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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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