Real-World Effectiveness and Safety of Psychedelic-Assisted Psychotherapy: Outcomes from a Large-Scale Compassionate Use Cohort in Switzerland

Background 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(2,178) = 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. Competing Interest Statement The authors have declared no competing interest. Clinical Trial NCT07164287 Funding Statement This study did not receive any funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approval by the Geneva local ethics committee Commission Cantonale d'Ethique de la Recherche sur l'être humain (CCER) was obtained (ID: BASEC 2022- 02015) and all patients had signed a general informed consent. The study was registered at clinical trial.gov (NCT:07164287). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors