354. Effects of psilocybin treatment on cognitive function in Japanese patients with treatment-resistant depression: an open-label study
Sota Tomiyama, K Yonezawa, K Kusudo, Lisa Harada, M Matsui, K Suzuki, D Stoliker, S Nakajima, H Tani, Hiroyuki Uchida
International Journal of Neuropsychopharmacology September 9, 2026 DOI: 10.1093/ijnp/pyag040.263 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Single-arm, open-label feasibility study Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Japanese adults aged 20-59 years with a DSM-5 diagnosis of major depressive disorder who showed insufficient treatment response to at least two antidepressants during the current episode |
| Interventions | Psilocybin psychological support |
| Dose | 10 mg (the former six participants) or 25 mg (the latter six participants), with the same dose used for both dosing sessions |
| Duration | Two dosing sessions approximately 2-3 weeks apart; follow-up up to eight weeks after the second dosing session |
| Measures | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Letter-Number Sequencing, Stroop Neuropsychological Screening Test, Trail Making Test, Montgomery-Åsberg Depression Rating Scale, Hamilton Depression Rating Scale, Quick Inventory of Depressive Symptomatology-Self Report |
| Topics | Depression Psilocybin |
| Key points | The study is designed to test whether psilocybin therapy changes cognitive function in treatment-resistant depression and whether such changes are direct or mediated by reduced depressive symptoms. No cognitive outcomes are reported yet: as of December 14, 2025, 10 of 12 enrolled participants had completed all assessments, one had withdrawn, and one was still undergoing treatment, with detailed results to be presented at the congress. |
Abstract
Abstract Background Cognitive dysfunction is associated with impaired psychosocial functioning in patients with major depressive disorder (MDD). Patients with treatment-resistant depression (TRD) exhibit more pronounced cognitive dysfunction than those with non-resistant MDD, underscoring the need for effective therapeutic strategies. Psilocybin has emerged as a promising treatment for depression due to its rapid onset and sustained antidepressant effects. However, the previous study examining the effects of psilocybin on cognition in TRD reported only non-significant improvement in global cognitive performance. That study was used a single screening measure, and comprehensive assessments of cognitive function are lacking. Moreover, it remains unclear whether cognitive changes following psilocybin therapy reflect a direct pharmacological effect or are secondary to improvements in depressive symptoms. Aims & Objectives This study aimed to examine the effects of psilocybin treatment on cognitive function in Japanese patients with TRD and to clarify the relationship between changes in cognitive function and depressive symptoms.
Method: This single-arm, open-label feasibility study was conducted at Keio University Hospital in Tokyo, Japan (clinical trial registration number: jRCTs031230351). Twelve Japanese adults aged 20–59 years with a DSM-5 diagnosis of MDD who showed insufficient treatment response to at least two antidepressants during the current episode were enrolled. Participants received two courses of psilocybin therapy with psychological support. Psilocybin was administered orally at 10 mg (the former six participants) or 25 mg (the latter six participants) with the same dose used for both dosing sessions. The two dosing sessions were administered approximately 2–3 weeks apart in an inpatient setting under the supervision of a psychiatrist and a clinical psychologist. Follow-up continued for up to eight weeks after the second dosing session. Cognitive function was assessed using the Japanese translation of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Letter-Number Sequencing, Stroop Neuropsychological Screening Test, and Trail Making Test. The RBANS is a repeatable battery that evaluates immediate and delayed memory, attention, language, and processing speed. Depression symptoms severity was assessed using the Montgomery-Åsberg Depression Rating Scale, the Hamilton Depression Rating Scale, and the Quick Inventory of Depressive Symptomatology-Self Report. Changes in cognitive function before and after treatment were analyzed using paired t-tests. Path analysis was conducted to examine whether changes in cognitive function were directly attributable to psilocybin treatment or mediated by improvements in depressive symptoms.
Results: As of December 14, 2025, 12 participants have been enrolled: 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. Detailed results regarding changes in cognitive function following psilocybin treatment will be presented at the congress. Discussion & Conclusions This study will provide preliminary evidence on the effects of psilocybin treatment on cognitive function comprehensively in Japanese patients with TRD, including domains such as language and delayed memory. Furthermore, path analysis will help clarify whether observed cognitive changes are directly attributable to psilocybin or mediated by improvements in depressive symptoms, thereby offering insight into the mechanisms underlying psilocybin therapy.