Comment · Sat, November 24, 2012
MDMA Neurotoxicity Part 1 Metabolites)
Original post in this thread
MisterYouAreSoDumb · 129 points
This is probably going to be the first in a series of discussions I start about MDMA. There's just too much information for one post. Therefore, I am going to start with one that is very interesting to me: MDMA's metabolites and their role in neurotoxicity. I pre-appologise for the length and terminology used.
_________________________________________________
First off, let's discuss how MDMA is metabolized. The human cytochrome CYP450 is responsible for the metabolism of MDMA. The primary enzyme responsible is CYP2D6, using O-demethylation. This process adds two hydrogen atoms to the two open oxygen atoms in MDMA to create HHMA. Let's look at the structure for a minute.
________________________________________________
MDMA is 3,4-methylenedioxy-N-methylamphetamine
HHMA is 3,4-dihydroxy-N-methylamphetamine
So your CYP2D6 enzyme added two hydrogen atoms to the methylenedioxy structure to create a dihydroxy structure. Once it's been o-demethylated to HHMA, it is no longer active like MDMA is. HHMA can then be 0-methylated further to HMMA, or 4-hydroxy-3-methoxy-N-methylamphetamine. Here is an image to help you visualize this process.
This is…
What they were answering
slyman928 · 2 points
will any of this work to reduce neurotoxicity from MDA? also, what you say about 2d6 is interesting because i think i'm a slow metabolizer of dxm so it's probably from a lower level of 2d6. from asking people it also seems like mdma to me is a little more mda-ish than most. i wonder if i truly do have a lower 2d6 and that's why. you say that people have a "genetic condition" which i disagree with, it's just different genes
u/MisterYouAreSoDumb
My whole point was that MDA WAS the cause of MDMA neurotoxicity. If you are taking MDA, there is no way to prevent the toxic metabolites. Your best bet is to load up on antioxidants, and smoke some THC.
If you are one of those with lower CYP2D6, then it very well may be you are getting more metabolism to MDA. If you are noticing your MDMA rolls are a little psychedelic, then that might be why.
And by condition, I do not mean disorder. It's simply that your genetics have left you with lower CYP2D6 than what is normally in the majority of the population. Just like those of Asian descent have lower alcohol dehydrogenase, causing them to be less tolerant of ethanol. It's not really a disorder, but it is a genetic condition that has certain side effects.