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Best starter psychedelic?

Wow, I just realized that we've posted a whole thread of advice without ever asking why you were interested in a psychedelic in the first place. Is there something in particular that you are trying to get out of them (personal insight, therapy, spiritual revelation, etc.) or is it out curiosity that it is driving you forward? That might help narrow down the guidance.

After re-reading your question, it seems to be that 2C-B and 4-AcO/HO-MET are reasonably good candidates unless there is a specific need like one of the above that you are seeking to address
 
2C-I
2C-T-2
2C-EF

And also the relatives-
2CB-FLY
25B-NBOH

2CB has always been just out of reach, really wish I got a chance for 2CE as well.


May I ask which other 2C-X compounds you have tried? In my case, this is:
2C-B
2C-C
2C-D
2C-I / 2C-TFM mixture/false synthesis

I liked 2C-B best of these four compounds. Later in my life, I definitely plan to take 2C-E, 2C-P, 2C-T-2, 2C-T-4 and 2C-T-7, but I had no time for them yet (those compounds take 12-18 hours in total)... ;)
 
I know you've gotten a lot of responses so far and most of them are good. I just wanted to chime in to say for a newbie I always start them with the two classics: LSD and Shrooms. LSD is probably the most mild out of the two because it allows the newbie to have more control over the first experience. Mushrooms, while more capable of getting a bit wacky at lower doses than LSD is "natural" and tends to put a newbie's mind as ease due to the fact that they've been used for so long throughout human history and come directly from the ground.

My first trip was on 2-3.5g of decent mushrooms and I still consider that to be the best starting point for a newbie.
 
In my opinion 2-CB would be a horrible starters choice, I dont know the logic behind many people recommending it for first timers but the first time I tried it I just feel extremely weird like it wanted to be a psychedelic and not really at the same time and I was extremely uncomfortable (this was reagent tested 2-CB) and keep in mind I had eaten ton of shrooms before this, 5 strips of LSD, mescaline, DMT, etc....

In my opinion the best would be shrooms since they are more sedating than LSD in general and feel a little bit calmer and also dont last long so if you have a bad trip its over soon, they are also easier to accurately measure your dosage and know exactly how much you are consuming unlike with LSD blotters, mescaline containing cactus and ayahuasca brews, after shrooms I would say LSD, then ayahuasca and mescaline lasts, mescaline is the longest acting and for me was the most stimulating... not a good idea for a first timer, either shrooms in a small dosage or LSD from a trustable source in a small dosage and reagent tested.
 
Ungelsene_bettlek- With all due respect, maybe try the drugs your trying to school others about??

MDA isn?t a delierient in the classical sense of the word no, but if you actually take the drug one day you?ll see that the hallucinations mimic that of deliriants over traditional psychedelics. (It should be noted MDA can vary though as well batch to batch, that?s for another thread though.)

For example, on MDA you?ll see things that aren?t there, you?ll hear things that aren?t there, etc. I?ve never had patterns, or melting or anything closely resembling traditional psychedelics. (Classic MDA is seeing hats on people or glasses on people, smoke with no source of origin, shit like that.)

The only psychedelic that comes close is Mescaline, which ALSO can have delerient esque visuals. For example, one time I was hiking down a forest road tripping on Mesc and I saw a car driving at me until I blinked and it disappeared. I?ve seen spiders crawling along only to vanish in thin air, watched humans take on alien forms, all clear as can be with no other visual distortions.

Maybe delerient isn?t the best term, as it seems like dream world is meeting reality.

Now please get off the computer and go actually eat a few of the drugs your trying to tell others about. Knowing binding affinities for receptor subtypes is great and all but you get such a narrow, often skewed, view of the drug with our extremely limited current pharmacological knowledge.

-GC
 
Sorry if I wasn't clear normal dose for al-lad is 150 ug, 4-ho-met/4-aco-met 15-25 mg.

