Real-world effectiveness and safety of psychedelic-assisted psychotherapy: Outcomes from a large-scale compassionate use cohort in Switzerland.

In a real-world clinical setting, a single session of psychedelic-assisted psychotherapy with either LSD or psilocybin was well tolerated and linked to significant reductions in depression and anxiety among adults with treatment-resistant disorders. Symptoms improved substantially, with large effects for depression and moderate effects for anxiety. Cognitive changes included less self-blame, rumination, and catastrophizing, along with more positive refocusing and reappraisal. Adverse effects were mild and temporary, with no serious complications. The findings suggest that both substances can be effective and safe in specialized routine care.

Study at a glance

Abstract

Classic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but real-world data from routine clinical care remain limited. This study retrospectively analysed routine data from adults with treatment-resistant depressive and/or anxiety disorders who received a first standardized Psychedelic-assisted Psychotherapy (PAP) cycle with 100 µg LSD or 25 mg psilocybin at a Swiss university hospital (May 2024-October 2025). Self-reported depression (BDI) and trait anxiety (STAI-T) were assessed at screening, one month before treatment, and 1-3 months post-treatment. In a subset of participants, cognitive emotion regulation (CERQ) was assessed pre- and post-treatment. Subjective drug effects and adverse events were recorded on the treatment day. The sample consisted of 115 patients (56.5 % female; Mean age = 47.5 years). Depressive and anxiety symptoms significantly decreased over time (BDI: F(2178) = 63.50, p < 0.001, partial η² = 0.42; STAI-T: F(1.74,145.9) = 16.97, p < 0.001, partial η² = 0.17), with no main effect of substance. CERQ analyses indicated reduced self-blame, rumination and catastrophizing, and increased positive refocusing and reappraisal. Perceived intensity followed distinct temporal profiles for LSD and psilocybin, but comparable subjective drug effects and clinical outcomes. Adverse events were mostly mild and transient, with no serious complications or treatment discontinuations. In this compassionate-use real-world cohort, a first fully-active dose PAP session with LSD or psilocybin was well tolerated and associated with significant improvements in depressive and anxiety symptoms. These findings support the feasibility and effectiveness of PAP in specialised routine care.