Quantitative PET studies of the serotonin transporter in MDMA users and controls using [11C]McN5652 and [11C]DASB.
(+/-)3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') is a widely used illicit drug that produces toxic effects on brain serotonin axons and axon terminals in animals. The results of clinical studies addressing MDMA's serotonin neurotoxic potential in humans have been inconclusive. In the present study, 23 abstinent MDMA users and 19 non-MDMA controls underwent quantitative positron emission tomography (PET) studies using [11C]McN5652 and [11C]DASB, first- and second-generation serotonin transporter (SERT) ligands previously validated in baboons for detecting MDMA-induced brain serotonin neurotoxicity. Global and regional distribution volumes (DVs) and two additional SERT-binding parameters (DV(spec) and DVR) were compared in the two subject populations using parametric statistical analyses. Data from PET studies revealed excellent correlations between the various binding parameters of [11C]McN5652 and [11C]DASB, both in individual brain regions and individual subjects. Global SERT reductions were found in MDMA users with both PET ligands, using all three of the above-mentioned SERT-binding parameters. Preplanned comparisons in 15 regions of interest demonstrated reductions in selected cortical and subcortical structures. Exploratory correlational analyses suggested that SERT measures recover with time, and that loss of the SERT is directly associated with MDMA use intensity. These quantitative PET data, obtained using validated first- and second-generation SERT PET ligands, provide strong evidence of reduced SERT density in some recreational MDMA users.
McCann
Una D
UD
Department of Psychiatry, The Johns Hopkins School of Medicine, Baltimore, MD 21224, USA. umccann@jhmi.edu
Szabo
Zsolt
Z
Seckin
Esen
E
Rosenblatt
Peter
P
Mathews
William B
WB
Ravert
Hayden T
HT
Dannals
Robert F
RF
Ricaurte
George A
GA
D000328:Adult; D001596:Benzylamines / Q000493:pharmacokinetics*; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003710:Demography; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D015233:Models, Statistical; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D011869:Radioligand Assay / Q000379:methods; D019275:Radiopharmaceuticals / Q000378:metabolism; D012702:Serotonin Antagonists / Q000493:pharmacokinetics*; D050486:Serotonin Plasma Membrane Transport Proteins; D013223:Statistics as Topic
D001596:Benzylamines; D002250:Carbon Radioisotopes; D006213:Hallucinogens; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C058079:McN 5652; D018817:N-Methyl-3,4-methylenedioxyamphetamine