Actively Recruiting
Psilocybe Cubensis Mushrooms With or Without Fluoxetine for Refractory Depression
Led by Federal University of Latin American Integration · Updated on 2026-03-27
24
Participants Needed
1
Research Sites
115 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This Phase 2a pilot, exploratory, randomized, double-blind, placebo-controlled, parallel-group trial will estimate whether concurrent fluoxetine alters the antidepressant effect, acute psychedelic experience, or safety of a psychedelic-assisted psychotherapy session in adults with treatment-resistant major depressive disorder (TRD). Eligible participants (ages 25-64) have DSM-5-TR MDD, moderate-severe, MADRS ≥20, and partial response in the current episode (≥1 adequate antidepressant trial of 6-12 weeks with \<50% symptom reduction). All participants receive one dosing session with 3g of standardized Psilocybe mushrooms - with batch assay (e.g., LC-MS) to determine the amount of psilocybin and psilocin present in the sample - with manualized preparation and integration. Participants are randomized 1:1 to fluoxetine 20 mg/day or matching placebo for 4 weeks, started 2 weeks before the psychedelic session and continued 2 weeks after. Masking is quadruple (participant, care provider, investigator, outcomes assessor). The primary outcome is change in MADRS from Baseline to Week 4, assessed by a remote, blinded rater. Key secondary outcomes include response (≥50% MADRS reduction) and remission (MADRS ≤10) at Week 4, and durability at Week 6. Exploratory outcomes assess the psychedelic experience (5D-ASC, SOCQ), psychological flexibility (AAQ-10), and safety/tolerability (UKU and adverse events). Findings will be interpreted as estimates with 95% confidence intervals to inform the design of a subsequent confirmatory trial.
CONDITIONS
Official Title
Psilocybe Cubensis Mushrooms With or Without Fluoxetine for Refractory Depression
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 25 and less than 65 years
- Current moderate to severe major depressive disorder confirmed by DSM-5-TR and SCID-5
- Baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or higher
- Partial response in current depressive episode with at least one adequate antidepressant trial (6-12 weeks at therapeutic dose with 80% adherence) showing less than 50% symptom reduction or significant residual symptoms
- Clinical stability and ability to provide informed consent
- Willingness to comply with all study procedures including preparation, dosing session, integration, and follow-ups
- For participants with reproductive potential, negative pregnancy test and agreement to use effective contraception during the study
You will not qualify if you...
- Bipolar I or II disorder, any psychotic disorder, or current major depressive disorder with psychotic features
- First-degree family history of psychotic or bipolar disorder
- Acute suicide risk including active suicidal thoughts with intent or plan, recent attempt, or clinical judgment requiring urgent intervention
- Current use of serotonergic antidepressants or pro-serotonergic agents that cannot be discontinued per protocol
- Unstable doses of antipsychotics, mood stabilizers, or long-acting benzodiazepines within the last 2 weeks
- Need for medications that would compromise blinding on the dosing day
- Initiation or major change in psychotherapy within 2 weeks prior to baseline
- Clinically significant or unstable medical illness including cardiovascular, neurological, hepatic, renal conditions, prolonged QTc, or hypersensitivity to fluoxetine or study materials
- Pregnancy or breastfeeding
- Current substance use disorder (excluding nicotine or caffeine) within the past 3 months
- Non-medical cannabis use that cannot meet the pre-dose abstinence window (72 hours)
- Any condition that would make participation unsafe or interfere with assessments as judged by the investigator
AI-Screening
AI-Powered Screening
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Trial Site Locations
Total: 1 location
1
Federal University of Latin American Integration
Foz do Iguaçu, Paraná, Brazil, 85870-650
Actively Recruiting
Research Team
F
Francisney P Nascimento, 1
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
TRIPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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