Psilocybin with talk therapy for treatment-resistant depression and substance use
Tests psilocybin with psychotherapy in adults with resistant depression and substance use.
Plain-language title generated from the registry record
Registry title: Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder
Key facts
- Where
- Indianapolis, United StatesSee the 2 sites
- Phase
- Phase 1/2
Where in United States
- Goodman Hall, Dept of Psychiatry, Indiana UniversityIndianapolis, United StatesNo longer taking part
- The Stark Neuroscience Building (Goodman Hall)Indianapolis, United StatesNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- Indiana University
- Trial code
- NCT07499583
- Record updated
- 23 October 2026
- Original description
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:Read full original descriptionShow less
Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder
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
Inclusion: 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.
Exclusion: 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; 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); 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; 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.