Comment · Sat, December 22, 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.
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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.
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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 Once it's been o-demethylated to HHMA, it is no longer active like MDMA is.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.
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What they were answering
zeekip · 1 points
How common is this CYP2D6 genetic condition? Could this be the reason some people start to hallucinate really hard on 150mg, whilst others have no visual distortion with 180mg of MDMA ?(Because these people end up with more MDMA being metabolized to MDA)
Then, is this a good indicator for such condition ? Should people who experience that also be more cautious ?
u/MisterYouAreSoDumb
Yes, that is possible. Those with lower CYP2D6 will have more of their dose metabolized by CYP3A4 to MDA, which can be hallucinogenic. However, it probably also has something to do with inducing CYP3A4 as well. It could also be another mechanism that we are unaware of, or a combination of things. A good test for this is take grapefruit juice and quercetin before and during your next roll. This will inhibit CYP3A4. If that stops the hallucinogenic properties, you know it's your enzymes. I do this anyway because of my whole theory about MDA being the cause of MDMA's neurotoxicity. It's known that MDA is MUCH more neurotoxic that MDMA, so preventing that metabolism can only help.