Plants - Drugs Mind - Spirit Freedom - Law Arts - Culture Library  
Follow @Erowid on Instagram!
MDMA Neurotoxicity Study
Comments by Lamont Granquist

Positron emission tomographic evidence of toxic effect of MDMA ('Ecstasy') on brain serotonin neurons in human beings,
by U. D. McCann; Z Szabo; U Scheffel; R.F. Dannals; G. A. Ricaurte
The Lancet Vol 352, Oct 31, 1998, 1437

It seems on a preliminary examination of Ricaurte's study (in other words i skimmed it pretty fast) that Figure 3 and Figure 4 are where the "meat" of this study is, and they're not terribly impressive. It has already been reported that subchronic (less than a month) administration of 5-HT transporter ligands like antidepressants (SSRIs, TCAs and tianeptine) reduce 5-HT transporter mRNA and radioligand binding to 5-HT transporter[1,2,3]. These results call into question the interpretation of reduced [11C]McN-5652 binding in human brain as "neurotoxicity." To reach this conclusion Ricaurte would really need to show decreases in binding to the 5-HT transporter in excess of a 25% reduction -- I would accept that as valid evidence since there is no known non-neurotoxic 5-HTT ligand which "down-regulates" the 5-HTT by this amount, while the neurotoxic doses of MDMA (5 mg/kg x 2/day x 4 days in non-human primates, 20 mg/kg x 2 x 4 in rats) do produce more substantial reductions. However, eyeballing Figure 3, I don't see such a clear and substantial reduction. Furthermore in Ricaurte's Figure 4 barring one outlying point in a user of appx 150 MDMA doses, none of the MDMA users range lower than the low end of the control subjects, and the reduction (if i understand this plot correctly) is of the order of 25% and therefore not significant.

The line they drew through this plot also tends to make me cringe -- it just smells bad -- the phrase "how to lie with statistics" leaps to mind.

And, of course, there are other issues with the study -- such as the possible exposure to other neurotoxins like methamphetamine, and possible selection effects (perhaps MDMA users with low initial 5-HTT counts tend to be the ones that wind up using it 300 times). Ultimately, I think these matched retrospective studies are probably worthless in general unless there are very strong correlations, which I just don't see. The more I look at this study the more I think there's even less to worry about here than there was in the CSF 5-HIAA studies of human users...

[1] Watanabe, Y, Sakai, RR, McEwen, BS, Mendelson, S. Stress and
Antidepressant effects on hippocampal and cortical 5-HT1A and 5-HT2
receptors and transport sites for serotonin. Brain Research. Vol 615. P 87-94. 1993.

[2] Kuroda, Y, Watanabe, Y, McEwen, BS. Tianeptine Decreases Both
Serotonin Transporter mRNA and Binding Sites in Rat Brain. European
Journal of Pharmacology. Vol 268. P R3-R5. 1994.

[3] Lesch, PK, Aulakh, CS, Wolozin, BL, Tolliver, TJ, Hill, JL, Murphy,
DL. "Regional Brain Expression of Serotonin Transporter mRNA and its
Regulation by Reuptake Inhibiting Antidepressants." Molecular Brain
Research. Vol 17. P 31-35. 1993.