Comment · Wed, November 14, 2012
Research Suggests no Neurotoxicity in MDMA
Original post in this thread
PuffyCheek · 194 points
In partial response to what I've been reading in the bestof'd thread here at /drugs, I think it would be good to start a discussion about the neurotoxicity in MDMA.
I feel as if the harmful effects discussed in the thread were overblown. According to a research done by the Harvard Medical School last year in 2011, users who were asked to use MDMA under a controlled setting over a certain period of time showed no signs of cognitive impairment nor decreased mental ability.
So the question remains, why do we have so much evidence from past research studies that show otherwise? The researchers at Harvard Medical School responded by saying that past research studies lacked a proper control environment. What that means is that past research studies did not control their test group to make sure they didn't engage in unhealthy activities after ingesting MDMA (i.e. going to a rave and dancing for 8 hours straight).
No research since 2011 has proved Harvard Medical School's conclusion wrong, that MDMA is actually harmful to your brain. No other research studies that I could personally find had settings as controlled as the one conducted by HMS.
That being said, research was done…
What they were answering
[deleted] · 3 points
Here's another good study, but this one experimental.
u/MisterYouAreSoDumb
Ok, I've been racking my brain over this, but I think I figured it out. The study you linked did not cover all the bases. It tested 3,4-dihydroxymethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), which are the only two direct metabolites of MDMA via the CYP2D6 enzyme. They found them to not be neurotoxic. End of story? NOPE! They totally forgot that MDMA is also metabolized by CYP3A4 into 3,4-methylenedioxyamphetamine (MDA). MDA is then metabolized into 3,4-dihydroxyamphetamine (HHA) and 4-hydroxy-3-methoxyamphetamine (HMA). Basically they are the same metabolites without the n-methyl group. MDA is widely know to be more neurotoxic than MDMA, and some have postulated that's due to it's higher affinity for dopamine. However, what if it is in fact due to it metabolizing much more HHA and HMA? Both of those substances are known neurotoxins, and are only formed during first pass metabolism. This would explain this study that showed MDMA injected directly into the brain was not neurotoxic because it skipped first pass metabolism. That study was written off because those with a CYP2D6 deficiency did not show lower neurotoxicity than normal user. In fact they showed slightly higher. That makes sense though, since a CYP2D6 deficient person would have more of the MDMA metabolized by CYP3A4, causing higher levels of HHA and HMA. They forgot the other damn enzyme! It explains everything.