Using Psilocybe Cubensis Mushrooms with or without Fluoxetine for Treatment-Resistant Depression
Psilocybe Cubensis Mushrooms With or Without Fluoxetine for Refractory Depression
This study is testing if taking Psilocybe cubensis mushrooms with or without fluoxetine can help people with treatment-resistant depression feel better.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 25 Years to 65 Years |
| Sex | All |
| Sponsor | Federal University of Latin American Integration Academic / other |
| Locations | 1 site (Foz do Iguaçu, Paraná) |
| Trial ID | NCT06898606 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the effects of Psilocybe cubensis mushrooms, a natural psychedelic, in combination with fluoxetine, a common antidepressant, for patients suffering from treatment-resistant Major Depressive Disorder. Participants will be randomly assigned to receive either the combination of mushrooms and fluoxetine or mushrooms with a placebo, while undergoing psychotherapy. The study aims to assess the differences in antidepressant effects and side effects between the two treatment groups. The trial will include both quantitative and qualitative analyses to evaluate the outcomes.
Who should consider this trial
Good fit: Ideal candidates are adults aged 25 to 65 with treatment-resistant depression who have not adequately responded to standard antidepressant treatments.
Not a fit: Patients under 25 or over 65, pregnant or breastfeeding women, and those with a history of major psychiatric disorders may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a novel treatment option for patients with refractory depression who do not respond to conventional therapies.
How similar studies have performed: Other studies have shown promising results with psilocybin for depression, indicating potential for success in this novel approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria Age: ≥25 and \<65 years. Diagnosis: Current Major Depressive Disorder (MDD), moderate to severe, per DSM-5-TR, confirmed with SCID-5. Baseline severity: MADRS ≥20 at baseline (reassessed at the pre-dose visit to confirm ongoing eligibility). Partial Response in the current episode (PRD): ≥1 adequate antidepressant trial in this episode (therapeutic dose for ≥6-12 weeks, adherence ≥80%) with \<50% symptom reduction or clinically significant residual symptoms. Clinical stability and ability to provide informed consent; willingness to comply with all study procedures (preparation, dosing session, integration, and follow-ups). Contraception: For participants with reproductive potential, negative pregnancy test and agreement to use effective contraception during the study. Exclusion Criteria Psychiatric disorders: Bipolar I/II disorder, any psychotic disorder, or current MDD with psychotic features; first-degree family history of psychotic or bipolar disorder. Suicide risk: Acute suicidal risk, e.g., active suicidal ideation with intent or plan, recent attempt, or clinical judgment requiring urgent intervention. Interacting medications: Current use of serotonergic antidepressants (SSRI/SNRI/MAOI, clomipramine) or other pro-serotonergic agents (e.g., triptans, linezolid, lithium, tramadol, dextromethorphan) that cannot be discontinued per protocol-defined washout. Other psychotropics: 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. Psychotherapy changes: Initiation or major change in psychotherapy within 2 weeks prior to baseline (to preserve clinical stability). Medical conditions: Clinically significant or unstable medical illness (cardiovascular, neurological, hepatic, renal), prolonged QTc, known hypersensitivity/contraindication to fluoxetine or study materials. Pregnancy or breastfeeding. Substance use: Current substance use disorder (excluding nicotine/caffeine) within the past 3 months; non-medical cannabis use that cannot meet the pre-dose abstinence window (e.g., ≥72 h). Any condition that, in the investigator's opinion, would make participation unsafe or interfere with the assessments. Washout note (to include in Procedures/Eligibility): SSRIs/SNRIs: 7 days or ≥5 half-lives; prior fluoxetine: ≥6 weeks; MAOIs: ≥14 days before randomization/dosing. Participants must be willing and able to follow the washout schedule.
Where this trial is running
Foz do Iguaçu, Paraná
- Federal University of Latin American Integration — Foz do Iguaçu, Paraná, Brazil (Recruiting)
Study contacts
- Study coordinator: Francisney P Nascimento, 1
- Email: ensaios.clinicos.lcp@unila.edu.br
- Phone: +55 45 99933-3479
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.