Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these.

To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine, cocaine and cannabis as part of The Netherlands XTC Toxicity (NeXT) study.

Effects of ecstasy and other substances were assessed with 1H-magnetic resonance spectroscopy, diffusion tensor imaging, perfusion weighted imaging and [123I]2β-carbomethoxy-3β-(4-iodophenyl)-tropane ([123I]β-CIT) single photon emission computed tomography (serotonin transporters) in a sample (n=71) with broad variation in drug use, using multiple regression analyses.

Ecstasy showed specific effects in the thalamus with decreased [123I]β-CIT binding, suggesting serotonergic axonal damage; decreased fractional anisotropy, suggesting axonal loss; and increased cerebral blood volume probably caused by serotonin depletion. Ecstasy had no effect on brain metabolites and apparent diffusion coefficients.

Converging evidence was found for a specific toxic effect of ecstasy on serotonergic axons in the thalamus.

A large number of studies, reviews and meta-analyses have reported cognitive deficits in ecstasy users. However most ecstasy users are polydrug users, and therefore it cannot be excluded that these deficits are (partly) the result of drugs other than ecstasy. The current study, part of the Netherlands XTC Toxicity (NeXT) study, investigates the specific sustained effects of ecstasy relative to amphetamine, cocaine and cannabis on the brain using neuropsychological examination.

A stratified sample of 67 subjects with such a variation in type and amount of drug use was included that correlations between the consumption of the various drugs were relatively low allowing stepwise linear multiple regression analyses to differentiate between the effects of ecstasy and those of other substances. Subjects were assessed with neuropsychological tests measuring attention, working memory, verbal and visuospatial memory, and visuospatial ability.

Ecstasy use [mean 327 (s.d.=364) tablets in lifetime] had a specific significant dose-related negative effect on verbal delayed recall after adjusting for the use of other drugs.

These findings strongly suggest a specific sustained negative effect of ecstasy use on verbal memory. The clinical relevance is not immediately clear, because test performance generally remained within the normal range. However the magnitude of the effect is substantial (d>0.5) and long-term consequences cannot be excluded.