Is DMT a 5ht3 agonist?

[Aum_Shanti]

My experience with DPT was mostly insufflated as HCl. 200mg is a pretty wild ride for about two hours.

Wow 200mg insufflated?
Isn't that a lot of substance going up your nose? I mean can the nose even absorb that much?
Or do you have it in solution?

I also heard DPT is quite the nose burner, so 200mg sound like quite painful.

I'm actually quite happy vaping it. Gives me about 1h wild ride and 1-2hours of comedown.
To me it also seems not that aggressive as DMT, but again I never IVed it.
But at around low dose 30mg vaped it is IMHO the ultimate sex drug. Even as a man no problem with multiple orgasms...you can just go on. And tactile sensations are strong.

But back on topic:

If this stems from some kind of motion sickness problem, shouldn't using the standard solutions for this work also for aya (e.g. a Dramamine or Scopolamine)?
I heard it works for Iboga.

 

[Mindlusion]

My experience with DPT was mostly insufflated as HCl. 200mg is a pretty wild ride for about two hours.

Wow 200mg insufflated?
Isn't that a lot of substance going up your nose? I mean can the nose even absorb that much?
Or do you have it in solution?

I also heard DPT is quite the nose burner, so 200mg sound like quite painful.

I'm actually quite happy vaping it. Gives me about 1h wild ride and 1-2hours of comedown.
To me it also seems not that aggressive as DMT, but again I never IVed it.
But at around low dose 30mg vaped it is IMHO the ultimate sex drug. Even as a man no problem with multiple orgasms...you can just go on. And tactile sensations are strong.

But back on topic:

If this stems from some kind of motion sickness problem, shouldn't using the standard solutions for this work also for aya (e.g. a Dramamine or Scopolamine)?
I heard it works for Iboga.

I spent a lot of time trying to 'breakthrough' with DPT. Something like the DMT breakthrough experience is eventually reached, in terms of overwhelming intensity and alienness, but at the same time it is completely incomparable..

I tried nasal and rectal routes with 100-200mg, but could not achieve the desired effect

The first time i attempted to vaporize 200mg of DPT freebase, is when I got something different. This required 5-6 hits and by the last few i was incapable of recognizing the device in my hands. One thing I noticed about DPT and related tryptamines at low doses, even smoked, the effects around 10 minutes to build completely. However, when the dose is high enough, akin to DMT breakthrough, it hits instantaneously and builds and lasts longer.. which is overwhelming to say the least.

the IV dose was only 40mg HCl..... and it was thousands of times more intense than the 200mg attempt... I came to the conclusion that it was very inefficiently vaporized and absorbed by smoking and the other routes.. because this was way way too much

 

[syberdelic]

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[Aum_Shanti]

I would like to point out that Dramamine and Benadryl are contraindicated with MAOIs. As for scopolamine, I'd rather not.

Interesting. Didn't know that.
But why no scopolamine? In the dosages used it's AFAIK harmless and the best substance against kinetosis known. Usually applied with a transdermal patch.
As a cholinergic acting substance, I wouldn't expect much interaction with the Harmalas. Although I'm not sure if there's any other interaction.

 

[syberdelic]

delete me

 

[dragonrider]

So, I had my last experiment with oral DMT last night. I can't speak for anyone else, but for me DMT in my gut seems to have dire consequences. It seems that by putting ondansetron into the mix, the nausea was helped tremendously but the anxiety was through the roof. I also used meclizine. I could feel the vertigo effects, but it was never translated into motion sickness.

My speculation is that by antagonizing the 5-HT3A, somehow the DMT ended up binding with other 5-HT3 receptors which are responsible for anxiety and also somehow changes the visual response to DMT. I had virtually no visuals and last night, I had by far the worst anxiety/depression I've ever had.

That is not such a strange theory. I sometimes take some ginger (wich i believe is also a 5-HT3A antagonist) before ingesting ayahuasca, and i also definately do experience a somewhat reduced visual activity then.

