Substance Use Disorders, Treatment Resistant Depression
Conditions
Keywords
treatment resistant depression, substance abuse disorder, psilocybin assisted psychotherapy, stress
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) 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
Detailed description
This is a double-blind randomized clinical trial to examine the safety and efficacy of a single dose of psilocybin (5mg or 10mg or 25mg) in reducing substance use severity and depression symptoms in N=50 veterans and first responders with treatment resistant depression (TRD) and co-occurring substance use disorder (SUD). The study will be conducted at Goodman Hall outpatient clinic located at Indiana University, Department of Psychiatry. All participants will take part in two intake visits (one to conduct safety tests and establish eligibility, and one to collect baseline and covariate data). They will then participate in three preparatory psychotherapy sessions with a certified psilocybin counselor before receiving one of three, randomly assigned, psilocybin doses during an 8 to 10 hour administration session. Following psilocybin administration, participants will participate in three weekly integrative psychotherapy sessions. We will also conduct three, two-week bursts of Ecological Momentary Assessment (EMA) during weeks 1 and 2, weeks 5 and 6 and weeks 10 and 11 of study participation, to measure daily substance use patterns and depression symptoms both during stressful and non-stressful situations. A pre- and post- fMRI paradigm will additionally be conducted to determine psilocybin-related changes within and between the default mode network, the salience mode network and the central executive network, during both resting state and stress. We will also explore the extent to which elevations in subjective mystical and existential experience contributes to psilocybin's therapeutic and mechanistic effects. It is anticipated that all three doses of psilocybin will be safe and well-tolerated in this sample of veterans and first responders. We additionally expect that 25mgs of psilocybin compared with 5mgs will attenuate substance use severity and depressive symptoms six weeks following administration, and during both stressful and non-stressful situations. In addition, we expect that 25mg Vs 5mg psilocybin will decrease resting state functional connectivity within the default mode network (DMN) and modulate connectivity between the DMN, salience network, central executive network, and the amygdala during stress exposure.
Interventions
DRUGPsilocybin
Participants will be randomly administered a single dose of either 5mg or 10mg or 25mg psilocybin
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind
Intervention model description
Randomized, double-blind, dose trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 urines | Weekly for 12-weeks | urine toxicology screens for alcohol and substance use will be collected |
| Change in % number of days spent using substances | Weekly 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 symptoms | Weekly 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 exposure | Change 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in amount of substance consumed per occasion | Weekly 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 TLFB and brief EMA items |
| Change in number of binge episodes | Weekly 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 TLFB and brief EMA items |
| Change in craving | Weekly for 12-weeks (various dependent upon participants substance of choice) and 5 times per day in weeks 1, 2, 5, 6, 10 & 11 (brief items) | Various standardized craving scales will be used to collect self-report craving data in addition to brief EMA items |
| Change in anxiety | Weekly for 12-weeks (STAI) and 5 times per day in weeks 1, 2, 5, 6, 10 & 11 (brief items) | The State-Trait Anxiety Inventory (STAI) will be used to collect self-report anxiety data in addition to brief momentary assessment items |
| Changes in emotion regulation | Change from baseline (week 2) to post psilocybin administration (weeks 5 and 10)and 5 times per day in weeks 1, 2, 5, 6, 10 & 11 (adapted DERS) | The Difficulties in Emotion Regulation Scale (DERS) will be used to collect emotion regulation data in addition to the DERS adapted for EMA |
| Changes in brain functional connectivity during stress exposure | Change from baseline (week 2) to post psilocybin administration (week 5) | functional connectivity will be assessed during stress exposure in the scanner |
Countries
United States
Contacts
CONTACTSusan K Conroy, MD
CONTACTHelen C Fox, PhD
PRINCIPAL_INVESTIGATORSusan K Conroy, PhD
Indiana University
Outcome results
None listed