Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled randomised partial crossover trial
Zeina Beidas, Anya Ragnhildstveit, Adam Blackman, Thomas Anderson, Emily C. Fewster, Omer A. Syed, Valentyne Sobolenko, Ismail Kaan Kanca, Magdalena Jaglinska, Tatiana Son, Norman A. S. Farb, Rotem Petranker
BJPsych Open February 16, 2026 DOI: 10.1192/bjo.2025.10968 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Phase II, double-blind, placebo-controlled, randomised partial crossover trial Randomized Open-label Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Adults with major depressive disorder |
| Interventions | Psilocybin Placebo (maltodextrin) |
| Dose | 2 mg |
| Duration | 4-week experimental phase, 4-week open-label phase, follow-ups every 6 months for up to 2 years |
| Topics | Depression Microdosing Psilocybin |
| Citations | 1 |
| Registration | NCT05259943 |
| Key findings | The trial's primary outcome—change in depression symptoms after four weeks of microdosing psilocybin versus placebo—has not yet been reported, as this is a study protocol. |
Abstract
Background: Major depressive disorder (MDD) is the leading cause of disability worldwide, affecting roughly 322 million people. Recently, doses of psilocybin have shown promise in treating mood disorders, sparking interest in other dosing practices. According to anecdotal reports and observational studies, microdosing psilocybin yields benefits to mental health; however, rigorously controlled trials have failed to produce compelling evidence for this.
Aims: To conduct a phase II, double-blind, placebo-controlled, randomised partial crossover trial to compare microdosing psilocybin to placebo for MDD, evaluating its safety, tolerability and preliminary antidepressant effects.
Method: Forty adults with MDD will be randomised to four doses of psilocybin (2 mg) or placebo (maltodextrin) once weekly over 4 weeks, then four doses of psilocybin (2 mg) once weekly for an additional 4 weeks. The primary efficacy end-point will be change in depression symptoms, as measured at baseline (0 weeks), after the experimental phase (4 weeks), and after the open-label phase (8 weeks). A battery of mood, well-being, attention, creativity, mindfulness and pro-sociality measures will be administered at each time point. Follow-ups will occur every 6 months for up to 2 years after the trial start date, as part of a long-term extension study.
Results: The results of the primary outcome of this trial will be published as a manuscript in a peer-reviewed science or medical journal regardless of the magnitude or direction of effect.
Conclusions: Findings will inform future research on microdosing psilocybin for MDD, regarding dose regimens, effect sizes and expectancy bias. Findings will also facilitate discussions on the comparable benefits of sub- versus threshold doses of psilocybin and the therapeutic value of radically altered perception.
Trial Registration: ClinicalTrials.gov identifier: NCT05259943.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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This is a study protocol; the primary outcome of change in depression symptoms after four weeks of microdosing psilocybin versus placebo has not yet been reported.
Synthesized
Comparable studies
Other randomized controlled trials on psilocybin and microdosing, most cited first.