 

[syberdelic]

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[syberdelic]

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[Sabnock1990]

I would also pose the question, "Has anyone else other than ShamansStamen tried the oral combination of moclobemide and DMT orally." And if so, what were the results?

I would like to know this as well. Surely there are other people out there who have taken it with Moclobemide, i know i've come across a few posts here and there online of people who've used Moclobemide for purge-free oral DMT experiences, that's how i found out about it and why i tried it. I'd also like to know if anyone else out there has been adventurous enough to consume common to strong dosages of the Harmalas regularly like i have, and managed to build up the reverse tolerance, which i've also seen some people besides myself mention here and there.

As for your post above this one, imo the Harmalas could very well be 5-HT3 agonists, but if they aren't, then there's definitely some mechanism of action the Harmalas have that causes the nausea/vomiting. Syberdelic, i would highly recommend either trying Moclobemide with DMT yourself, or taking just the Harmine/Harmalas for awhile and build up that reverse tolerance, if you can, i think the Harmalas only needs to be taken about maybe 3 to 4 times week for a couple weeks or so to build up the reverse tolerance a good bit and then add DMT back into the mix and see how it goes. Quite a few people actually recommend for people to work with just the Harmalas for awhile anyways, which i think is a good idea.

As for Zofran blocking the visuals, i'm telling you, when i tried 8mgs of Zofran on top of a strong dosage of Pharma, it completely altered the experience in a very unfavorable way. It seemed like it blocked out some of the Harmalas effects, and made some of the DMT's effects more pronounced but it felt constrained in a way, like the combo just didn't seem to work all that well and wasn't a good combo, though it's probably because i used too much Zofran, so as i said, probably only 0.5 to 2mgs of Zofran would be needed, imo. I hardly get visuals from oral DMT anyways no matter what dosage of Mimosa or Acacia i've used, so i can't speak to the visual aspect, but the Zofran definitely altered the Harmala aspects and did something funky to the DMT aspect, though i did notice relief of nausea when using the Zofran. it's also worth noting that when i've tried Ginger root tea with my Pharma, it did a very similar thing, but i think i may have used too much Ginger at the time and didn't ever get back around to trying it out again. And it's the DMT that's responsible for most of the Pharma/Aya-related anxiety, though Harmaline can cause some anxiety as well due to the GABA-A inverse agonism, but it's by far the DMT that's mostly responsible for the anxiety/intensity/fear/panic and all that, which the anxiety/intensity seemed to be magnified in a way when using Zofran or Ginger ime.

 

[dreamer042]

Since there are so many individuals insisting that harmalas are responsible for the nausea/purge, I would also like to pose the question, "Are harmine/harmaline 5-HT3 agonists?

Not according to this study (See table 2).
Grella, Brian, et al. "Binding of β-carbolines at 5-HT 2 serotonin receptors." Bioorganic & medicinal chemistry letters 13.24 (2003): 4421-4425.*Attached

 

[syberdelic]

delete me

 

[Sabnock1990]

2 mg of Zofran would have done next to nothing for my nausea on that dosage. That should put things into perspective as to how much nausea I experience on aya/pharma. 16mg did a fairly good job of eliminating most of it, but not until I had 24mg in me, did the nausea subside.

From the information available to me, I would think that DMT is indeed a 5-HT3 agonist but somehow does not have the ability to significantly agonize the receptor on its own and requires something like a beta-carboline to catalyze the affinity and/or ion exchange once it has bound to the receptor.

