Psilocybin-Enhanced Psychotherapy for Methamphetamine Use Disorder

• ClinicalTrials.gov Identifier: NCT04982796
• Recruitment Status: Recruiting
• First Posted: July 29, 2021
• Last Update Posted: May 3, 2023
• Sponsor: Portland VA Research Foundation, Inc
• Collaborator: Steven & Alexandra Cohen Foundation
• Information provided by (Responsible Party): Portland VA Research Foundation, Inc

Study Description

Brief Summary:

This is a proof-of-concept randomized clinical trial of psilocybin-enhanced psychotherapy versus treatment-as-usual among individuals being treated for methamphetamine use disorder.

Condition or disease	Intervention/treatment	Phase
Amphetamine-Related Disorders	Drug: Psilocybin; Behavioral: Treatment-as-usual	Phase 1; Phase 2

Detailed Description:

The trial will take place with individuals admitted to a residential rehabilitation treatment program. The treatment protocol will consist of 4 preparatory therapy visits, 2 psilocybin sessions (25-30mg), and 8 total integration therapy visits. Primary aims assess acceptability, feasibility, and safety with a primary endpoint at the conclusion of the study intervention. An additional aim assesses preliminary efficacy for methamphetamine use disorder and overall functioning at follow-up assessments 60 and 180 days after discharge from the residential treatment program.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Clinical interviewers will be blinded to condition and study timepoint.
• Primary Purpose: Treatment
• Official Title: Psilocybin-Enhanced Psychotherapy for Methamphetamine Use Disorder
• Actual Study Start Date: July 7, 2022
• Estimated Primary Completion Date: December 31, 2024
• Estimated Study Completion Date: April 30, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Psilocybin-enhanced psychotherapy; Psilocybin will be administered twice (25mg & 30mg two weeks apart) in addition to a 6-week psychotherapy protocol while admitted to a residential rehabilitation treatment program.	Drug: Psilocybin; See description of psilocybin-enhanced psychotherapy arm.; Behavioral: Treatment-as-usual; See description of treatment-as-usual arm.
Treatment-as-Usual; Treatment-as-usual while admitted to a residential rehabilitation treatment program.	Behavioral: Treatment-as-usual; See description of treatment-as-usual arm.

Outcome Measures

Primary Outcome Measures :

1. Acceptability [ Time Frame: End of 6-week intervention; approximately 42 days ]
   We will use a 7-point Likert scale to measure each participant's perceived benefit and perceived harm of the intervention.
2. Proportion of patients who complete the intervention and follow-up [ Time Frame: End of 6-week intervention to 180 days post-discharge follow-up; approximately 180 days ]
   We will observe the proportion of patients who complete the intervention and follow-up to determine feasibility.

Secondary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 180 day post-discharge follow-up; approximately 222 days post-enrollment ]
   Number of Participants Who Experienced Treatment-related Adverse Events as defined by the FDA (21 Code of Federal Regulations [CFR] 312.32(a)). Adverse events assessed at every study visit by clinical observation and patient interview.
2. Methamphetamine Use, self-report [ Time Frame: 60 days post-discharge follow-up; approximately 102 days post-enrollment ]
   Using the Timeline Follow-Back procedure, average number of days per week used methamphetamine over the past four weeks.
3. Methamphetamine Use, self-report [ Time Frame: 180 days post-discharge follow-up; approximately 222 days post-enrollment ]
   Using the Timeline Follow-Back procedure, average number of days per week used methamphetamine over the past four weeks.
4. Methamphetamine Use, urine [ Time Frame: 60 days post-discharge follow-up; approximately 102 days post-enrollment ]
   Urine drug screen
5. Methamphetamine Use, urine [ Time Frame: 180 days post-discharge follow-up; approximately 222 days post-enrollment ]
   Urine drug screen
6. Change from baseline in Sheehan Disability Scale (SDS) at end-of-intervention [ Time Frame: approximately 42 days post-enrollment ]
   Sheehan Disability Scale total score, a measure of clinician-rated functional impairment. SDS scores range from 0 (not impaired) to 30 (highly impaired).
7. Change from baseline in Sheehan Disability Scale at 60 day post-discharge follow-up [ Time Frame: approximately 102 days post-enrollment ]
   Sheehan Disability Scale total score, a measure of clinician-rated functional impairment
8. Change from baseline in Sheehan Disability Scale at 180 day post-discharge follow-up [ Time Frame: approximately 222 days post-enrollment ]
   Sheehan Disability Scale total score, a measure of clinician-rated functional impairment

Other Outcome Measures:

