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New study: Phenethylamines produce more tolerance than tryptamines

T

TheChin

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Not sure if this has been posted yet, but the key point of this new study is that phenethylamines produce more tolerance than tryptamines. The chemicals studied were DOI, 2C-T-7, DPT, and DIPT.

Source:

http://www.ncbi.nlm.nih.gov/pubmed/25271256

J Pharmacol Exp Ther. 2014 Sep 30.

Tolerance and cross-tolerance to head twitch behavior elicited by phenethylamine- and tryptamine-derived hallucinogens in mice.

Abstract

The serotonin 5-HT2A receptor is a potential therapeutic target to a host of neuropsychiatric conditions, but agonist actions at this site are linked to abuse-related hallucinogenic effects which may limit therapeutic efficacy of chronic drug administration. Tolerance to some effects of hallucinogens have been observed in humans and laboratory animals, but the understanding of tolerance and cross-tolerance between distinct structural classes of hallucinogens is limited. Here we used the drug-elicited head twitch response (HTR) in mice to assess the development of tolerance and cross-tolerance with two phenethylamine-derived (2,5-dimethoxy-4-iodoamphetamine [DOI] and 2,5-dimethoxy-4-propylthiophenethylamine [2C-T-7]) and two tryptamine-derived (N,N-dipropyltryptamine [DPT] and N,N-diisopropyltryptamine [DIPT]) drugs with agonist affinity for 5-HT2A receptors. Tolerance developed to HTR elicited by daily DOI or 2C-T-7, but not to HTR elicited by DPT or DIPT. DOI-elicited tolerance was not surmountable with dose, and a similar insurmountable cross-tolerance was evident when DOI-tolerant mice were tested with various doses of 2C-T-7 or DPT. These studies suggest that the use of phenethylamine-derived hallucinogens as therapeutic agents may be limited not only by their abuse potential, but also by the rapid development of tolerance which would likely be maintained even if a patient were switched to a different 5-HT2A agonist medication from a distinct structural class. However, these experiments also imply that tryptamine-derived hallucinogens might have a reduced potential for tolerance development, as compared to phenethylamine-derived 5-HT2A agonists, and might therefore be more suitable for chronic administration in a therapeutic context.

PMID: 25271256 [PubMed - as supplied by publisher]
 
Thanks this is really interesting. I wonder if the fact that the tryps they studied are both simple tryptamines (DPT and DiPT as opposed to their 4-ho, 5-meo etc counterparts) come into play. I remember hearing that DMT causes little to no tolerance, but it seems that 4-ho-dmt does.
 
I find this to be opposite, I can do 2c-e two nights in a row with very similar effects but I have greatly diminished effects the next night with 4-aco-dmt and psilocin.
These chemicals are active on a wide range of receptors and if this HTR is caused by agonism/antagonism of only one specific subset of these receptors then this study holds no real value.

perpetualdawn said:
I remember hearing that DMT causes little to no tolerance, but it seems that 4-ho-dmt does.
Click to expand...

In my experience DMT has tolerance effects equal to that of mushrooms (dysphoric head space with little visuals), the difference being the tolerance is short lived
 
Mmm, not sure I agree either. Obviously phens like DOx cause heavy tolerance but when comparing tolerance from something like 2c-c to 4-aco-dmt, these results don't apply, or at least aren't in line with my experiences. I'm not sure you can classify either group of drugs as causing more tolerance as each substance has usually has it's own tolerance build I find. Throwing two drugs from each class (DOI, really?) and measuring the tolerance at only one target site is just not enough to gather the conclusion that phens build more tolerance than tryptamines.
 
I've always found oral DMT has an enormous tolerance - I can't trip on oral DMT more often than once every couple of months if I want the full psychedelic effects.

Not sure where this study is coming from anyway - who in their right mind would use chronic admin of psychedelics for anything? The whole point is that you use them at most once a week or they lose their effects. It just sounds both clueless and stupid.
 
.:Holy::Toast:. said:
In my experience DMT has tolerance effects equal to that of mushrooms (dysphoric head space with little visuals), the difference being the tolerance is short lived
Click to expand...

Ismene said:
I've always found oral DMT has an enormous tolerance - I can't trip on oral DMT more often than once every couple of months if I want the full psychedelic effects.
Click to expand...

Sounds like I'm wrong about DMT not causing tolerance. I have no first hand experience with DMT, I think I just passed on some bad info I had lodged in my brain.

Anyways the study is drawing a pattern in Phenethylamines vs. Tryptamines based on a sample size of only 2 from each class. It should really just say DOI or 2C-T-7 cause more tolerance than DPT or DiPT
 
When I smoke DMT my tolerance is at baseline in about 3 hours.
I've never tried it orally however
 
My tolerance to IM DMT only goes to certain point and at that point and beyond there isn't any tolerance to speak of...what I mean is that certain parts of the DMT trip will always be there no matter how much I do or how often I do it, but other aspects do disappear quickly and I need to "reset" myself periodically if I want those particular aspects of the trip to present themselves...I've noticed this with all ROA's of DMT, but I didn't notice that things were missing until I started looking for them and they weren't there and it took a few days/weeks to bring back to starting point.
I haven't done any DMT or AL-LAD in quite some time now...currently into dissos...anyone know of cross tolerance of tryptamine and PEAs w/dissos?
 
perpetualyawn said:
Sounds like I'm wrong about DMT not causing tolerance. I have no first hand experience with DMT, I think I just passed on some bad info I had lodged in my brain.

Anyways the study is drawing a pattern in Phenethylamines vs. Tryptamines based on a sample size of only 2 from each class. It should really just say DOI or 2C-T-7 cause more tolerance than DPT or DiPT
Click to expand...

Exactly! Stupid study only had four compounds! DPT is a simple tryp and you pretty much never gain much of a tolerance like with DMT. Also DOI, fucking really?!? Thanks for nothing again dip shit government!
Edit: there is none, they work on completely different receptors
 
Well, at least it was new to me that DOI causes big tolerance, but sounds like that was already a known. It would be cool if someone did the same study with a much wider selection of phens and tryps.
 
From just the abstract this sounds like somebody trying to rationalize a theory to fit with a research agenda for addiction studies because they got near a deadline. You can't begin to generalize the properties of two entire classes of psychedelic drugs in humans (esp. with DOI being a substituted amphetamine of relatively high potency) based on two samples from each using rodent head twitch responses.
 
In my limited experience - aMT can be used with frequency without losing much of the experience, though dosage does climb.
BK-2CB however, I have to leave around a fortnight between uses otherwise the experience is incomplete and not aided by a dosage increase.
 
psood0nym said:
From just the abstract this sounds like somebody trying to rationalize a theory to fit with a research agenda for addiction studies because they got near a deadline. You can't begin to generalize the properties of two entire classes of psychedelic drugs in humans (esp. with DOI being a substituted amphetamine of relatively high potency) based on two samples from each using rodent head twitch responses.
Click to expand...

I couldn't help but laugh because this seems like exactly what they did. After what Snowden revealed about the NSA and the government, and tons of other examples, I'll just label this study as one big pile of crap. (I read the link to make sure the study came from the U.S....lol, as expected).

Heh, typo. Bunch of morons, esp with weed being on Schedule 1...War on Drugs...Land of the not so free.
 
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