Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder

This study is looking at whether a single dose of psilocybin, given along with therapy, can help veterans and first responders who have both treatment-resistant depression (TRD) and a substance use disorder (SUD). TRD means your depression hasn't gotten better with at least two different antidepressant medications. Researchers want to see if different doses of psilocybin (5mg, 10mg, or 25mg) are safe and can reduce substance use and depression symptoms. The study is currently unclear about its recruitment status, but plans to enroll 50 participants between 18 and 70 years old. Success will be measured by tracking any side effects, changes in substance use, and the number of days spent using substances over 12 weeks and during a 60-day follow-up.

Study design
This is a double-blind, randomized clinical trial involving 50 participants. This means neither you nor the study team will know which dose of psilocybin (5mg, 10mg, or 25mg) you receive.
What's involved
You would have two intake visits, three preparatory therapy sessions, one 8-10 hour psilocybin administration session, and three weekly integrative therapy sessions. You would also complete daily surveys on your phone during specific weeks.
Compensation
Not stated in the trial record.
Follow-up
You will be followed weekly for 12 weeks, and then once during a 60-day follow-up period.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT07499583

Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder

Not Yet Recruiting
PHASE1Ages 18–70InterventionalTreatment
Indiana University
~50 participants
Updated 2026-03-30 on ClinicalTrials.gov
What's tested:Psilocybin

At a glance

Recruiting sites
0 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
percentage number of participants with Adverse Events (AEs)
Measured over Weekly for 12-weeks and once during a 60-day follow-up
+5 more outcomes measured
Treatment Resistant Depression
Substance Use Disorders
2 sites across 1 states
Indiana2
  • Susan K Conroy, PhD · PRINCIPAL_INVESTIGATOR · Indiana University

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  • percentage number of participants with Adverse Events (AEs)Weekly for 12-weeks and once during a 60-day follow-up

    AEs that occur after administration of the single psilocybin dose or worsen from a pre-treatment state.

  • Change in % number of positive urinesWeekly for 12-weeks

    urine toxicology screens for alcohol and substance use will be collected

  • Change in % number of days spent using substancesWeekly for 12-weeks TLFB and 5 times per day in weeks 1, 2, 5, 6, 10 & 11 (brief items)

    Self reports of alcohol and substance use, using the timeline followback (TLFB) and brief ecological momentary assessment (EMA) items

  • Change in severity of depression symptomsWeekly for 12-weeks QIDS and 5 times per day in weeks 1, 2, 5, 6, 10 & 11 for PANAS

    Self reports of depressive symptomatology, using the Quick Inventory of Depression Symptoms-Self-Report (QIDS-SR) and brief EMA items using the Positive and Negative Affect Schedule (PANAS)

  • Changes in plasma brain-derived neurotrophic factor (BDNF) during stress exposureChange from baseline (week 2) to post psilocybin administration (week 5)

    Levels of BDNF in response to stress will be assessed during brain scanning

  • Change in resting brain functional connectivity of the default mode network (DMN).Change from baseline (week 2) to post psilocybin administration (week 5)

    Resting-state functional connectivity will be assessed using functional magnetic resonance imaging (fMRI)