Cognition in Novice Ecstasy Users with Minimal Exposure to Other Drugs: a Prospective Cohort Study

Context: Ecstasy (street name for [+/-]-3,4-methylenedioxymethamphetamine [MDMA]) use has been associated with cognitive deficits, especially in verbal memory. However, owing to the cross-sectional and retrospective nature of currently available studies, questions remain regarding the causal direction and clinical relevance of these findings.

Objective: To examine the relationship between Ecstasy use and subsequent cognitive performance.

Design: A prospective cohort study in Ecstasy-naive subjects with a high risk for future first Ecstasy use, as part of the Netherlands XTC Toxicity study. The initial examination took place between April 10, 2002, and April 28, 2004; follow-up was within 3 years after the initial examination.

Setting And Participants: One hundred eighty-eight healthy Ecstasy-naive volunteers (mean age, 22 years) were recruited. Of these, 58 subjects started using Ecstasy (mean cumulative dose, 3.2 tablets; median cumulative dose, 1.5 tablets). They were compared with 60 persistent Ecstasy-naive subjects matched on age, sex, intelligence, and use of substances other than Ecstasy. Differences in cognition between Ecstasy users and Ecstasy-naive subjects were adjusted for differences in cannabis and other recreational drug use.

Main Outcome Measures: Change scores between the initial examination and follow-up on neurocognitive tests measuring attention, working memory, verbal and visual memory, and visuospatial ability.

Results: At the initial examination, there were no statistically significant differences in any of the neuropsychological test scores between persistent Ecstasy-naive subjects and future Ecstasy users. However, at follow-up, change scores on immediate and delayed verbal recall and verbal recognition were significantly lower in the group of incident Ecstasy users compared with persistent Ecstasy-naive subjects. There were no significant differences on other test scores.

Conclusions: Our findings suggest that even a first low cumulative dose of Ecstasy is associated with decline in verbal memory. Although the performance of the group of incident Ecstasy users is still within the normal range and the immediate clinical relevance of the observed deficits is limited, long-term negative consequences cannot be excluded.