Is DMT a 5ht3 agonist?

[Sabnock1990]

It's definitely the Harmalas man. I really wish you could do some experimentation and you'd realize that. Imo just stop wondering about it unless you're willing to experience things directly to determine what's going on rather than merely speculating/thinking about what could be going on.

The MAO-A inhibition has no role in the nausea/vomiting/diarrhea, and i'm pretty sure it's the Acetylcholinesterase inhibition especially since most Acetylcholinesterase inhibitors i've looked at have the exact same side-effects. You'd be surprised at how much Serotonin, Dopamine, Norepinephrine/Epinephrine, Acetylcholine etc, your body can produce especially if something is inhibited. I can take Moclobemide by itself and instantly notice the rise in neurotransmitters (especially Serotonin and Norepineprhine).

For me, encapsulated Harmalas/Rue with or without DMT consistently and reproducibly causes nausea and/or vomiting around an hour and a half to two hours, every single time unless the Harmala reverse tolerance is built up. It's very obvious really that it's the Harmalas especially if you're experienced with the Harmalas, it's so obvious that really idk why people even debate it.

Once again i will state, the Harmalas are the source of nausea, vomiting, diarrhea and some other side-effects, especially in higher dosages. In moderate dosages, by themselves, they do not seem to cause those side-effects, but when DMT is added to the mix, the Harmalas effects come out more, including it's side-effects, idk why, but it does. As for the cause of the nausea/vomiting/diarrhea, Acetylcholinesterase inhibition, imo, would be the most likely responsible candidate, but once again my beliefs/opinions are not set in stone and i go by what i experience, observe, understand/learn, and research.

DMT is not involved in the purgative effects, this can be very easily determined by taking it with Moclobemide as simple reversible MAO-A inhibition with oral DMT does not cause nausea/vomiting/diarrhea. So there is some other action of the Harmalas that causes the purgative effects, not the MAO-A inhibition, and not the DMT, so far Acetylcholinesterase inhibition seems to fit the bill.

I would highly suggest you try out some oral DMT with Moclobemide, i can pretty much assure/guarantee you that it will not cause the Harmala-related side-effects and will not make you nauseous. You'd be surprised, if you just took a chance. I mean really, what are you afraid of happening with one trial run? I can tell you it'll make you have to poop, but it'll be just a regular bowel movement ime (not diarrhea), there will be the body sensations/intensity/mental effects, maybe some visuals, but as far as the stomach goes, it's fine. Also you might wanna eat a light meal about 4 to 6 hours beforehand, just so your stomach will be alright during an experience, as an empty stomach (if i haven't eaten all day) even in my day to day life can be a bit crampy and such (maybe some sort of hunger pain?).

 

[syberdelic]

delete me

 

[Sabnock1990]

I'm pretty much done with this conversation, i've said all that i can say, if people wanna take my advice or observations they'll take it, if not, they won't. I'm just telling you what i know to be true, and yes, i do know it to be true. Harmalas on their own can cause nausea/vomiting/diarrhea in higher dosages, and in moderate dosages with DMT in the mix, it's that simple. I guess Huasca just isn't for you.

 

[Sabnock1990]

It's really not difficult at all to figure this stuff out, geez. People make this stuff out to be so much more complicated than it actually is. Experimentation will show you how these things work, without personal experience/experimentation, you just don't know.

But i at least have this stuff figured out, and that's good enough for me, if others wanna find their way, they will find it.

 

[Sabnock1990]

Everytime i try to tell someone what's going on, or what these plants do, or what i've figured out through trial/error and experimentation, hardly anyone is appreciative. Some are, and some have taken my advice and realize i was right, but most just think i'm full of shit apparently because they don't think it's at all possible that i could be right, well i am, either get with the program or leave it alone. I have taken this stuff too many times to not know what the hell is going on. It's very consistent, very reproducible, at least for me.

If you want a purge-free experience, go with oral DMT with Moclobemide or build up the Harmala reverse tolerance, or perhaps try out some Lemon EO with the Harmalas and DMT. Other than that, i have nothing else to offer.

People act like i couldn't possibly know what i'm talking about, well, i do, so take it or leave it. it's that simple.

 

[dreamer042]

The wise researcher remembers that an n=1 does not a truth make and seeks to remain humble in their observations and flexible in their interpretations as new evidence is amassed.

A testable hypothesis has been presented. Let us gather data from a reasonably representative population sample before we draw hasty conclusions.

For example, there is at least one report on Erowid of someone purging using the Moclobemide/DMT combination.

Robert Gable suggests it's actually serotonin stimulating the vagus nerve which is responsible for the purge:

To this author’s knowledge, there have been no deaths caused by hoasca or any other traditional DMT/bcarboline ayahuasca brews. The probability of a toxic overdose of ayahuasca is seemingly minimized by serotonin’s stimulation of the vagus nerve which, in turn, induces emesis near the level of an effective ayahuasca dose. The risk of overdose appears to be related primarily to the concurrent or prior use of an additional serotonergic substance. People who have an abnormal metabolism or a compromised health status are obviously at a greater risk than the normal population, and might prudently avoid the use of ayahuasca preparations.

Gable, Robert S. "Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids." Addiction 102.1 (2007): 24-34. *Attached

 

[Mindlusion]

a more simple explanation in my eyes, but not the mainstream example, is that of stress.

While my experience and that of others is anecdotal, the effect of stress on the body is well known, I am sure there is no doubting that. Neither is the influence of the mind on the body. You control your receptors, not the other way around.

In my experience the nausea/purge is present only during the time of resistance. After the point of surrender, the nausea is entirely vanished. Even experiences where this effect is intermittent, when the resistance comes back, in the form of thoughts, worrying, or any general not necessarily negative state of mind outside of the present moment. When this returns, so does the nausea and the feeling to purge. As soon as its given up, so is the feeling of the nausea/purge. This can happen a single time or multiple times over the course of a few hours. This has been my own experience as well as others.

This explanation is rejected by the mainstream because it can't easily be reduced down to a single variable like a serotonin receptor. As well, it assumes personal responsibility..
It's actually extremely absurd to assume a such a complex system and process could be explained entirely by looking a single receptor like 5ht3 isolated out of the system. It is like like observing a single plant in an entire forest ecosystem and expecting to come up with an explanation for the entire system.

 

[Sabnock1990]

The wise researcher remembers that an n=1 does not a truth make and seeks to remain humble in their observations and flexible in their interpretations as new evidence is amassed.

A testable hypothesis has been presented. Let us gather data from a reasonably representative population sample before we draw hasty conclusions.

For example, there is at least one report on Erowid of someone purging using the Moclobemide/DMT combination.

Yes, one can voluntarily purge using Moclobemide, it's a mental intensity thing, i said on here that i've purged using Moclobemide, but not due to any stomach-related issues, merely due to the mental intensity and the overwhelming body sensations and it was too much so i threw up which slowly but surely helped calm me down over the course of a few minutes and then i stabilized. Which that's the only thing the purge is good for, in my eyes, with Aya, is that i can vomit and not only does my stomach feel better but it seems to calm things down and then i stabilize. But with Harmalas, there is consistent nausea/vomiting/diarrhea that does not happen when using Moclobemide, the only way you'll purge using Moclobemide, imo/ime, is if you're mentally overwhelmed but the stomach seems to do just fine.

Also in that report, that person used 600mgs, far more than one would need, i only needed 150mgs to 375mgs or so for partial to full inhibition of MAO-A. Higher dosages of Moclobemide is said to cause a bit of nausea but one doesn't need that much for full inhibition, but also there is some dizziness and some motion sickness that can occur as well, i know the dizziness was from the Moclobemide, but the motion sickness seemed like it came from the DMT (or possibly the Tobacco i was smoking on). Chances are the purge for that person was due to the psychological intensity and not anything physical, though anxiety/stress can cause some stomach discomfort even in one's daily life, for me anyways, i almost always have to go take a crap if i feel some anxiety/stress.

And yes, "and seeks to remain humble in their observations and flexible in their interpretations as new evidence is amassed", i completely agree, that's why my views aren't set in stone, but i go by research and by experience/personal experimentation and based on my observations, experimentation, regular use, understanding through experience/learning from the plants, and my scientific-mindset, has led me to understand that it is without a doubt, purely the result of the Harmalas. Whether there is some sort of synergy between Harmalas and DMT that makes the Harmala purge noticeable with moderate Harmalas dosages, idk, there could be, but there's something the Harmalas do that is aside from MAO-A inhibition, that causes a purge that does not happen with Moclobemide, and this purge with Harmalas, in my limited experience mixing Lemon EO with purified Harmala/Rue extract seems to be blocked out by something the Lemon EO does, but idk that for sure as i've only had limited experience with that combination and it may alter/flavor the DMT part of things, in an interesting but weird way, so i've gotta try that combination a lot more before i can draw some conclusions about it.

But as for my knowledge about the Harmalas, and about Harmalas and DMT, the purge is purely Harmala-related, so if we can find out what it is the Harmalas do that causes the purge (which happens with Harmalas by themselves, and with DMT in the mix), then we can prevent/counteract the effects of the Harmalas that leads to the purge. If 5-HT3 is involved, so be it, but if it doesn't happen when mixing DMT with Moclobemide, then it's something the Harmalas are doing, not the DMT, whether it be Acetylcholinesterase inhibition, or the Harmalas activating 5-HT3, or a mix of both, there's something going on, on the Harmala's side of things, not the DMT's. The DMT ime/understanding/observations, seems to only induce a purging as a psychological reaction to the intensity and overwhelming nature of the experience or body sensations, has nothing to do with the gut.

Surely some senior Nexus members have tried alternative MAO-A/I sources for activating their oral DMT... If you haven't, try out Moclobemide, see how that goes, and report back. I'm pretty certain of my understanding on this because of what i've experienced, i wouldn't be saying it if i wasn't certain. People really need to do some good and deep experimentation and get back to us on this.

I've experienced the effects and side-effects of the Harmalas come out a lot more when DMT is added to the mix, whereas without DMT the same dosage (a moderate dosage) wouldn't have those effects/side-effects, but something the DMT does brings out the Harmala's effects and side-effects more, even if you don't feel those effects/side-effects when the Harmalas are taken alone in a moderate dosage, some of this can be down to the change in headspace by the DMT which seems to bring out more of it's psychological effects, but the Harmala's physical effects also come out a lot more.

Harmine is also a good bit weaker/gentler compared to Harmaline, i mainly use Rue seed powder in capsules or freebased Rue extract or freebased purified Harmala extract (Harmaline/Harmine mix via manske) so what i work with is Harmaline-dominant, i haven't taken pure Harmine but a few times, but even on a dosage of up to 300mgs, i didn't really feel much from it, Harmaline is by far way more noticeable, but extra Harmine with the Rue seed/extract or the purified Harmalas extract, is more noticeable. Even though you don't feel much from the Harmine at dosages used, with DMT in the mix it's effects will come out more, including it's side-effects/purgative properties. I really don't see how people haven't noticed this yet or if they have they haven't mentioned it.

Also we must remember that the vagus nerve is capable of being triggered by other neurotransmitters as well, like Dopamine, maybe Opiates, as well as Cholinergics.

Also we need to keep in mind that Harmalas/Caapi/Rue in and of themselves cause nausea/vomiting/diarrhea and some other side-effects like headache, salivation, abdominal pains, etc. Also there's no Tyramine reaction with Harmalas or with Moclobemide, it's physiologically impossible and the gut's MAO-A inhibition is so short, especially in tea form (which can be tested out by trying to make DMT orally active, and if you wait too late it will be deactivated or only partially activated), and because of it's reversible nature and also MAO-B which can metabolize Tyramine. If someone says they've experienced a Tyramine-related side-effect, but haven't done a good bit of experimentation to determine that's what it is rather than looking for possible alternatives, then they don't know what they're talking about. Tyramine can even competitively counteract Moclobemide and Harmala's gut MAO-A inhibition because of the reversibility of the inhibition, but can also be metabolized via MAO-B, and the duration of inhibition is rather short so having a Tyramine-related issue is pretty much impossible. If someone experiences a headache for example, one must take into consideration that Harmalas themselves can cause headaches regardless of diet, which headaches are a side-effect of vasodilation/lowered blood pressure, also dehydration, also Acetylcholinesterase inhibition. As for an increase in blood pressure/heart rate, that doesn't happen with Harmalas alone, usually with DMT in the mix because of the DMT's intensity and Adrenergic effects. I've taken heavy heavy dosages of Rue with and without DMT in the mix, and with the reverse tolerance built up, and have never experienced anything dietary-related even when eating right before or after taking the Harmalas, especially with the reverse tolerance built up because of the lack of side-effects.

