NCT07499583Not yet recruitingPhase 1/2
Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder
Source: ClinicalTrials.gov · Last updated 23 Oct 2026
Brief summary (registry, in English)
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
- Status (registry)
- Not yet recruiting
- Phase (registry)
- Phase 1/2
- Study type
- Interventional
- Enrollment
- 50 (estimated)
- First submitted
- 24 Mar 2026
- Start date
- 1 Feb 2027
- Primary completion date
- 1 Feb 2031
- Lead sponsor
- Indiana University
- Diseases
- Depression
- NCT number
- NCT07499583
What you commit to
- Study type: Interventional · Phase 1/2
- Planned participants: 50
- From 1 Feb 2027 to the primary completion date, 1 Feb 2031
- 2 sites in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Use of selective serotonin reuptake inhibitors (SSRIs) and other medications are acceptable if dose has remained stable for 6 months and is not contra-indicated with psilocybin, as per the study physician
- Any prior use of classic psychedelics, including psilocybin
Other illness
- Exclusionary psychiatric conditions include schizophrenia, schizoaffective disorder, bipolar disorder, current post-traumatic stress disorder, or history of medically serious suicide attempt
- A family history of schizophrenia or schizoaffective disorder (first- or second-degree relatives), or bipolar disorder type 1 (first degree relatives)
- Medical conditions that would preclude safe participation in the trial (e.g., seizure disorder, significantly impaired liver function, coronary artery disease, heart failure, history of cerebrovascular accident, severe asthma, hyperthyroidism, narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, or bladder-neck obstruction)
Lab values
- EKG evidence of any clinically significant conduction abnormalities, including a Bazett's corrected QT interval (QTc) of \>450 msec for men and QTc \>470 msec for women
Other
- Actively/imminently suicidal (QIDS-SR question 12 score \>2, Hamilton Depression Scale (HAM-D) question 3 score \>3, or Montgomery-Åsberg Depression Rating Scale (MADRS) question 10 \>4)
- Sitting blood pressure below 90/50 mmHg or above 165/95 mmHg
- Women who are pregnant or lactating
Who the study is looking for
- Men and Women 18 years or over (veterans and first responders encouraged)
- Meets criteria for TRD (current major depressive episode without psychotic features by the Mini-International Neuropsychiatric Interview - MINI, with failure to respond to 2 or more evidence-based anti-depressants in the current episode)
- Meets moderate to severe use criteria for one primary substance (alcohol, cocaine, opioids/heroin, or cannabis). Moderate to severe co-use of nicotine also acceptable, as well as mild/recreational use of other substances
- Able to read English and complete study evaluations and consent
- In good health as verified by screening examination and medical history
- Able to safely receive MRI
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
Sites (2)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Goodman Hall, Dept of Psychiatry, Indiana University Coordinator of this site? Confirm its status | Indianapolis | United States | Unknown status |
| The Stark Neuroscience Building (Goodman Hall) Coordinator of this site? Confirm its status | Indianapolis | United States | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.