Comment · Thu, November 22, 2012
MDMA Neurotoxicity Part 1 (Metabolites)
Original post in this thread
MisterYouAreSoDumb · 77 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 Once it's been o-demethylated to HHMA, it is no longer active like MDMA is.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
metocin · 1 points
No, your term was not vague, but most people use "neurotoxicity" in a way that's extremely broad and nondescript. As I stated, I don't doubt that any of this is true. And it IS worrying. But it would be interesting to know what effect it has on functioning since there's not much info relating to the functional side of things. We can argue about in vitro studies all day, but if people don't see the real-world side effects of MDMA, it's easier for them to remain in denial about the dangers.
Thanks for the links.
u/MisterYouAreSoDumb
There are many studies that address your concern.
Long-term effects of MDMA use in humans.
Mood and cognition deficits in humans even after 2.5 years of abstinence.
Significant decreases in SERT expression in MDMA users.
MDMA users have impaired memory even after abstinence.
Even a low first dose of MDMA induced lower verbal memory.
More memory deficits in MDMA users.
MDMA users show hippocampal damage.
This one shows that the MDMA induced hippocampal damage leads to memory impairment.
These are all human studies. So there are a great many studies that not only prove 5-HT neurotoxicity in humans, but also show lasting cognitive deficits due to said damage. Given this information, no logical person could remain in denial about the risks!
However, what I am trying to do it figure out how to prevent this damage. My supplementation has done it, and now I am 90% sure I know why. There's no point for someone to argue that the dangers aren't there, especially when I know how to prevent it.