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Cortical Serotonin Transporter Density and Verbal Memory in Individuals Who Stopped Using 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy")
Preliminary Findings
Liesbeth Reneman, MD;
Jules Lavalaye, MD;
Ben Schmand, PhD;
Frederik A. de Wolff, PhD, DSc;
Wim van den Brink, MD, PhD;
Gerard J. den Heeten, MD, PhD;
Jan Booij, MD, PhD
Arch Gen Psychiatry. 2001;58:901-906.
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 2ß-carbomethoxy-3ß-(4-iodophenyl)
tropane ([123I]ß-CIT) by quantification of brain 5-HT transporter
densities. Verbal memory performance was assessed with the Rey Auditory Verbal
Learning Test.
Results Mean cortical [123I]ß-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 [123I]ß-CIT binding to cortical 5-HT transporters
or duration of abstinence from MDMA.
Conclusion 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.
From the Graduate School of Neurosciences, Department of Nuclear Medicine
(Drs Reneman, Lavalaye, and Booij); Departments of Neurology (Dr Schmand),
Human Toxicology (Dr de Wolff), and Radiology (Dr den Heeten); and Amsterdam
Institute for Addiction Research and Department of Psychiatry (Dr van den
Brink), Academic Medical Center, Amsterdam, the Netherlands; and Toxicology
Laboratory, Leiden University Medical Center, Leiden, the Netherlands (Dr
de Wolff).
Corresponding author and reprints: Liesbeth Reneman, MD, Department
of Nuclear Medicine, F2-210, Academic Medical Center, Meibergdreef 9, 1105
AZ Amsterdam, the Netherlands (e-mail: l.reneman{at}amc.uva.nl).
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