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Psilocybin-facilitated Treatment for Cocaine Use

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ClinicalTrials.gov Identifier: NCT02037126
Recruitment Status : Recruiting
First Posted : January 15, 2014
Last Update Posted : May 6, 2021
Sponsor:
Information provided by (Responsible Party):
Peter Hendricks, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE January 13, 2014
First Posted Date  ICMJE January 15, 2014
Last Update Posted Date May 6, 2021
Study Start Date  ICMJE May 2015
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2021)
  • The difference between the psilocybin and placebo groups in the percentage of days abstinent from cocaine, verified by urine drug screen. [ Time Frame: From the psilocybin or placebo administration session to end-of-treatment (approximately 4 weeks in most participants), from end-of-treatment to 12 weeks after end-of-treatment, and from 12 weeks after end-of-treatment to 24 weeks after end-of-treatment. ]
    Percentage of days abstinent from cocaine among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview and with biochemically verified cocaine presence as assessed via a urine drug screen.
  • The difference between the psilocybin and placebo groups in sustained/complete abstinence from cocaine, verified by urine drug screen. [ Time Frame: From the psilocybin or placebo administration session to 24 weeks after end-of-treatment. ]
    Sustained/complete abstinence from cocaine among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview and with biochemically verified cocaine presence as assessed via a urine drug screen.
  • The difference between the psilocybin and placebo groups in time to cocaine lapse. [ Time Frame: From the psilocybin or placebo administration session to 24 weeks after end-of-treatment. ]
    Number of days to first use of cocaine after the drug administration session among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview and with biochemically verified cocaine presence as assessed via a urine drug screen.
Original Primary Outcome Measures  ICMJE
 (submitted: January 14, 2014)
The difference between the treatment and placebo groups in the number of participants with biochemically verified cocaine abstinence. [ Time Frame: 16 and 28 weeks after psilocybin or placebo administration. ]
Number of subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) with biochemically verified cocaine presence as assessed via a urine drug screen.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2021)
  • The difference between the psilocybin and placebo groups in the severity of cocaine dependence. [ Time Frame: Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment. ]
    Ratings on the Severity of Dependence Scale (SDS) among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed via self-report.
  • The difference between the psilocybin and placebo groups in the severity of cocaine withdrawal symptoms. [ Time Frame: Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment. ]
    Ratings on the Cocaine Selective Severity Assessment (CSSA) interview among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo).
  • The difference between the psilocybin and placebo groups in cocaine craving. [ Time Frame: Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment. ]
    Ratings on the Cocaine Craving Questionnaire-Brief among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed via self-report.
  • The difference between the psilocybin and placebo groups in situational cocaine abstinence self-efficacy. [ Time Frame: Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment. ]
    Ratings on the Brief Situational Confidence Questionnaire among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed via self-report.
  • The difference between the psilocybin and placebo groups in motivation to quit/remain abstinent, confidence in the ability to quit/remain abstinent, and perceived difficulty quitting/remaining abstinent. [ Time Frame: Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment. ]
    Ratings on the Thoughts About Abstinence Questionnaire among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed via self-report.
  • The difference between the psilocybin and placebo groups in depression, anxiety, and stress. [ Time Frame: Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment. ]
    Ratings on the Depression, Anxiety, and Stress Scale (DASS-21) among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed via self-report.
  • The difference between the psilocybin and placebo groups in satisfaction with life. [ Time Frame: Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment. ]
    Ratings on the Satisfaction with Life Scale among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed via self-report.
  • The difference between the psilocybin and placebo groups in income, employment, and living situation. [ Time Frame: At 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment. ]
    Responses on a brief demographic questionnaire among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed via self-report.
  • The difference between the psilocybin and placebo groups in the percentage of days abstinent from alcohol. [ Time Frame: From the psilocybin or placebo administration session to end-of-treatment (approximately 4 weeks in most participants), from end-of-treatment to 12 weeks after end-of-treatment, and from 12 weeks after end-of-treatment to 24 weeks after end-of-treatment. ]
    Percentage of days abstinent from alcohol among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview.
  • The difference between the psilocybin and placebo groups in the percentage of days abstinent from heavy alcohol use. [ Time Frame: From the psilocybin or placebo administration session to end-of-treatment (approximately 4 weeks in most participants), from end-of-treatment to 12 weeks after end-of-treatment, and from 12 weeks after end-of-treatment to 24 weeks after end-of-treatment. ]
    Percentage of days abstinent from heavy alcohol use among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview.
  • The difference between the psilocybin and placebo groups in the percentage of days abstinent from tobacco. [ Time Frame: From the psilocybin or placebo administration session to end-of-treatment (approximately 4 weeks in most participants), from end-of-treatment to 12 weeks after end-of-treatment, and from 12 weeks after end-of-treatment to 24 weeks after end-of-treatment. ]
    Percentage of days abstinent from tobacco among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview.
  • The difference between the psilocybin and placebo groups in the percentage of days abstinent from cannabis. [ Time Frame: From the psilocybin or placebo administration session to end-of-treatment (approximately 4 weeks in most participants), from end-of-treatment to 12 weeks after end-of-treatment, and from 12 weeks after end-of-treatment to 24 weeks after end-of-treatment. ]
    Percentage of days abstinent from cannabis among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Psilocybin-facilitated Treatment for Cocaine Use
Official Title  ICMJE Psilocybin-facilitated Treatment for Cocaine Use: A Pilot Study
Brief Summary

