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Miscellaneous The Big & Dandy Cross Tolerance Thread

Dr. J

Dr. J

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Sep 30, 2001
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This is the main thread for all information and questions about psychedelic drug cross tolerance. Discuss here how tryptamines and phenethylamines interact over time and what you know of the involved biochemistry.

[original post:]

I tried asking this in the ecstasy forum and they took it off topic, so I'll ask here. I shroomed last night, Sunday, and the plan is to roll Tuesday afternoon. Does rolling a couple days after eating mushrooms change lead to a diminished roll at all?
Thanks
Dr. J
 
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Originally posted by Dr. J:
I tried asking this in the ecstasy forum and they took it off topic, so I'll ask here. I shroomed last night, Sunday, and the plan is to roll Tuesday afternoon. Does rolling a couple days after eating mushrooms change lead to a diminished roll at all?
Thanks
Dr. J
Naw, the issue with cross tolerance is usually between shrooms and acid, not shrooms and ecstasy. I don't see why shrooms would cause cross tolerance, so you should be fine. I'd just advise on getting some good nights of sleep and make sure to keep up your nutrition in the meantime. Doing drugs so frequently isn't always the best idea, but that is your decision.
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Cross tolerance shouldn't be an issue between those two substances. They operate by very different mechanisims.
 
^^^^^^^^^^^
Are they? Where did you discover than AET and MDMA are crosstolerant. I searched TIHKAL and PIHKAL, but didn't seem to see it. Perhaps I just missed it.
 
From TIHKAL #11
(with 150 mg, orally) "My dosage level was the highest of the group, but to my surprise, it had almost no effect whatsoever. A plus-one, if anything. After the peak, as I was slowly coming down, I was aware of feeling slightly depressed. This state continued until I achieved baseline, but was not severe enough to prevent me from participating in the general good spirits of the group. There is a real possibility that my weekly use of MDMA for writing might have built up a tolerance to the stimulation of this material. I think that that may be close to the answer. Would I take it again? Not with much enthusiasm. It didn't give enough exciting rewards."
So there's only a hypothesis of cross tolerance.
 
Originally posted by morninggloryseed:
Cross tolerance shouldn't be an issue between those two substances. They operate by very different mechanisims.
don't MDMA, psilocybin, LSD, and other tryptamines work mainly on the seritonin nerotransmitters though?
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AET is a pretty tricky one.
Until recently i had always thought about it as an unusual MDMA-like tryptamine. The TiHKAL entry make it sound akin to MDMA. Then there was this pharmacological study that AET is a 5ht (serotonine) releaser (just like MDMA that is), produced neuronal change/damage similar to those of MDMA and produced a postive response in MDMA trained rats in stimulus generalization studies (ie AET substitute for MDMA in rats trained to discriminate MDMA from saline). If you add the fact that it was sold in the mid 80's as MDMA well all that seemed to suggest AET to be an MDMA-like substance.
However more recently i have heard from someone who is unlikely to spread bullshit about that that he knew another trustworthy person who tried AET and found it all in all more LSD-like than anything.
And then finally i've read how Richard Glennon had actually characterizied that one isomer is a stimulant and MDMA-like suubstance while the other isomere is stimulant again but LSD-like !!!
I found that really fascinating and it had strengthened my curiosity fro AET - i really wish i could nibble this one :D !
Perhaps that some people are more sensitive to the LSD-like factor while other more senitive to the MDMA-like factor.
In any case really intriguing stuff !!!
 
If I tripped on Mushrooms Saturday night, and I want to trip on acid monday night, will I have a problem with cross tolerance? Or will the tolerance largely have faded by then?
 
There may be small issues with tolerance. It is really dependant on the dosage. As a general rule of thumb, one should wait a week after a trip before dosing another psychedelic.
 
Meilikhios said:
And then finally i've read how Richard Glennon had actually characterizied that one isomer is a stimulant and MDMA-like suubstance while the other isomere is stimulant again but LSD-like !!!
I found that really fascinating and it had strengthened my curiosity fro AET - i really wish i could nibble this one :D !
Perhaps that some people are more sensitive to the LSD-like factor while other more senitive to the MDMA-like factor.
In any case really intriguing stuff !!!
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Indeed it is! Do you know which enantiomers had which effects?
If this is true, it is likely that AMT and perhaps even 5-MeO-AMT could operate by this mechanism, which explains why so many people think those drugs feel like candyflipping.
 
Originally posted by Hong et al., 2001
The results of this investigation suggest that both optical isomers of alpha-ET are capable of producing an MDMA/PMMA-like effect at nearly comparable doses, and that the stimulant or amphetamine-like nature of alpha-ET resides primarily with its (-)isomer whereas hallucinogenic or DOM-like character resides primarily with the (+)enantiomer.
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I thought I'd read that AMT works in part by releasing amines, but perhaps that was more of a suspicious because of its amphetamine like structure...

Maybe this odd reference would help us out, if someone could find it

Marsden CA.
Evidence for the release of hippocampal 5-hydroxytryptamine by alpha-methyltryptamine [proceedings]
Br J Pharmacol. 1979 Nov;67(3):438P-439P
 
Phenethylamines and cross-tolerance

We had a question lately on DS which got me pondering PEA's and the issue of cross-tolerance. I couldn't readily find any information, in the form of studies or first-hand trip reports, which would give a clue as to whether or not, and to what degree, some of the more commonly found PEA's (e.g. 2C-B, 2C-I, 2C-E) are cross-tolerant with one another. It is not infeasible that some effect different 5-HT receptors than others.

With no data to be found on the net, I thought maybe a thread in this forum would provide some personal anecdotal response. Has anyone got any experience to share with using different PEA's in close enough succession to gather any opinions? Many thanks for any response, my curiousity is piqued!
 
I try and avoid using PEA's more than once a week (though I failed miserably over xmas/new year).

Although I still get effects when I use them more often, the Law of Diminishing Returns takes effect and even huge doses don't give me what I'm looking for.

I'd even go so far as to say that they shouldn't be used more than once a fortnight, but there's so many compounds I need to try before they all get banned, it would take forever!

If you simply MUST do RC's more than once a week, I would suggest alternating phens with tryptamines.
 
^^^ An exception to the once a week max rule is when you are doing very low doses and working your way up. Say you are trying 2C-E for the first time and you start with 8mg, it would probably be ok to try say, 12mg 3 or 4 days later, and 16mg 3 or 4 days after that. It works for me or the lower doses but when I get into 'full-on' trip territory, longer gaps are needed.
 
If you simply MUST do RC's more than once a week, I would suggest alternating phens with tryptamines.
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You're going to have some cross tolerance with tryptamines too.
 
Right, thanks for these answers.

What I was wondering was if anyone had noticed anything unexpected. For example, one would expect MDMA and MDA to be cross-tolerant. I've never put this to the test, but at least according to Shulgin they are not. Well, OTOH, I've always wondered if that one documented experiment wasn't just a fluke.

Anyway, I was just thinking about receptor affinities and got curious whether anyone had noted, through accident or experimentation, anything unexpected between different PEA's tolerance or cross-tolerance.
 
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