Clinical TrialTreatment-Resistant Depression (TRD)PsilocybinPsilocybinPsilocybinNot yet recruiting

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

This Phase I/Phase II, randomised, double-blind, quadruple-masked trial (n=50) will evaluate a single oral dose of psilocybin 5 mg, 10 mg or 25 mg, given alongside psychotherapy, in veterans and first responders with treatment-resistant depression (TRD) and co-occurring substance use disorder (SUD). The study will assess safety and tolerability, as well as whether psilocybin-assisted psychotherapy can reduce substance use severity and depressive symptoms. Participants will be assigned in parallel to one of three psilocybin dose groups and will complete two intake visits, three preparatory psychotherapy sessions, an 8 to 10 hour dosing session, and three weekly integrative psychotherapy sessions afterwards. Outcomes include adverse events, urine drug results, days of substance use, depression symptom ratings, plasma brain-derived neurotrophic factor (BDNF) during stress exposure, and resting brain functional connectivity on MRI, with repeated daily assessments across 6 weeks and follow-up through 12 weeks, including a 60-day follow-up.

Target Enrollment
50 participants
Study Type
Phase I/II interventional
Design
Randomized, quadruple Blind

Detailed 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) in veterans and first responders. We 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 veterans and first responders 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

Study Arms & Interventions

Psilocybin Dose - Low

experimental

Experimental: Participants receive a single oral dose of psilocybin 5mgs

Interventions

  • Psilocybin5 mg
    via Oral• single dose• 1 doses total

Psilocybin Dose - Moderate

experimental

Experimental: Participants receive a single oral dose of psilocybin 10mgs

Interventions

  • Psilocybin10 mg
    via Oral• single dose• 1 doses total

Psilocybin Dose - High

experimental

Experimental: Participants receive a single oral dose of psilocybin 25mgs

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

Participants

Ages
18 – 70
Sexes
Male & Female

Inclusion Criteria

  • i) Veterans or first responders ii) 18 -70 years of age iii) 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), iv) 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, v) Able to read English and complete study evaluations and consent vi) In good health as verified by screening examination and medical history vii) able to safely receive MRI

Exclusion Criteria

  • i) Exclusionary psychiatric conditions include schizophrenia, schizoaffective disorder, bipolar disorder, current post-traumatic stress disorder, or history of medically serious suicide attempt ii) 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) ii) A family history of schizophrenia or schizoaffective disorder (first- or second-degree relatives), or bipolar disorder type 1 (first degree relatives) iii) 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, Dr Conroy iii) Individuals with any prior use of classic psychedelics, including psilocybin iv) 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) v) Sitting blood pressure below 90/50 mmHG or above 165/95 mmHg vi) 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 vii) Women who are pregnant or lactating

Study Details

Locations

Goodman Hall, Dept of Psychiatry, Indiana University — Indianapolis, Indiana, United States
The Stark Neuroscience Building (Goodman Hall) — Indianapolis, Indiana, United States

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