonin itself blocks DMT binding. serotonin is more, how should we say, important to regular
brain function than DMT. From an adaptation standpoint, and Shulgin has also mentioned this in Dirty Pictures, it may just be that over the course of human evolution, the human brain developed metabolic pathways to supress endogenous psychedelic ligands...a sort of filter mechanism...for self preservation, survival as a species.
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burnt
#14 Posted : 1/12/2011 8:17:01 PM

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Quote:
From an adaptation standpoint, and Shulgin has also mentioned this in Dirty Pictures, it may just be that over the course of human evolution, the human brain developed metabolic pathways to supress endogenous psychedelic ligands...a sort of filter mechanism...for self preservation, survival as a species.


Thats an interesting one. Makes sense if its more of a by product.

One question...what is the typical breakdown pathways for serotonin? Where is INMT important in tryptamine biosynthesis? Why not just deevolve that enzyme instead of making new enzymes to break down its products?
 
benzyme
#15 Posted : 1/12/2011 11:44:03 PM

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good questions..unfortunately, the referenced pathway doesn't shed light on them

from the KEGG pathway, you can see in the side-pathway, 2.1.1.49, along with 4.1.1.28, which are involved with producing NMT, second pass metabolism with SAM supposedly yields DMT.. you can also see 2.1.1.49 is involved with N-methylation of serotonin.... perhaps a second pass produces bufotenine?
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pau
#16 Posted : 1/13/2011 3:42:05 AM

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Benzyme suggests:
"From an adaptation standpoint, and Shulgin has also mentioned this in Dirty Pictures, it may just be that over the course of human evolution, the human brain developed metabolic pathways to supress endogenous psychedelic ligands...a sort of filter mechanism...for self preservation, survival as a species."

While that could be true, consider the forward-looking, flip side of that statement: an opportunity in our future evolution - possibly a necessity if we're not going to blow ourselves to smithereens - is to develop the metabolic pathways to encourage endogenous psychedelic ligands.

I happen to strongly believe that "something" happens to one's biochemistry by following "this path". Whether Dr Strassman's blood and urine assays to measure the levels of endogenous tryptamines with at least 1000X greater sensitivity than ever before proves successful (you can read about it at http://cottonwoodresearch.org/index.php/projects ), at some point in the future many of the right pieces of understanding are going to fall into place.

A number of Buddhist practitioners I know believe, for example, that the "relics" known as sarira or ringsel, found in the cremated remains of teachers they consider "spiritually advanced", are connected to the change in the amino acids in their bodies that arise from many years of meditation and spiritual practices: http://www.maitreyaproject.org/en/relic/gallery.html.
I don't know what to say about that, but you can see them for yourself at many cities in USA and Europe between now and April.
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clouds
#17 Posted : 1/13/2011 4:29:54 AM

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Nicholas Cozzi - N,N-DMT pharmacology

Quote:
The plant hallucinogen N,N-dimethyltryptamine (DMT) has been used for religious and other purposes for many centuries. The psychological effects of ingested DMT are characterized as an intense dream-like state with fantastic visual imagery, altered time and space perceptions, changes in body image and sensations, and feelings ranging from euphoria to sadness to amazement. Over the past several decades, scientists have linked the psychoactive effects of DMT to various neurochemical processes including action at serotonin receptors and transporters and monoamine oxidase enzymes.
We recently identified the sigma-1 receptor as the latest molecular target for DMT. We reported that DMT binds to sigma-1 receptors at low micromolar concentrations, inhibits sigma-1 receptor-regulated sodium ion channels at higher concentrations, and induces a hypermobility response in wild-type mice that is abolished in sigma-1 receptor knockout mice (Fontanilla 2009). In a later study, we reported that DMT and other psychedelic tryptamines exhibit substrate behavior at plasma membrane and synaptic vesicle uptake transporters (Cozzi 2009). We hypothesize that these uptake processes may allow the accumulation of DMT within neurons to reach relatively high levels and, when stored in synaptic vesicles, to function as a releasable transmitter. We have now obtained direct experimental evidence in support of this hypothesis by observing that DMT can be taken up by model neuronal cells (PC12 cells) and subsequently released by these cells under conditions of controlled depolarization. The psychedelic effects of DMT and related compounds likely arise from a complex interplay among all of these enzyme, receptor, and transporter mechanisms.



 
burnt
#18 Posted : 1/13/2011 8:07:54 AM

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I've seen that lecture clouds. While they certainly have accumulated evidence I still feel the jury is still out. Although its cool work I think there is more to do. I can't remember what I thought he should test next but I am sure there will be more papers coming out from that group on this topic.

Quote:
While that could be true, consider the forward-looking, flip side of that statement: an opportunity in our future evolution - possibly a necessity if we're not going to blow ourselves to smithereens - is to develop the metabolic pathways to encourage endogenous psychedelic ligands.


The selection pressure would have to be quite strong for something like that to happen and it would take a very long time to become a general trend in our biochemistry. I just don't see how such pressure could exist. The only thing I could imagine is that as humans are forced to live so close to each other in order to better survive they have to get along with each other better and being more prone to having a "get along" type personality might help with survival. But again the selection pressure is so weak I can hardly seeing it mattering any time soon.

Quote:
A number of Buddhist practitioners I know believe, for example, that the "relics" known as sarira or ringsel, found in the cremated remains of teachers they consider "spiritually advanced", are connected to the change in the amino acids in their bodies that arise from many years of meditation and spiritual practices


That makes no sense.
 
polytrip
#19 Posted : 1/13/2011 5:35:05 PM
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For me, the intruiging question remains: is it just coïncidence that activity of so many of the receptors DMT binds to, leads to psychedelic effects?

If binding to just any receptor has a high chance of psychedelic effects, either visual or psychological or otherwise, then you would expect almost any substance to have psychedelic effects.

So seen from that perspective, you would assume there to be some sort of a connection between all of the receptors DMT binds to.

I'm asking whether the psychedelic state could be a naturally ocurring mindstate, like dreaming.

I could imagine that in a sense we're always under the influence of endogenous tryptamine psychedelic's, but just to such a limited degree that we normally don't notice it. That it could have a function simmilar to that of dreaming. Let's say that parts of our brain are always 'dreaming' when we're not using them counsciously, to proces information, to integrate new experiences and to be able to learn new things, rewire, etc.

I just cannot believe that the brain can generate such extreme states of mind, with so little side-effects, without that somehow being either a vital part of it's functioning, or the other way round, without that being an expression of vital principles that lay at the foundation of counsciousness.
 
benzyme
#20 Posted : 1/13/2011 7:02:41 PM

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polytrip wrote:

I could imagine that in a sense we're always under the influence of endogenous tryptamine psychedelic's, but just to such a limited degree that we normally don't notice it.


this sentence contradicts itself; to be under the influence of endogenous tryptamines means that subjective effects are present. given normal concentrations in serum, it just doesn't happen. depolarization signals are too weak, well below threshold levels, to get any sort of subjective effects; also consider that receptors bind serotonin more readily, given that it's a 'normal' neurotransmitter to the binding sites, present in much higher concentrations.
figuring that in with rapid metabolism of endogenous tryptamines by MAO, how can you be under the influence of something you can't perceive?
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