Comment · Mon, December 10, 2012
What are the components of MDMA neurotoxicity and how does it compare/relate to meth- and amphetamine neurotoxicity?
Original post in this thread
[deleted] · 22 points
Original thread (feel free to comment/discuss there as well):
http://www.reddit.com/r/Drugs/comments/14mc0n/what_are_the_components_of_mdma_neurotoxicity_and/
From what I've read MDMA induced neurotoxicity consists from the following:
* Oxidation damage due to dopamine being absorbed into serotonin releasing cells. I believe I got this from a neuroimaging study.
Irreversible, but easy to prevent with anti-oxidants and a normal body temperature.
* Reduced SERT (5-HTT)-channel activity. David Erritzoe's neuroimaging study had pretty cool data on this including how it relates to dose and usage frequency.
Changes back over time except for in the neocortex. Unpreventable but dose and frequency dependable.
* Downregulation (is this the same as tolerance?) of your DA and 5-HTxy receptors
The sensitivity of your 5-HTxy receptors returns to baseline after ~7 days and you can't really prevent this either. I can't remember where I read this though.
I assume that the oxidation damage and downregulation (on the DA receptors) phenomena that are common in MDMA, amphetamine and methamphetamine as they all work as dopamine releasing agents and methamphetamine is relatively pretty neurot…
What they were answering
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb
There is much much more to the pharmacodynamics for those substances. However, your basic understanding is mostly correct. I do not agree that dopamine is the direct cause for 5-HT axon damage, though. There are many drugs that instigate a release of 5-HT and DA, but are not damaging to serotonin axons. Even MDMA and MDA themselves, injected directly in the brain, do not show 5-HT system damage. The specifics of exactly what oxidative substance is responsible are still not proven.
I have a theory about MDMA induced 5-HT system damage that I have written about on some other posts here. I am still going back and forth with others to try and specifically confirm it.
The substances responsible in my theory:
* 2,5-bis(glutathion-S-yl)-R-methyldopamine
* 5-(N-acetylcystein-S-yl)-R-methyldopamine
* 2,4,5-trihydroxyamphetamine
All three of these are O-demethylated or ring-hydroxylated metabolites of MDA, which is itself an N-demethylated metabolite of MDMA. Basically, they are hepatic metabolites of MDMA.
2,4,5-trihydroxy-N-methylamphetamine is also slightly to blame. However, it reduced tryptophan hydroxylase significantly less than it's N-demethylated cousin, 2,4,5-trihydroxyamphetamine.
My whole premise is that MDMA's metabolism to MDA is largely to blame for it's 5-HT system toxicity. I have a lot of evidence for that theory, but it is still unproven.
Dopamine system damage is a whole different story.