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

Brief summary

The goal of this clinical trial is to learn if a single dose of psilocybin (5mg Vs 10mg Vs 25mg) alongside psychotherapy is safe and can help treat treatment resistant depression (TRD) with co-occurring substance use disorder (SUD). The participant sample will be enriched for veterans and first responders. Investigators seek to answer: * Whether 5mgs, 10mgs and 25mgs of psilocybin are safe in individuals with co-occurring TRD and SUD * Whether psilocybin assisted psychotherapy will reduce substance use severity and depression symptoms * What neurobiological processes are associated with the effects of psilocybin assisted psychotherapy. The researchers will compare the effects of a single dose of psilocybin (either 5mgs or 10mgs or 25mg) alongside psychotherapy on substance use severity and depression symptoms over six weeks in a sample of individuals with TRD and co-occurring SUD. In this 14-week study, participants will: * Visit the clinic for two intake sessions * Complete seven psychotherapy sessions. This will include three sessions before psilocybin administration, an 8 to 10 hour dosing session, and three sessions following psilocybin administration * Complete short, repeated daily assessments for six weeks, in total, before and after psilocybin administration * Complete two brain scans before and after psilocybin administration

Source: ClinicalTrials.gov (U.S. National Library of Medicine), data processed 2026-10-29T09:00:05; modifications: selected fields only; whitespace normalized; brief summary truncated to 2,000 characters. Not a U.S. Government endorsement.

Trial details

status

NOT_YET_RECRUITING

phase

PHASE1, PHASE2

study type

INTERVENTIONAL

enrollment

50

sponsor

Indiana University

conditions

Treatment Resistant Depression; Substance Use Disorders

interventions

DRUG: Psilocybin

start date

2027-02-01

start date type

ESTIMATED

primary completion date

2031-02-01

has results

false

data source

ClinicalTrials.gov

data processed

2026-10-29T09:00:05

modifications

selected fields only; whitespace normalized; brief summary truncated to 2,000 characters