Purpose: Neurocognitive, brain imaging: To investigate whether ecstasy users show decrements in memory performance compared with non-user controls, and to investigate whether changes in performance on a measure of memory relate to changes in N-acetylaspartate, considered a marker of neuronal injury, as measured through MRS. Specific Hypotheses Tested - That ecstasy users would perform worse on a measure of memory than people who have not used ecstasy, and that decreased performance on the memory test would be associated with increased NA in pre-frontal cortex only, and not in other areas (such as parietal white matter or occipital gray matter).

Design: Non-experimental (retrospective) 2-group between-group design, with drug use (ecstasy use versus no reported ecstasy use) as a between-group variable, and with all participants completing a measure of verbal memory. Only ecstasy users underwent MRS scans.

Subjects: 8 male ecstasy users and 7 male non-user controls residing in the Amsterdam (Netherlands) area. Ecstasy users were recruited via flyers distributed in locations associated with the dance event ("rave") scene, and non-user controls were selected from a database of individuals, with controls specifically selected to match ecstasy users on the basis of age, gender and Verbal IQ (estimated via DART). Matching - Groups matched on gender, age and estimated verbal IQ.

Criteria for Inclusion, Ecstasy Users - No information is provided concerning minimum lifetime ecstasy exposure; previous papers selected participants if they had used at least 50 ecstasy tablets in a lifetime. Non-Users - No reported lifetime use of ecstasy. All Groups - Male, absence of past or current psychiatric illnesses as measured via psychiatric interview, and abstinent from all psychoactive drugs for at least 1 wk prior to study day, with abstinence verified via urinary analysis on study day.

Drug User Parameters - Ecstasy Use - Ecstasy users reported taking 902 +/- 801.2 ecstasy tablets over a lifetime, and average dose per use was 2.6 +/- 0.7 tablets per use. Average duration of use, in months, was 79.2 +/- 39.6 months, with no information provided about frequency of use per month. Average time since last use, in days, was 213 +/- 333 days. Other Drugs - All drugs reported as amount used in 3 mo prior to study day. Ecstasy users consumed alcohol 210 +/- 165.1 times, and non-user controls consumed alcohol 158.6 +/- 140.7 times. Tobacco; Ecstasy users smoked 1044.6 +/- 1312 cigarettes, and non-users smoked 516.1 +/- 517.1 cigarettes. Cannabis; Ecstasy users smoked 138.5 +/- 174.8 joints (cannabis), and non-users smoked 1.3 +/- 1.3 joints. Amphetamines: only ecstasy users reported amphetamine use in the last 3 months, with ecstasy users reporting taking 4.4 +/- 8.2 g amphetamine in that time. Ecstasy users, but not non-users, reported sporadic use of cocaine and magic mushrooms.

Group Demographics and Matched Variables - The authors matched samples on gender and age and estimated verbal IQ. Gender, as M/F ratio - Ecstasy users, 8/0; non-users, 7/0. Age - Average age, in years, for ecstasy users, was 28.3 +/- 7, and average age for non-users was 29.3 +/- 6.9. Estimated verbal IQ - Average estimated verbal IQ for ecstasy users was 92.6 +/- 5.6, and estimated verbal IQ was 92.4 +/- 4.8 in non-users/ Other variables. Education - Average amount of education attained, in years, was 11.5 +/- 2.1 for ecstasy users and 15 +/-1.1 for non-users.

Measures: Imaging - MRS was performed in ecstasy users only. [1H]-MRS performed with a 1.5 T MRI scanner. Regions selected for examination were pre-frontal cortex, occipital gray matter, and temporo-parietal white matter, with pre-frontal cortex selected because PET studies found it to be a maximal site of increased CBF during an auditory memory task. Substances assayed were N-acetylaspartate and creatine kinase. NA/Cr ratio was computed after measuring concentration of these substances in each selected brain area. Verbal Memory - Verbal memory was measured via RAVLT. Scores for immediate and delayed recall were calculated for all participants.

Analyses: Verbal Memory - Differences in immediate and delayed RAVLT recall scores were analyzed via analysis of covariance (ANCOVA), with drug use (ecstasy user versus non-user control) serving as a between-group factor and participant's age and DART score serving as covariants.

Relationship Between NA/Cr Ratio and RAVLT Scores - Because MRS was not performed on non-user controls, comparisons of NA/Cr ratios were not made between ecstasy users and non-users. Possible associations between NA/Cr ratios in 3 selected ROIs and RAVLT scores were examined via linear regression, with immediate and delayed RAVLT scores as predictors and NA/Cr ratios in pre-frontal cortex, occipital gray matter, and temporo-parietal white matter serving as dependent variables, with p. = 0.017.

Relationship Between RAVLT Scores and Drug Use - A linear multiple regression was used to assess the degree of association between immediate and delayed RAVLT recall scores and lifetime use of MDMA, and between recall scores and past 3 months' use of cannabis, with p. = 0.017.

Results - Significant Differences: Verbal Memory - Ecstasy users had significantly lower delayed recall scores compared with non-user controls.

Relationship Between NA/Cr Ratio and RAVLT Scores - NA/Cr ratios in pre-frontal cortex were significantly associated with delayed recall scores in ecstasy users (but not with immediate recall score).

Relationship Between RAVLT Scores and Drug Use - There was a significant association between extent of lifetime ecstasy use and delayed recall score, with a lower delayed recall score predicting a greater number of ecstasy tablets used in a lifetime.

Results - No Differences Found: Verbal Memory - There were no differences in immediate recall scores between ecstasy users and non-user controls.

Relationship Between NA/CR Ratio and RAVLT Scores - There was no significant association between NA/Cr ratios in pre-frontal cortex in ecstasy users and immediate recall score, (but significant associations between delayed recall score and pre-frontal NA/Cr ratios.) There were no significant relationships between delayed recall score and NA/Cr ratios in occipital gray matter or in temporo-parietal white matter. There were no significant associations between immediate recall score and NA/Cr ratios in any of the brain regions examined (pre-frontal cortex, occipital gray matter, temporo-parietal white matter).

Relationships Between RAVLT Scores and Drug Use - There was no association between lifetime ecstasy use and immediate recall score. There was no association between amount of cannabis used in 3 months prior to study and either of the recall scores (immediate or delayed).

Overall Effects: A small sample of male ecstasy users performed less well on a measure of delayed verbal recall when compared with participants matched for age, gender and estimated verbal IQ, but with no reported use of ecstasy. However, ecstasy users did not differ from non-user controls on a measure of immediate verbal recall. NA/Cr ratios in pre-frontal regions were associated with delayed recall score in ecstasy users, with greater NA associated with lower RAVLT delayed recall score. (NA/Cr ratios were either not computed or not reported for non-user controls). However, there was no relationship between NA/Cr ratios in the other two brain regions examined (occipital gray matter and temporo-parietal white matter) and either immediate or delayed recall scores, as measured by RAVLT. While amount of cannabis used in last 3 months failed to predict immediate or delayed recall scores, lifetime use of ecstasy was associated with delayed, but not immediate, recall score, with people reporting use of more tablets having lower delayed recall scores. The authors' hypotheses were partially confirmed, as performance on the verbal memory score that differentiated ecstasy users from non-user controls (delayed recall) was associated only with NA/Cr ratios in pre-frontal areas, and not with NA/Cr ratios in other brain regions examined. However, while ecstasy users did not perform as well as non-users on delayed recall, there was no significant difference between ecstasy users and non-users on a measure of immediate recall.