David Nutt's comments about a potential system for legal MDMA regulation

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There's a lot of research on humans that suggest MDMA causing long term cognitive and emotional impairment, as well as changes in serotonergic function similar to those observed in rat studies. After looking at a handful of research those studies found reduced binding of an SSRI, suggesting serotonergic damage. Serotonin reuptake transporter is only on the pre-synaptic neuron and reduced binding would suggest the absence of serotonin neurons. This isn't just tolerance either as people who have abstained for long periods of time still show similar bindings. They use this same method to determine neurotoxicity in rats as well, and is potentially the more accurate way to determine neurotoxicity over just looking at 5-HT and 5-HIAA (serotonin's metabolite) concentrations in cerebral spinal fluid. That's not to say that practicing harm reduction could potentially reduce or eliminate potential harm but the vast majority of people do not practice harm reduction.

reduced binding of an SSRI proves nothing.
first of all, taking SSRIs for just a few days can reduce SERT density by up to 90%.[source]

second, the doses usually administered to rats are way higher than for humans. to get comparable pharmacokinetics (and if we're talking about toxicity by ROS, Cmax is obviously the most interesting value), you have to administer comparable mg/kg doses to rats and humans. [source]

third, a "low dose" of 3mg/kg of mdma protects against neurotoxicity caused by a challenge dose of >10mg/kg [source]

fourth, the most reliable marker for the kind of cell death we would expect with mdma is silver staining. we don't even see this with doses of 20mg/kg. [source]


also, there were (two iirc?) european studies in humans that found the decreases in SERT reversible within weeks, but i can't find the source right now.

so yes, mdma can cause alterations in serotonergic function that sticks around for a while, but it's reversible. with these data we have now ricaurte's hypthesis of 5-HT neurotoxicity is pretty much dead.