Presumably, supplementing a bit of methionine wouldn't hurt either?
I'm a teeny bit concerned about the 5-hydroxylation side route (being a major pathway for tryptophan/tryptamine) and its subsequent methylations leading to formation of of mexamine and homologs up to 5-MeO-DMT, this last one presenting higher than usual risk in combination with harmalas. Would there be any simple ways of minimising the action of TPH, DDC and HIOMT to help circumvent this? And what about the converse?
Yeah, Methionine should help too, although worth keeping in mind that a lot of Methionine = a lot of SAM = a lot of SAH = a lot of Homocysteine = a lot of demand on the B12 and Folate for recycling that Homocysteine back into Methionine and keeping the cycle going. So you want enough Methionine for enough SAM, but not too much that will put extra pressure on Methionine Synthase and B12/Folate, especially if one has some deficiencies it might make things a bit harder to recover, perhaps. But yeah you definitely need some dietary or perhaps supplemental Methionine.
Ime, the B6 seems to force Tryptophan's decarboxylation to Tryptamine, it feels like it does this fully/completely, like with the B6 there doesn't seem to be any Tryptophan going towards Tryptophan Hydroxylase/5-HTP synthesis, i can feel the differences between Tryptophan without B6, and Tryptophan with B6, without B6 it seems to go down it's usual metabolic route turning into 5-HTP and Niacin at the least and then like a few hours later turns into Tryptamine cerebrally, that much i can feel, but, when the B6 is taken with the Tryptophan, it's like it forces all of the Tryptophan to decarboxylate in the gut to Tryptamine and stops it from going down it's usual metabolic route of 5-Hydroxylation. Though if enough Tryptamine's were allowed to build up in the body/brain (like if MAO-A would irreversibly inhibited), we could see more Tryptamine/DMT going down the 5-Hydoxylation, 5-Methoxylation, and other routes and potentially producing 5-MT, 5-MEO-DMT and 5-HO-DMT. This is why it'd be interesting imo to try this out with an irreversible MAO-A inhibitor.
There could maybe be a theoretical risk if 5-MEO-DMT or perhaps 5-HO-DMT built up to high enough levels, though i'm not sure how that might look or how possible it might be compared to straight Tryptamine/NMT/DMT production, but theoretically, if trace amines were able to build up due to lack of MAO-A, it could give the body enough DMT to be methoxylated or hydroxylated enough to become those metabolites, and then that could have some potential risks but i haven't detected more than NMT/DMT yet personally so i don't think that's a risk at the moment. Also it's worth keeping in mind that 5-MEO-DMT (and probably 5-HO-DMT) are metabolized in the liver by CYP2D6 (as well as by MAO-A), which Harmalas potently inhibit, as such, with both CYP2D6 and MAO-A inhibited by the Harmalas, it can increase bioavailability of ingested (and endogenously synthesized) 5-MEO-DMT which can necessitate a lowering of 5-MEO-DMT dosage to account for the increase in bioavailability, then, it might be potentially safer/less risky and might be something some folks haven't factored in yet, so it's possible that 5-MEO-DMT and 5-HO-DMT could maybe be safely combined with MAO-A and CYP2D6 inhibition, so if anybody were to experiment with (or experience endogenous synthesis of) 5-MEO-DMT, i think dosage is key. Now, who knows how much 5-MEO-DMT the body might spurt out, but with the inhibition in place, i don't think the body would need much? Heck, i think we should test this out on some mice or rats or something, just keep MAO-A inhibited, maybe CYP2D6 too if possible, feed em' B6, B12, and Tryptophan and see if things build up and how they metabolize over time.
I'm not sure how to go about minimizing the activity of Tryptophan Hydroxylase or HIOMT, but i must admit it would interesting to find out if they will increase in the consistent presence of Tryptamine and DMT and how they as substrate might end up producing other trace metabolites, i think it really should be studied lol.
That could make it easier and encourage other people to try it.