Most people find these very easy to handle if not too weak (especially for al-lad which is very weak for some)
I took 150 ug AL-LAD recently and enjoyed it a lot, but still I prefer higher doses (i.e two blotter papers, so 300 ug). BUT: on 300 ug AL-LAD, I cannot leave my flat any longer. ;)

For 4-HO-MET, 20 mg was my standard dose. I will go mcuh higher when I take this compund next time, i.e. 30-40 mg. I have no 4-AcO-MET at home, but I think everybody will agree that this is only a prodrug to 4-HO-MET.

Not him, but 2c-b, 2c-c, 2c-d, 2c-e, 2c-p, 2c-t-7
Thank you for answering my question anyways! I have the highest hopes on 2C-T-2 and 2C-T-7. I have heared that they are most euphoric, most beautiful, most Shulgin, so to say. ;) I mean, Sasha Shulgin had his list "magical half dozen" in PiHKAL, and it contained those two compounds, besides 2C-B, 2C-E, Mescaline and DOM. I would like to take all those 6 compounds in my lifetime, but unfortunately, I see no way of getting DOM, and I don't really care, since it has a way too long duration (14-20 h in normal doeses according to PiHKAL).

BTW: I do not quite understand how 2C-C is one of your favourite 2C-X compounds and 2C-D is "too bland". Do you know that 2C-D is said to start to shine in very high dosages (60-150 mg)? What is the highest dose of 2C-D you ever took? Unfortunately, I cannot remember my dosage, but I don't think it went over 30 - 40 mg, and that was truely boring.

Ungelsene_bettlek- With all due respect, maybe try the drugs your trying to school others about??
Mr. G_Chem,

maybe you should start reading my posts more properly?

MDA isn?t a delierient in the classical sense of the word no
I know that MDA (wich I haven't tried yet) is a 5HT2A-partial-agonist and a triple releasing agent, very similar to 6-APB (which I have tried).

For example, on MDA you?ll see things that aren?t there, you?ll hear things that aren?t there, etc.
The very same thing is true for every 5HT2A-partial-agonist that causes so-called pseudo hallucinogens, at least in high enough doses.

Maybe delerient isn?t the best term, as it seems like dream world is meeting reality.
OK, we completely seem to agree to that.

Now please get off the computer and go actually eat a few of the drugs your trying to tell others about.
Have you noticed that I had eaten twelve of the drugs I've written about, and MDMA and MDA are the only ones I have not taken yet, but I compare them to two drugs I have taken (5-MAPB and 6-APB), because of their similar binding affinities.
 
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I'd have a hard time imagining you having a bad time on 1/2 8th of mushrooms. They'll hit you hard, but not TOO hard. You'll laugh your ass off. You might get a mild stomach ache and they taste like hell, but it'll be worth it.

Plus, you get to experience the beautiful post shroom afterglow where you feel like a million bucks.

I'm sure MDMA or an RC might be lighter and that's good for a first timer. But in my experience, you'd have a hell of a good time on a 1/2 8th. You get a tour of the trip universe without a big risk of staying a little too long.
 
I'd have a hard time imagining you having a bad time on 1/2 8th of mushrooms.
I have no FXXXING idea what you mean!

(i) Please use the metric system (kg, g, mg, ug).
(ii) Please identify the species of the mushroom. There are around 200 different Species of Psilocybin-containing mushrooms, each with its own profile! The strongest ones are around 10 times stronger than the weaker ones.
There is also Amanita muscaria and related Amanita mushrooms, they are even stronger Psychedelics!
(iii) are the Mushrooms fresh or dried?
(iv) Do you mean Mushroom fruiting bodys and/or Sclerotia and/or mycelium?
(v) Which way of mushroom consumtion do you mean?
(vi) Please don't write shit about Psilocybin-containing Mushrooms or they WILL KICK YOU IN THE ASS!
(vii) If you "might get a mild stomach ache and they taste like hell", your are doing SOMETHING wrong!

in that seven senses, enjoy 5HT2A-partial-agonists!
 
I have no FXXXING idea what you mean!

