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Vollenweider FX, Gucker P, Schönbächler R, Kamber E, Vollenweider-Scherpenhuyzen MFI, Schubiger G, Hell D. 
“Effects of MDMA on 5-HT uptake sites using PET and [11C]-McN5652 in humans”. 
Conference of the German Society for Psychiatry, Psychotherapy and Neuromedicine. 2000.
INTRODUCTION: Animal studies suggest that the psychotropic effects of 3,4-methylenedioxymethamphetamine (MDMA) are mainly attributable to increased serotonin (5-HT) release by interaction of MDMA with the 5-HT uptake site. Moreover, animal studies also suggest that repeated or high-doses of MDMA (10-20mg/kg) may lead to neurotoxic alterations of serotonergic neurons as indexed by measures of 5-HT update side density. However, whether MDMA interacts with the 5-HT uptake site and whether a single moderate dose of MDMA leads to long-term changes in 5-HT update sites in healthy human volunteers has not yet been studied.

METHODS: 5-HT update site binding was measured in healthy volunteers using PET and [nC](+) McN-562 on day one during baseline and after a single dose of MDMA (1.5mg/kg), and a third time after one month again during baseline condition (n=5). A control group (n=5) received 3 baseline scans only using the same protocol as in group one. Arterial blood samples were collected and analyzed to correct the input function for metabolized radioligand.. Psychological effects of MDMA were rated before and after PET scanning using the EWL mood rating scale and the Altered State of Consciousness Questionnaire (APZ).

RESULTS: At the dose tested, MDMA mainly produced a state of enhanced mood, moderate euphoria, and a slight intensification of visual and tactile perception. Concomitantly, MDMA decreased [nC](+)MeN-5652 binding as indexed by distribution volumes (DV's) significantly in the caudate (36%), putamen (33%), thalmus (31%), midbrain (28%), followed by occipital (23%), temporal (20%), frontal cortex (6%), parietal (5%) cortices. No changes in 5-HT uptake sites as measured by [nC](+)McN-5652 binding could be detected one month after MDMA treatment. Within-subject test-retest variability of [nC](+)McN-5652 binding under baseline condition was only 1-4%. Conclusions: In parallel with the known distribution and density of 5-HT uptake sites, MDMA reduced [nC](+)McN-5652 binding more in subcortical than cortical regions. These observations suggest that the reduction in [nC](+)McN-5652 binding may be attributable to a direct competition of MDMA with [nC](+)McN-5652 at 5-HT trasnporter sites. The small test-retest variability together with the finding of almost identical [nC](+)McN-5652 binding across brain regions in baseline conditions after MDMA treatment makes it extremely unlikely that a moderate dose of MDMA (1.5mg/kg) leads to neurotoxic damage e.g., long-term changes in 5-HT uptake sites. [Published in Der Nervenarzt, 71, p. 5189]
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