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Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled
Zeina Beidas1,2,3,4, Anya Ragnhildstveit1,2,5,6, Adam Blackman1,7,8,9
1Canadian Centre for Psychedelic Science, Toronto, Ontario, Canada.
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.
Insights
This study investigates microdosing psilocybin for major depressive disorder (MDD). Results will clarify its effectiveness and inform future research on psychedelic therapy for mood disorders.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Major Depressive Disorder (MDD) is a leading global cause of disability.
- Psilocybin shows promise for mood disorders, with interest in microdosing.
- Controlled trials have not yet provided compelling evidence for microdosing benefits.
Purpose of the Study:
- To conduct a phase II, double-blind, placebo-controlled trial on microdosing psilocybin for MDD.
- To evaluate the safety, tolerability, and preliminary antidepressant effects of psilocybin microdosing.
- To compare microdosing psilocybin against a placebo in adults with MDD.
Main Methods:
- Forty adults with MDD were randomized to psilocybin (2 mg) or placebo weekly for 4 weeks.
- A partial crossover design was used, with an additional 4-week open-label psilocybin phase.
- Primary endpoint: change in depression symptoms at 4 and 8 weeks; secondary measures included mood, well-being, and cognitive functions.
Main Results:
- The primary outcome results will be published in a peer-reviewed journal, irrespective of the findings' magnitude or direction.
- Data on safety, tolerability, and preliminary antidepressant effects will be presented.
Conclusions:
- Findings will guide future research on psilocybin microdosing for MDD, including optimal dosing and effect sizes.
- The study will contribute to discussions on sub-threshold versus threshold psychedelic doses and altered perception's therapeutic value.
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