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Current Understanding of MDMA Neurotoxicity?

Cowboy Mac

Cowboy Mac

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I have searched the forum for this one, and referred to the current literature but I am unsure what the current understanding of MDMA neurotoxicity is. Feel free to correct me if I am wrong but it seems the older theory of oxidisation caused via dopamine entering the reuptake transporter is questionable and an alternate theory is damage caused by free radicals due to MDMA-induced hypothermia. If anyone could clarify the currently accepted theory (or alternate theories) as it stands in 2005 as well as any literature references it would be appreciated.
 
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This is the latest info that I could find.....hope this helps

Neuroscientists interested in studying pharmacological and toxicological effects of MDMA continue to conduct studies in rats, mice, and monkeys, and in vitro studies with human, rodent, and other cell lines. The bulk of the research published between March 2004 and January 2005 focused on MDMA neurotoxicity, metabolism, and pharmacology, while other studies focused on specific issues relating to MDMA pharmacology or toxicity.

Here is the link for more info ;)

http://www.maps.org/research/mdma/litupdate3/


Here is another link to check out

http://www.channel4.com/health/microsites/0-9/4health/drugs/dus_ecstasy.html
 
I really don't have time to get all the references, but it would be a waste of time anyway, because it would just end with "but we don't really know"

The dopamine link has been quite strongly shot down. Yuan et al., MDMA and meth.

It's definately free-radicle mediated, no one is gonna disagree with that. The question is, where do they radicles come from? Probably the "leading theory" (even though it's shit in it's current state) is a toxic metabolite theory. The two most important papers on this subject are Escobedo et al's so close but so far attempt (which I reviewed here). And Jones et al., completely pathetic logic (reviewed here).
 
^I don't mean to go off topic, but are free radicals also what causes methamphetamine neurotoxicity?

Would having a pill of meth+mdma increase neurotoxicity of both substances?
 
Yes, meth neurotoxicity is also free-radicle mediated. Meth+MDMA is going to be more neurotoxic than either seperately.
 
Well in lab animals, given neurotoxic dosing regiems of MDMA, the effects repair somewhat, but are permanent. In humans, physical measures of brain changes seem to completely reverse (or largely reverse) after some time (months), behavioural data shows a tendency towards the same, but not a complete reversal of damage generally.... but I'm sure after responsible MDMA usage, damage/changes will reverse after a couple of months. But with irresponsible use, judging by reports on here, I might take much longer.
 
What do we make of the fact that some studies appear to indicate that MDMA's neurotoxicity is mediated via increasing body temperature? Should we all start injecting intercranially? :)

ebola
 
What do we make of the fact that some studies appear to indicate that MDMA's neurotoxicity is mediated via increasing body temperature
Click to expand...

Well it's not that the neurotoxicity is CAUSED by hyperthermia, just that it is dependent on hyperthermia.

And this might be of help to the question above.
51144MDMA_metabolism.gif
 
>>Well it's not that the neurotoxicity is CAUSED by hyperthermia, just that it is dependent on hyperthermia.>>

There is a reason I said "mediated". :)
What I'm wondering, though, is why these free radicals would not cause observable dammage at typical body temperatures.

ebola
 
ebola! said:
What I'm wondering, though, is why these free radicals would not cause observable dammage at typical body temperatures.
Click to expand...
An excellent paper by Green, Mechan, Elliott, O'Shea, and Colado (2003) has the following sections:
4. Effects of Preventing Acute MDMA-Induced Hyperthermia.
and
7. Effects on Free Radical Production in the Brain.
i'll find the paper and paste it tomorrow.. check it out beforehand if you are interested.
Click to expand...

Green R. A., Mechan A O., Elliott J. M., O'Shea E., & Colado M. I. (2003). The Pharmacology and Clinical Pharmacology of 3,4-
Methylenedioxymethamphetamine (MDMA, “Ecstasy”). Pharmacological Review, 55,436-508
 
Well, my current best understanding is that mystery chemical A is being broken down by the enzyme MAO-B producing oxidizing chemicals in the process. At some point, this oxidation can become severe enough to destroy the serotonin axons. Body temperature plays a critical role; increased temp will increase the production/propagation of oxidizers, but my suspicion is that the more serious aspect is that high temp reduces the effectiveness of protective mechanisms (such as enzymes that break down said oxidizers.)

What the mystery chemical is remains unproven. The now apparently discredited theory was that it was dopamine. The currently most popular theory is that it's a metabolite of MDMA (the 'glutathione adduct of alpha-methyldopamine' if you want to be picky.)
 
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