N,N-Dimethyltryptamine (DMT) found in the CNS

[bit_pattern]

Interesting. Seems it is quite widely distributed in the CNS but was previously mistaken for an opioid reactor

Interesting, seems DMT isn't just locked away in the pineal gland it's also widely distributed through the CNS but was earlier mistaken as an opioid receptor

The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator
Dominique Fontanilla,1 Molly Johannessen,2 Abdol R. Hajipour,3 Nicholas V. Cozzi,1 Meyer B. Jackson,2 Arnold E. Ruoho1*

The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.

SOURCE

 

[PepperSocks]

Thanks for the tid-bit

Here our Big & Dandy Endogenous Psychedelics Thread for more discussion on the matter.

 

[dread]

You should post this on the DMT-nexus. They'd probably be the most excited to hear this...

 

[bit_pattern]

Thanks for the tid-bit

Here our Big & Dandy Endogenous Psychedelics Thread for more discussion on the matter.

Ah yeah, I did a quick search and didn't find anything on his. can you merge it with with the wider discussion?

 

[swilow]

^There was a thread in ADD about this; also, its affinity for SIGMA is mentioned in wikipedia, so I guess this isn't new news. News new. Hmm.

I don't see any evidence that DMT is widely spread in the CNS as opposed to being "locked away" in the pineal; just that DMT binds to the sigma receptor. ??

 

[fastandbulbous]

Well to produce it, all the enzymes needed are present, the most important mone being methionine S-methyl transferase which N methylates tryptophan which is then decarboxylated (or is it the other way around, decarboxylation then N-methylation? Answers on a postcard...)

 

[Shakti]

I don't see any evidence that DMT is widely spread in the CNS as opposed to being "locked away" in the pineal; just that DMT binds to the sigma receptor. ??

I agree with this. The fact that there are receptors that bind with it in no way indicates its presence. Does anyone expect to find valium endogenously?

 

[dread]

Does anyone expect to find valium endogenously?

There's already a ligand for the receptor diazepam binds to, it's called GABA and it's very endogenous.

Anyway morphine has been found to be synthed endogenously, as has GBL and GHB although in trace amounts. So who knows what else are we going to find there?

 

[cegli]

There's already a ligand for the receptor diazepam binds to, it's called GABA and it's very endogenous.

Correct me if I'm wrong here, but GABA doesn't bind to the benzodiazepine receptor does it? I thought the benzo receptor just modulated how often the Cl gates open when GABA binds to the receptor. They don't fit in the same spots. Is there an endogenous ligand for the BZD receptor?

 

[Swerlz]

diazepam has been found in potatoes.. I thought that was cool

 

[Shakti]

There's already a ligand for the receptor diazepam binds to, it's called GABA and it's very endogenous.

Anyway morphine has been found to be synthed endogenously, as has GBL and GHB although in trace amounts. So who knows what else are we going to find there?

I'm sure there are many things in trace amounts. However, the presence of a receptor that one transmitter happens to fit into, does not mean that the transmitter is ubiquitous, let alone present. Receptor sites can be activated by many chemicals, as we drug aficionados all should know. Anyway, I believe I read that dmt binds much more strongly to serotonin receptors and wouldn't hit the sigma-1 sites almost until the serotonin sites were flooded.

 

[dread]

Correct me if I'm wrong here, but GABA doesn't bind to the benzodiazepine receptor does it?

There's no such thing as benzodiazepine receptor, there's just the benzodiazepine binding site on the GABA-A receptor complex.

Receptor sites can be activated by many chemicals, as we drug aficionados all should know. Anyway, I believe I read that dmt binds much more strongly to serotonin receptors and wouldn't hit the sigma-1 sites almost until the serotonin sites were flooded.

True, but DMT is the only endogenous ligand found for the sigma receptor so far. Also to further complicate matters, DMT also binds to the TAAR receptors...

 

[swilow]

diazepam has been found in potatoes.. I thought that was cool

Main reason for that (I think) is the large amounts of diazepam in water....used to water potato crops. I don't think its actually naturally present. Either way, potatoes are good 'uns

 

[Dondante]

^There was a thread in ADD about this; also, its affinity for SIGMA is mentioned in wikipedia, so I guess this isn't new news. News new. Hmm.

I don't see any evidence that DMT is widely spread in the CNS as opposed to being "locked away" in the pineal; just that DMT binds to the sigma receptor. ??

ADD thread

According to the journal article mentioned, "DMT has been hypothesized to act through an unknown "hallucinogen" receptor."

This quote from the Science paper refers to an article published in 1981 ... so much for being up to date. The sigma receptor hypothesis is interesting, but the fact that they choose not to mention DMT's known 5-HT1A/2A binding profile is simply dishonest. It has been known for a good 20 years that that DMT binds to 5-HT1A/2A, the same receptors bound by psilocin/psilocybin, making it a much more likely candidate for the characteristic hallucinogenic effects.

I suppose giving the appearance of making a major discovery allowed them to publish in a reputable journal ... seems shady to me

More interesting tidbits: DMT is not solely produced in the pineal (sorry, can't find reference at the moment). As far as evolutionary history of the pineal gland, there are a couple species of lizards that still have a parietal eye (probably the ancestral pineal gland), and it serves a similar function to other pineal glands with its primitive photoreceptor cells. The function is to regulate the sleep/wake cycle which makes it evolutionarily a semi-conserved structure in even in higher mammals. There are at most a few species of lizard that still have the primitive lens and retina. As evolution progressed, the two primary eyes formed connections with the pineal gland as it took up residence at the base of the forebrain allowing it to lose its photoreceptor functions. So yes, the cells do resemble photoreceptors, and it still regulates cycles, but this is not surprising. MAOI seems to be present in high concentrations in the pineal to tightly control the levels of serotonin (it is highly concentrated in the pineal), thereby allowing it to also tightly control melatonin production.

 

[explorer83]

Main reason for that (I think) is the large amounts of diazepam in water....used to water potato crops. I don't think its actually naturally present. Either way, potatoes are good 'uns

That's a possibility given the large amounts of pharmaceuticals that are being introduced to the water supply, but I'm not sure of any mechanism that the potatoes would be able to uptake and store the diazepam. Any link to this study? Not questioning you, just curious. I've read numerous studies of morphological changes in fish due to human generated hormones in water.