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Oral Cannabidiol for Opioid Withdrawal

Primary Purpose

Opioid Withdrawal, Opioid Craving, Opioid Use Disorder

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Epidiolex
Placebo
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid Withdrawal

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Johns Hopkins University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Epidiolex (CBD) Then Placebo

Placebo Then Epidiolex

Arm Description

Participants first receive 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) during which prescribed methadone is withheld. After 1 week, they receive 20 mL of inactive cherry syrup delivered every 12 hours for 48hours total (4 doses) during which prescribed methadone is withheld.

Participants first receive 20 mL of inactive cherry syrup delivered every 12 hours for 48hours total (4 doses) during which prescribed methadone is withheld. After 1 week washout, they receive 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) during which prescribed methadone is withheld.

Outcomes

Primary Outcome Measures

Safety as Assessed by Number of Adverse Events
Number of Adverse Events reported across sessions with and without study drug. Adverse events were collected for the entire 57 hour session.
Number of Participants Whose Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) Levels >3x Upper Limit of Normal
Number of participants whose AST/ALT levels >3x upper limit of normal (ULN) at the end of a study session when they receive Epidiolex and Placebo. This will be used in the assessment of safety.
Change in Withdrawal Scores From Baseline AfterReceiving Placebo
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

Initial Efficacy of Study Drug as Assessed by Area Under the Curve for the Subjective Opiate Withdrawal Scale (SOWS) Scores
Withdrawal symptom suppression during active and placebo conditions. Area Under the Curve (AUC) analyses will be calculated to characterize withdrawal on the Subjective Opiate Withdrawal Scale (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.
Acceptability Assessed by Number of Participants Who Would Recommend the Medication to a Family Member or Friend
Number of participants who would recommend the medication to a family member or friend trying to taper down from opioid medications.
Acceptability Assessed by Visual Analog Ratings
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.
Acceptability Assessed by Rating of Medication Acceptance on a 5-point Acceptance Rating Scale
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.

Full Information

First Posted
January 17, 2020
Last Updated
August 4, 2023
Sponsor
Johns Hopkins University
Collaborators
Dalio Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04238754
Brief Title
Oral Cannabidiol for Opioid Withdrawal
Official Title
A Randomized Placebo-Controlled Evaluation of the Safety of Oral Cannabidiol in a Clinically Relevant Model of Opioid Withdrawal
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
November 1, 2020 (Actual)
Primary Completion Date
June 30, 2022 (Actual)
Study Completion Date
June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
Dalio Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Withdrawal, Opioid Craving, Opioid Use Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
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)
Masking Description
Epidiolex is flavor masked with cherry syrup.
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Epidiolex (CBD) Then Placebo
Arm Type
Experimental
Arm Description
Participants first receive 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) during which prescribed methadone is withheld. After 1 week, they receive 20 mL of inactive cherry syrup delivered every 12 hours for 48hours total (4 doses) during which prescribed methadone is withheld.
Arm Title
Placebo Then Epidiolex
Arm Type
Placebo Comparator
Arm Description
Participants first receive 20 mL of inactive cherry syrup delivered every 12 hours for 48hours total (4 doses) during which prescribed methadone is withheld. After 1 week washout, they receive 8 mL of Epidiolex (800 mg of cannabidiol) + 16 mL of inactive cherry syrup delivered every 12 hours for 48 hours total (4 doses) during which prescribed methadone is withheld.
Intervention Type
Drug
Intervention Name(s)
Epidiolex
Other Intervention Name(s)
Cannabidiol
Intervention Description
Epidiolex 100 mg/mL Oral Solution
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Cherry syrup oral solution
Primary Outcome Measure Information:
Title
Safety as Assessed by Number of Adverse Events
Description
Number of Adverse Events reported across sessions with and without study drug. Adverse events were collected for the entire 57 hour session.
Time Frame
through completion of the two study sessions, an average of 17 days
Title
Number of Participants Whose Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) Levels >3x Upper Limit of Normal
Description
Number of participants whose AST/ALT levels >3x upper limit of normal (ULN) at the end of a study session when they receive Epidiolex and Placebo. This will be used in the assessment of safety.
Time Frame
End of residential stay, prior to discharge
Title
Change in Withdrawal Scores From Baseline AfterReceiving Placebo
Description
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.
Time Frame
Baseline, during residential session up to 57 hours
Secondary Outcome Measure Information:
Title
Initial Efficacy of Study Drug as Assessed by Area Under the Curve for the Subjective Opiate Withdrawal Scale (SOWS) Scores
Description
Withdrawal symptom suppression during active and placebo conditions. Area Under the Curve (AUC) analyses will be calculated to characterize withdrawal on the Subjective Opiate Withdrawal Scale (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.
Time Frame
After first administration of study drug and up to 48 hours
Title
Acceptability Assessed by Number of Participants Who Would Recommend the Medication to a Family Member or Friend
Description
Number of participants who would recommend the medication to a family member or friend trying to taper down from opioid medications.
Time Frame
at the end of the 57-hour residential session, prior to discharge
Title
Acceptability Assessed by Visual Analog Ratings
Description
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.
Time Frame
at the end of the 57-hour residential session, prior to discharge
Title
Acceptability Assessed by Rating of Medication Acceptance on a 5-point Acceptance Rating Scale
Description
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.
Time Frame
at the end of the 57-hour residential session, prior to discharge

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cecilia L Bergeria, PhD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Oral Cannabidiol for Opioid Withdrawal

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