Is DMT a 5ht3 agonist?

[Sabnock1990]

It's also worth noting that i've taken medications before that antagonized the 5-HT3 receptor, while on SSRI medication, and didn't notice any SS. The only time i've ever experienced legit SS, was when i was put on 2 or 3 different medications (an SSRI anti-depressant, an anti-psychotic, and a mood stabilizer), which i'm not sure if it was solely due to excess Serotonin, or if it was because the medications were contraindicated and some CYP enzymes were inhibited and thus potentiated the dosage of the SSRI which caused my SS. The psychiatrist i was seeing at the time was careless and didn't know what he was doing, imo.

But 5-HT3 receptor antagonists are not known for interacting with or causing SS with SSRI's, MAOI's, or other Serotonergic substances. I've never come across anything that would suggest a 5-HT3 receptor antagonist would be capable of that. My mom has taken Zofran because she had breast cancer and was undergoing chemo, and she's on a long list of medications, especially Prozac and Amitriptyline (even though it appears that Amitriptyline can also antagonize the 5-HT3 receptor), and no negative reaction with Zofran was noticed. Speaking of which, i really wish my mom could come off those anti-depressants and such, i don't think they're good medicine but she says they help.

 

[syberdelic]

I'm done

 

[syberdelic]

delete me

 

[SnozzleBerry]

And you can review the table yourself...but unless I'm misunderstanding something (and my apologies if I am), none of the compounds tested were identified as 5ht3 agonists.

Ki, the inhibitor constant. The inhibitor constant, Ki, is an indication of how potent an inhibitor is; it is the concentration required to produce half maximum inhibition.

By this definition of Ki value, it only applies to antagonist properties (inhibition). The >10,000 value means essentially that it has very little value as an antagonist. It says nothing about DMT's value as an agonist (trigger).

I'm not so sure that's the takeaway, as the paper goes on to state (emphasis mine)

The raw Ki values are distributed over several orders of magnitude, thus a log transformation is a good first step in the analysis. In addition, higher affinities produce lower Ki values, thus it is valuable to calculate: pKi = −log10(Ki). Higher affinities have higher pKi values, and each unit of pKi value corresponds to one order of magnitude of Ki value.

And, the paper that nen shared states

The objective of this paper is to present the receptor binding profiles of the thirty-five drugs of this study in such a way that they can be easily compared in both their similarities and their differences. This is intended to serve as a reference work on the multi-receptor affinity pharmacology of psychedelic drugs.

...

Receptor affinity profiles of psychedelic drugs, ordered by decreasing affinity...

DMT: 4.00 5ht7, 3.97 5ht1d, 3.91 5ht2b, 3.53 Alpha2B, 3.53 Alpha2C, 3.51 D1, 3.42 5ht2c, 3.28 5ht1e, 3.25 5ht6, 3.16 5ht5a, 3.13 Imidazoline1, 2.95 Alpha1B, 2.75 Alpha2A, 2.70 Alpha1A, 2.58 5ht2a, 2.37 SERT, 2.23 Sigma1; 0.00: 5ht1a, D4, D5, Beta1, D2, D3, DAT, NET, 5ht1b, Beta2, Sigma2, CB2, KOR, Ca+Channel, M1, M2, M3, M4, M5, H2, CB1; ND: H1, DOR, MOR, NMDA

I don't see 5ht3 there...

But again, like I said, I'm no expert, as should be abundantly clear from my comments here.

So we have two papers (and certainly at least the paper nen shared) that seem to indicate that DMT has little to no affinity for the 5ht3 receptor/is not a 5ht3 agonist, and we still appear to be lacking any evidence that DMT is a 5ht3 agonist.

As an aside, earlier you stated:

I know that I have seen charts listing DMT as a 5HT3 agonist right next to LSD

Yet as far as I can tell, both of these papers also fail to show any affinity for 5ht3 by LSD (and a cursory googling failed to return any hits), so I'm kind of curious as to what chart that might have been.

 

[dreamer042]

But 5-HT3 receptor antagonists are not known for interacting with or causing SS with SSRI's, MAOI's, or other Serotonergic substances.

That OR is the keyword here. You not mixing it with an SSRI or an MAOI or a serotonergic. You are mixing it with an MAOI AND a serotonin active compound AND potentially an SSRI (if THH is present). That is a whole different ballgame.

