I am starting a new thread on this topic in the science section as previous attempts to understand this thing have not really led anywhere constructive.

If you want to pan over previous discussions, go here.
Is DMT a 5-HT3 agonist
But I intend to start this conversation fresh, so don't bother reading this long and redundant thread unless you just really want to.

I would love to be able to eliminate the purge as it makes the whole experience completely untenable for me, but that is not the purpose of this. I intend to understand the mechanism/s behind what specifically causes the nausea and vomiting with Ayahuasca and pharmahuasca. Once the mechanism/s are understood, then we can consider whether the purge can be eliminated but again, that is not the intention of this query.

First, I am going to take off the table things other than DMT and harmalas. I know from first hand experience that tannins, terpins, and other plant materials contribute to the nausea and upset digestive tract, but the mechanisms behind this are fairly straight forward and don't need revisited. Fairly pure pharmahuasca seems to invoke La Purga just fine and in the same way, I would like to distill this discussion to the most basic components: DMT and harmalas.

Second, I am taking off the table things like spiritual purging and intensity. Maybe there is some validity to it, but these are roads that lead to nowhere in this quest for knowledge. And as an example, my partner has had Ayahuasca six times and purged every time. The purge seems to come on at 25-35 minutes, but she feels no other effects until around one hour. This tells me that the purge is something separate from the psychedelic experience. I'm sure that for most of us, the anxiety that can come along with a strong trip will exacerbate this nausea, but I'm considering this a separate entity as it will only serve to complicate the issue.

Third and finally, I would like to take off the table the notion that harmalas are 100% responsible for the nausea and vomiting. They are no doubt a contributor and probably a major one. Yes, if enough is taken, it will make one extremely nauseous and purge their guts out but this is not the scenario that we are examining here. We are talking about a moderate dosage that is adequate to inhibit MAO, say for instance 150-200mg of pure harmine HCl. This dosage does not seem capable of causing La Purga in most individuals, but rather just mild nausea/vertigo and maybe a mild upset stomach. BUT, by adding DMT into the gut, at least one purge is almost guaranteed and for those like myself, it lasts the duration of the trip.

So, to start things out, I will offer a couple of theories:

1) DMT, being a tryptamine makes it a likely candidate as a 5-HT3 agonist. Many things however contradict this including my own experience of mixing pharmahuasca with a large dose of 5-HT3 antagonist. This theory would require that DMT is a very weak agonist or binds very weakly to the receptor. But there may be some synergistic action when harmalas are introduced that cause DMT to bind more strongly to 5-HT3 or cause it to have a greater effect at opening the ion-gate. We have some data (need more) that by using moclomebide in place of harmalas as the MAOI, there is no discernible nausea. This implies that DMT on it's own is incapable of producing any significant nausea even when it is unimpeded by MAO. But others report nausea/vomiting from inhaling freebase DMT. Maybe some of it enters the esophagus/stomach? This is where we need more data of pharmahuasca use with moclomebide as the RIMA.

2) DMT is a strong agonist of the sigma-1 receptors. This receptor does not seem to do a whole lot on it's own, but rather it modulates and "amplifies" other receptors including acetylcholine and serotonin receptors which outside the central nervous system can cause nausea. Harmalas inhibit enzymes that break down acetylcholine as well as serotonin. Moclomebide inhibits only the enzymes that break down serotonin, so our limited data would suggest that elevated levels of serotonin in the gut have little or no effect on nausea. But the elevated levels of acetylcholine alone or with elevated serotonin could be modulated by overactive sigma-1 receptors via DMT to create La Purga.

I agree that we need to keep the conversation ongoing and we need to get to the bottom of this and figure out the mechanics behind the vomiting/nausea. With that said though, i must once again point out, that in my experience, the Harmalas are indeed responsible for the nausea/vomiting, even at moderate dosages where one usually wouldn't have nausea/vomiting with a moderate dosage by itself, but that when DMT is added to the mix, it brings out the Harmalas purgative effects. So we know that it is indeed the Harmalas that are responsible for the purging, what we need to find out is why adding DMT to the mix seems to bring out more of the Harmalas effects, not just the purging, but also some of the Harmala headspace and some other effects of the Harmalas. In my experience, Harmalas by themselves at a certain dosage is more tolerable than with DMT in the mix, but once you add DMT to the mix, the Harmala's effects come out more. So what i'm saying is that it's the Harmalas that we need to be looking at, but we also must take into consideration that adding DMT, or even other non-DMT containing plants, to the mix seems to alter or bring out the effects of the Harmalas.

