Abstract

This presentation will go over the preliminary evidence for the efficacy and safety of psilocybin, a serotonergic psychedelic acting as a partial 5-HT2A agonist, in the treatment of treatment-resistant depression (TRD) and other psychiatric conditions. While the preliminary results are promising, many of the existing studies lack randomization, double-blinding, and a sufficient sample size, underlining the need for additional research.

The German EPIsoDE-Trial (NCT04670081) is a randomized-controlled trial that aims to investigate the safety and efficacy of oral psilocybin administered in a psychotherapeutic context in 144 patients with TRD in a bi-centric, parallel-group, double-blind design. Only this kind of study allows for firm conclusions on its efficacy, paving the way for future phase III studies. Specifically, in order to ensure an appropriate control condition, the trial investigates the efficacy of a therapeutic/high oral dose of psilocybin (25 mg) versus a low/supposedly inactive control dose (5 mg) versus placebo (100 mg Nicotinamide). We expect significant and stable treatment responses after the high psilocybin dose in comparison to the low/control dose and placebo. As a secondary objective, to inform on the optimization of psilocybin treatment regimes in clinical practice, it will be investigated whether a second high dose six weeks after the first therapeutic dose is superior to administration of only one high dose.

The trial is conducted at the Central Institute of Mental Health in Mannheim as well as the Charité Universitätsmedizin Berlin, Campus Charité Mitte. The trial is funded by the Federal Ministry of Education and Research (BMBF 01EN2006A); it has been approved by the Federal Institute for Drugs and Medical Devices (BfArM) and the responsible Ethics Committees.