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Psilocybe Cubensis Mushrooms With or Without Fluoxetine for Refractory Depression

NCT06898606 · Status: RECRUITING · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 24

Last updated 2026-03-27

No results posted yet for this study

Summary

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

  • Depressive Disorder

Interventions

DRUG

Psilocybin and Psilocyn

Oral dose administered via Psilocybe mushrooms material batch-assayed by LC-MS to standardize psilocybin and psilocyn content.

DRUG

Placebo

Matching capsules, once daily for 4 weeks (-14 to +14 days).

BEHAVIORAL

Psychotherapy-assisted session

Same manualized procedures as Arm 1.

DRUG

Fluoxetine

20 mg/day for 4 weeks (-14 to +14 days relative to dosing day).

Sponsors & Collaborators

  • Federal University of Latin American Integration

    lead OTHER

Principal Investigators

  • Francisney P Nascimento, 1 · Federal University of Latin American Integration

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Model
PARALLEL

Eligibility

Min Age
25 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2024-09-05
Primary Completion
2026-08-20
Completion
2026-11-20

Countries

  • Brazil

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06898606 on ClinicalTrials.gov