429. Association between subjective experiences and symptom improvement following psilocybin therapy in Japanese patients with treatment-resistant depression: an open-label study

Abstract Background Despite sequential treatments with conventional antidepressants, many patients with depression experience insufficient clinical improvement, referred to as treatment-resistant depression (TRD). Psilocybin, a serotonergic psychedelic acting as a 5-HT2A receptor agonist, has attracted increasing attention as a novel treatment, with clinical trials demonstrating rapid and sustained antidepressant effects. Previous studies have reported that the intensity of mystical-type experiences during psilocybin sessions is associated with the degree of symptom improvement, suggesting that therapeutic outcomes may depend not only on pharmacological effects but also on the subjective quality of the psychedelic experience. However, existing clinical studies have been conducted in Western countries, and no research has yet been performed in Asian countries. Therefore, it remains unclear whether cultural and ethnic factors influence psilocybin-induced subjective experiences or the relationship between those experiences and antidepressant effects. Aims & Objectives This study aimed to investigate the association between the intensity of subjective experiences following psilocybin administration and changes in depressive symptoms among Japanese patients with TRD, in order to clarify the potential contribution of such experiences to therapeutic outcomes in Asian populations.

Method: This study analyzed data from an open-label, single-arm feasibility trial evaluating the safety and efficacy of psilocybin therapy for TRD conducted at Keio University Hospital (jRCTs031230351). Twelve patients aged 20-59 years who met the DSM-5 criteria for major depressive disorder and demonstrated insufficient response to at least two adequate antidepressant trials were enrolled. Participants received two courses of psilocybin therapy with psychological support. Each course consisted of one preparatory session, one dosing session, and two integration sessions. Depressive symptoms were assessed at baseline, after the second dosing session, and at 4- and 8-week follow-up visits using the Montgomery–Åsberg Depression Rating Scale, Hamilton Depression Rating Scale, and Quick Inventory of Depressive Symptomatology–Self Report. The intensity and quality of subjective experiences were assessed immediately after each dosing session using the Mystical Experience Questionnaire, Challenging Experience Questionnaire, Ego-Dissolution Inventory, and Subjective Drug Intensity scales, which evaluated mystical experiences, psychological distress, altered self-perception, and perceived drug intensity, respectively. All assessments were conducted using Japanese translations of the questionnaires.

Results: As of December 12, 2025, 12 participants have been enrolled. Of these, 10 completed all the assessments, 1 withdrew from the study, and 1 is currently undergoing the treatment. The final participant is scheduled to complete all the study procedures in February 2026. Detailed results of subjective experience intensity and its association with changes in depressive symptoms following psilocybin treatment will be presented at the congress. Discussion & Conclusions This study represents the first clinical investigation of psilocybin therapy for TRD conducted in Asia and the first to characterize psychedelic subjective experiences in Japanese patients. By elucidating the relationship between subjective experiences and therapeutic outcomes, this study may contribute to the development of culturally informed treatment models and optimized psychological support frameworks for psilocybin therapy.