Administration of Psilocybe Cubensis Mushrooms with or Without Fluoxetine with or Without Fluoxetine for Refractory Depression: a Randomized Double-blind Controlled Trial Controlled Clinical Trial – COGUNILA (COGUNILA)

This randomised, quadruple-blind, placebo-controlled Phase I/II trial (n=50) will investigate the antidepressant, psychedelic, and adverse effects of Psilocybe cubensis mushrooms (equivalent to 30 mg of psilocybin) with or without daily fluoxetine (20mg) in adults with treatment-resistant depression (TRD).

Conducted by the Federal University of Latin American Integration in Brazil, the COGUNILA trial addresses whether combining a selective serotonin reuptake inhibitor (SSRI) like fluoxetine with psilocybin impacts the therapeutic and psychedelic experience.

Participants will be divided into two groups: one will receive fluoxetine for four weeks alongside one psilocybin-assisted psychotherapy session, while the control group will receive the same psilocybin session but with a placebo instead of fluoxetine. All participants will engage in preparation and integration therapy sessions. The primary aim is to assess changes in depressive symptoms using the Montgomery–Åsberg Depression Rating Scale (MADRS) from baseline to Week 4. Secondary outcomes include rates of remission, sustained effects at Week 6, and the relationship between the quality of the psychedelic experience (measured via tools like the Mystical Experience Questionnaire) and clinical outcomes. The study also explores whether fluoxetine moderates or intensifies psilocybin’s effects or side effects, offering crucial insights into the safety and compatibility of combining psychedelics with conventional antidepressants.

Topic Depression Treatment-Resistant Depression
Compound Psilocybin Placebo
Country Brazil
Visit trial

Trial Details



Trial Number

Data attribution

A large set of the trials in our database are sourced from ClinicalTrials.gov (CTG). We have modified these post to display the information in a more clear format or to correct spelling mistakes. Our database in actively updated and may show a different status (e.g. completed) if we have knowledge of this update (e.g. a published paper on the study) which isn't reflected yet on CTG. If a trial is not sourced from CTG, this is indicated on this page and you can follow the link to the alternative source of information.