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Comment · Fri, August 4, 2017

Difficulty understanding findings of a paper on MDMA neurotoxicity

Original post in this thread

o99o99 · 40 points

(I hope this is allowed under the first rule - I don't need an expert, I just need someone smarter than me!)

Could someone explain the conclusions of the paper below to me? I don't know enough neurology to understand the link between an increase in "receptor density" and "chronic neurotoxicity" - is anyone able to explain the mechanism behind this in a bit more detail?

Conclusions The recreational use of MDMA is associated with long-lasting increases in serotonin2A receptor density. Serotonin2A receptor levels correlate positively with lifetime MDMA use and do not decrease with abstinence. These results suggest that MDMA use produces chronic serotonin neurotoxicity in humans. Given the broad role of serotonin in human brain function, the possibility for therapeutic MDMA use, and the widespread recreational popularity of this drug, these results have critical public health implications.

From: http://doi.org/10.1001/archgenpsychiatry.2011.156

What they were answering

OceanFixNow99 · 2 points

Paging /u/misteryouaresodumb -

Serotonin2A receptor levels correlate positively with lifetime MDMA use and do not decrease with abstinence.

Is at odds with

Although reductions in serotonin transporter density are consistent with serotonin axon loss, there is evidence that transporter levels show some recovery with sustained abstinence,17,22 suggesting that partial recovery from initial axon injury may be possible.

Ignoring the seeming contradictions, one wonders if various compounds like NA-R-ALA, beta glucans, or something else could target this.

Also, how long did they wait to analyse the brains? Does waiting 5 or 7 years effect the outcome?

u/MisterYouAreSoDumb

As /u/GreenLeaff stated, the 5-HT2A receptor and 5-HT transporter are two different things.

Something like Trazodone can paradoxically down-regulate 5-HT2A receptors.

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