The primary purpose of this study is to evaluate the feasibility and estimate the efficacy of psilocybin-facilitated treatment for cocaine use. We also will monitor the impact of psilocybin-facilitated treatment on the use of other drugs and outcomes relevant to cocaine involvement (e.g., criminal involvement).

MRI assessment is a unique aspect of this study. As a potential biological mechanism of psilocybin's effect includes changes in default mode network functional connectivity (Carhart-Harris et al., 2012), we will determine if psilocybin's therapeutic effects are mediated by such changes. Moreover, as Glx (a brain metabolite that reflects glutamate) abnormalities have been shown to play a role in cocaine addiction, we will determine if psilocybin impacts Glx in the anterior cingulate cortex and hippocampus.

Detailed Description

Individuals who are eligible to participate and provide informed consent will complete baseline questionnaires and be randomly assigned in a double-blind manner to the Psilocybin or Active Placebo group. The first MRI assessment will take place shortly thereafter using a 3T head-only Magnetic Resonance Imaging and Spectroscopy scanner (Magnetom Allegra, Siemens medial Solutions, Malvern, PA), optimized for neuroimaging applications.

Preparation sessions (see below) and the drug administration session will take place in a room at the Clinical Research Unit designed to be as comfortable, aesthetically pleasing (i.e., living-room like), and safe (e.g., no furniture with sharp corners or glass objects) as possible, with a directly adjacent, private restroom.

All participants will undergo four weekly preparation sessions of approximately 2 hours each. The purpose of these sessions is to: 1) develop strong therapeutic alliance between the participants and the guide (Dr. Hendricks) and secondary monitor (Dr. Cropsey); 2) establish comfort and rapport between participants and the remainder of the research team; 3) discuss participants' aspirations with regard to their drug administration experience (e.g., What do participants hope to gain from their experience?); 4) discuss the treatment rationale and putative mechanisms of action of psilocybin (e.g., insight and reorientation that boost motivation to quit and abstinence self-efficacy, reduction of withdrawal/craving secondary to mood improvement); 5) obtain a detailed personal history of the participant, with a focus on those factors contributing to their current difficulties; 6) prepare participants for drug administration, including a detailed account of all potential effects of the drug; 7) discuss all aspects of the drug administration protocol (i.e., logistics and procedures), including plans of action in the event that participants experience acute distress; and 8) administer cognitive-behavioral treatment for cocaine use. Any participant who demonstrates significant anxiety, discomfort, or unease regarding drug administration at the conclusion of the four preparation sessions will be provided up to two additional preparation sessions. If these sessions are unsuccessful at mitigating the participant's anxiety, discomfort, or unease, the participant will be removed from the study.

Approximately one week after their final preparation session, participants will be instructed to eat a low-fat breakfast prior to presenting for their drug administration session at 8:00 am, approximately 1 hour before drug administration. A urine sample will be collected to verify drug-free status and participants will be encouraged to relax and reflect before drug administration. The drug administration session will take place over the course of 8 hours. The guide and secondary monitor will be present with participants throughout this session (at least one individual will always be present with the participant, even during brief intervals when the guide or monitor may be using the restroom). During this time, participants will be encouraged to lie down, use an eye mask to block external visual distraction, and use headphones through which a supportive music program will be played. Participants will be instructed to focus their attention on their inner experiences throughout the session.