Also as for people getting nauseous and vomiting from vaped DMT, i've gotten nauseous and vomited from Changa, but from my understanding people usually don't get nauseous or vomit from vaped pure DMT, unless they burn it. The reasons i've vomited from Changa, was because for one i'd get this feeling in the back of my throat from burning the DMT that felt like there was a lump of plastic in my throat, and it'd make me gag and throw up, the other reason i've thrown up was there's been a few times smoking Changa where i'd get this kind of contraction-like pain in my upper abdomen like in the middle right below my ribcage, which is the same place i felt the powerful/painful gut contractions from taking a heavy heavy dosage of purified Harmalas by itself one night. But properly vaped/smoked Changa compared to oral Aya, usually doesn't cause me any nausea/vomiting, but if i burn it or perhaps if i use too much Harmalas, i can get nauseous, and sometimes vomit.

So while i'm quite sure the DMT itself isn't responsible for the nausea/vomiting at all, and that it is indeed the Harmalas we should be focusing on, i do admit that there's something about the Harmalas that gets brought out more when DMT-containing plants or even other plants are consumed. Think of it this way, i have a program on my computer called Realtek Audio Manager, and it has a loudness setting that when checked, can make the sound/music louder, so say you're listening to a song and the volume is a bit low, you turn on the loudness setting and it gets louder, apply that to the Harmalas and DMT, you take the Harmalas and while you may get some effects, a lot of the effects and side-effects are absent, but when you add the DMT, the Harmala's effects/side-effects come out more and are more noticeable. It's not the adding of the DMT that is the issue, it's that adding in some plant with the Harmalas seems to alter the headspace and bring out certain effects of the Harmalas. I'm not dismissing the possibility that DMT does do something, but that the purgative effects are definitely coming from the Harmalas themselves, and not the DMT, so we need to focus on what it is the Harmalas are doing, or the combination of Harmalas and DMT, rather than thinking it's the DMT. I completely understand, as i've stated before, why people would think DMT is the culprit, believe me i do, and if i had a reason to think some of it was coming from the DMT, i would definitely say so, but so far my experience has showed me it's the Harmalas, not the DMT, the DMT may cause the effects to come out more, but the source is definitely the Harmalas.

And yes, we need more data on the Moclobemide and DMT combination, and judging by the reduction in available Moclobemide on the site i get it from i'd say there are people here who have bought some and are most likely experimenting around with it, so hopefully if they are, they will report back on how it all goes. For me, DMT with Moclobemide definitely causes no nausea or vomiting, though one could still voluntarily vomit due to the psychological intensity, at least i know i have, but as far as the stomach goes, no problems ime. Moclobemide may cause a little nausea itself in some individuals at higher dosage (like 600mgs or more) but i've gone up to 450mgs i think of Moclobemide and haven't really noticed any stomach issues with it, even with DMT in the mix. So the Ayahuasca purge doesn't seem to be DMT-related, it doesn't seem to be MAO-A related, so there's something else the Harmalas are doing that is causing the purge.

I hope we do get this figured out though because i do not believe the purge has to be a part of the experience, if people want the purge they can have at it, but we shouldn't have to embrace undesirable side-effects if there's a way around them. I've had plenty of purge-free experiences that were just as powerful if not more so, than the experiences where i've purged. Purging for me, seems to calm things down, lessens the intensity and stabilizes the effects/experience, whereas for some others they experience an intensification of effects after purging. So for me at least it's better for my body to be able to process it normally rather than vomiting it back up. The nausea sucks but Cannabis can handle the nausea for me most of the time, but i'd really rather not vomit. Don't get me wrong though, i've embraced the purge before, i've accepted it for what it is for me, but i do not see it as a necessary part of the experience.

