Psilocybin is currently intensively researched in the treatment of depressive disorders with promising results [e.g. 1]. The German EPIsoDE trial (EudraCT number: 2019-003984-24; NCT04670081) is a bicentric, prospective, randomized, double-blind, active placebo-controlled parallel-group study investigating the effects of a high-dose psilocybin (25 mg) and a low-dose psilocybin (5 mg) versus an active placebo (100 mg nicotinamide) administered orally in a psychotherapeutic context in patients with Treatment-Resistant major Depression (TRD) [2]. 

144 patients have been randomized and treated in the trial from July 2021 until February 2024 at two trial sites, the Central Institute of Mental Health (CIMH) in Mannheim and the Charité Berlin. All patients have been randomly assigned to one of four treatment arm – receiving either one or two psilocybin doses. For ethical reasons and to reduce the risk of nocebo effects, all patients received at least one supposedly therapeutic high psilocybin dose (25 mg).

During this talk, the rationale as well as the first study results will be presented. Beyond the numeric study results in terms of change in depressive symptoms, the researchers and therapists have gained important insights from conducting therapy with psilocybin in patients with TRD – a vulnerable patient population oftentimes characterized by chronicity of disease, adverse childhood experiences or interpersonal traumatization and limited resources. This talk will also provide some insights into the practical work within the EPIsoDE trial, particularly focusing on experienced challenges and implications for future clinical trials and practice.