 

[Sabnock1990]

And yes, we can feel an immediate increase, at least i can, in the amount of Serotonin, Dopamine, Norepinephrine, Acetylcholine, etc, when using Moclobemide, Dopamine Reuptake Inhibitors, also some SRI's, Harmalas, Acetylcholinesterase inhibitors, it's really quite obvious. I can spot Acetylcholinesterase inhibition, as well as DRI, or SRI, or MAO-A inhibition, from a mile away. It may be due to my Autism/Aspergers, but i would think it's like that for everyone else too, and certainly not placebo. I can even notice the SRI from 50mgs of Benadryl, especially because i've been on SRI's before so i know what SRI feels like. I've also taken a few Dopamine, as well as Norepinephrine reuptake inhibitors and can feel an immediate effect from them. Some SRI's may need a week or two to start working, but others do not, and have an immediate effect. Kanna is even an SRI.

When i take Moclobemide, it's effects on it's own are quite noticeable, and i notice the extra Serotonin and Norepinephrine, i also notice some of the Dopamine as well. Same goes for the Harmalas, except they're flavored/altered a bit by their other actions.

Also it's noticeable when you add something else to the mix which is potentiated by the inhibition of MAO-A, or the Serotonin/Dopamine/Norepinephrine transporters, or Acetylcholinesterase.

 

[Sabnock1990]

"The chemoreceptor trigger zone (CTZ) is an area of the medulla oblongata that receives inputs from blood-borne drugs or hormones, and communicates with other structures in the vomiting center to initiate vomiting. The CTZ is located within the area postrema, which is on the floor of the fourth ventricle and is outside of the blood–brain barrier. It is also part of the vomiting center itself. The neurotransmitters implicated in the control of nausea and vomiting include acetylcholine, dopamine, histamine (H-1 receptor), substance P (NK-1 receptor), and serotonin (5-HT3 receptor). There are also opioid receptors present, which may be involved in the mechanism by which opiates cause nausea and vomiting. The blood brain barrier is not as developed here, therefore drugs such as dopamine which cannot normally enter the CNS may still stimulate the CTZ."

Chemoreceptor trigger zone - Wikipedia

en.wikipedia.org

 

[Sabnock1990]

And, once again, anytime i look into Acetylcholinesterase inhibition, i see things along the lines of "Adverse events are consistent with the cholinergic actions of the drug, and include nausea, vomiting, diarrhea, anorexia (appetite loss), headache, syncope, abdominal pain and dizziness." Which fits the bill for the Harmala-related side-effects imo/ime, and it's especially noticeable with higher/heavier dosages of Acetylcholinesterase inhibitors. So maybe the Harmalas through the Acetylcholinesterase inhibition makes the stomach more sensitive to things or there's something about DMT that when added to the Harmalas brings the Harmalas effects/side-effects out more, but it is entirely the Harmalas responsible for the purge, if you take enough Harmalas by themselves, you will encounter the same purgative effects that you get using moderate dosages with DMT in the mix. As for what DMT may do to bring out the Harmala's effects more, i'm still not sure, but the purgative effects are definitely coming from the Harmalas themselves, not the DMT, as DMT does not cause purgative effects with simple MAO-A inhibition like with Moclobemide. So there's obviously something about the Harmalas that is causing the purgative effects, with and without DMT.

As i said, the Harmalas effects and side-effects are brought out more when DMT is in the mix, there's just no way around the side-effects unless you've consumed the Harmalas regularly for a bit and built up the reverse tolerance, then those side-effects go away. So it's OBVIOUSLY the Harmalas........ Lemon EO may help, imo, but i still need more experience to say for sure, but based on my limited experience with Lemon EO with my Aya/Pharma, it does seem to work, so perhaps give it a try and see how it goes if you're feeling experimental enough.

 

[Sabnock1990]

Also coughing or dry heaving might be enough to make one nauseous or vomit. If i smoke Cannabis and start coughing quite a bit, i've gotten nauseous or thrown up because of that quite a few times, including while on Aya. Another thing that seems to make me throw up on Aya/Pharma seems to be if i eat a tums for heartburn, something about that just doesn't sit right with the Rue/Harmalas and i consistently vomit from that combination, though Zantac does just fine for heartburn during Aya/Pharma.

 

[syberdelic]

delete me

 

[Sabnock1990]

It is very interesting to learn that moclomebide + DMT can cause nausea. Despite it being a very large dose of moclomebide, that still points to a smaller, yet similar synergy between moclomebide and DMT as to harmalas and DMT. I'm guessing that the larger dose of moclomebide would produce less nausea if not zero on its own.

For myself, I do not feel like the nausea is being caused in the CNS. Some of the nausea at an hour or so into the trip feels like motion sickness, but the sudden onset early on as well as much of the nausea during the trip feels more like food poisoning where the brain might get involved with coordinating a purge, but is otherwise hands off.

Well a side-effect of Moclobemide can be nausea, but it's nothing like the nausea from Harmalas and from my understanding only comes around in large dosages, larger than the dosages needed for full MAO-A inhibition. Has nothing to do with DMT, and certainly nothing like what one would get from Harmalas. Remember, i didn't notice anything gut-wise when taking DMT with Moclobemide, the only reason i would purge at all when using Moclobemide was due to DMT's mental intensity but my gut was absolutely fine, no nausea at all. So once again, nothing about DMT with Moclobemide causes nausea, there are no gut issues when using Moclobemide.

And i understand what you're saying when you say food poisoning, but that's definitely the Harmalas, i assure you. Harmalas on their own can seem like food poisoning.

 

[tregar]

For what it's worth...always found rue to be much, much more nauseating than caapi.
Meteor (vine only):

Absolutely-- cappi in and of itself is psycotropic.

And it is legal.

Double the dose for the tea. 60 grams instead of 30 to start (though higher amounts probably will not hurt)

The vine is powerful by itself, and the images that it can elicit are quite profound.

Dark, blues, greens-- jungle like landscapes with snakes, cats-- amazing things.

By contrast, Peganum harmala is more likely to make you sick before you have anywhere near the effects that cappi causes.

With all the discussion lately about how important DMT (illegal) is, (and we know that it is) the fact is that the Vine of the Soul (Ayahuasca) is the vine itself.

It is the core of the experience, its trunk if you will. Though P. harmala makes a good substitute when used with the admixture plants-- P harmala, in and of itself, is not the trunk, as only Banisteriopsis cappi (Ayahuasca) can be.

It is good to touch the trunk now and then.

And the images, insights and such are no less profound even if they lack the brightness that the admixture plants provide.

A dark jungle landscape can be a very interesting place to be.

 

[syberdelic]

delete me

 

[syberdelic]

delete me

 

[Sabnock1990]

So maybe the Harmalas through the Acetylcholinesterase inhibition makes the stomach more sensitive to things or there's something about DMT that when added to the Harmalas brings the Harmalas effects/side-effects out more, but it is entirely the Harmalas responsible for the purge...

This seems to be self contradicting. I think I understand what you are trying to say. Harmalas are the prime suspect in aya/pharma nausea. DMT potentiates their nauseating capacity.
If this is what you mean, then it would be inaccurate to say that the nausea is entirely caused by harmalas. And if this is what you're trying to say, then I have no issue with this theory.

I don't think it's inaccurate, the way i see it, it's entirely the Harmalas responsible for the purgative effects, because if you take enough Harmalas dosage-wise by themselves, you get the purgative effects, the exact same purgative effects you get from moderate dosages with DMT in the mix. There's something the Harmalas do that causes the purgative effects, if we find a way around the Harmala's purgative effects, there'd be no purging. There's something about the Harmalas where it's effects/aspects seem more noticeable with DMT in the mix. I've taken strong Harmala dosages before and didn't even know how strong they were until i added DMT to the mix, because it felt so clean due to the reverse tolerance i couldn't tell how strong it was, but when the DMT came in i could feel how strong it was mentally, as well as physically, so i think DMT changes the headspace and because it alters neurochemistry, it seems to make the Harmala's effects more noticeable compared to the Harmalas by themselves.

So it isn't just side-effects of the Harmalas that become more noticeable with DMT in the mix, but also some of the Harmala's psychoactive effects as well. There's definitely some sort of synergy thing going on, but the source of the nausea/vomiting/diarrhea and such comes from the Harmalas, if you find a way around the side-effects of the Harmalas, then the side-effects of the Harmalas won't be there when DMT is added to the mix. And it seems rather clear that due to the reverse tolerance building up and those side-effects going away, and the Harmalas feeling much cleaner, that it's the Harmala's responsible for the purgative effects, as DMT with Harmalas with the Harmala reverse tolerance built up is purge-free and the purgative effects are gone, so something about the Harmala reverse tolerance reduces/does away with the purgative effects, so DMT isn't the source of the purgative effects. DMT may rush the Harmala's purgative effects along, but it isn't the source of the purgative effects. I would like to know why the Harmala's effects are brought out more with DMT in the mix compared to Harmalas by themselves.

I wish more people would do experiments with the Harmala reverse tolerance built up. sure it takes a bit of trial and error but i think there's a lot we could learn from it. They should really study this stuff scientifically.

 

[syberdelic]

delete me

 

[syberdelic]

delete me