My experience with both Aya and pharma is that I start tripping with some really nice visuals, then I start feeling the pressure and stomach contracting. I get a bit of anxiety about the whole thing and then purge. I do not fight it. I let it come up and actually embrace it as this is supposed to end the nausea. The visuals diminish greatly after the purge and are replaced with dark visions. Death, disease, despair, anxiety, helplessness, etc. If I've taken enough, I continue to purge every five to ten minutes until I'm dry heaving.

Eventually I embrace the fact that no amount of heaving is going to diminish the nausea. I feel deathly sick and poisoned until I sober up. I wait for the drugs to wear off. I get horribly constipated for the next 7-10 days. Around day 3-4 I get crippling abdominal pains.

Since trying Ayahuasca over a year ago and subsequently experimenting with pharmahuasca, I've had gut issues that are yet a mystery and horrible problems with anxiety that I've never had before even close to this extent. My first full on panic attack was during this period. I'm fairly sure that whatever is going on is nuerological and I won't go as far as to blame ayahuasca, but I'm pretty sure that it plays a role. I've taken many different kinds and even large amounts of psychedelic drugs to include DMT over about 20 years and never had any issues of this sort until bringing harmalas into the mix.

This is one of the reasons that I'd like to figure out the mechanism by which Aya/pharma causes nausea. It may hold some clues as to the awful state of my gut and my anxiety issues.

Well said. First off, do you fast before taking this stuff or do you eat the day of like maybe 4 to 6 hours beforehand, or even after? Going in on an empty stomach can be a bit worse than eating something earlier on in the day, there seems to be a bit less stomach issues if you've eaten but the purgative issues can still be there. Have you tried perhaps eating a little something, maybe some crackers or bread, after vomiting to maybe settle the stomach? Have you tried drinking some water or soda after vomiting? (as i've noticed sometimes a bit of liquid can help settle my stomach, sometimes).

As for the constipation, i feel your pain lol, literally. I too get constipated from Harmalas (even just taking them on their own), and after a few days i'll start getting abdominal pains too, heck for the longest time i had abdominal pains and didn't know what was going on until i realized i wasn't pooing like i should be and was most likely constipated. Granted there's probably some other reason or so that contributed to the stomach pains i used to get, but i think constipation had/has a good bit to do with it, i've apparently had constipation issues all my life, even my dad had issues. One thing that comes to mind is perhaps the gut bacteria, which i know for a fact influences digestion and bowel movements, which could be wiped out by antibiotics or even altered by diet, so maybe check into that if you haven't already, like probiotics and even certain natural antibiotics or antifungals or what not and see if maybe it'll help clear up the stomach in your everyday life. Also keep in mind that Harmalas themselves have antibiotic and antifungal properties if i remember correctly, so that could've shifted something in your gut.

As for constipation related to Harmalas though, i think it's the Acetylcholinesterase inhibition, because i've noticed that Lemon EO seems to do something similar, and the Alpha-Pinene in there seems to be an Acetylcholinesterase inhibitor as well, and higher dosages of Lemon EO give me diarrhea (at least at first), and then i notice i start getting a bit constipated over a few days, it also seems to be harder to pass gas, both with Harmalas and with Lemon EO. Though i will say that Lemon EO helps my gut, ime, but it also seems to cause me some constipation, which i'm not completely constipated, it's just harder to poo or pass gas from time to time. What's weird though is Acetylcholinesterase inhibitors are said to help with constipation and bowel movements, but ime while they do help me poo better, they can also constipate me it seems. Oh and another possibility for constipation (and possibly nausea/vomiting) at least when it comes to Syrian Rue could be that "the alkaloid extract of Peganum harmala seems to have both central and peripheral antinociceptive activities which may be mediated by opioid receptors", which idk if that applies to pure Harmine or Harmaline, but it's something to think about i guess.

As for the anxiety, i started getting quite a bit of anxiety after awhile of taking Aya/Pharma, i think a lot of it had to do with Cannabis but i think it was originally there and maybe the Cannabis just amplified it perhaps, or it could've just been the Cannabis. But also i think some of it could've been the intense experiences from the DMT, or maybe had something to do with the Harmala's GABA-A inverse agonism. But it's gotten quite a bit better over time, for me anyways, since i've been on my break. Also keep in mind that the intense nature of DMT/Aya/Pharma experiences, as well as other Psychedelics i'm sure, can cause a kind of PTSD, so that's something to look out for.

Getting back to the nausea/vomiting though, basically, we know it's not the MAO-A inhibition causing the purgative effects, we know that it's not the DMT causing the purgative effects, we know it's not the combination of MAO-A inhibition and DMT causing the purgative effects, so that only really leaves us with something else that the Harmalas do that causes the purgative effects, whether it be Acetylcholinesterase inhibition, or if it triggers the Serotonin 3 receptor, or if it does something with the Nicotininc Acetylcholine receptors, it's definitely the Harmalas doing something that is causing the purgative effects. The only thing i've noticed DMT doing with the Harmalas, is that it cuts through the Harmala-only headspace/effects, alters the feel/effects, and seems to bring out some of the Harmala's effects, like with that change in headspace from the DMT you're able to notice more of the Harmala's aspects than you would at the same dosage without the DMT. I don't think DMT itself is particularly triggering or causing nausea/vomiting/diarrhea, i just think there's a kind of synergy there that brings out more of the Harmala's effects and thus can cause the Harmala purge, even at a moderate dosage. So we need to look more into the Harmalas and figure out what all it is that they do, and from there we can figure out what's going on to cause the purge and hopefully find a way around it. I do wonder if some sort of anti-cholinergic would help, but if not it could be something as simple as the Harmalas triggering 5-HT3 or something but idk, the Acetylcholinesterase inhibition side-effects seem to line up perfectly. Maybe the Tropane alkaloids/plants would be useful, but i'm not sure, there's also Nicotinic Acetylcholine receptors that may need to be looked at.

delete me

As I pointed out previously, 5ht2 excitation in the emetic nervous system is significantly more likely than than the same thing you fellows keep making new threads to pitch over and over, and over, and over, again, despite substantial evidence contradicting your respective positions.

That doesn't account for the purgative effects of the Harmalas though, Psychedelics do not cause the type of purging associated with Harmalas, so i highly doubt 5-HT2A activation causes this kind of purging. Also, there is evidence that Harmalas inhibit Acetylcholinesterase, both Harmine and Harmaline, and not only scientifically, but also from my own personal experimentation.

And i don't see how people don't recognize that it's the Harmalas causing the purging. DMT does not cause purging, Harmalas do (by themselves, and with DMT in the mix). So clearly it's something the Harmalas are doing, that's not MAO-A inhibition, that's not 5-HT2A related, and probably not 5-HT3 related, so that leaves the question, is it the Acetylcholinesterase inhibition? And seeing as how the side-effect profile of known Acetylcholinesterase inhibitors matches up perfectly 100% with the side-effects i've experienced from pure Harmalas and Rue, then why would it not be the Acetylcholinesterase inhibition, which also leads to feelings of being poisoned in a way? (especially since irreversible Acetylcholinesterase inhibitors are used as nerve gases and insecticides/poisons, whereas reversible inhibitors like the Harmalas aren't used in that way and are used medicinally but i'd say it can definitely still make you feel like you've been poisoned, it makes perfect sense.)

And also, why aren't people studying this? Surely some Nexus members are in the academic/scientific communities and could perhaps run some tests rather than having this keep being brought up over, and over, and over again. And i know studies cost money and all that but this is definitely something worth looking into and i'm not sure why it hasn't yet been studied to determine what's causing the vomiting. It should be pretty straight forward if you ask me.

delete me

Lots of tannins in the brew can make you feel pretty bad... been there, but I find the purge enjoyable, because it tends to be more of an emotional purge.

syberdelic, how do you make your Ayahuasca brews? With what ingredients, and how much?

Pharma without discomforts. Might help you.

You'll forgive me for saying (actually, you probably won't) but this sounds rather paranoid/conspiratorial. Do you honestly believe that there is a conspiracy to prevent people from unraveling "the mystery of la purga"? Considering the degree to which scientific inquiry and open-source spreading of info are at the core of the Nexus, it seems like an odd accusation to level.

