In a randomised double-blind trial the subjective, neuropsychological and brain activation effects of the two enantiomers of the MDMA (ecstasy-) like drug N-ethyl-3,4-methylenedioxyamphetamine (MDE) were studied in five normal subjects using functional magnetic resonance imaging (fMRI). (S)-MDE produced elevated mood, impairments in conceptually driven cognition and marked right frontal activation. In contrast, (R)-MDE produced increased depression, enhanced visual feature processing, and activation of visual cortical and left frontal areas. Plasma concentrations were higher for the (R)-enantiomer. The so-called entactogenic effects of MDE are likely to be caused by the (S)-enantiomer, whereas (R)-MDE appears to be responsible for neurotoxic effects.