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Neuroimaging findings with MDMA/ecstasy: technical aspects, conceptual issues and future prospects

Maartje M. L. de Win

Graduate School of Neurosciences, Department of Radiology, Academic Medical Centre, AZ 1105 University of Amsterdam, Amsterdam, The Netherlands

Wim van den Brink

Amsterdam Institute for Addiction Research and Department of Psychiatry, Academic Medical Centre, AZ 1105 University of Amsterdam, Amsterdam, The Netherlands

Jan Booij

Department of Nuclear Medicine, Academic Medical Centre, AZ 1105 University of Amsterdam, Amsterdam, The Netherlands

Gerard J. den Heeten

Graduate School of Neurosciences, Department of Radiology, Academic Medical Centre, AZ 1105 University of Amsterdam, Amsterdam, The Netherlands

Users of ecstasy (3,4-methylenedioxymethamphetamine; MDMA) may be at risk of developing MDMA-induced injury to the serotonin (5-HT) system. Previously, there were no methods available for directly evaluating the neurotoxic effects of MDMA in the living human brain. However, development of in vivoneuroimaging tools have begun to provide insights into the effects of ecstasy on the human brain. Single photon emission computed tomography (SPECT), positron emission computed tomography (PET) and proton magnetic resonance spectroscopy (1H-MRS) studies which have evaluated ecstasy's neurotoxic potential will be reviewed and discussed in terms of technical aspects, conceptual issues and future prospects. Although PET and SPECT may be limited by several factors such as the low cortical uptake and the use of a non-optimal reference region (cerebellum) the few studies conducted so far provide suggestive evidence that people who heavily use ecstasy are at risk of developing subcortical, and probably also cortical reductions in serotonin transporter (SERT) densities, a marker of 5-HT neurotoxicity. There seem to be dose-dependent and transient reductions in SERT for which females may be more vulnerable than males. 1H-MRS appears to be a less sensitive technique for studying ecstasy's neurotoxic potential. Whether individuals with a relatively low ecstasy exposure also demonstrate loss of SERT needs to be determined. Because most studies have had a retrospective design, in which evidence is indirect and differs in the degree to which any causal links can be implied, longitudinal studies in human ecstasy users are needed to draw de.nite conclusions.

Key Words: ecstasy • MDMA • neuroimaging • serotonin • SPECT • 1H-MRSpectroscopy

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