(i) Please use the metric system (kg, g, mg, ug).
(ii) Please identify the species of the mushroom. There are around 200 different Species of Psilocybin-containing mushrooms, each with its own profile! The strongest ones are around 10 times stronger than the weaker ones.
There is also Amanita muscaria and related Amanita mushrooms, they are even stronger Psychedelics!
(iii) are the Mushrooms fresh or dried?
(iv) Do you mean Mushroom fruiting bodys and/or Sclerotia and/or mycelium?
(v) Which way of mushroom consumtion do you mean?
(vi) Please don't write shit about Psilocybin-containing Mushrooms or they WILL KICK YOU IN THE ASS!
(vii) If you "might get a mild stomach ache and they taste like hell", your are doing SOMETHING wrong!

in that seven senses, enjoy 5HT2A-partial-agonists!

1) 1.75g

2) Myself, like the majority of people who do magic mushrooms, don't really have any clue what species of mushroom they're doing. But I feel confident saying a newbie is likely to find p cubensis or liberty caps from their local street dealer (at least where I live in the mid atlantic of the US.)

3) Dried

4) The fruit

5) I was gonna say eat them, but I've done tea plenty and it's great if only sliiiiightly less potent.

6) And no, I don't think you're doing anything wrong if you get mild stomach discomfort from mushrooms. And I would say the consensus is that they taste pretty bad. I don't know what you're talking about. Yes, you can virtually mask the flavor of them if you make tea with them. But it's not like the tea tastes great.

Sorry for the confusion. Although, nobody else in the thread gave a full length synopsis on mushrooms when they mentioned them.
 
I have no FXXXING idea what you mean!

(i) Please use the metric system (kg, g, mg, ug).
(ii) Please identify the species of the mushroom. There are around 200 different Species of Psilocybin-containing mushrooms, each with its own profile! The strongest ones are around 10 times stronger than the weaker ones.
There is also Amanita muscaria and related Amanita mushrooms, they are even stronger Psychedelics!
(iii) are the Mushrooms fresh or dried?
(iv) Do you mean Mushroom fruiting bodys and/or Sclerotia and/or mycelium?
(v) Which way of mushroom consumtion do you mean?
(vi) Please don't write shit about Psilocybin-containing Mushrooms or they WILL KICK YOU IN THE ASS!
(vii) If you "might get a mild stomach ache and they taste like hell", your are doing SOMETHING wrong!

in that seven senses, enjoy 5HT2A-partial-agonists!

Generally when people refer to mushrooms, you can assume they mean the fruiting bodies and that they're dried. Most people don't know much about the fungi themselves, they just know what they might buy from a dealer which is the dried fruiting bodies, almost always cubensis. It would be nice if everyone knew everything about what they were taking but the reality of the matter is that most people don't and we're here to help people, so there's really no need to make people feel bad or awkward for not knowing. It makes people less likely to try to post here for help and we want people to post here for help so we can help them. :)

It's true, some people I know always get nauseous or even throw up from mushrooms. Not me, I never have, but some people are much more prone to nausea.

Also given that most people on this board are American, we use the term of 8th (meaning an eighth of an ounce, 3.5 grams) or a quarter (quarter of an ounce, 7 grams), etc when talking about drugs. I wish we would use the metric system also but we don't, so you can't expect everyone posting here to use the metric system, maybe if this was a German board, yes, but it's not. Again, most people posting here don't know this stuff, which is the whole reason we're here. Most people don't even know that an 8th is 3.5 grams, they just know it as "an 8th". It may seem odd to you, but it's just how we talk here. There's no harm in pointing it out but please do try to be gentler about it.
 
IMO the best starter psychedelic is LSD, followed by shrooms. Provided that you take a moderate dose off course. They are true psychedelics that offer the classic experience, unlike many other 'lighter' substances. Take some time to understand set & setting, like always. Make sure you have plenty of time and no occupations. Take it at home (not your parents home, your own). It's better to dose too low and slowly work your way up next try than taking too much.
 
Generally when people refer to mushrooms, you can assume they mean the fruiting bodies and that they're dried. Most people don't know much about the fungi themselves, they just know what they might buy from a dealer which is the dried fruiting bodies, almost always cubensis. It would be nice if everyone knew everything about what they were taking but the reality of the matter is that most people don't and we're here to help people, so there's really no need to make people feel bad or awkward for not knowing. It makes people less likely to try to post here for help and we want people to post here for help so we can help them. :)

It's true, some people I know always get nauseous or even throw up from mushrooms. Not me, I never have, but some people are much more prone to nausea.

Also given that most people on this board are American, we use the term of 8th (meaning an eighth of an ounce, 3.5 grams) or a quarter (quarter of an ounce, 7 grams), etc when talking about drugs. I wish we would use the metric system also but we don't, so you can't expect everyone posting here to use the metric system, maybe if this was a German board, yes, but it's not. Again, most people posting here don't know this stuff, which is the whole reason we're here. Most people don't even know that an 8th is 3.5 grams, they just know it as "an 8th". It may seem odd to you, but it's just how we talk here. There's no harm in pointing it out but please do try to be gentler about it.

Not only mushrooms, but i have 2 friends that get stomach aches from LSD. One immediately has to use the bathroom once they kick in and one feels like he has to use the bathroom for the entirety of the trip. Drugs sometimes make people sick, let alone a drug that's also a food and in the opinion of many people, a food that tastes like dirt flavored mushroom crackers.

I'm honestly jealous of ungelesene that not only has he never felt stomach discomfort on mushrooms, but it's so foreign to him that he assumes you must be doing something wrong to feel that way. I've done them well over 10 times, probably half in tea and half just straight up (whether with Peanut Butter or plain) and almost every time I have to have an inner monologue with myself letting my body know that I'm gonna keep this shit down. One time I did throw up (as did many in my crew of like 7 that took them) on some monstrous mushies that looked like they grew out of the grim reapers shit. That trip also resulted in ego death. Honestly, that's where not knowing my mycology bit us in the ass. If I were able to recognize them like the poster said, I probably would have realized they were a potentially stronger species that I shouldn't have taken 4G's of.

But to the OP, I legitimately believe 1.75g's of mushrooms would be a great first psych for you to do. There are certainly lighter options, but I think 1.75g's of mushrooms is like getting a 5 hour easy pass to Trip World. You get to experience the entire park without staying too long if you don't enjoy, and your chances of having a terrible time are low.
 
Myself, like the majority of people who do magic mushrooms, don't really have any clue what species of mushroom they're doing. But I feel confident saying a newbie is likely to find p cubensis or liberty caps from their local street dealer (at least where I live in the mid atlantic of the US.)
Then it is most likely Psilocybe cubensis, because it grows almost around the world in tropical and subtropical regions on cow shit, i.e. it follows humankind around the earth. Sprores have been collected in lots of countries, Dennis and Terence McKenna were the first humans who grew these Mushrooms in large parts.

I have eaten friuting bodies of Psilocybe cubensis and Psilocybe semilanceata and Sclerotia of Psilocybe mexicana yet, and there are still some Psilocybe cyanescens in my fridge for future consumtption. Alone those fruiting bodies of those three species have a very different Psilocybin/Psilocin/Baeocystin level, and even more for the Sclerotia.

It's true, some people I know always get nauseous or even throw up from mushrooms. Not me, I never have, but some people are much more prone to nausea.
Luckily, the same is true for me! :)
 
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IMHO, Cannabis sp. is very psychedelic! Not for daily users, though.


Psilocybin-containing mushrooms have a duration of about 6 hours, and I'm sure that "liberty caps" (Psilocybe semilanceata) or similar mushrooms of the genus Psilocybe also grow outside in the place you are living! IMHO, this is the best way of taking psychedelics: going out into nature, identifying them (We all of course know that a certainty of 100% is necessary before eating any mushroom?) and eating them!

The same duration (6 h) is also approximately true for 2C-B.


IMHO, this is only partially true. For example, I tripped quite hard on 300 micrograms AL-LAD, definitely harder than on one average LSD blotter (with estimated 50-100 micrograms LSD, typical for black market acid according to www.checkyourdrugs.at).

Also, by taking 40-50 mg 4-HO-MET or 4-AcO-MET, one will definitely trip harder than on 2 grams of self-collected "liberty caps" (Psilocybe semilanceata)....