If you are taking pharmaceutical medications you must be getting them from a physician, the prudent course of action would be to tell your prescribing physician that you intend to take this combination, they are the medical professional with the training to advise about medication interactions, you are not, nor am I. Unfortunately they won't really be able to tell you much either because these things have never been studied with 5ht active psychoactives and complex plant based MAOI's.

Harmalas are generally pretty safe, many people have gotten away with mixing them with MDMA or SSRI's or 5-HTP and these kind of things without fatal consequences, but it's not a given that everyone will get away with such behavior all the time. Just because you got away with it a few times does not mean it's necessarily safe, or that it applies anyone else.

Conversely, 25 % of overdoses of SRIs and moclobemide will result in life-threatening ST, the risk being higher with older MAOIs.

Can 5-HT3 Antagonists Really Contribute to Serotonin Toxicity? A Call for Clarity and Pharmacological Law and Order

Let's remember this is a harm reduction based forum, you are free to do with your own body what you want, but given the lack of research on these specific interactions, pronouncing them safe is fallacious and irresponsible.

And to be completely honest, If I could get a similar purging experience to the norm, I would probably be ok just leaving it as is. Four hours of food poisoning while tripping is not ok.

This is clearly an issue with your personal biochemical makeup, the majority of the thousands and thousands of people that have reported their experiences on these compounds feel fantastic after a nice cathartic purge. This is all the moar reason you should be consulting a medical professional and be extremely cautious in exploring untested interactions.

 

[Sabnock1990]

Dreamer, i'm not sure why you have such an issue with a 5-HT3 antagonist with MAO-A inhibition and DMT. There's absolutely no reason what so ever to be worried about Serotonin Syndrome. I'm not sure why you even brought this up. There's absolutely no interaction/reaction between something like Zofran and Aya/Pharma or any other drug/medication.

If you have some legit science behind your reasoning, please do explain. But there's absolutely no reason to be worried or concerned, and there's no possibility whatsoever for Serotonin Syndrome. You're making a big deal out of absolutely nothing.

Nothing i've ever come across would indicate Zofran would have even the smallest ability to cause SS regardless of what it's mixed with. It's a simple antagonist, it's not an SSRI for christs sake.

And this is not MDMA, an SSRI, or 5-HTP, it's just a simple antagonist and will cause no issues whatsoever, and certainly it won't have fatal consequences hahahaha. I'm all for harm reduction but your point is invalid. You're making a big deal out of absolutely nothing. In fact, i see way more of an issue taking something like MDMA, an SSRI, or 5-HTP with Harmalas before i'd ever see any issue with a 5-HT3 antagonist.

I do agree though, Harmalas are pretty safe, safer than most seem to think they are, but still, i would suggest people be careful what they mix with them and do their research, but a 5-HT3 antagonist? Come on man, there's no reason to be concerned with a 5-HT3 antagonist lol.

 

[Sabnock1990]

This is clearly an issue with your personal biochemical makeup, the majority of the thousands and thousands of people that have reported their experiences on these compounds feel fantastic after a nice cathartic purge. This is all the moar reason you should be consulting a medical professional and be extremely cautious in exploring untested interactions.

As for me personally, i do feel a lot better after vomiting, but as i've said before, that's in general, regardless if i'm on Aya or sober, if my stomach is bothering me, and i vomit, i do feel better. But that doesn't mean i wanna put up with the nausea/vomiting, when i could feel fine regardless. A purge for me is NOT cathartic, it may be rather quick and painless (on most occasions), but it's not cathartic, it's a nuisance, and is not necessary.

 

[syberdelic]

??

 

[syberdelic]

I should learn scripting

 

[nen888]

And you can review the table yourself...but unless I'm misunderstanding something (and my apologies if I am), none of the compounds tested were identified as 5ht3 agonists.

Ki, the inhibitor constant. The inhibitor constant, Ki, is an indication of how potent an inhibitor is; it is the concentration required to produce half maximum inhibition.

By this definition of Ki value, it only applies to antagonist properties (inhibition). The >10,000 value means essentially that it has very little value as an antagonist. It says nothing about DMT's value as an agonist (trigger).

I'm not so sure that's the takeaway...
...

And, the paper that nen shared states

The objective of this paper is to present the receptor binding profiles of the thirty-five drugs of this study in such a way that they can be easily compared in both their similarities and their differences. This is intended to serve as a reference work on the multi-receptor affinity pharmacology of psychedelic drugs.

...

Receptor affinity profiles of psychedelic drugs, ordered by decreasing affinity...

