Efficacy and safety of two versus three high dose psilocybin-assisted therapy sessions in comparison to a placebo for treatment resistant major depressive disorder (TR-MDD): A double blind, 3-arm Phase 2b randomised controlled trial

This double-blind, 3-arm Phase IIb randomised controlled trial (n=160) will investigate the efficacy and safety of two versus three high-dose psilocybin-assisted therapy sessions compared to a placebo for treatment-resistant major depressive disorder (TR-MDD).

Participants, aged 18 to 65, experiencing TR-MDD will be randomly allocated to one of three arms: Arm 1 receives 3 dose-sessions of 25 mg oral psilocybin + psychotherapy, Arm 2 receives 2 dose-sessions of 25 mg oral psilocybin + psychotherapy followed by 1 dose-session of oral inactive placebo + psychotherapy, and Arm 3 (control) receives 3 dose-sessions of oral inactive placebo + psychotherapy. The trial involves face-to-face psychotherapy sessions alongside the medication, administered by trained co-therapists. Each dose session lasts 6-8 hours and occurs at specific time points.

The primary outcome measures the reduction in depressive symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS) immediately after the second dosing session and at short-term follow-up 3 months after the second dosing session.

Recruitment for the trial began on 14/08/2023, with an anticipated end date for participant enrolment on 28/06/2024. The study will be conducted at Swinburne University of Technology, Hawthorn, Australia, with funding from Woke Pharmaceuticals.

Status Recruiting
Results Published No
Start date 14 August 2023
End date 30 June 2025
Phase Phase II
Design Blinded
Type Interventional
Generation First
Participants 160
Sex All
Age 18- 65
Therapy Yes

Trial Details

This is a 3-arm study using psilocybin-assisted psychotherapy. A randomised controlled, multi-arm design will be used with the same control group all the way through the 57 weeks of the study. Potential participants will be screened to ensure suitability for trial inclusion, and 160 participants will be accepted into the trial upon completion of informed consent. The schedule for all participants will consist of two courses of therapy separated by 4 weeks, each course is comprised of a dosing session plus preparatory and post-integrative psychotherapy sessions with a co-therapist dyad that will generally consist of one female and one male therapist. After the 3-month face to face follow-up session, a third course of therapy (preparatory, dosing, post-integrative) will occur. Participants randomly allocated to the treatment arm will receive an active dose of psilocybin during the first two dosing sessions. Participants in the treatment arm will then be randomly re-allocated to receive either active psilocybin (Arm 1) or an inactive placebo (Arm 2) for the third and final dosing session. Participants allocated to the control group (Arm 3) will receive an in-active placebo at all three dosing sessions. Self-report follow-up assessments will be conducted for all participants every 4 weeks after the first dose-session until 12 months after the second dosing session. Face to face follow-up sessions will occur at 3 months, 6 months and 12 months after the second dosing sessions.

NCT Number ACTRN12623000667617

Sponsors & Collaborators

Woke Pharmaceuticals
Woke Pharmaceuticals is an Australian biotech company developing novel psychedelic compounds.

Swinburne University of Technology
Swinburne University of Technology, located in Melbourne, Australia, is known for its focus on innovation, industry engagement, and social inclusion.

Data attribution

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