I dont think it is wise to advise someone new to the world of psychedelics, probably young, maybe a minor to go out and identify Psychedelic Mushrooms with no training. Its best to have VERY trusyed and knowledgeable guide with to teach the art of finding psychedelic mushrooms. We all know that it can be dangerous

Also, you know MDA and MDMA from books only. I promise G-Chem know these two intimately. MDA has very little, subjectively and pharmacologically, with classical psychedelics. It does not produce the types of visions LSD and DMT would, and are
Much more in common with delusions. For example I once saw someone turn into a character from an MC Escher drawing, and often would drift inbetween delusional dreamy visions and waking reality.

I think the consensus that 2CB is a great beginner candidate. As would a low dose LSD or Mushroom trip. While they dont produce the same closed eyed patterns or visial distortions, MDMA and MDA do have a similar head space and feeling to psychedelics and would indeed be a good introduction to the headspace.
 
All psys can make people nauseous and different people get it from different psys. Some are more sensitive than others and some psys are more likely to cause nausea (2c-e I'm looking at you).

The only 100% way to prevent nausea is ondansetron or a similar drug that blocks serotonin receptors in your gut and prevents the cause of the problem directly. Other ways like different roas and such are only partially effective since the psy still gets in your blood stream and to the gut although at lower concentration than if you take the psy orally.
 
All psys can make people nauseous and different people get it from different psys. Some are more sensitive than others and some psys are more likely to cause nausea (2c-e I'm looking at you).

The only 100% way to prevent nausea is ondansetron or a similar drug that blocks serotonin receptors in your gut and prevents the cause of the problem directly. Other ways like different roas and such are only partially effective since the psy still gets in your blood stream and to the gut although at lower concentration than if you take the psy orally.

That's my understanding of psychedelic nausea, as well. Well put.

Incidentally, I realize that there is a whole group of psychedelics that we overlooked, likely because collectively we don't have enough experience with them to represent them correctly. Perhaps in ten years time, the answer to this wisdom might include them.

Several novel tryptamines might actually be well suited. MET, EPT, and MiPT are cognitively non-threatening and fairly short acting. They all have quite a positive push, too, in my experience. MPT is deeper, but also quite short as I understand it.

Several 4-subs might be even better suited, if significantly more psychedelic. We mentioned 4-AcO/HO-MET, but 4-AcO/HO-EPT is gentle and 4-AcO/HO-DiPT is short. 4-AcO/HO-MPT might be uniquely well-suited, as I've heard it described as friendly, powerful, and very short.

Finally, there's 5-MeO-MiPT. A light dose of this is likely to have quite the positive push to offset a genuinely psychedelic headspace, but one still lighter than most 4-subs. My only hesitation is that an above average percentage of people experience a rough comeup and irritating stimulation, although more often at common to strong dosage levels. While the duration is long on paper, I find the experience has two distinct stages, one of which isn't psychedelic or challenging at all. I find it almost transparent in the body and fairly empathogenic in character, so I'm biased towards it. Still, it doesn't fit the bill as well as some of the other ones mentioned above
 
Maybe, but like you said they are still relatively new and untested vs 4-aco-dmt/4-ho-met/4-aco-met/4-ho-mipt/4-aco-mipt. And imo 4 subs are more suitable as starter psychedelics because you can just weigh the powder and eat it + they feel friendlier and produce more classic trips (you mentioned this later but I wrote the first paragraph before seeing that) while unsubstituted ones sometimes have to be freebased, sometimes not, can be taken with a maoi or not, work best vaped, work fine oral or not, work fine snorted but you need a very large amount and so on. 4-subs (especially the classic ones) are much friendlier in this regards and in my experience the least prone to causing nausea or other uncomfortable bodyload (especially in pure powder form and not as whole mushrooms.

Personally I wouldn't reccommend 5-meos as starter psychedelics because they, are at least for me, too nauseating and prone to uncomfortable body load (you mentioned it as well) and the doses are smaller which makes accurately measuring them harder (that's the real problem, a low dose of 5-meo-mipt is a few mg which is basically impossible to measure on a normal mg scale and taking just a few mg more produces much stronger effects while 20 mg of 4-ho-met is much easier to measure and even if you actually take 25 mg you'll be fine ..... I'd much rather take 100 mg 4-ho-met Im than 30 mg 5-meo-mipt orally.

But as was said, the nausea/bodyload from psychedelics is mostly caused by activation of serotonin receptors outside the brain which ondansetron and similar medications block but since they are highly selective for 5-HT3 (the one responsible for nausea) the trip isn't affected because it's mediated by 5ht2a, 5ht1 and (not 100% sure about the last) 5h2b serotonin receptors + other receptors (afaik 5h2a activation alone is not enough to make you trip) not involved in nausea nor affected by ondansetron.

Some part of the uncomfortable body load is caused by over stimulation but this is more of a problem with 2cs than with tryptamines.

And some by pretrip anxiety which can be helped with a low (what is low depends on tolerance) benzo dose (which wont really interfere with the trip), phenibut, pregabalin (this one is especially nice because even in large (~1g doses it doesn't dampen your trip but if anything makes it better (source took 250ug ald-52 + 1g Lyrica and had a great and quite strong trip with not a hint of anxiety + fell asleep quickly after (I was still tripping lightly and normally wouldn't have been able to sleep for a few extra hours without pharmaceutical help), ....
 
I also think that 5-MeO-tryptamines aren't good starter psychedelics. They produce significant bodyload, at the very least during the come-up, which is difficult to navigate when you haven't tripped before and makes you much more prone to giving in to anxiety and having a really rough trip. Also, for the other reasons listed above. 5-MeO-MiPT is not a beginner's drug, you should at least have some experience first, but on the other hand I think a modest dose of 4-HO-MiPT is a great first trip candidate.
 
Hmm....

First, to respond to the original post: in my opinion, there is no such thing as a mild psychedelic. 4-HO-MET, AL-LAD, and 2C-C have all given me some of the deepest and more powerful psychedelic experiences I've ever had, even though they were at the same time less confusing than most LSD or mushroom trips for me. If you want mild psychedelia as a starter, just take low dosages of something first and work your way up, but on that note, I'll also add that I like some others here am also of the opinion that actually starting with a reasonably intense trip is likely to be a better introduction to psychedelics than working your way up slowly as long as you're properly prepared for it, but you should do whatever makes you feel most comfortable when you take it. While there are plenty of good options to start with, I would very much have to agree based on your requirements that 4-HO-MiPT may be an excellent choice. First of all, the majority of worthwhile lysergamides and phenethylamines are out based on taking too long, often at least as if not longer than LSD, so if you're avoiding LSD already for that reason that clearly won't do. The handful of shorter-acting phenethylamines already mentioned plenty such as 2C-B and 2C-C are also very fun and worthwhile and I generally wouldn't have much of a problem with recommending them to a first-timer, however I have so far found in my travels and those I have encountered (though of course others may have a totally different story still) that phenethylamine psychedelics in general are more likely to lead to uncomfortable bodily sensations while tripping than tryptamine psychedelics are, for the most part, and this is something I see as bad because it could add a negative edge to your first time both in terms of simple enjoyment and possibly in terms of creating a more negative headspace overall even with the often mentally lighter trips like these short-lived phenethylamines, though for the record I still highly recommend them in general as a bad body load is something you can look beyond with experience if you really want to get something out of a psychedelic.

As for tryptamines, while I do agree that base and 5-substituted tryptamines are more easygoing in a lot of ways than 4-substituted tryptamines, first of all they both have a much greater potential to produce physical side effects in me, some of the worst body loads in the whole psychedelic experience for the 5-substituted tryptamines and potentially very powerful purges for the base tryptamines, and I also find their trips to be not that mental but still quite spectacular and overwhelming when really explored in a way that I feel requires some level of psychedelic experience to properly make use of. 4-Substituted tryptamines may have a bit more of a mindfuck than most things, but they're usually very clean on the body, easy to use, and typically not that overwhelming relative to other extremely powerful psychedelis even though they might feel like it at the time, and plus they last for a shorter amount of time as requested but also not too short. Actually contained within the realm of the 4-substituted tryptamines then, there are still plenty of great options to choose from, but I think 4-HO-MiPT stands out at likely the best of all of them for a beginner for two reasons: unlike most other 4-substituted tryptamines which are powerful in a mushroom-like way already from low dosages for me, 4-HO-MiPT as more of a plateau division-like thing going on where higher dosages of it are similarly powerful to the others if not even more so but lower dosages are some of the most easygoing but simultaneously also euphoric and meaningful trips found within this entire class, and they have just enough of a psychedelic headspace to give you more of a real taste of what things like LSD can do than something like 2C-C would for me, but still not enough to be particularly confusing or disorienting particularly, just a fun trippiness. So yes.... 4-HO-MiPT, that would probably have to be my recommendation as well.

Now, I just want to address a couple things....

Not that it really matters much, but first of all, I want to point out that the commonly passed around wisdom that ondansetron directly blocks the nausea of psychedelics by interfering with their binding at serotonin receptors doesn't make any sense. As was already stated, ondansetron is a very selective 5-HT3 receptor antagonist, but to my knowledge literally no psychedelic except 5-HO-DMT, bufotenine, has been shown to bind to 5-HT3 receptors, whereas an extremely wide array of psychedelics including all the classics as well as decent representation from nearly every class of research chemical psychedelics have specifically been shown not to bind to them, and also not to 5-HT4 receptors, suggesting that it's highly unlikely that the psychedelics people are getting nausea from are causing that nausea via binding to 5-HT3 receptors. I'm not saying ondansetron doesn't work to help with that, but if it really does it almost certainly must be through an indirect mechanism, like perhaps the signaling pathways of gut 5-HT3 receptors also overlap with other 5-HT receptor sinaling pathways and thus blocking either one could raise the nausea threshold, but that's just one idea that comes to mind. This has been on my mind every time I've ever seen or heard someone metion using ondansetron this way and just thought I'd actually bring it up this time.

And second, I'd like to make the argument that the odds of MDMA being a genuine anticholinergic deliriant are, in fact, actually quite high. First and foremost, the PDSP did a specific certified wide-array binding study of MDMA, the results of which can be found in their Ki database, which only measured hits that were active below 10,000 nM. At this concentration, MDMA failed to bind to any of the monoamine transporters, including for serotonin, dopamine, and norepinephrine, but did bind to 5-HT2B at 700 nM, α2A-adrenergic at 2,532 nM, α2B-adrenergic at 1,785 nM, α2C-adrenergic at 1,123 nM, and H1 at 2,138 nM, as well as calcium channels at 1,198 nM, and on top of these, it also bound to M3, M4, and M5 muscarinic acetylcholine receptors at 1,185, 8,245, and 6,339 nM, respectively. In other words, MDMA's most potent receptor binding affinities are for 5-HT2B, α2-adrenergic, H1, and M3 muscarinic receptors, and both M4 and M5 it at least has higher potency for than monoamine transporters. I have actually been looking into this myself recently because I have been doing more research on myristicin, the active molecule in nutmeg, which is a very close structural analogue of both MDMA and mescaline, and would actually be MMDA, the MDMA analogue known for producing particularly powerful "mind movie" experiences, if you replaced its allylbenzene tail with an amphetamine tail. Street wisdom often claims that nutmeg has both psychedelic and deliriant effects, but despite this I could find no scientific data whatsoever verifying that myristicin has anticholinergic effects and only indirect evidence that it can lead to the activation of serotonin receptors, so I decided to take matters into my own hands and run the molecule and some receptors through a receptor docking prediction simulator. As I personally expected, myristicin was predicted to have ligand efficiency at the 5-HT2A receptor similar to serotonin itself, and furthermore, it was shown to have nearly identical efficiency as a ligand at the M3 muscarinic receptor, but significantly less so at the M2 receptor, perhaps paralleling the lack of M2 or M1 receptor binding affinity measured for MDMA. Out of curiosity, I then ran DMT, psilocin, LSD, and mescaline through the same simulations and it was predicted that all of them were high efficiency ligands for 5-HT2A receptors, but DMT, psilocin, and LSD had low relative efficiency at the M3 muscarinic receptors, while mescaline in fact was also a high efficiency ligand there similar to at 5-HT2A receptors, but slightly less so at M3 relative to 5-HT2A compared to myristicin.

In other words, it would appear to me that the rough molecular structure estimated not only by MDMA but also by other similar molecules such as myristicin and mescaline may in fact be likely to allow for affinity to at least the M3 muscarinic receptor if not others as well in addition to their affinity at serotonergic sites such a the 5-HT2A receptor. I think it is worth considering that people have a tendency to look for certain familiar subjective signs in identifying deliriants and one of those is the horrendous body load, but from what I've always gathered from years of research I was under the impression that the worst physical problems they cause are related to blockade of M1 and M2 receptors, so I looked into the M3 receptor and found that its primary physiological role seems to be in activation of the salivary glands; from what I can tell, the main side effects you might be able to expect from blocking M3 receptors are things like dry mouth and eyes and retention of water from reduced sweating, the former two of which are widely reported and known to occur on both traditional deliriants and nutmeg and the latter of which is known to contribute to possibly dangerous circumstances from reckless abandon on MDMA and other related empathogenic substances such as 6-APB and other benzofurans which share this rather unique form of molecular structure. Another thing that people look for to identify deliriats is a heavy disuption of cognitive function, but a selective M3 receptor antagonist in humans in fact either had no effect or enhanced cognitive function in contrast to hyoscine hydrobromide. Despite this, M3 receptors do exist in the brain in a similar distribution to M1 receptors and in areas such as the frontal cortex and hippocampus, so they are indeed positioned in a such a way that it's believable that significantly altering their activity could lead to mind-altering and/or hallucinogenic effects, and these would still be "deliriant hallucinations" despite the differences from deliriants like tropanes and diphenhydramine if they're all still caused by blocking the M3 receptor regardless, and even if there are other effects like those of psychedelics and empathogens running behind them.

This is all scientific and some of it quite theoretical, but I do have anecdotal evidence as well that helps corroborate it in my mind.... While I have not used mescaline, a full dose of nutmeg, MMDA, or any research chemical empathogen analgoues like 6-APB, there was a period in my life where MDMA and diphenhydramine were my two most commonly used drugs after cannabis, and I loved both them. At this time I was seeking hallucinogenic experiences on everything imaginable, including not only the known atypical hallucinogens like salvinorin A and muscimol but even things like purposing taking large doses of amphetamine and methylphenidate to experience the hallucinogenic effects specific to monoamine releasing agents and reuptake inhibitors. Furthermore, in all my time taking drugs period, I have used a total of fifty-two different specifically psychedelic substance and several other non-psychedelic hallucinogens. Yes, any hallucinogen pushed far enough will produce fully dream-like hallucinogenic experiences, but no, they do not suddenly become specifically deliriant-like in that way. I spent years chasing deliriant hallucinations because they were my favorite style of all, and I felt from the very start that MDMA produced deliriant-like hallucinations that were comparable to diphenhydramine despite obviously also being filtered through some other very different effects, and nothing else from the amphetamine-based hallucinations to any dosage of any other psychedelic I've taken so far has produced the same kind of experience for me and satisfied my desire to have the kinds of hallucinations that those two drugs have given me, and that's exactly why I was looking into nutmeg and myristicin in the first place....

Do I know that MDMA is a deliriant? I do not. But I do think it is? Abso-fucking-lutely. I think it is highly likely and supported both anecdotally and scientifically that MDMA has genuine deliriant effects through muscarinic acetylcholine receptor antagonism, even if its selectivity for that and non-selectivity compared to other neurotransitter systems makes them come through a very different overall subjective and physiological experience, and I think it's also quite possible if not probable that this deliriant-psychedelic/empathogen hybrid style is also shared by MMDA, 6-APB, and other structurally similar empathogens as well as myristicin, mescaline, and perhaps some of their close analogues. However, unlike some I might expect, that doesn't turn me off to them at all.... I specifically don't like diphenhydramine anymore due to its toxicity concerns and awful body load, but if I can get a genuine fun and safe deliriant with actual deliriant hallucinations, the more the merrier, if you ask me.

Anyway, that's just my view which I felt was worth sharing on all that.
 
Top post Kaleida. :) Really interesting stuff, I had no idea MDMA bound to H1 and M3 receptors.
 
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