1. Change from baseline in Stimulant Craving at end-of-intervention [ Time Frame: approximately 42 days post-enrollment ]
   Stimulant Craving Questionnaire-Brief
2. Change from baseline in Stimulant Craving at 60 day post-discharge follow-up [ Time Frame: approximately 102 days post-enrollment ]
   Stimulant Craving Questionnaire-Brief
3. Change from baseline in Stimulant Craving at 180 day post-discharge follow-up [ Time Frame: approximately 222 days post-enrollment ]
   Stimulant Craving Questionnaire-Brief
4. Change from baseline in Depression Symptoms at end-of-intervention [ Time Frame: approximately 42 days post-enrollment ]
   Beck Depression Inventory-II
5. Change from baseline in Depression Symptoms at 60 day post-discharge follow-up [ Time Frame: approximately 102 days post-enrollment ]
   Beck Depression Inventory-II
6. Change from baseline in Depression Symptoms at 180 day post-discharge follow-up [ Time Frame: approximately 222 days post-enrollment ]
   Beck Depression Inventory-II
7. Change from baseline in PTSD Symptoms at end-of-intervention [ Time Frame: approximately 42 days post-enrollment ]
   PTSD Checklist for Diagnostic and Statistical Manual (DSM)-5
8. Change from baseline in PTSD Symptoms at 60 day post-discharge follow-up [ Time Frame: approximately 102 days post-enrollment ]
   PTSD Checklist for DSM-5
9. Change from baseline in PTSD Symptoms at 180 day post-discharge follow-up [ Time Frame: approximately 222 days post-enrollment ]
   PTSD Checklist for DSM-5
10. Change from baseline in Anxiety Symptoms at end-of-intervention [ Time Frame: approximately 42 days post-enrollment ]
    Measured by Generalized Anxiety Disorder-7 (GAD-7). Scores range from 0 (minimal anxiety) to 21 (severe anxiety).
11. Change from baseline in Anxiety Symptoms at 60 day post-discharge follow-up [ Time Frame: approximately 102 days post-enrollment ]
    Generalized Anxiety Disorder-7
12. Change from baseline in Anxiety Symptoms at 180 day post-discharge follow-up [ Time Frame: approximately 222 days post-enrollment ]
    Generalized Anxiety Disorder-7
13. Change from baseline in Attachment Insecurity at end-of-intervention [ Time Frame: approximately 42 days post-enrollment ]
    Experiences in Close Relationships-Short form
14. Change from baseline in Attachment Insecurity at 60 day post-discharge follow-up [ Time Frame: approximately 102 days post-enrollment ]
    Experiences in Close Relationships-Short form
15. Change from baseline in Attachment Insecurity at 180 day post-discharge follow-up [ Time Frame: approximately 222 days post-enrollment ]
    Experiences in Close Relationships-Short form
16. Change from baseline in Immune Markers at end-of-intervention [ Time Frame: approximately 42 days post-enrollment ]
    C-Reactive Protein, Interleukin (IL)-6, Tumor Necrosis Factor (TNF)-a, IL-8, IL-10, IL-1β, CCL2, CCL3
17. Change from baseline in Heart Rate Variability at end-of-intervention [ Time Frame: approximately 42 days post-enrollment ]
    heart rate variability, 7 minutes, resting

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• United States military Veteran
• Moderate to severe methamphetamine use disorder using the DSM-V diagnostic criteria
• Desire to cease or reduce methamphetamine use

Exclusion Criteria:

• Have uncontrolled hypertension or clinically significant cardiovascular disease
• History of seizure disorder in adulthood
• CNS metastases or symptomatic central nervous system (CNS) infection
• Poorly controlled diabetes mellitus
• Taking certain medications that may interact with psilocybin
• History of any primary persistent psychotic disorder, including schizophrenia, schizoaffective disorder, bipolar disorder with psychosis, major depressive disorder with psychosis, or schizophreniform disorder
• History of bipolar I disorder
• Current eating disorder with active purging
• History of hallucinogen use disorder
• Pregnant or breast feeding

Contacts and Locations

Contacts

Contact: Jenna Kachmarik, BS; (971) 409-7908; Jenna.Kachmarik@va.gov

Contact: Kevin Rothstein-Kightly, MS; (360) 450-9349; Kevin.Rothstein-Kightly@va.gov

Locations

United States, Washington

Portland VA Health Care System; Recruiting

Vancouver, Washington, United States, 98661

Contact: Kevin Rothstein-Kightly, BS 360-450-9349 Kevin.Rothstein-Kightly@va.gov

Sponsors and Collaborators

Portland VA Research Foundation, Inc

Steven & Alexandra Cohen Foundation

Investigators

• Principal Investigator: Chris Stauffer, MD; Oregon Health and Science University

More Information

• Responsible Party: Portland VA Research Foundation, Inc
• ClinicalTrials.gov Identifier: NCT04982796
• Other Study ID Numbers: 01
• First Posted: July 29, 2021
• Last Update Posted: May 3, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Portland VA Research Foundation, Inc:

methamphetamine, stimulant, psilocybin, psychedelic, psychotherapy

Additional relevant MeSH terms:

Amphetamine-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Psilocybin; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs