Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression

Brief Summary

The study aims to investigate the safety and efficacy of oral psilocybin administered under supportive conditions in treatment-resistant major depression (TRD).

The study is a bi-centric, prospective, randomized, active placebo-controlled study investigating the effects of 25 mg and 5 mg (p.o.) psilocybin versus placebo (100 mg nicotinamide) in a psychotherapeutic context in 144 patients with TRD from moderate to severe degree (ICD-10 F32/F33). After giving written informed consent and down-titration of their monoaminergic medication under supervision of the treating psychiatrist and the study team, patients will be randomly assigned to one of four trial arms using an online randomization tool: 1) receiving placebo (100 mg nicotinamide) at the first session and the full dose (25 mg) at the second; 2) receiving the presumably sub-effective dose (5 mg) at the first session and the full dose (25 mg) at the second; 3a) receiving the full dose (25 mg) at the first session and 5 mg at the second; 3b) receiving the full dose at both sessions. The two dosing sessions are accompanied by three preparatory and four integration sessions.

Drug administration must occur under psychotherapeutic conditions. Two trained therapists (one male, one female) will be assigned to each patient and be present during each dosing, preparatory and integration sessions. We will follow the safety guidelines provided by Johnson et al. (2), including a thorough preparation, establishment of trust/rapport, a safe and pleasing physical environment and sufficient interpersonal support. For safety reasons and close monitoring, patients will stay hospitalized for one night after each dosing session (i.e. in-patient setting).

Intervention / Treatment

  • Drug: Psilocybin
  • Drug: Nicotinamide

Condition or Disease

  • Treatment-Resistant Depression


Study Design

Study type: Interventional
Status: Recruiting
Study results: No Results Available
Age: 25 Years to 65 Years   (Adult, Older Adult)
Enrollment: 144 ()
Funded by: Other


Clinical Trial Dates

Start date: Jun 10, 2021
Primary Completion: Mar 01, 2023
Completion Date: Mar 01, 2024
Study First Posted: Dec 17, 2020
Last Updated: Jul 29, 2021

Sponsors / Collaborators

Lead Sponsor: N/A
Responsible Party: N/A

Eligibility Criteria

Sex: All

This clinical trial is recruiting

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More Details

NCT Number: NCT04670081
Acronym: EPIsoDE
Other IDs: EPIsoDE_01
Study URL: https://ClinicalTrials.gov/show/NCT04670081
Last updated: Mar 23, 2022