Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users. MARK A WETHERELL & CATHARINE MONTGOMERY RUNNING HEAD: BASAL HPA FUNCTION IN ECSTASY USERS

Rationale: Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long term changes in HPA functionality in recreational users. Objectives: The current study is the first to explore the effects of ecstasy-polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period. Method: Seventy-six participants (21 nonusers, 29 light ecstasy-polydrug users 26 heavy ecstasy-polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 minutes post awakening, between 1400-1600hrs and pre bed time). On day two, participants also attended the laboratory to complete a 20-minute multitasking stressor. Results: Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day one, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day two, heavy users demonstrated elevated levels upon awakening and all ecstasy-polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day. Conclusions: The increases in anxiety and depression are in line with previous observations in recreational ecstasy-polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy.