Joint Symposium of the Society for the Study of Addiction and the Faculty of Substance Misuse of the Royal College of Psychiatrists

The UK and the Netherlands are the two countries in the European Union with the highest consumption of ecstasy. Formany years,MDMA has been the main component of most ecstasy pills in theNetherlands and probably also inmost other countries. Animal studies have shown that MDMA can cause serious serotonergic and possibly also dopaminergic brain damage, in rodents and in non-human primates In humans, the use of ecstasy has been associated with memory problems and with increased levels of depression, anxiety and possibly impulsivity. The objective of the current study is to test the hypothesis that ecstasy use is related to (irreversible) serotonergic abnormalities in the human brain and that these abnormalities are related to memory problems and depressed mood. – 7 A total of 69 subjects were enrolled in the study: 15 ecstasy naive subjects, 15 moderate ecstasy users (life-time use 555 pills; mean 29 pills), 23 heavy ecstasy users (life-time use 455 pills; mean 530 pills) and 16 ex-ecstasy users (life-time use 455 pills, last use412months prior to the study; mean 268 pills). The effects of ecstasy on brain serotonergic neurones was studied in all subjects using [I]b-CIT Photon Emission Computed Tomography (SPECT) and in a subgroup of seven ecstasy naive subjects and eight heavy ecstasy users with Proton Magnetic Resonance Spectroscopy ([H] MRS). Verbal memory performance was assessed with the Rey Auditory Verbal Learning Test (RAVLT). The presence of depressed mood and DSM-IV major depression was assessed with the Beck Depression Inventory (BDI) and the Composite International Diagnostic Interview (CIDI). In female (but not in male) heavy ecstasy users, significant decreases in overall [I]b-CIT binding ratios were observed. In female (but not in male) ex-ecstasy users also significantly decreased serotonine transporter binding was observed in the parieto-occipital and occipital cortex. Heavy ecstasy users and ex-ecstasy users recalled significantly fewer words than ecstasy naive controls on the immediate and delayed recall tests of the RAVLT. The magnitude of the memory impairment was associated with the number of pills, but not with the duration of abstinence and not with the [I]b-CIT binding to cortical serotonine transporters. Using [H] MRS in a subgroup of heavy ecstasy users, delayed memory scores on the RAVLT were significantly associated with lower NAA/Cr levels in the prefrontal cortex. Depression scores on the BDI were significantly higher in heavy ecstasy users and ex-ecstasy users compared to ecstasy naı̈ve subjects, and the number of ecstasy pills was significantly associated with the BDI score. However, no significant associations were observed between the BDI and [I]b-CIT binding ratios. No significant differences were observed in the frequency of life-time and current major depression between the different groups. In females, heavy ecstasy use seems to be related to Addiction Biology (June 2003) 8, 233 – 250