Allow me to explain this one more time. Harmalas inhibit CYP1A2 and CYP2D6, the two main enzymes responsible for Zofrans metabolization. If you inhibit those two enzymes, it's going to potentiate the Zofran quite a lot. Once again, as an example, i take a medication for sleep called Tizanidine which is metabolized by CYP1A2, if i take a good dose of the Harmalas, i only need a half of a tablet (2mgs) for the same effects i would get from 8 to 10mgs (2 to 2 and a half tablets), therefore with both CYP1A2 and CYP2D6 inhibited, Zofran would have similar, if not more, potentiation than the Tizanidine, resulting in the dosage needing to be lowered to 0.5 to 2mgs for the same effects as about 8mgs to 10mgs or more. Caffeine is also potentiated by CYP1A2 inhibition since it's metabolized by CYP1A2 and as a result not much Caffeine is needed for the same effects as Caffeine without the CYP1A2 inhibition.

Secondly, higher dosages of Zofran seem to negatively alter the Pharma experience, resulting in some of the Harmala's effects being blocked or altered, and some of the DMT's effects negatively being altered. Also, higher dosages of Zofran could potentially cause some side-effects that interact in some way with Pharmahuasca. Furthermore, higher dosages of Zofran, ime 8mgs, seems to be too much and interferes with the Pharmahuasca experience in a negative way, so a lower dosage of Zofran would be needed which is why i say maybe 0.5mgs would be alright. Imo, 2mgs of Zofran with the Harmalas' potentiation would be about equal to 8mgs of Zofran without the Harmalas' potentiation, and idk if the effects of 8mgs itself is too much or not when it comes to Pharma, so you might need to lower the dosage to about 0.5mgs or so, which would possibly be about equal to 4mgs of Zofran without the potentiation. Otherwise, if you can't find a good lower dosage of Zofran with the potentiation that's enough to block out the nausea/vomiting without causing negative side-effects or alterations of the experience, then i'd say Zofran just isn't worth it. Which i myself in the time to come will be experimenting further with Zofran and Harmalas and will most likely update this page with my results whenever i get around to doing the experimentation.

DMT is NOT a 5-HT3 agonist, it's just not, and you would know this had you taken it with Moclobemide already, so stop saying it is unless you're willing to do a bit more experimentation. As for Harmalas being 5-HT3 agonists, idk if they are or not, but it's definitely the Harmalas THEMSELVES that are responsible for the nausea/vomiting, with or without DMT in the mix. It really does not take much experimentation at all to figure this out, you just have to be willing to sacrifice some time and comfort to do some personal experimentation and try to figure this out if you're that serious about trying to figure it out, as i was.

Besides, i'm sure there's some other mechanisms in the body or from the Harmalas that can cause nausea/vomiting, so the 5-HT3 receptor might not even be involved at all. So the best way, as i currently understand, to get around the nausea/vomiting for oral DMT, is either to use Moclobemide with oral DMT, or to build up the Harmala reverse tolerance, both of which will produce oral DMT experiences without nausea/vomiting, in my experience. Alternatively, you could try taking about 6 drops or so of Lemon EO about an hour before taking Pharma and see if that will block out the nausea/vomiting, as ime it did seem to help but also might alter the DMT experience in some way, and cleans up how the Harmalas feel. Lemon EO might need to build up in the body for a few days though, i'm not sure, i haven't done as much experimentation with Lemon EO as i would've liked before i took my break from Aya/Pharma.

Another thing you can try, as i've said before, is to take a few puffs of Cannabis with your Aya/Pharma, which at least will greatly help the stomach and put an end to the nausea, but it won't stop the vomiting.

 

[Legarto Rey]

I too have had reasonable luck with ondansetron mitigating n+v associated with ingestion of anahuasca brews and shrooms. To be honest I typically use rue harmala extracts, in modest doses(@250-300mg), which I have found to be gentle in that regard, with or without ondansetron prophylaxis. Personally, the n+v from the hamarla dose is not profound, however I do indeed usually experience a rather intense, though short lived(@15-30min) wave of n+v(with some retching) as the DMT carrier tea floods my CNS. This wave is often coincident with onset of typical geometric OEVs, in fact a strong retch or three, usually prodromes a strong DMT journey, with that "uh ohh, no turning back now" sensibility that heralds onset of potent psychotomimetics.

