Effect of Psilocybin and Structured Integrated Reframing Therapy on Gut-Brain Axis Biomarkers and Depression in Major Depressive Disorder

Summary

Trauma-related Major Depressive Disorder (MDD) is frequently associated with poor response to conventional antidepressants, persistent psychological distress, and alterations in gut-brain axis function. Existing assessment tools primarily diagnose depression or PTSD but provide limited guidance for integrated clinical management. This study aims to develop and validate the Trauma Anxiety Depression Emotion (TADE) management tool while simultaneously evaluating the effectiveness of psilocybin-assisted Structured Integrated Reframing Therapy (SIRT) in improving clinical and biological outcomes. This prospective, four-arm randomized controlled trial will compare conventional therapy, psilocybin therapy, SIRT, and psilocybin-assisted SIRT. Participants will undergo assessment using the newly developed TADE tool together with established psychometric scales including HAM-D, PCL-5, and GAD-7. Biological outcomes will include serum gut-brain axis and inflammatory biomarkers, including Short-Chain Fatty Acids (SCFAs), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Zonulin, Occludin, and Glial Cell Line-Derived Neurotrophic Factor (GDNF). Assessments will be performed at baseline, during treatment, and at 12-week follow-up. The study aims to determine whether combining psilocybin with SIRT provides superior clinical improvement and favorable biological changes compared with either intervention alone while establishing the validity and clinical utility of the TADE management tool.

Timeline

Start

2026-04-01

Primary completion

2027-10-22

Completion

2027-11-22

Publications

• Background Cui L, Li S, Wang S, Wu X, Liu Y, Yu W, Wang Y, Tang Y, Xia M, Li B. Major depressive disorder: hypothesis, mechanism, prevention and treatment. Signal Transduct Target Ther. 2024 Feb 9;9(1):30. doi: 10.1038/s41392-024-01738-y.
• Background Ahern E, White J, Slattery E. Change in Cognitive Function over the Course of Major Depressive Disorder: A Systematic Review and Meta-analysis. Neuropsychol Rev. 2025 Mar;35(1):1-34. doi: 10.1007/s11065-023-09629-9. Epub 2024 Feb 5.
• Background Martire G, Sipple D, Baron D, Gold MS, Lewandowski KU, Dennen CA, Sharafshah A, Elman I, Thanos PK, Modestino EJ, Badgaiyan RD, Pinhasov A, Bowirrat A, Makale M, Roy AK, Sunder K, Murphy KT, Mahajan S, Mahajan Y, Levin C, Blum K. Theorizing that Psychedelic Assisted Therapy May Play a Role in the Treatment of Trauma-Induced Personality Disorders. J Addict Psychiatry. 2024;8(2):161-165. Epub 2024 Nov 15.
• Background Rosenblat JD, Meshkat S, Doyle Z, Kaczmarek E, Brudner RM, Kratiuk K, Mansur RB, Schulz-Quach C, Sethi R, Abate A, Ali S, Bawks J, Blainey MG, Brietzke E, Cronin V, Danilewitz J, Dhawan S, Di Fonzo A, Di Fonzo M, Drzadzewski P, Dunlop W, Fiszter H, Gomes FA, Grewal S, Leon-Carlyle M, McCallum M, Mofidi N, Offman H, Riva-Cambrin J, Schmidt J, Smolkin M, Quinn JM, Zumrova A, Marlborough M, McIntyre RS. Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin. Med. 2024 Mar 8;5(3):190-200.e5. doi: 10.1016/j.medj.2024.01.005. Epub 2024 Feb 14.
• Background Euteneuer F, Neubert M, Salzmann S, Fischer S, Ehlert U, Rief W. Biomarkers as predictors of CBT responsiveness in major depressive disorder: The role of heart rate variability and inflammation. J Psychosom Res. 2024 Nov;186:111885. doi: 10.1016/j.jpsychores.2024.111885. Epub 2024 Aug 13.
• Background Dziedzic A, Maciak K, Blizniewska-Kowalska K, Galecka M, Kobierecka W, Saluk J. The Power of Psychobiotics in Depression: A Modern Approach through the Microbiota-Gut-Brain Axis: A Literature Review. Nutrients. 2024 Apr 4;16(7):1054. doi: 10.3390/nu16071054.

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