Phase 2a Study of Psilocybe Cubensis Mushrooms With or Without Fluoxetine in Adults with Treatment-Resistant Major Depression

What this Trial Is About

Researchers are studying whether taking fluoxetine alongside a psychedelic-assisted psychotherapy session changes its antidepressant effects, the immediate psychedelic experience, or safety in adults with treatment-resistant major depressive disorder TRD. This Phase 2a trial includes adults aged 25 to 64 with moderate to severe depression who have shown only a partial response to prior antidepressant treatments. The study aims to explore how fluoxetine, a selective serotonin reuptake inhibitor SSRI, impacts the therapy when given before and after a single psychedelic session. All participants receive one oral dose of 3 grams of standardized Psilocybe cubensis mushrooms during a psychotherapy session. They are randomly assigned to take either fluoxetine 20 mg daily or a matching placebo for four weeks, starting two weeks before the psychedelic dose and continuing two weeks after. The study includes preparation and integration psychotherapy sessions around the dosing day. Masking is quadruple, meaning participants, care providers, investigators, and outcome assessors do not know who receives fluoxetine or placebo. Participants are involved in multiple assessments including depression severity ratings at several time points up to six weeks after dosing, questionnaires measuring the psychedelic experience, psychological flexibility, and side effects. Safety is monitored throughout with symptom rating scales and adverse event tracking. The main measure of interest is the change in depression symptoms four weeks after treatment. The trials results will help guide future research on combining SSRIs with psychedelic therapy for depression.

Psilocybe Cubensis Mushrooms With or Without Fluoxetine for Refractory Depression