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Are we dosing tryptamines wrong?

I dunno, with mushrooms I typically just eat 2.5g on average, occasionally venturing as far as 5g, I personally sometimes trip out pretty hard on lower dosesof most psychedelics, but it's very unpredictible.

With RC's and synthetic psychedelics it's easier to gauge because it's in it's pure form, but I still feel like i've tripped harder when i took 20mg of 4-AcO-DMT versus when i took 30mg of the same batch (two weeks earlier), so i have to say that set and setting are really more important than the dose in a lot of cases.

Just my 2 cents based on what I've experienced and heard from friends.
 
While I don't want to completely discount size as a factor, I tend to doubt it's a huge factor. I'd imagine things like 5-HT receptor subtype densities in various parts of the brain is likely the more important factor. Clearly this isn't really testable at the moment & complete speculation on my part, but seems legit, right? ;)

I'd also think metabolic factors that affect peak plasma concentrations are likely not insignificant either, but again no real data to back that up, just my 2 cents.

Looking at mg/kg doses could certainly be interesting though. I might just look at erowid reports (as most of them contain weight, in kgs no less) before going to a lot of trouble to set up an online survey or start trying to gather new data.
 
just remember that lots of those reports that specify the dose at the beginning later say they eyeballed it
 
black53 said:
thanks, I added the roa part

A bit off topic, how did you do the injection?
Did you use the ideal HR procedures (micron filters) or a bit more lax?
Did you inject all of the solution or store some for a later time (did anything special to prevent degradation in that case)?
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I extracted from mimosa using A/B ext. tek. (CH3COOH/NaOH) I then took that product and did a double recrx using heated heptane and crystalized using the freezer.
I don't filter, I decant. My end product looks like snow. The yellow goo that remains in my heptane after the decant stage I let dry out for smoking. The "snow" I make into a fumarate salt using FASA, decanting off the remaining acetone, and washing with two clean acetone rinses. NEVER evaporate your acetone after FASA, you WILL end up with unreacted fum. acid as well as unreacted base in your final product...FYI
I do the IV using u-100 syr. and the IM using a 3cc syr w/25 ga. needle
I keep the extra in freezer.
 
TL;DR The pharmacokinetics of tryptamines means their dose is minimally affected by body mass and therefore a constant dose without much variation is appropriate. Below I have given a grossly oversimplified explanation. those familiar with pharmacology will see many mistakes as a result.

Dose is affected by many factors. The important part for us is what the concentration of the drug is in the target tissue. In this case the brain is the target. If a drug is evenly distributed through the entire body then the concentration in the brain will equal the dose in mg/kg. However, most drugs do not distribute evenly through the body. Take for example orally administered GABA. It is unable to pass the blood-brain barrier and as a result it can only diffuse into tissues outside of the brain.

Exactly where in the body a drug goes is part of pharmacology called pharmacokinetics.A drug's transport is controlled by its polarity and as a part of this, its solubility.

Drugs which are very fat soluble will dissolve into many tissues quite readily and their concentration in the watery brain will not be that high. Alcohol is a good example of this. Such drugs typically relatively high doses and their doses will vary quite linearly with weight.

Drugs which are very water soluble (within reason) dissolve mainly in the blood and don't pass well into tissues. this means they're almost concentrated into the brain and a much reduced dose is needed. Since the amount of blood a person has doesn't vary massively with weight, the dose doesn't vary massively with weight either. Tryptamines fall pretty firmly into this category. Individual neurological differences are likely to play a larger role than body mass.

As a rule of thumb, you can judge the dose dependence of a drug on its regular dose. 0-50mg = minimally weight-dependent; 51-500mg some weight-dependence; >500mg approaching linear weight -dependence.
 
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Transform said:
As a rule of thumb, you can judge the dose dependence of a drug on its regular dose. 0-50mg = minimally dose dependent; 51-500mg some dose dependence; >500mg approaching linear dose-dependence.
Click to expand...

That is interesting stuff. That must be why ibogaine (which requires several hundred milligrams, on up to a gram or even a gram and a half) is always dosed according to a mg/kg formula. Cool stuff man.
 
It's quite appropriate for comparisons to animal trials, where obviously allometric scaling will need to be applied as varying species really does change the volume of blood.


For humans, perhaps a cross between convention and convenience. It's a pain to work out a formula like 90 + [weight in kg/2] = dose of MDMA in mg for everything and explain the rationale behind it when it's really not as simple as I've made out..
 
So do you think the current dosing guidelines are good enough or that they could be improved? If yes, how would you improve them?
 
I was always told not to take more than 2 mg/kg MDMA in a sitting. That contradicts what I said earlier about psychedelic sensitivity not really being affected a lot by body weight considerations, much more simplified and not as well-understood or well-explained as Transform's contribution... but the question is: does that MDMA recommendation make just as little sense? Or is this different because it is about toxicity and not about sensitivity to psychoactive effects? Also the monoamine releasing effects are different from psychedelic serotonin receptor agonism, but no idea how relevant that is.
It would seem such a value is just as misguided and it would just be better to put the recommended maximum at a universal 140 or so mgs.

Should we have a look at the oct:h2o partition coefficient of MDMA?

Black, I think Transform confirmed that matters are too complex to benefit from such corrections. It may even very well work out badly: if sensitivity from neurological differences between individuals is unpredictable then recommending rather high doses to heavy built people can be unfounded and inappropriate, leading to overdosing in those people and underdosing in light-weight people.
 
also I imagine body mass tends to correlate with blood volume pretty well so taking measurements of blood content is more easily comparable. It's pretty difficult to measure actual blood volume without killing the subject
 
Up to 40 ish mg's 4aco met or 4 ho met. Weird tough as I find 20-30 mg 4 aco dmt to be a nice comfortable experience. Much more and there is unpleasant body load. 4 ho mipt is ok until a similar mark but it has a more heavy body load vs the other two. i think body load being uncomfortable is the indication that you may have had a few mg's to much, back off 5 mg and there you have your optimum dose. Re-dosing can be fun. as is using PEA's and tryptamine's together or taking one on the tail end of a trip as a re-dose but of a different substance but doses require some experimentation. Mg's per kg does not equate to receptor site activity. 4 ho met I find is the most forgiving tryptamine (4 aco met is THE most forgiving) in terms of dosage per mg vs unwanted adverse effects. Once the drug passes the blood brain barrier... oh fuck it just study pharmacology it'd be easier for my finger's. Toxicity is the primary concern. As for mg's per kg in a research setting see my previous comment by a fucking pharmacology text book instead of drugs. Sorry to be blunt but see the following example of a "discussion" I had with a VERY misinformed individual (or one that talks utter shit).

Note: Some people will tell you eating 16 grams of shrooms, taking 60 mg 4 aco dmt, smoking 35 mg's 4 ho mipt, add a mg of LSD and I forget what else is a "fun" time. All at the tender age of 15. Sounds more like they are talking out their ASS!!
 
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MrPorter said:
also I imagine body mass tends to correlate with blood volume pretty well so taking measurements of blood content is more easily comparable. It's pretty difficult to measure actual blood volume without killing the subject
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Not really. Buy a biology text book, blood volume does not vary as greatly between individuals as physical mass can and does: ie a really fat person does not have 2 extra liter's of blood pumping around inside them just cause they weigh 350 lb.
 
also I imagine body mass tends to correlate with blood volume pretty well so taking measurements of blood content is more easily comparable. It's pretty difficult to measure actual blood volume without killing the subject
Click to expand...

Body mass does correlate to blood volume in a fairly linear manner, but as I said, I’ve grossly oversimplified the matter. Personally I am quite happy with the existing dose recommendations for psychedelics.

I was always told not to take more than 2 mg/kg MDMA in a sitting. That contradicts what I said earlier about psychedelic sensitivity not really being affected a lot by body weight considerations, much more simplified and not as well-understood or well-explained as Transform's contribution... but the question is: does that MDMA recommendation make just as little sense? Or is this different because it is about toxicity and not about sensitivity to psychoactive effects? Also the monoamine releasing effects are different from psychedelic serotonin receptor agonism, but no idea how relevant that is.
It would seem such a value is just as misguided and it would just be better to put the recommended maximum at a universal 140 or so mgs.
Click to expand...

I agree completely with this. Notice that MDMA falls in the region where I’ve said there is some weight-dependence. This is not a mistake. I always calculate MDMA dose by the formula I gave in my other post

90 + [weight in kg/2] = dose in mg

There isn’t a concrete “you can’t go above x” for any drug really, but I would advise against significant deviations from that formula for MDMA especially because of its acute neurotoxicity.

Again, the oct/water coefficient is just a single parameter and it’s hard to say anything for sure based on this alone. Pharamaceutical companies spend millions (literally) determining the pharmacokinetics of drugs, ideal dosing regimens and optimum formulations. It’s a credit to us that we manage to cope so well but I don’t think we have the resources to do a whole lot better.
 
The only tryptamine I've had extensive use of is aMT. However, I believe that tryptamines, or at least aMT, are very individual.

A lot of people recommend 20-30mg as being a good first time dose for aMT. Although I got some euphoria from 30mg, I had no psychedelic effects whatsoever. It wasn't until I re-dosed & potentiated it with some weed that I got a real trip. In fact, for me 40mg is more of a threshold for the true nature of the drug with 50-60mg hitting the sweet spot. I'm not a big guy either - quite the opposite. I even did 80mg once, albeit with a little tolerance.
 
aMT is a real nightmare for the purposes of this discussion. It has a complex pharmacology which is compounded by rumours of potent active contaminants and salts of varying activity.
 
I can't speak for this mg/kg idea in a scientific sense, but I have a gut feeling that it isn't wise and it shouldn't be decided by body weight.

While tryptamines are most definitely either some of or absolutely my favorite chemicals, I use them somewhat rarely, maybe 2-3x a year. I have a batch of independently tested 4-ACO-DMT that is absolutely 99%+ pure. I have found that there is just as much anxiety/'mindfuck'/bodyload in 30mg as there is in 80mg. I feel that out of HR (which is good, don't get me wrong) and a sometimes false assumption that with dosage increase = all negative effects increase, tryptamines are often dosed low. I have found the exact kind of thing happening with 4-HO-MET. The trip is in fact more intense, but side effects do not increase with dose. It can often be more pleasant to be immersed in the experience rather than anxiously half in/half out...

I am not AT ALL proposing that anyone recklessly go and double their dose, nor especially advocating the dose of 80mg 4-aco-dmt being standard. I am only speaking of my experience, which also has only to do with a range of tryptamines in their relation to negative effects increasing. In my experience, the recommendations by the 'net are great doses for introduction into tryptamines, but so far the doubling of the starting dose has been more my speed and in actually less prone to anxiety, with no increase in side effects. They generally seem to be very tame on the body. Would certainly not entertain the idea with phens or ergoloids...

edit: hey everyone, first post! %)
 
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I think 4-substituted tryptamines, given their safety profile, really should be dosed high (same way I feel about LSD and any other highly safe psych). If you really wanna see the profound, mystical side of psychedelics, that's how your gonna do it (this is a part of why I don't favor mushrooms, it's so much harder to get to this level- unless they're very high potency- most 8ths just aren't "enough" for me, but I'm a hardhead sadly).

High doses of 4-AcO-DMT for example are like smoked DMT stretched out into a mushroom timeline, much more worthwhile then dropping just 20-30mgs! And I really do experience less anxiety overall at higher doses of 4-subs; the come-up will still have anxiety, possibly even a lot of it, but then a little after the peak hits I'm in heaven (while on lower doses, there is less anxiety initially, and it's not nearly as intense, but it will pop up more regularly during the main part of the trip). Higher doses also just feel like I'm "all the way there", I can just lay back and see what happens, metaphorically speaking, it's just a much fuller trip, and much more "real" feeling.

Of course more stimulating/potentially dangerous tryptamines (5-MeO's and such) should be dosed more conservatively in the interest of safety. I mean I take like 3x the Shulgin reccomendation for 5-MeO-MiPT, but that's because it's like not even tripping at the Shulgin doses (just tryptamine rolling I guess), you need at least 10mgs for it to be actually psychedelic (I like around 15mgs a lot, nice full trip, with more of a physical aspect then classic psychs).
 
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