DMT: 4.00 5ht7, 3.97 5ht1d, 3.91 5ht2b, 3.53 Alpha2B, 3.53 Alpha2C, 3.51 D1, 3.42 5ht2c, 3.28 5ht1e, 3.25 5ht6, 3.16 5ht5a, 3.13 Imidazoline1, 2.95 Alpha1B, 2.75 Alpha2A, 2.70 Alpha1A, 2.58 5ht2a, 2.37 SERT, 2.23 Sigma1; 0.00: 5ht1a, D4, D5, Beta1, D2, D3, DAT, NET, 5ht1b, Beta2, Sigma2, CB2, KOR, Ca+Channel, M1, M2, M3, M4, M5, H2, CB1; ND: H1, DOR, MOR, NMDA

I don't see 5ht3 there...

But again, like I said, I'm no expert, as should be abundantly clear from my comments here.

So we have two papers (and certainly at least the paper nen shared) that seem to indicate that DMT has little to no affinity for the 5ht3 receptor/is not a 5ht3 agonist, and we still appear to be lacking any evidence that DMT is a 5ht3 agonist.

As an aside, earlier you stated:

I know that I have seen charts listing DMT as a 5HT3 agonist right next to LSD

Yet as far as I can tell, both of these papers also fail to show any affinity for 5ht3 by LSD (and a cursory googling failed to return any hits), so I'm kind of curious as to what chart that might have been.

..it's been a while for me this sort of stuff.. the paper i linked is only indicating the binding affinity, not whether things are agonist or antagonist, with the Ki value..most classical psychedelics are agonists ('operators' )..but as i understand it, to determine if a compound is an antagonist (blocker) a more specific test needs to be done, where a known agonist is applied and theorised antagonist applied to see the interaction, and receptor occupying, with a IC50 value or similar..an antagonist can equally have a strong binding affinity which is how it blocks the usual neurotransmitter or agonist the receptor operates with..or it at least is shown to inhibit uptake of the agonist..affinity is one measurement, efficacy is the other kind to determine antagonism too.

the paper found 42 receptor types to have some kind of binding affinity, however weak, with least one of the list of classical psychedelics tested, with >10,000 Ki, that being the noise floor..it also found

seven sites at which most compounds were assayed, but at which there were no hits: 5ht3 (serotonin-3 receptor), H3 (histamine-3 receptor), H4 (histamine-4 receptor), V1 (vasopressin-1 receptor), V2 (vasopressin-2 receptor), V3 (vasopressin-3 receptor), GabaA (GABA-A

so it's interesting no common entheogens affect these sites..so it's not a 5ht3 agonist, in this study anyway
a specific test would have to have been done with a known 5ht3 agonist showing DMT blocking if there were any chance of antagonist activity..antagonists commonly have affinity, that's how they block..

another explanation for the nausea as i suggested is the MAO inhibition..i think we can safely assume that there are different causes of vomiting..and different levels of threat to the system which cause this.. i suggested it's amines in general, dreamer042 nominated Serotonin build up as a possible cause, and it and DMT are amines..alternatively some amines within the system (dietary or supplemental) could possibly act on 5ht3..very few people vomit on smoked DMT, but that in sufficient doses it has mild MAOI activity could explain that..it is also worth noting freebase dmt will hit the stomach and metabolise a bit differently to the original salt form..
i am sympathetic of safe methods to reduce nausea in some..

personally i can't help but feel vomiting with harmalas is to do with things in the system directly related to the action of the MAOIs..amines, incl. dietary, and potentially left over from generated moods, stresses etc, which the body has a usual reason for trying to keep at bay..but i am sympathetic that some people experience higher levels of discomfort than others..

i do also note, though, that one of ayahuasca's names in the Amazon is 'la Purga' - that's what it 'does'..

i wish all good luck and safety with their experimentation and experiences..

 

[downwardsfromzero]

There may also exist serotonin receptor subtypes we haven't discovered yet, or syberdelic may even have evolved a new one

Further, we need to be aware that other mechanisms of nausea induction will exist in parallel to the 5HT3 receptor. For example, the simple act of drinking salt water is a fairly effective way of inducing vomiting. Does that involve the 5HT3 receptor?

