Rationale Studies reporting ecstasy-induced serotonintoxicity and (neuro)psychological dysfunctions have been conducted in young adults. Little is known about ecstasy effects later in life, when serotonin levels and cognition decrease as a consequence of normal ageing. Objective This study aimed to assess whether harmful effects of ecstasy only add to or also interact with agerelated neuropsychological decline. Methods Attention, verbal and visual memory, visuospatial ability, self-reported depression, sensation-seeking and impulsivity were assessed in middle-aged moderate to heavy ecstasy/polydrug users (n=17) and compared with none or very mild ecstasy using polydrug users (matched for age, gender, intelligence and other drugs; n=16) and a group of drug-naive controls (n=20). Results Moderate to heavy ecstasy/polydrug users performed significantly worse on a verbal memory task than none or very mild ecstasy using polydrug users and drug naives. Moderate and heavy ecstasy/polydrug users also differed significantly from drug-naives on measures of depression, sensation-seeking and impulsivity but not from none or very mild ecstasy-using polydrug users. Conclusion This study in middle-aged ecstasy/polydrug users replicated findings of studies in younger ecstasy users, showing a harmful effect of ecstasy on verbal memory. There was no clear support for an interaction between harmful effects of ecstasy use and age-related memory decline or mid-life depression.