A phase II randomized, double-blind, active placebo-controlled parallel group trial to examine the efficacy and safety of psilocybin in treatment-resistant major depression (EPIsoDE)

This therapeutic exploratory trial (n=144) will investigate the efficacy and safety of Psilocybin-Assisted Psychotherapy (PAP/PAT) in adults aged 25 to 65 with treatment-resistant major depressive disorder (TRMDD).

Led by Prof. Dr. med. Gerhard Gründer, the trial will be conducted at the Central Institute of Mental Health (CIMH) Mannheim and Charité Berlin, Campus Mitte. Participants must have a diagnosis of moderate to severe major depressive disorder without psychotic features and must have shown treatment resistance to two different classes of antidepressants. They must also have discontinued monoaminergic psychiatric medications for at least two weeks prior to the study.

The trial will involve two doses of psilocybin (25 mg each), administered three weeks apart, alongside psychotherapy sessions. The primary endpoint, evaluated six weeks after the first dose, is the number of treatment responders, defined as a ≥50% reduction in symptoms measured by the Hamilton Depression Scale (HAM-D). Secondary endpoints include assessing treatment response, rates of remission, safety parameters, and follow-up evaluations at six and twelve months after the first dose.

The trial is controlled, randomised, and double-blind. It has a parallel group design and three treatment arms: nicotinamide, 5 mg psilocybin, and 25 mg psilocybin.


You can find more info about the EPIsoDE trial here.

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

Trial Details



Trial Number

Sponsors & Collaborators

Central Institute of Mental Health
This company doesn't have a full profile yet, it is linked to a clinical trial.

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.