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Oral Cannabidiol for Opioid Withdrawal

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04238754
Recruitment Status : Not yet recruiting
First Posted : January 23, 2020
Last Update Posted : July 23, 2020
Sponsor:
Collaborator:
Dalio Foundation
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
This pilot study will examine the safety of the cannabinoid cannabidiol (Epidiolex) in a human laboratory model of clinically relevant withdrawal. The study will be a residential within-subject comparison; all participants will receive placebo dosing and active cannabidiol. Results may be used to support an R01 grant application to more closely examine this hypothesis.

Condition or disease Intervention/treatment Phase
Opioid Withdrawal Opioid Craving Opioid Use Disorder Drug: Epidiolex 100 mg/mL Oral Solution Other: Cherry Syrup Oral Solution Phase 1 Phase 2

Detailed Description:
Based on preclinical research and emerging human research, cannabidiol (CBD; a major constituent of the cannabis plant) is a promising pharmacotherapy for the treatment of opioid withdrawal. Most recently, CBD decreased cue-induced craving and anxiety (two common withdrawal symptoms) among abstinent heroin-dependent individuals relative to placebo. As of June 2018, Epidiolex, an oral formulation of plant-derived pure CBD, has been approved by the U.S. Food and Drug Administration (FDA) for treating severe forms of epilepsy and can be prescribed for other off-label indications. Epidiolex has a low side effect and high safety profile. Given the recent FDA approval of Epidiolex, and a growing interest to develop existing pharmaceuticals to address issues related to Opioid Use Disorder (OUD) and its recovery, the investigators are proposing a pilot study to examine the safety of Epidiolex in a human laboratory model of clinically relevant withdrawal. The study will be a residential within-subject comparison; methadone-maintained participants will undergo spontaneous withdrawal and receive placebo dosing and active cannabidiol. Data collected for this study will establish: (1) the safety of administering two dosing regimens of Epidiolex within the investigators' withdrawal paradigm and (2) the feasibility of the investigators' withdrawal paradigm for demonstrating clinically meaningful increases in withdrawal. Results may be used to support an R01 grant application to more closely examine this hypothesis.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Within subject comparison of Epidiolex to placebo. The order of study drug (active Epidiolex or placebo) is randomized across participants. Epidiolex is flavor masked with cherry syrup
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Placebo-Controlled Evaluation of the Safety of Oral Cannabidiol in a Clinically Relevant Model of Opioid Withdrawal
Estimated Study Start Date : October 1, 2020
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2021

Arm Intervention/treatment
Experimental: All Participants
Each participant will receive Epidiolex oral solution and Cherry syrup oral solution (placebo) in a randomized fashion.
Drug: Epidiolex 100 mg/mL Oral Solution
8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses)
Other Name: cannabidiol

Other: Cherry Syrup Oral Solution
20 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses)




Primary Outcome Measures :
  1. Safety as assessed by number of Adverse Events [ Time Frame: 57-hour residential session ]
    Number of Adverse Events reported across sessions with and without study drug

  2. Number of participants whose aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels >3x upper limit of normal [ Time Frame: 57-hour residential session ]
    Number of participants whose AST/ALT levels >3x upper limit of normal (ULN) at the end of a study session when they receive Epidiolex. This will be used in the assessment of safety.

  3. Feasibility of Spontaneous Withdrawal Model as assessed by change in withdrawal scores [ Time Frame: Baseline, 57-hour residential session when Epidiolex is received ]
    Change in withdrawal scores during laboratory evaluation of spontaneous withdrawal. Withdrawal is measured with the Subjective Opiate Withdrawal Scale (SOWS). That has a range of 0-64 where a mild score is represented by a score of 1-10, a moderate score is represented by a score of 11-20 and a severe score is considered anything greater than 21.


Secondary Outcome Measures :
  1. Initial Efficacy of Study Drug as assessed by area under the curve for SOWS scores [ Time Frame: 57-hour residential session ]
    Withdrawal symptom suppression during active and placebo conditions. Area Under the Curve (AUC) analyses will be calculated to characterize withdrawal (SOWS) scores across time. SOWS AUC will be compared between the two conditions. AUC will range from 0 to 3072 where 0 represents no withdrawal during study drug administration and 3072 represents the most severe withdrawal during study drug administration.

  2. Acceptability assessed by percentage of participants who would recommend the medication to a family member or friend [ Time Frame: 57-hour residential session ]
    Percent of participants who would recommend the medication to a family member or friend trying to taper down from opioid medications.

  3. Acceptability assessed by visual analog ratings [ Time Frame: 57-hour residential session ]
    Visual analog ratings of the degree to which the medication suppressed opioid withdrawal symptoms. The visual analog ratings will be scored on a scale from 0-100 where 0 represents no suppression of withdrawal and 100 represents complete suppression of withdrawal.

  4. Acceptability assessed by rating of medication acceptance on a 5-point acceptance rating scale [ Time Frame: 57-hour residential session ]
    Participant rating of medication acceptance on a 5-point acceptance rating scale. The acceptance rating scale will range from 0-4 where 0 represents no acceptance of the medication and 4 represents complete acceptance of the medication.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Medically cleared to take study medication
  • Are not pregnant or breast feeding
  • Willing to comply with the study protocol
  • Provides urine that tests positive for methadone
  • Maintained on 80-120 mg of daily methadone with no dose changes in the past 2 weeks (verified through a medical release with the participant's provider)

Exclusion Criteria:

  • Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for alcohol/substance use disorder other than opioid use disorder
  • Previous adverse reaction to a cannabinoid product
  • Self-report any illicit drug use or cannabinoid use in the past 7 days
  • Presence of any clinically significant medical/psychiatric illness judged by the investigators to put subject at elevated risk for experiencing an adverse events
  • Past year suicidal behavior as assessed via the Columbia Suicide Severity Rating Scale
  • History of seizure disorder
  • Past 14 day use of any of the following contraindicated medications:

    • Clobazam, Valproate
    • Moderate or strong inhibitors of CYP3A4 or CYPC19 (with the exception of methadone, as outlined in the Protection Against CBD Risks section).
    • Strong CYP3A4 or CYP2C19 inducers
    • UGT1A9, UGT2B7, CYP1A2, CYP2C8, CYP2C9 and CYP2C19 substrates (with the exclusion of caffeine).
    • Central nervous system (CNS) depressants that are contraindicated with Epidiolex
  • Breathalyzer that tests positive for alcohol prior to session admission
  • Self-reported consumption of grapefruit juice within 24 hours of session admission
  • Have a history of clinically significant cardiac arrhythmias or vasospastic disease
  • Have circumstances that the study investigators believe are contraindicated with study participation and/or would interfere with study participation (e.g., impending jail).
  • Moderate-severe hepatic impairment as indicated by ALT or AST levels > 3x ULN and/or Bilirubin levels >2x ULN as evidenced by a blood test.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04238754


Contacts
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Contact: Cecilia L Bergeria, PhD 410-550-1979 cberge21@jhmi.edu
Contact: Kelly E Dunn, PhD 410-550-2254

Locations
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United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21224
Contact: Cecilia L Bergeria, PhD    540-604-4853    cberge21@jhmi.edu   
Sponsors and Collaborators
Johns Hopkins University
Dalio Foundation
Investigators
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Principal Investigator: Kelly E Dunn, PhD Johns Hopkins University
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04238754    
Other Study ID Numbers: IRB00232412
First Posted: January 23, 2020    Key Record Dates
Last Update Posted: July 23, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Substance Withdrawal Syndrome
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Epidiolex
Pharmaceutical Solutions
Anticonvulsants