Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled...

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.