Endogenous DMT using nutrients. Testable science. Should be studied.

[Sabnock1990]

As for dosages, imo, try 25mgs of P5P B6, 10mgs of Methylcobalamin B12, 500mgs of Tryptophan, an hour into a dose of Harmalas (dosage typical of that for oral DMT activation).

If it doesn't work, lmk, we'll figure it out together

 

[Transform]

It's simple. Take the P5P form of vitamin B6, the Methylcobalamin form of vitamin B12, and Tryptophan, together/at the same time, an hour into Harmalas/MAO-A inhibition = Endogenous Tryptamine/NMT/DMT. You're welcome (for those who can't be bothered to read a little bit about something as interesting as endogenous Dimethyltryptamine lol).

It works, and if people can't figure it out, then i guess oh well since they apparently can't be bothered to read enough to understand how it works.

Who cares about understanding? I JUST WANNA GET HIGH, GODDAMMIT!! /jk


Dou you think that supplementation with something like choline or betaine might also help to bump up the methylation levels? I saw that you mentioned the betaine methylase enzyme that once, without going into too much detail.

Moreover, it sets me thinking that a thorough mapping of all the interlocking mechanisms including up- and downregulation of relevant areas of gene expression would help in further refining this method. There's a chance that simply chucking in 'all the right ingiredients' might not work for some people.

How consistent and ubiquitous is the expression of these methylase systems? Are there further supplements that might be useful in reliably inducing enhanced methylation?

 

[Sabnock1990]

Supplementing with/dietarily consuming Choline/Betaine/Trimethylglycine should/could be helpful imo because it should take some of the burden off of B12/Folate for the recycling of Homocysteine back into Methionine, but i as far as i know the BHMT enzyme is mainly more in the liver, i've gotten some conflicting info on if there's BHMT in the brain, most things say it's in the liver, some things have said it could also be to some extent in the brain, however the Methionine Synthase enzyme (which uses B12/Folate) is available in both brain and liver, and is said to be the dominant source of Homocysteine recycling, but theoretically, BHMT activity should help imo. I haven't yet ventured into BHMT as deeply as i have with Methionine Synthase, but imo the more the merrier.

And that's a good point to make about the potential effects of epigenetic expression and up-regulation or down-regulation of certain enzymes and processes. I know i've read that SAM/methylation can lead to an increased expression in Tryptophan Hydroxylase activity which converts Tryptophan into 5-HTP, so it could potentially up-regulate other enzymes involved in Tryptophan's metabolic pathways, potentially including INMT expression which could increase the methylation of Tryptamine into NMT/DMT. So that's definitely worth taking into consideration as well, especially over the long term (potentially if one is inhibiting MAO-A more regularly enough that would tell the system "we need more INMT to process Tryptamine for methylation", could definitely add to it imo). And i know some people may have some genetic predispositions or SNP's for certain enzymes which too may influence the results, and so some forms of things may be better suited for some folks than other forms, but i figure if you just go for the active forms to begin with, less guesswork.

I think for the most part, so long as one has enough SAM for methylation (especially in the brain), and has enough B6 to force Tryptophan's decarboxylation into Tryptamine, and has enough MAO-A inhibition (as well as proper timing between inhibiting gut MAO-A and consuming the Tryptophan), it should work. I don't think it's much of a complex process, it seems pretty simple both experientially so far and as far as understanding how the process works, it's only a few easy steps and one should see results, imo.

AADC/DOPA Decarboxylase and Methionine Synthase are pretty significantly expressed in Humans, they're basically how we get our neurotransmitters and methylation and are basic to Human physiology, so it's pretty necessary for bodily function, they're not small enzymes like DHFR for example (which in Humans is rather limited, thus is one reason Folic Acid can cause issues for us since it relies on DHFR to be metabolized into Folate's the body uses), they're used on a daily basis by the body, AADC/DOPA Decarboxylase mainly decarboxylates 5-HTP and L-Dopa into Serotonin and Dopamine, and Methionine Synthase is the main enzyme needed to recycle Homocysteine back into Methionine to keep the SAM cycle going, so they're pretty important to everyday function, but it seems to me that a main issue today is that our Methionine Synthase enzyme is under-functional due to lack of B12, imo.

Also for the record, i care about understanding lol, i'm convinced i'm playing my part in helping to reverse engineer the Human body, figure out how this thing works lol. (getting "high" is just a bonus lol).

 

[Sabnock1990]

As for other supplements, basically just anything that would help ensure proper activity of enzymes involved, Folate is a big one, and things like Riboflavin, Niacin, Potassium, Magnesium, Zinc, Copper, Iron, potentially Selenium, vitamin B5, still unsure about Thiamine but it's probably in there somewhere lol, vitamin C, vitamin A, vitamin D, basically imo cover all the bases, all these nutrients and some others are involved to some degree whether directly or indirectly along the metabolic chains for proper enzymatic functioning. Not that they're needed in the endogenous Tryptamine mix, but worth making sure of overall to make sure things are functioning as they should. You would be surprised at how nutrients all work together at different steps along the way for the overall functioning of the whole. Different co-factors are needed by different enzymes to function properly, if an enzyme doesn't have what it needs then it can't function. So i'd just look at all the enzymes involved and figure out any of the co-factors that it may need and just make sure of that and one should do alright imo.