Who has quashed your inquiry? People have only said why they disagree with you at various points in your reasoning. That's part of what happens when you start theorizing on a public message board.

As to the notion of nausea-free ayahuasca becoming "a drug of abuse" that seems unlikely, not only given DMT's self-regulating effects (see the countless "hyperslap" reports) but also similar phenomena vis a vis psychedelics more generally.

It has become painfully obvious that I will find none of the answers I seek on the Nexus.

You all can carry on with the psychedelic pseudo intellectual circle jerk without me.

With that attitude, you'll never get the answers you seek...

Perhaps, but no blame to nexus imho. I'm still wondering what you were after. What were you expecting people to say or do actually? I offered a high potential solution but that is not interesting or worth a thx-for-the-hint?

Relax dude.

I think a way to start to answer some of your questions is do the following:

1- Eat a bunch of DMT without taking MAOI. Do you get nausea? I've never done this so I dunno.

2- Eat a bunch of MAOI without DMT. Do you get nausea? I do.

3- Take DMT and MAOI purified. Do you get nausea? I do.

4- Take ayahuasca. Do you get nausea? I do and way worse then 2 and 3.

Nausea has a lot of causes. I know people who can do a shot of cactus extract and not puke whereas I'll purge out both ends for like an hour. Same goes for ayahuasca. Its partially an individual thing. Its partially a diet thing. Its partially a chemical thing (from the chemicals you are ingesting).

I dunno if speculations about what receptors are triggering nausea make much sense unless you have antagonists to those receptors available to see if you block one does the nausea go away. My guess is its multiple things and blocking a specific receptor won't stop nausea. But it might make it better.

Although there are some anti-nausea drugs that are prescribed during chemotherapy that I think work by blocking seretonin receptors. Might be good place to look for evidence to confirm / refute your ideas.

Edit: Here is the drug I was thinking of.

https://en.wikipedia.org/wiki/Ondansetron

Notice the similarity in the structure to harmala alkaloids

Take this with 1,2,3, and 4 and then you'll know the answer. I see that you said you've combined pharmahuasca with 5-HT3A antagonist. Do you have more details on that?

I've drunk many different Ayahuasca brews in group ceremonies as well as my own home brews.
In my first couple of years I purged almost every time, but haven't purged once in the last 7-8 years.
I don't think I get nausea, but I'm not exactly sure what nausea is, so maybe I do?

My friends don't usually report nausea, so I presume it's not a big deal for them either.

Whatever it is in the tea that causes the nausea, it may be that the body develops tolerance with repeated use. Nausea serves to deter us from ingesting a substance that is recognized as a poison, so when we continue to take it anyway, maybe the body eventually gets the message and gives up on protecting itself from that particular substance?

Just to add I've only purged twice in all the times I've drank dmt/maoi. And both times I'm pretty sure were related to what I'd ate not too long prior [earlier on in my journeying, mistakes] All the other times it just never progressed to the degree of "oh its coming up!". Wasn't even fighting it either, was pretty much letting whatever come - come. And most of my dosing wasn't with lighter dosages either, so for me I don't think dosages I was taking had too much of a bearing on me purging [then again I'm sure if I took a gargantuan amount of vine or rue by itself or in combination with dmt it'd cause me to purge].

My dosages typically were anywhere from 70-90g [ or 230-250mg caapi freebase] vine in addition to the dmt admix. Rue's around 4-5g [or 230-250mg rue freebase] usually. These dosage tiers pretty much knock me clean into the dirt, just that the bit of nausea never really develops to the degree of me having to go do something about it.

Hey burnt, syberdelic discussed Ondansetron and his other experiences with nausea-prevention attempts in this thread. Unfortunately, it appears the he took most if not all of his posts with him when he ragequit the forum so...

That said, there's still some discussion on it that's readable/coherent.

From what ive read ondansetron can cause serious cardiac problems especially if combined with other drugs so id strafe away from the idea of combining it with DMT and/or harmalas. Both have serious effects on the heart as is. Id rather purge than get a heart attack or cardiac arrhythmia while tripping.