The german EPIsoDE-study investigates the efficacy, safety, and treatment mechanisms of oral psilocybin (25mg vs 5mg vs 100mg nicotinamide) in a psychotherapeutic context for TRD. We present a case-report of a female participant who faced adverse reactions, including exacerbation of dissociative symptoms, anxiety, depressive symptoms, and a decline in overall functioning, leading to post-study hospitalization.

Case: The patient initially presented with severe depressive symptoms (HAM-D = 32) after multiple failed antidepressant therapies (multiple pharmacotherapies and ECT).

Acutely, the patient experienced aversive symbolic imagery, physical sensations and feelings that were re-experienced loop-like and could not be resolved  the end of the substance session. While there were no signs of persistent changes in perception or consciousness at the end of the dosing day, the patient developed a severe level of dissociation  in the weeks after (flashbacks). Pre-occupying questions regarding the validity of the experience remained and could not be resolved in the study context.

We discuss ethical concerns when dealing with experiences associated with high levels of psychological distress (e.g., troubling “revelations”, the risk of false memory syndrome) and the importance of integration (Timmermann et al., 2022). We caution the careful screening of patients presenting with a rather obscure set of symptoms, possibly hinting towards trauma-related disorders and indications of a tendency towards dissociation.

This representative case raises awareness that there are patients who could potentially carry long-term harms from this therapy. It is the responsibility of psychedelic researchers to investigate these risks in depth and report them in detail.