Any participant reporting significant distress will be provided reassurance verbally or physically (e.g., with a supportive touch to the hand or shoulder). Although no contemporary studies have reported the need for pharmacological intervention, in the event that psychological distress is insufficiently managed with reassurance alone, medication will be administered under the guidance of the study physician.

Blood pressure will be assessed at regular intervals via automatic blood pressure monitor (e.g., pre-administration, and at 30, 60, 90, 120, 180, 240, 300, and 360 minutes post-administration), and medication for the treatment of acute hypertension will be administered should blood pressure exceed 190 systolic and 100 diastolic.

Sessions will be videotaped and reviewed to verify session procedures.

Seven hours after drug administration, when the major drug effects have subsided, participants will complete questionnaires assessing their experience. Participants will then be released into the care of a friend or family member oriented to be emotionally supportive of the participant (as arranged during preparation sessions) and instructed not to drive an automobile or engage in any other potentially dangerous activity for the remainder of the day. Participants will be provided with the guide's pager number should they feel the need for support that evening.

Within 2 days after the drug administration session, participants will meet with the guide for approximately 2 hours to discuss and reflect on their experience. The guide will assess for potential adverse effects at this time. The second MRI session will take place shortly thereafter. Participants will then meet with the guide once per week over the next 4 weeks with an emphasis on integration of their medication session experience in the context of achieving abstinence from cocaine; continued cognitive-behavioral treatment for cocaine use will be provided during these follow-up meetings.

Long-term assessment visits will take place 3 and 6 months after the final follow-up meeting. A battery of measures will be delivered at these times. At the conclusion of the 6-month assessment meeting, participants will be debriefed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cocaine-Related Disorders
Intervention  ICMJE
  • Drug: Psilocybin
    this has been used in treating obsessive-compulsive disorders, cluster headaches, anxiety, and drug dependence.
    Other Name: psychedelic compound
  • Drug: Diphenhydramine
    This drug will be used as the control. Diphenhydramine is a histamine blocker.
    Other Name: Benadryl
Study Arms  ICMJE
  • Experimental: Psilocybin administration
    Psilocybin will be administered in pill form at a dose of .36 mg/kg. Psilocybin will be administered in one session over the course of 8 hours.
    Intervention: Drug: Psilocybin
  • Active Comparator: Diphenhydramine administration
    Diphenhydramine will be administered in pill form at a dose of 100 mg. Diphenhydramine will be administered in one session over the course of 8 hours.
    Intervention: Drug: Diphenhydramine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 14, 2014)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 25 years of age and older
  • Score of at least 3 on the Severity of Dependence Scale
  • Desire to cease cocaine use as indicated by a goal of complete cocaine abstinence on the Thoughts about Abstinence questionnaire
  • Ability to read/write in English
  • No prior hallucinogen use or it will have been at least 3 years since their last use of a hallucinogen
  • Availability of 3 community observers to complete community observer forms via telephone around baseline and follow-up assessments.
  • Availability of a friend or family member into whose care the participant can be released following their drug administration session.
  • In good general health as assessed by detailed medical history and physical examination
  • Abstinence from cocaine for at least 7 days prior to experimental drug administration as confirmed via urinalysis and no signs of intoxication on other drugs.

Exclusion Criteria:

  • 24 years of age and younger
  • Women who are pregnant or breast feeding
  • Current psychiatric diagnoses other than substance abuse/dependence
  • Current hypertension (exceeding 140 systolic and 90 diastolic at resting as described below)
  • Use of tricyclic antidepressants, lithium, Selective Serotonin Reuptake Inhibitors, Monoamine Oxidase Inhibitors, haloperidol, St. John's Wort, or other antipsychotic medications, mood stabilizers, or medications with serotonin activity
  • History of any psychotic disorders
  • History of bipolar I or II disorder
  • First or second-degree relatives with any psychotic disorders, or bipolar I or II disorders
  • Current suicidal or homicidal ideation
  • Planning to move from the Birmingham area in the next 6 months
  • Contraindications of MRI (metallic objects in the body, claustrophobia, difficulty with prior MRI)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Peter S. Hendricks, Ph.D. 205-202-1387 phendricks@uab.edu
Contact: Sarah Simpson, B.S. 205-975-7721 sks09f@uab.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02037126
Other Study ID Numbers  ICMJE IND_121000
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Peter Hendricks, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter S. Hendricks, Ph.D. UAB School of Public Health Department of Health Behavior
PRS Account University of Alabama at Birmingham
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP