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Dosage measured in hundreds of milligrams?

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demon66

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As many of you may know psychedelics have a wide range of potency. Mescaline is active around 200+ milligrams were as LSD is active at around 100+ micrograms. Psilocybin in the 10+ mgs. I am curious as to why there is such a vast difference in dosage for these chemicals. In particular does any body know why mescaline requires such a high dose. From every other psychedelic I've heard the dosage never goes higher then the 10's of milligrams for a typical trip. Mescaline appears to require by far a higher dose than anything else. Any speculations as to why?
 
Maybe depends on the concentration of the powder or something, well i don't know :x For exemple 4-ho-met which is a psilocin-like is also 10-20mg :\
 
It depends on a few different factors. First of all, it depends on the receptor affinity of the chemical in question and secondly it depends on the bioavailability of the compound, which in turn depends on how it is metabolized in the body.
Shulgin has actually theorized that mescaline might somehow be affected by monoamine oxidase, and that it would be active in much smaller doses if this enzyme was to be inhibited.
 
Culpepers said:
It depends on a few different factors. First of all, it depends on the receptor affinity of the chemical in question and secondly it depends on the bioavailability of the compound, which in turn depends on how it is metabolized in the body.
Shulgin has actually theorized that mescaline might somehow be affected by monoamine oxidase, and that it would be active in much smaller doses if this enzyme was to be inhibited.
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You would think that someone (unknowingly perhaps) would have out that theory to the test by now lol.
 
True :D I've always been told that one should not combine mescaline and MAOIs, but someone really should try a small dose of mescaline with a MAOI, in the name of science ;)
 
I've done it many times (as I'm sure others have) and while it Was stronger, I still took 400 mg without it being overly intense at all. So metabolism by MAO is definitely not even close to the whole picture for mescalines low potency.


And I think the advice is to not combine CACTUS with MAOIs (due to who knows what compounds it may contain that could be contraindicated), not the active chemical mescaline.
 
Mescaline is not metabolized by MAO, and there is very old data showing this. Shulgin got it wrong about that. Mescaline is metabolized by another enzyme, SSAO. There are lots of trip reports combining MAOIs with either mescaline or cactus. There is some synergism of mescaline and harmala, but it is not due to MAO inhibition. Mescaline has weak affinity for 5HT-2a receptors, which accounts for the roughly 10-fold higher dosage.
 
Think i'd read somewhere in ADD that mescaline has to pretty much fully saturate a metabolic pathway before it starts getting into the brain. I could be wrong, but pretty sure i read it some where. As for its accuracy, eh, I dunno
 
Look in PiHKaL. The only reason you know of so many that are active at the ~10s level is that the RC vendors took the reasonably active compounds (mainly 2Cs) and ran with them. No one wants to synth and ship 10 kg when 1 kg of a different compound gives the same number of doses.

Additionally, many compounds taken in doses of 100+ mg begin to affect many other receptors/systems within the body before they become appreciably 'trippy', meaning that they are either unpleasant or unexplored (notice how often Shulgin stops below mescaline like doses because things 'look rough ahead')
 
The theory that chemicals taken in 100's of milligrams will start to affect other receptors than 5ht2a seems very plausable. Does this mean that mescaline is more likely than other psyches to bring about negetive and/or good side effects.

With this theory in mind do you think this speaks to the purely psychedelic effect of LSD regarding it's extremely high affinity for 5ht2a.
 
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With this theory in mind do you think this speaks to the purely psychedelic effect of LSD regarding it's extremely high affinity for 5ht2a.
Click to expand...
No, not really. While LSD has a very high affinity for a few different serotonin receptors, it has some affinity for other receptors as well (most notably dopaminergic and adrenergic receptors).
See this overview of the various receptor affinities of LSD:
(The lower the bar, the higher the affinity)
LSDaffinities.GIF


EDIT: After reviewing the graph, I actually don't think that the non-serotonergic receptor affinities are high enough to do much of a difference...
 
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The other receptor affinities are why high doses (10 strip, etc.) seem to have a slightly different character to them. Its hard to really say though, as most extremely high dose acid ("thumbprint" doses and the like) seem to involve a sufficiently long blackout period.
 
jebus said:
You would think that someone (unknowingly perhaps) would have out that theory to the test by now lol.
Click to expand...

I've combined syrian rue and san pedro cactus twice and both times I took about a third of the dose I would have needed to get the same level of effects. Not a lot different than with other psychedelics, maybe a bit more potentiation. Nothing crazy. Then again, that's not pure mescaline but mescaline with a collection of other psychoactives so who knows what might be different about the mechanism of action and effects of cactus?
 
I've done syrian rue with cactus too. I'd agree it makes things about 3 or 4 times stronger. It kicks in within half hour too.
 
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