My lightbringer teas are typically leaf(chacruna, chaliponga) or rootbark(mhrb, arcb) or a combo. They are fltered via "Tregar's" method(large necked funnel with cotton), then reduced. Rue harmala extract caps are ingested @20min prior.

SS, or others, I'm interested in specifics re use of moclobemide as a forcebringer. Particularly comments on, dose, timing, side effects(n+v), mindframe and efficacy, would be much appreciated!

What a "hobby", used entheogenically, by me at least, I'm ceaselessly impressed by the PROFOUND capacity of plant tryptaminics to deconstruct consensus reality(briefly) yielding deep states of wonder, insight, gnosis, and often healing! Synthetics are of course similarly endowed, just a bit trickier to source for this student.

Peace

 

[syberdelic]

delete me

 

[Sabnock1990]

Just a thought that popped into my head, but would reversible Acetylcholinesterase inhibition by Harmine or Harmaline be enough to cause the nausea/vomiting/diarrhea, especially with higher dosages? We know that the Harmalas can inhibit Acetylcholinesterase, so it could be a possibility.

On the wikipedia page for Acetylcholinesterase inhibitors, it says diarrhea, headache, nausea and vomiting can be side-effects, and can even cause what is called SLUDGE syndrome which can cause salivation, tearing, urination, diarrhea, gut issues like cramping, and vomiting. Also on an article titled "Acetylcholinesterase inhibitors in Alzheimer’s disease" it said "Many of the side effects of the AChe inhibitors are attributable to peripheral cholinergic effects. Nausea, vomiting and diarrhoea were the most frequently reported."

But if that's the case, then how would DMT play into this? Perhaps it somehow increases Cholinergic activity as well, maybe through Serotonergic activation? Or maybe the Harmalas make the gut more sensitive to things so when the DMT is consumed the enhanced Acetylcholine response causes the purging? And what if some of the reverse tolerance has to do with getting used to the Acetylcholinesterase inhibition and thus the side-effects go away, if that is the case? Also if this is the case, how might some sort of anti-cholinergic deal with this, like maybe Brugmanisa or some other anti-cholinergic containing plant or substance? Anyone ever include anti-cholinergics with their Aya/Pharma and noticed any less nausea/vomiting? Or would anti-cholinergics even counteract the Acetylcholinesterase inhibition or just merely block off some receptors?

 

[syberdelic]

delete me

 

[Sabnock1990]

Yeah but i still don't see DMT as being a 5-HT3 receptor agonist, if that was the case it would cause nausea/vomiting with Moclobemide or with Harmalas with the reverse tolerance, or would cause it if it were smoked/vaped. It's only when it's combined with the Harmalas, and based on my experience/observations/understanding, it's the Harmalas we need to be investigating, not the DMT. The Harmalas cause the nausea/vomiting, DMT doesn't, i really wish i could explain my view on this better but the best way really that i can put it is that Harmalas on their own at a certain dosage feels one way, but when DMT is consumed the Harmalas' effects get brought out more and are more noticeable, not only the nausea/vomiting but also how strong the Harmalas are headspace wise and their effects, it's like with DMT in the mix the Harmalas' effects get amplified and you're able to notice the Harmala effects better than you can with Harmalas alone.

I would definitely put my money on the Harmalas being the issue, even with moderate dosages, rather than the DMT, based on my experience/observations/understanding. Study the Harmalas, learn about their effects/side-effects, and you will find the answers you're looking for.

I would say though that it might be worth it for people to consume the Harmalas alone in moderate dosages to build up the Harmala reverse tolerance and then add DMT in the mix when the reverse tolerance is built up. That's the only sure fire way of getting around the nausea/vomiting ime/imo, but i know some people probably won't wanna do that so we need to find a more immediate way around the nausea/vomiting so that people don't have to build up the reverse tolerance.

But yeah, idk what it is about the Zofran or Ginger that seems to affect the overall experience and increase anxiety and such, but ime/imo it has more to do with the Zofran and Ginger affecting something the Harmalas do, as well as affecting something the DMT does.

One thing i've learned about Aya/Pharma is that it can be so easily altered by things, probably more so than other Psychedelics though i'm not sure. Like you can add a plant to the mix and it can absolutely change the nature of the experience/medicine, it can very easily be altered by things. There was even a few times i was taking a Zinc Gluconate supplement (50mgs) and some Magnesium Oxide and had some really weird, consistent/reproducible effect on the Aya/Pharma that would not only give me some weird heart effects (Magnesium) but also some weird brain zap thing (Zinc) that was so different and uncomfortable compared to the usual/regular brain zaps people can get from this stuff, so there's definitely things out there that can interfere with the medicine/experience or alter it unfavorably. I think in the case of Zofran or Ginger though, it could just be that i took too much, but on the other hand, i need to experiment around more with them to say for sure.

 

[syberdelic]

delete me

 

[Sabnock1990]

Well all i'm saying is that based on my own extensive experimentation/observations, it's the Harmalas themselves that are the issue, DMT isn't. The only way one can learn more about this, is by direct experience. I'm pretty certain it's the Harmalas causing the nausea/vomiting, and if people experimented around more they'd come to that conclusion as well. DMT is not the cause of the nausea/vomiting, i know that with 100% certainty, of course i'm always willing to be proved wrong, but i'm telling you, it's the Harmalas.

You personally don't seem to have nearly as much experience with this stuff as i do, so i can see/understand why you and others would think it's the DMT, but that's why i say people need to be scientific about it and really experiment around to try to figure things out. Speculation is one thing, but there are understandings about both the Harmalas and the DMT, and what they do in the body, that you learn from direct experience.

If it wasn't the Harmalas, i wouldn't be saying it's the Harmalas, so take my word for it or don't, or do your own experimentation. I'm just telling you what i know, it's your choice to believe it/go with it or to find other explanations, but everything i've learned about this stuff both from research and from personal experience, indicates it's primarily the Harmalas that cause the nausea/vomiting. I know it can be difficult to wrap your head around, but it's definitely the Harmalas. I took this stuff daily/near daily for 2 and a half years, i think i know pretty well what this stuff does, more so than most people on here most likely.

 

[Sabnock1990]

All i can really say is, people need to do more experimentation with Harmalas by themselves, and with Harmalas and DMT. After quite a bit of experimentation, you learn more about what's going on in the body when you consume this stuff. And like i said, the nausea/vomiting/diarrhea goes away when the Harmala reverse tolerance is built up, so if it was the DMT, DMT would still cause the nausea/vomiting even with the Harmala reverse tolerance, or with Moclobemide, or if you vaped/smoked it, even Changa has made me purge before, so everything that i've experienced, everything i've learned from this stuff, everything i know, indicates it's the Harmalas, and you just can not draw such a conclusion that it's the DMT unless you've personally experimented around with it as much as i and some others have. You can't just have a few experiences and think you know what's going on, you need a lot of experience to be able to clearly tell/understand what is going on.

Like i said, with DMT in the mix, even with a moderate Harmala dosage, the Harmala's effects come out more and are more noticeable than the effects are with just the Harmalas by themselves. The Harmalas cause the purgative effects, DMT does not, even if you're fine with a moderate dosage of Harmalas by themselves, you just have to learn more about the Harmalas to see what they're really doing in the body. But the Harmalas/Caapi/Rue are known for their purgative effects, yes it comes on more fully with Harmalas by themselves when they're consumed in higher dosages, but even in moderate dosages, they can still cause the purgative effects when DMT is added to the mix. So the answers you and others seek, lies in the Harmalas, i'm telling you, with 100% certainty, it's the Harmalas. There's no other explanation for it, imo/ime.