 

[Sabnock1990]

another explanation for the nausea as i suggested is the MAO inhibition..i think we can safely assume that there are different causes of vomiting..and different levels of threat to the system which cause this.. i suggested it's amines in general, dreamer042 nominated Serotonin build up as a possible cause, and it and DMT are amines..alternatively some amines within the system (dietary or supplemental) could possibly act on 5ht3..very few people vomit on smoked DMT, but that in sufficient doses it has mild MAOI activity could explain that..it is also worth noting freebase dmt will hit the stomach and metabolise a bit differently to the original salt form..
i am sympathetic of safe methods to reduce nausea in some..

personally i can't help but feel vomiting with harmalas is to do with things in the system directly related to the action of the MAOIs..amines, incl. dietary, and potentially left over from generated moods, stresses etc, which the body has a usual reason for trying to keep at bay..but i am sympathetic that some people experience higher levels of discomfort than others..

Ime, i just don't see the build up of Serotonin being the cause of the vomiting, maybe some to do with the nausea but even that i don't think is the case. As i've said before, taking Moclobemide in higher dosages i've never gotten a forceful purge or any other stomach issue from Moclobemide, with or without DMT-containing plants, i haven't even had nausea with it that i can remember, though that's not to say that nobody can't get some nausea from MAO-A inhibition, but it certainly won't cause the vomiting/purge. The purge is related to something the Harmalas are doing, and if it's not 5-HT3 agonism, then it's definitely something else but it's not because of the MAO-A inhibition or a build up of Serotonin or other amines. My extensive experimentation with Harmalas and DMT, leads me to believe there's something about the Harmalas themselves that generates/causes the purge. And once again, with the Harmala reverse tolerance, the purge goes away, so it can't be MAO-A inhibition causing the purge. And diet has never affected/impacted the Harmalas/DMT for me, as well as others, one guy i was talking to on the Aya fb group who does things the traditional way has even noted that diet does not affect/impact his experience (he's dieted and not dieted), that a diet is not necessary/required to take Aya and acknowledges that it's the Harmalas that cause the purge.

I think people really need to deeply experiment around with this stuff, as have i, and really figure this stuff out. I know what causes the purge for me personally, and it's very consistent and reproducible, and the purge always goes away by building up the reverse tolerance. And i have a feeling that 5-HT3 antagonism can help with the nausea/vomiting, but if that's not the case, then maybe something to get digestion going will help. I know Lemon EO seemed to help me block out the nausea/vomiting, whether that was because of 5-HT3 antagonism by some compound in the Lemon EO, or because it was helping to get digestion going forwards, idk.

The only other thing i can think of that could possibly cause the nausea/vomiting is something to do with the cholinergic system. Which if that was the case, then some sort of anti-cholinergic could prevent the nausea/vomiting as well as motion sickness. But idk, something tells me it's very similar to the 5-HT3 receptor being triggered, whether or not that is actually the case. Idk what the exact mechanism behind the purge is, all i know is it's because of the Harmalas, it's consistent and can be gotten rid of by building up the reverse tolerance, or perhaps by taking Lemon EO, or by using Moclobemide.

 

[Sabnock1990]

I'm willing to admit that there are probably different factors that can come into play, like tannins or plant gunk, that can cause some nausea (but not vomiting), but there is definitely some mechanism of the Harmalas that causes the nausea/vomiting, and that mechanism can be desensitized by building up the reverse tolerance. I really wish they would study this scientifically so we'd know what's going on, but yes, the reverse tolerance, imo, is the sure fire way of getting around the nausea/vomiting. Other methods may work, but i'd rather not alter the experience with another plant or something else just to get rid of the nausea/vomiting if i don't have to, the reverse tolerance is just fine for me.

I mainly work with Syrian Rue seed, full spectrum Syrian Rue extract, and purified Harmala extract, but the Harmala-related nausea/vomiting has always been consistent and reproducible for me, even when taking the Harmalas/Rue by itself without DMT. And remember, i've taken DMT-containing plants (even root bark powder encapsulated), tannins and all, with Moclobemide, and no nausea/vomiting was noticed. The only reason i've vomited when using Moclobemide is because of DMT's mental intensity but never noticed any stomach sickness at all when using Moclobemide.

 

[Aum_Shanti]

Strangely it is a bit different for me:
Oral Harmalas alone are not the problem. No purge. Just a bit motion sickness at the beginning.
Oral Harmalas with vaped DMT is also no problem.
But oral Harmalas with oral DMT is a problem.

So IMHO it cannot be just the Harmalas, at least for me. The DMT must have an effect on my intestines, which only happens when taken orally.
For me it's as it seems the combination of DMT with Harmalas. Never tried any other MAOI.