 

[Sabnock1990]

Also, i've taken Methylcobalamin B12 a lot so far, in varying dosages, and 10mgs a day works wonders, especially taken all at once, but i think even 5mgs twice a day is rather nice. For me personally, 10mgs is where i see benefits, in general (aside from the Tryptamine methylation), so i think i tend to recommend 10mgs of Methylcobalamin, it works nicely, haven't had much in the way of side-effects from B12, contrarily i've had quite a few side-effects from too much Folate, but more B12 seems to help. So when it comes to B12 in general, and for this Tryptamine thing, i'd say try 10mgs, it works well for me, anything less generally doesn't seem to work as well for what i'm taking it for, and so it's worth considering that higher B12 dosages may be worth exploring for endogenous Tryptamine methylation.

 

[Transform]

Ofc, the other fun thing about methylation is that it's one of the main forms of epigenetic marking, which in turn does various things regarding gene expression. Is this something you'd also be taking into account?

I'd need to look into the specifics of enzymatic DNA methylation to check for instances of overlap with the small-molecule systems being discussed here.

Speculatively, increasing the activity of the tryptamine methylation system might conceivably lead to a more rapid response to factors which in turn lead to epigenetic control of enzyme- and other protein synthesis. Interesting, also, to think that this could be perceived as a kind of active evolutionary tool…

 

[Sabnock1990]

Ofc, the other fun thing about methylation is that it's one of the main forms of epigenetic marking, which in turn does various things regarding gene expression. Is this something you'd also be taking into account?

I'd need to look into the specifics of enzymatic DNA methylation to check for instances of overlap with the small-molecule systems being discussed here.

Speculatively, increasing the activity of the tryptamine methylation system might conceivably lead to a more rapid response to factors which in turn lead to epigenetic control of enzyme- and other protein synthesis. Interesting, also, to think that this could be perceived as a kind of active evolutionary tool…

As far as epigenetics go, it's something i've wondered about as well, and if it's involved somehow it could perhaps have some benefits (reinforcing INMT for example, or some other enzyme involved in the metabolic processes), technically low methylation could definitely dampen methyltransferases (for example Melatonin has been reported to be low in Autism, and i have definitely noticed an increase in natural Melatonin synthesis mainly due to B12 (Homocysteine to Methionine and thus SAM synthesis), but B5 also plays a role (for acetylation), it's definitely Melatonin, so clearly my methyltransferases have improved, as i imagine INMT activity can also improve, and so simply by supplying SAM itself probably has the main benefits, but increasing expression of INMT or other enzymes could reinforce that and "open up the highways" so to speak, or, it could down-regulate/knock down the INMT enzyme. It seems to me from what i've read that most of these things are supposedly self-regulating based on feedback loops, and that excess SAM may actually knock down INMT, but that hasn't been my experience, my experience says more B12 = greater SAM which so far seems promising. And with feedback loops happening, epigentic modification could signal an increase in activity, or the reverse, but so far the former is what aligns with my personal experience whether that's just the SAM/methylation, or epigenetics. I will probably end up doing a deep dive on epigenetics and methylation impacts and all that to learn more at some point though.

And yeah, active evolutionary tool indeed. I get the impression that this whole thing is doable at least to some extent, how far it may go? i hope to find out, in time lol. Imo it also has implications for potential synthesis of 5-MEO-DMT and Bufotenin as well, also 5-Methoxytryptamine, perhaps even 5-Hydroxy/Methoxy-N-Methyltryptamine (5-Hydroxy/Methoxy-NMT), and also aren't supposed endogenous Tryptolines like Pinoline also supposed to come from Tryptophan? It makes me wonder what would happen if one's MAO-A enzyme was low-functioning (or knocked out irreversibly) and consuming a diet heavy in Tryptophan (or just pure Tryptophan) so that the Tryptamine/NMT/DMT can become systemically active due to MAO-A's lack of functionality, which could allow for the buildup of these "trace" amines, allowing them to take greater and greater effect which could then spill over to other enzymes that process those metabolites into other compounds, so like DMT maybe going through Tryptophan Hydroxylase to become 5-Hydroxy-DMT (Bufotenin) or going through Acetylserotonin O-methyltransferase (ASMT) to become 5-Methoxy-DMT, especially 5-MEO could be more effective with greater SAM levels.

Seriously, if anyone out there has access to an irreversible preferably selective for MAO-A inhibitor, like maybe Clorgiline for example, they should seriously take one for the team and give it a go with this method (Tryptophan+P5P B6+Methylcobalamin B12), see what may happen lol, or heck send me some and i'll try it myself lol. I think the only irreversible MAOI's i could maybe get ahold of via a doctor would be like Phenelzine or Isocarboxazid, maybe Tranylcypromine, but those also have MAO-B inhibition which i'm not wanting, so if one has an irreversible MAO-A inhibitor it would be an interesting thing to check out.

 

[Sabnock1990]

Also, imo it would be something worth thinking about as far as meditative or yogic practices go, like if you inhibit MAO-A and take Tryptophan+P5P B6+Methylcobalamin B12, and then do whatever practice, if you could maybe more easily induce endogenous synthesis, maybe increase it by breathing exercises for example. It seems to me, ime, taking the Tryptophan and B's with MAO-A inhibited already gives noticeable Tryptamine/NMT/DMT synthesis, so that's a given, but if it can be increased with breathwork, it's worth trying out imo.