Study of Psilocybin and Structured Integrated Reframing Therapy for Trauma-Related Major Depressive Disorder Evaluating Effects on Gut-Brain Biomarkers and Depression Symptoms

What this Trial Is About

Researchers are studying trauma-related Major Depressive Disorder MDD, a condition often linked with poor response to standard antidepressants, ongoing psychological distress, and changes in gut-brain axis function. This study aims to create and validate a new assessment tool called the Trauma Anxiety Depression Emotion TADE management tool, while also evaluating the effects of psilocybin-assisted Structured Integrated Reframing Therapy SIRT on clinical and biological outcomes. The goal is to explore whether combining psilocybin with SIRT offers better improvements compared to either therapy alone. Participants will be randomly assigned to one of four groups conventional therapy with a stable selective serotonin reuptake inhibitor SSRI, psilocybin therapy alongside SSRI, SIRT alongside SSRI, or a combination of psilocybin-assisted SIRT alongside SSRI. Psilocybin is given in two supervised oral doses during an 8-week period, while SIRT is delivered once weekly for 8 weeks by trained therapists. The conventional therapy group continues stable SSRI treatment without psilocybin or SIRT. Throughout the study, participants will be assessed using the new TADE tool and established scales such as HAM-D, PCL-5, and GAD-7 at baseline, during treatment, and at 12-week follow-up. Blood samples will be collected at baseline, Week 4, Week 8, and Week 12 to measure gut-brain axis and inflammatory biomarkers. The researchers will monitor depression severity, trauma-related symptoms, anxiety severity, and biomarker changes to evaluate treatment impact, safety, and the clinical usefulness of the TADE tool over the study duration.

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