This randomised, double-blinded, 4 arm parallel adaptive trial (n=140) aims to explore the therapeutic benefits, tolerability, and acceptability of psychedelic therapy using psilocybin for treatment-resistant depression (TRD).
Led by The Australian National University and funded by the Australian Department of Health and Aged Care – Medical Research Future Fund, in collaboration with Mynd Life Sciences, this study investigates the efficacy and safety of psilocybin-assisted psychotherapy (PAP) compared to an active comparator medication, dexamfetamine.
The trial employs an adaptive design, comparing three different psilocybin regimens to a control, with all participants engaging in identical study procedures and therapy sessions, with only the drug used within the groups being varied.
The primary outcome, continuous scores on the Hamilton Depression Scale (HAM-D), will be assessed from baseline compared to post cycle 1, post cycle 2, post cycle 3, and then 1, 3, and 6 months post the third cycle. Secondary outcomes include changes in depressive symptoms, emergence of unipolar depression symptoms, overall clinical outcomes, self-reported depression and anxiety symptoms, assessment of suicidal symptoms, quality of life/functioning, mystical experiences, adverse effects, symptoms related to past trauma, cognitive safety, inflammatory markers, and mentalization imbalances.
The study is not yet recruiting participants and is expected to continue until October 2028. Individual participant data will be made available for future research projects beginning three months following main results publication.
Trial Details
The purpose of this study is to explore the therapeutic benefits, tolerability and acceptability of psychedelic therapy using psilocybin and its potential to improve symptoms of treatment resistant depression (TRD), depression in people which has not resolved with a number of courses of standard treatment. Prior research has suggested that this type of treatment may have significant antidepressant effects, but we require further evidence to fully understand the therapeutic value, benefits, and risk of psilocybin in a treatment setting. The design includes an adaptive, dose finding, single phase 2b clinical trial exploring the efficacy and safety of psilocybin assisted psychotherapy (PAP) in the treatment of people diagnosed with treatment resistant major depressive disorder (TRD). If successful, this will lead to the conduct of a subsequent multi-site phase 3 trial to report findings of the therapeutic value, benefits and risks of psilocybin for the treatment of mental health conditions, including the size of effect, the quality of evidence and the relevance to real-world use in Australia.Trial Number ACTRN12623001004651