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

Heavy ecstasy (MDMA) use may cause injury to the brain's serotonin system. Neuroimaging techniques like SPECT, PET, and proton magnetic resonance spectroscopy have been used to study this potential neurotoxicity in living humans. The few available studies suggest that heavy users risk reductions in serotonin transporter (SERT) densities in subcortical and possibly cortical brain regions, a marker of serotonin neurotoxicity. These reductions appear dose-dependent and transient, with females possibly more vulnerable than males. Proton magnetic resonance spectroscopy seems less sensitive for detecting ecstasy's neurotoxic effects. Whether lower exposure also leads to SERT loss remains unknown. Most studies are retrospective, providing indirect evidence, so longitudinal studies are needed for definitive conclusions.

Study at a glance

Abstract

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.