Comment · Mon, April 1, 2013
MDMA Supplementation
Original post in this thread
MisterYouAreSoDumb · 205 points
Ok, I did promise that I would make another post regarding supplementation to mitigate MDMA induced neurotoxicity. I have just been putting it off. Since my last post, I have gathered more information regarding my theory about MDA metabolism being the main cause of MDMA's neurotoxic effects. I will try to not get into that in this post, and keep this mostly about supplementation. As seems to be the norm with me, this may be long winded. Obviously everything I put on this list is not necessary. I will be placing supplements into different categories, with reasonings and references. I will let you decide which ones will be a part of your regimen.
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Essential Supplements:
* Alpha Lipoic Acid- This is one that everyone should be taking. It is a powerful antioxidant that scavenges reactive oxygen and nitrogen species. It also has a nice benefit of regenerating other vitamins, like C, after redox cycling. It exists in two enantiomers, R-ALA and S-ALA. R-ALA is the biologically active isomer that we are looking for. Most supplements a…
What they were answering
AskQGetA · 1 points
Do you have a source for that? I can't seem to find anything in the literature regarding CYP2D6 being affected. Be sure to distinguish between piperine and black pepper.
I was under the impression that the O-demethylation route was safer than N-demethylation, and that inhibiting CYP2D6 meant that a greater percentage of MDMA gets metabolized into MDA, which we want to avoid (this is the message I got from your other post). Doesn't this imply that activation of CYP2D6, should it occur, is desirable? I'm unclear as to what role this enzyme plays in the equation; if I understand you correctly, both activation and inactivation lead to more neurotoxicity than baseline.
u/MisterYouAreSoDumb
You know I thought I had one, but I cannot seem to find it now. After doing some more searching I think it has very little CYP2D6 activity.
I was under the impression that the O-demethylation route was safer than N-demethylation
Well sort of. If you were to block all N-demethylation, you will still get ring hydroxylation to THA and THM. That lowers tryptophan hydroxylase levels. However, it is the conjugate of HHA that is really the bad one. The most likely pathway for that to occur is O-demethylation of MDA. However, the ring hydroxylated metabolite of MDA can also eventually be converted into HHA, so stopping the conversion to MDA in the first place is the only sure way to prevent it from happening. Since it's CYP3A4 that converts MDMA to MDA, that is the enzyme I would say is the most critical to inhibit.