BTW: All Harmalas were "Mansked"

 

[Sabnock1990]

Take higher dosages of Harmalas and you'll see. The reason people don't get nausea/vomiting from Harmalas alone is because they're not taking enough. And when combined with DMT, the DMT will force the Harmala purge, even if you're taking a more moderate Harmala dosage. Trust me, i've been down this road, i've experimented alot, i know what i'm talking about.

Or try oral DMT with Moclobemide and see how that goes.

 

[Sabnock1990]

I really, really, really wish i could explain this better lol. It's definitely the Harmalas that cause the nausea/vomiting. You may not get nausea/vomiting with Harmalas by themselves, but take a larger dosage and you will. As for why DMT seems to force the Harmala purge, i just can't put the reason into words, i just know from experience/experimentation that the source/cause of the nausea/vomiting is the Harmalas, and with the Harmala reverse tolerance built up, the nausea/vomiting goes away, even with DMT in the mix. There's something about the Harmalas that gets desensitized when consuming them regularly and building up the reverse tolerance, that puts an end to the nausea/vomiting. DMT is NOT the cause of the nausea/vomiting, although i can most definitely see/understand why it would seem like it is the cause of the nausea/vomiting, but i'm telling you, dig a bit deeper, do a bit more in-depth experimentation, and you will see what's going on.

 

[Sabnock1990]

The nausea with Harmala extracts is less than consuming the actual plant, but with a good enough dosage, you will definitely get the Harmala-related nausea/vomiting with the Harmalas by themselves. Even the purest of the purest Harmala extracts still cause nausea/vomiting with a good enough dosage because it's the Harmalas themselves that are the purgatives.

As i've said before on here, i once made a mansked purified Harmala extract that i turned into a tincture, and in trying to find the proper dosage, i ended up taking too much of the Harmala extract tincture (by itself, no DMT), and had the worst nausea/vomiting i've ever experienced in my time with these compounds/plants, i had wave after wave of nausea, followed by painful/powerful stomach contractions, followed by wave after wave of vomiting (vomited 6 times that night), and had the most uncomfortable and heavy body load, it felt very weird. So yes, the Harmalas themselves are purgatives. Just because you don't experience the Harmala-related nausea/vomiting from moderate dosages until you mix the DMT in, does not mean DMT is the cause, the Harmalas are still purgatives, the DMT just forces the Harmala purge unless the purgative effects of the Harmalas are desensitized with the reverse tolerance.

 

[nen888]

Ime, i just don't see the build up of Serotonin being the cause of the vomiting, maybe some to do with the nausea but even that i don't think is the case. As i've said before, taking Moclobemide in higher dosages i've never gotten a forceful purge or any other stomach issue from Moclobemide, with or without DMT-containing plants, i haven't even had nausea with it that i can remember, though that's not to say that nobody can't get some nausea from MAO-A inhibition, but it certainly won't cause the vomiting/purge. The purge is related to something the Harmalas are doing, and if it's not 5-HT3 agonism, then it's definitely something else but it's not because of the MAO-A inhibition or a build up of Serotonin or other amines. My extensive experimentation with Harmalas and DMT, leads me to believe there's something about the Harmalas themselves that generates/causes the purge. And once again, with the Harmala reverse tolerance, the purge goes away, so it can't be MAO-A inhibition causing the purge. And diet has never affected/impacted the Harmalas/DMT for me, as well as others, one guy i was talking to on the Aya fb group who does things the traditional way has even noted that diet does not affect/impact his experience (he's dieted and not dieted), that a diet is not necessary/required to take Aya and acknowledges that it's the Harmalas that cause the purge.

I think people really need to deeply experiment around with this stuff, as have i, and really figure this stuff out. I know what causes the purge for me personally, and it's very consistent and reproducible, and the purge always goes away by building up the reverse tolerance. And i have a feeling that 5-HT3 antagonism can help with the nausea/vomiting, but if that's not the case, then maybe something to get digestion going will help. I know Lemon EO seemed to help me block out the nausea/vomiting, whether that was because of 5-HT3 antagonism by some compound in the Lemon EO, or because it was helping to get digestion going forwards, idk.

The only other thing i can think of that could possibly cause the nausea/vomiting is something to do with the cholinergic system. Which if that was the case, then some sort of anti-cholinergic could prevent the nausea/vomiting as well as motion sickness. But idk, something tells me it's very similar to the 5-HT3 receptor being triggered, whether or not that is actually the case. Idk what the exact mechanism behind the purge is, all i know is it's because of the Harmalas, it's consistent and can be gotten rid of by building up the reverse tolerance, or perhaps by taking Lemon EO, or by using Moclobemide.

ShamensStamen.. i do think that harmalas possibly 'contraindicate' themselves, and in high doses yes they cause nausea alone, but it's very hard to factor out residual amines in the system as the cause, and also MAO inhibition is not 'on/off' so above a certain percentage there is increasing exposure to residual amines, or other things..i haven't tried moclobemide so that's interesting..

i find from personal experience that with particular attention to dietary and other intake, that full spectrum whole plant brews of aya analogues with harmalas can be consumed without nausea or purging...though everyone has different metabolisms..purging despite following diet i put down to either residual amines through stress etc ('emotional purging' ), or harmalas above a certain dosage interacting with themselves or something in the system..a lot of people find that it's the addition of dmt to harmalas which causes purging, as Aum Shanti did, which, given its not a known 5ht agonist suggests other mechanisms, such as an automatic purge amines response above a threshold of MAO inhibition.. but there could be other explanations sure

certainly, given the increased research going on into ayahusca this question could do with greater study, as there is no agreed on model for the mechanism(s) of purging..

a lot of people use ginger to reduce nausea, i have no theoretical idea how that would actually work though..

 

[Sabnock1990]

This issue definitely needs to be studied more, so we can put this stuff to the test and figure out exactly what's going on.

As i said though, i don't think diet, MAO-A inhibition, or residual amines are responsible for the nausea/vomiting. Back when i was experimenting heavily with this stuff, i was still eating a lot of crap, didn't make a bit of difference and many others have also noticed that diet does not impact the experience. I'm not ruling out the possibility that diet couldn't possibly be a cause (even though people who have dieted and then not dieted haven't noticed any differences, and they've even dieted and still had nausea/vomiting from the Harmalas), but ime, it's as simple as the Harmalas causing the nausea/vomiting through their purgative effects. Some people just don't vomit though, not sure why, but i know i sure vomit, but the Harmala reverse tolerance puts a stop to that.

I think people need to seriously experiment around a good bit more to see what i'm talking about here. My thing is, i have/had a lot of free time so i can dive in very regularly (i was taking Aya/Pharma daily/near daily for about 2 and half years and then occasionally for another year before i took my much needed break). I was able to get consistent and reproducible effects by building up the Harmala reverse tolerance to do away with the nausea/vomiting among other side-effects, which allowed me to consume stronger/heavier Harmala dosages with no side-effects, using both Rue seed powder in capsules, and freebased full spectrum Rue extract or purified Harmala extract in a capsule.

And i would say definitely try Moclobemide if you can, because that will help you to further determine the cause of the nausea/vomiting. I've never gotten any purging from Moclobemide with or without DMT, the only reason i've ever vomited from taking DMT-containing plants with Moclobemide is because of DMT's mental intensity, which at least then it's more of a voluntary purging rather than the purging being forced on you.

I would not be sitting here saying it's the Harmalas that are responsible for the nausea/vomiting, if i didn't know it to be so and wasn't 100% sure. But it definitely should be studied so we can put this debate to rest. Thing is, if we do find ways around the vomiting, i think a lot of people would be upset with that because they think the vomiting is an essential part of the experience, but imo and ime it does not have to be a part of the experience and can be gotten around just fine while still allowing for the medicine to be powerful, full on, healing/beneficial/medicinal/therapeutic/spiritual, etc. Removing the nausea/vomiting just further improves this medicine imo, it by no means detracts from it.

 

[nen888]

..i think it's good for each person to individually arrive at how to minimise nausea with ayahusca or analogues..the amazonian traditions arrived at diet (and mental cleansing) as an approach, but i'm not saying this is the 'correct' answer..

i do ponder from your post two things, firstly you say you purged from the 'intensity' of the dmt experience..in looking for a physiological explanation here, it still brings me to the amine theory, even if that's because of the dmt experience generating adrenal or other hormones..but i don't know for sure..

also, Moclobemide is a very specific MAO-B[edit: A, i meant here]inhibitor, whereas Harmalas (especially full spectrum mixed) work on both MAO-B and A, from rough recollection, to different extents, meaning they are exposing a wider range of amines to the system..

some people want to eliminate vomiting, others are disappointed without a good purge, as they see this as part of the 'cleansing' (probably the more amazonian approach, to generalise).. i wish everyone safe seas in finding what works best for them...