Purpose: Neurocognitive, brain imaging: To compare serotonin transporter binding, measured via SPECT with [123I]-b-CIT, and neurocognitive function in current ecstasy users, former ecstasy users and non-user controls.

Design: Non-experimental (retrospective) 3-group between subjects design comparing current ecstasy users, ecstasy users who had ceased use for at least 1 year and individuals who did not use ecstasy on density of cortical SERT binding and memory function, with all participants receiving SPECT scans and completing the RAVLT.

Subjects: 22 current ecstasy users, 16 former ecstasy users and 13 non-user controls residing in the Amsterdam (Netherlands) area, and recruited via flyers distributed at locations associated with the dance event (rave) scene. Matching - All 3 groups were matched on gender and age and approximately matched on estimated verbal IQ.

Criteria for Inclusion - Ecstasy Users - Self-reported lifetime use of at least 50 ecstasy tablets. Former Ecstasy Users - Self-reported lifetime use of at least 50 ecstasy tablets, but abstinence from ecstasy for at least a year prior to study date. Non-User Controls - No self-reported lifetime use of ecstasy, though use of other drugs was permitted. All Groups - Healthy, as apparently indicated through medical examination and no past or current psychiatric illness, between the ages of 18 and 45 years old, not pregnant, and abstinent from all psychoactive drugs for 3 wks before study day, with abstinence verified through urinary drug screen.

Drug Use Parameters, Ecstasy Use - Ecstasy users reported average lifetime use of 485 +/- 598 tablets, at an average dose of 2.2 +/- 0.7 tablets per use. No information is provided on frequency of use. Average duration of use, in months, was 66 +/- 32.4 months, with no information presented about frequency of use per month. Time since last use, in days, was an average of 72 +/- 72 days, with abstinence verified via self-report (and via urinary screening on study day). Former ecstasy users - reported average lifetime use of 268 +/- 614 tablets, at an average dose of 2.1 +/- 1 tablets per use. No information provided on frequency of use. Average duration of use, in months, was 55.2 +/- 31.2 months, with no information presented about frequency of use per month. Time since last use, in days, was an average of 870 +/- 612 days (approx. 2.4 years), with abstinence verified via self-report (and via urinary screening on study day). Other Drugs - Reported as times used in last year for all substances. Average alcohol consumption was 490.5 +/- 372.9 times for ecstasy users, 323.7 +/- 256.4 times for former ecstasy users and 478.8 +/- 452.0 times for non-user controls. Average tobacco use was 3302.4 +/- 3857.6 cigarettes for ecstasy users, 4572.5 +/- 2996.5 for former ecstasy users and 3590.4 +/- 1952.7 for non-users. Average cannabis consumption, in number of joints, was 326.9 +/- 514.9 for ecstasy users, 456.7 +/- 881.9 for former ecstasy users and 15.3 +/- 16 for non-users. Average amphetamine consumption was 12.8 +/- 18.7 times for ecstasy users, with no amphetamine use reported for former ecstasy users or non-users. Average cocaine use was 7.2 +/- 6.4 times for ecstasy users, 1.5 +/- 3.3 times for former ecstasy users and 0.07 +/- 0.25 times for non-users. Average LSD use was 1.9 +/- 3.5 times for ecstasy users, 3.3 +/- 12.9 times for former ecstasy users and 0 times for non-users. Average magic mushroom use (psilocybin) was 1.5 +/- 2.3 times for ecstasy users, 2.9 +/- 9.2 times for former ecstasy users and 0.08 +/- 0.28 times for non-users.

Group Demographics and Matched Variables - Ecstasy users, former ecstasy users and non-user controls were matched on the basis of gender, age and estimated IQ (via DART score). Gender, as M/F ratio - Ecstasy users, 11/11, former ecstasy users, 8/8, non-user controls, 7/6. Age - Average age of ecstasy users was 26.2 +/- 5.3, average age of former ecstasy users was 25.3 +/- 5.4 and average age of non-user controls was 25 +/- 3.6 years. Estimated IQ - As measured via DART score (Dutch version of NART) reading score of ecstasy users, was 105.2 +/- 8.5, 103.9 +/- 9.8 in former ecstasy users and 105.8 +/- 7.2 in non-user controls. Other Variables - Education, as average years of education attained, was 12.6 +/- 2.2 years for ecstasy users, 11.8 +/- 2.4 years for former ecstasy users and 14.5 +/- 1.3 years for non-user controls.

Measures: Imaging - SPECT scans were performed 4 h after injection of 3.8 mCi (140 MBq) [123I]-b-CIT. Participants were supine during SPECT scan, with heads parallel to orbitometeal line. An investigator blind to condition constructed a standard template with regions of interest. Selected ROIs were in frontal, temporal, parieto-occipital and occipital areas, and another template with cerebellum selected as ROI to compare with other areas. [123I]-b-CIT binding ratios were calculated by division of ROI bindings by binding in the cerebellum.

Verbal Memory - Memory was assessed within 1 day of SPECT scan with RAVLT. Immediate recall, delayed recall and recognition were measured, with measure of delayed recall and recognition (identification of targets versus distractors) occurring 20 min after list presentation.

Analyses: Imaging and Memory Performance - Differences between cortical b-CIT binding ratio and RAVLT were measured via analysis of covariance (ANCOVA) with drug use as a between-groups factor (current ecstasy user, former ecstasy user or non-user control), and age, gender and DART score serving as 3 covariants. Post-hoc comparisons were made via Bonferroni tests.

Associations Between Variables - Relationships between RAVLT scores (immediate and delayed) and b-CIT binding, between RAVLT score and MDMA drug use parameters and between RAVLT scores and use of other drugs (cannabis, amphetamines and cocaine) were investigated via correlational analyses, with p. set at .05. Partial correlations were used to control for the effects of gender, age and DART score.

Results - Significant Differences: Imaging - Current ecstasy users had significantly lower b-CIT binding than non-user controls. Verbal Memory - Both immediate and delayed RAVLT scores were lower in current and former ecstasy users versus controls (current ecstasy, former ecstasy < non-users).

Associations Between Variables - RAVLT score for immediate recall was significantly and negatively correlated with lifetime ecstasy use (number of tablets), where immediate recall score decreased as lifetime ecstasy use increased.

Results - No Differences Found: Imaging - There were no regional differences in b-CIT binding between any of the 3 groups (ecstasy users, former ecstasy users and non-user controls). There were no differences in b-CIT binding in former ecstasy users versus non-user controls. Verbal Memory - There were no differences between any of the 3 groups (current ecstasy users, former ecstasy users and non-user controls) on RAVLT recognition scores.

Associations Between Variables - RAVLT scores for immediate and delayed recall were not associated with degree of b-CIT binding. Immediate and delayed recall scores were not associated with time since last use of ecstasy. Delayed recall score was not associated with lifetime ecstasy use. There were no associations between immediate or delayed recall score and extent of cannabis, amphetamine or cocaine use in the previous year.

Overall Effects: When compared with former ecstasy users and non-user controls matched on age, gender and verbal IQ, current ecstasy users had lower b-CIT binding ratios, with b-CIT considered a ligand for the serotonin transporter site. However, former ecstasy users and controls displayed similar ligand binding ratios. In contrast, both current and former ecstasy users had lower RAVLT scores for immediate and delayed recall when compared with non-user controls. There was no relationship between degree of b-CIT binding and either immediate or delayed recall scores in any of the 3 groups. Correlational analyses did not find relationships between RAVLT scores and time since last ecstasy use or yearly use of cannabis, amphetamine or cocaine, but RAVLT immediate recall score was found to be inversely correlated with lifetime ecstasy use. There was no reported relationship between delayed recall score and lifetime ecstasy use. This would seem to suggest that ecstasy use affects performance on measures of verbal memory, with performance decreasing with increasing ecstasy use.