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Taking people in PakistanPhase 3

Psilocybin with talk therapy for depression linked to trauma

Compares psilocybin, talk therapy and standard care in trauma-related major depressive disorder.

Key facts

Who runs it
Khyber Medical University Peshawar
Where
Islamabad and Peshawar, PakistanSee the 3 sites
Trial code
Registry title
Effect of Psilocybin and Structured Integrated Reframing Therapy on Gut-Brain Axis Biomarkers and Depression in Major Depressive Disorder
Status
Recruiting
Phase
Phase 3
People taking part
60 people, planned
Started
1 Apr 2026
Expected to end
22 Nov 2027
Type of study
Interventional, 4 groupsOne group gets an existing treatment, for comparison.
Treatments tested
  • Psilocybin
  • Structured Integrated Reframing Therapy (SIRT)
  • Selective Serotonin Reuptake Inhibitor (SSRI)
Record updated
14 July 2026

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults aged 18-60 with major depression linked to trauma, who already take one stable SSRI antidepressant.

Age
18 to 60 years
Sex
All sexes can join.
Disease stage
Major Depressive Disorder (DSM-5) with trauma-related depression and clinically significant trauma symptoms. Scores needed: HAM-D above 16, PCL-5 above 33, GAD-7 above 10.
Earlier treatment
Must have taken a stable single SSRI antidepressant for at least 6 weeks before enrolment, taking it as prescribed.

Main reasons for not taking part

  • Significant heart disease, or serious liver or kidney problems
  • Significant neurological disorder
  • Current or past psychotic disorder or bipolar disorder
  • Current substance or alcohol use disorder, including ketamine or psychedelic drug use
  • Pregnancy, planned pregnancy or breastfeeding

The registry criteria, word for word

Show all 21 criteriaShow less

Who can take part

  • Adults aged 18-60 years
  • Diagnosis of Major Depressive Disorder (MDD) according to DSM-5 criteria
  • Trauma-related depression with clinically significant trauma symptoms
  • Hamilton Depression Rating Scale (HAM-D) score >16
  • PTSD Checklist for DSM-5 (PCL-5) score >33
  • Generalized Anxiety Disorder-7 (GAD-7) score >10
  • Receiving a stable single SSRI antidepressant regimen for at least 6 weeks before enrollment with adequate treatment adherence
  • Able and willing to provide written informed consent
  • Willing to comply with all study procedures and follow-up visits
  • Women of childbearing potential must agree to use effective contraception throughout the study

Who cannot take part

  • Use of more than one antidepressant medication
  • Participation in another interventional clinical trial within the previous 30 days
  • Significant cardiovascular disease
  • Clinically significant hepatic or renal impairment
  • Significant neurological disorders
  • Current or past psychotic disorder or bipolar disorder
  • Current substance or alcohol use disorder, including ketamine or psychedelic drug use
  • Known hypersensitivity or contraindication to psilocybin
  • Any medical or psychiatric condition that, in the investigator's opinion, would interfere with safe participation or study assessments
  • Pregnancy, planned pregnancy, or breastfeeding
  • Inability or unwillingness to provide informed consent

Check if you might fit

Answer for yourself. This is not a decision: only the study team can say whether you can take part.

  • Are you between 18 and 60 years old?

Where in Pakistan

  • Institute of Health Science, Khyber Medical UniversityIslamabad, PakistanContact: Bushra Riaz, PhD*No longer taking part
  • Hayatabad Medical Complex PeshawarPeshawar, PakistanContact: Dr Owais Qaiser, PhD*Taking people
  • Khyber Medical UniversityPeshawar, PakistanContact: Bushra Riaz, PhD*No longer taking part

About the trial

What the trial wants to find out

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.

Read full original descriptionShow less

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.

The 4 groups in the trial

  • Conventional Therapy (Control)Existing treatment, for comparison

    Participants will receive standard conventional treatment for trauma-related Major Depressive Disorder, consisting of a stable selective serotonin reuptake inhibitor (SSRI) regimen prescribed by the treating psychiatrist. No psilocybin or Structured Integrated Reframing Therapy (SIRT) will be administered. Treatment will continue for 8 weeks with routine clinical follow-up.

    Treatment: Selective Serotonin Reuptake Inhibitor (SSRI)

  • Psilocybin TherapyTreatment being tested

    Participants will continue standard SSRI therapy and receive oral psilocybin administered under medical supervision in a controlled clinical setting. Two supervised dosing sessions will be conducted during the 8-week intervention period according to the study protocol. No SIRT will be provided.

    Treatment: Psilocybin and Selective Serotonin Reuptake Inhibitor (SSRI)

  • Structured Integrated Reframing Therapy (SIRT)Treatment being tested

    Participants will continue standard SSRI therapy and receive Structured Integrated Reframing Therapy (SIRT), a trauma-informed psychotherapy integrating Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), mindfulness, cognitive reframing, and communication-focused therapeutic techniques. Therapy will be delivered once weekly for 8 weeks by trained therapists.

    Treatment: Structured Integrated Reframing Therapy (SIRT) and Selective Serotonin Reuptake Inhibitor (SSRI)

  • Psilocybin-Assisted Structured Integrated Reframing TherapyTreatment being tested

    Participants will continue standard SSRI therapy and receive both supervised oral psilocybin administration and Structured Integrated Reframing Therapy (SIRT). Psilocybin will be administered in two supervised dosing sessions during the 8-week intervention period, while SIRT will be delivered once weekly for 8 weeks. The combined intervention is intended to evaluate the synergistic effects of psychedelic-assisted psychotherapy on clinical outcomes and gut-brain axis biomarkers.

    Treatment: Psilocybin, Structured Integrated Reframing Therapy (SIRT), and Selective Serotonin Reuptake Inhibitor (SSRI)

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov.
Official title
Effect of Psilocybin and Structured Integrated Reframing Therapy on Gut-Brain Axis Biomarkers and Depression in Trauma-Related Major Depressive Disorder: Randomized Controlled Trial
Plain-language title
Psilocybin with talk therapy for depression linked to traumaGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 12 November 2026.
Fit questions
Built from NCT07703722, who can take part
Record updated
14 July 2026