Highs and Lows: A Multi-Method Investigation of MDMA and Mental Health

Abstract

3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is used by an estimated 20 million people globally, with Australians among the highest consumers. Amid growing interest in the therapeutic use of MDMA and limited longitudinal evidence on its mental health impacts, this thesis aimed to: (1) examine the short- and long-term associations between MDMA use and mental health outcomes, specifically anxiety, depression, and related internalising constructs, using contemporary epidemiological methods; and (2) assess clinician attitudes toward psychedelic-assisted therapies (PATs) in Australia. Using prospective cohort data, Study 1 found MDMA use, particularly persistent and frequent use, was associated with increased odds of anxiety disorder in mid-adulthood. Study 2 comprised a systematic review of 273 ecological momentary assessment (EMA) studies of substance use, revealing a strong focus on alcohol and cannabis, with psychedelics largely absent despite increasing clinical and recreational use. Using and EMA design Study 3, examined subacute mood effects of MDMA, finding little evidence of next-day changes in positive affect, negative affect, or affective variability following use. Study 4 surveyed Australian mental health and alcohol and other drug clinicians following the 2023 Therapeutic Goods Administration rescheduling of MDMA and psilocybin. Clinicians expressed cautious optimism toward PATs but raised concerns regarding safety, organisational readiness, equity, and access, with more favourable attitudes reported among those with personal psychedelic experience. Overall, this thesis provides evidence that while short-term mood effects of MDMA are not consistently detectable, longer-term anxiety-related risks may emerge with persistent use. Together, the findings inform future research and identify key considerations for policy and clinical practice aimed at reducing harm while supporting safe, evidence-based therapeutic innovation.