Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"): preliminary findings.
BACKGROUND
Although the popular drug 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to damage brain serotonin (5-HT) neurons in animals, the fate and functional consequences of 5-HT neurons after MDMA injury are not known in humans. We investigated the long-term effects of MDMA use on cortical 5-HT neurons in humans and memory function, because brain 5-HT has been implicated in memory function.


METHODS
Twenty-two recent MDMA users, 16 ex-MDMA users who had stopped using MDMA for more than 1 year, and 13 control subjects. The effects of MDMA use on cortical 5-HT neurons was studied by means of single-photon emission computed tomography with iodine 123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl) tropane ([(123)I]beta-CIT) by quantification of brain 5-HT transporter densities. Verbal memory performance was assessed with the Rey Auditory Verbal Learning Test.


RESULTS
Mean cortical [(123)I]beta-CIT-labeled 5-HT transporter density was significantly lower in recent MDMA users than in controls (1.17 vs. 1.28 [-9%]) but not in ex-MDMA users (1.24 vs. 1.28 [-3%]). Recent and ex-MDMA users recalled significantly fewer words than did controls on the immediate recall (47.0 and 48.0 vs 60.0, respectively; P =.001) as well as the delayed recall (9.8 and 10.1 vs. 13.1, respectively; P =.003). Greater use of MDMA was associated with greater impairment in immediate verbal memory. However, memory performance was not associated with [(123)I]beta-CIT binding to cortical 5-HT transporters or duration of abstinence from MDMA.


CONCLUSIONS
The present study suggests that, while the neurotoxic effects of MDMA on 5-HT neurons in the human cortex may be reversible, the effects of MDMA on memory function may be long-lasting.
Reneman
L
L
Department of Nuclear Medicine, F2-210, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. l.reneman@amc.uva.nl
Lavalaye
J
J
Schmand
B
B
de Wolff
F A
FA
van den Brink
W
W
den Heeten
G J
GJ
Booij
J
J
D000328:Adult; D001923:Brain Chemistry / Q000187:drug effects*; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000187:drug effects; D003042:Cocaine / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008569:Memory Disorders / Q000139:chemically induced / Q000175:diagnosis*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D009419:Nerve Tissue Proteins; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D020258:Neurotoxicity Syndromes / Q000000981:diagnostic imaging; D011379:Prognosis; D050486:Serotonin Plasma Membrane Transport Proteins; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000000981:diagnostic imaging; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000706:statistics & numerical data; D014706:Verbal Learning / Q000187:drug effects
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine