Oral Cannabidiol for Opioid Withdrawal

NCT04238754 | Completed Phase 1 Results FDA Drug

• 1 other identifier: IRB00232412
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid Withdrawal; Opioid Craving; Opioid Use Disorder

Outcome Measures

Primary Outcomes (3)

• 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.

  through completion of the two study sessions, an average of 17 days

• 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.

  End of residential stay, prior to discharge

• 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.

  Baseline, during residential session up to 57 hours

Secondary Outcomes (4)

• Initial Efficacy of Study Drug as Assessed by Area Under the Curve for the Subjective Opiate Withdrawal Scale (SOWS) Scores

  After first administration of study drug and up to 48 hours

• Acceptability Assessed by Number of Participants Who Would Recommend the Medication to a Family Member or Friend

  at the end of the 57-hour residential session, prior to discharge

• Acceptability Assessed by Visual Analog Ratings

  at the end of the 57-hour residential session, prior to discharge

• Acceptability Assessed by Rating of Medication Acceptance on a 5-point Acceptance Rating Scale

  at the end of the 57-hour residential session, prior to discharge

Study Arms (2)

Epidiolex (CBD) Then Placebo

EXPERIMENTAL

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.

Drug: Epidiolex; Drug: Placebo

Placebo Then Epidiolex

PLACEBO COMPARATOR

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.

Drug: Epidiolex; Drug: Placebo

Interventions

Epidiolex DRUG

Epidiolex 100 mg/mL Oral Solution

Also known as: Cannabidiol

Epidiolex (CBD) Then Placebo; Placebo Then Epidiolex

Placebo DRUG

Cherry syrup oral solution

Epidiolex (CBD) Then Placebo; Placebo Then Epidiolex

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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).

Sponsors & Collaborators

• Johns Hopkins University: lead
• Dalio Foundation: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Cecilia Bergeria
• Organization: Johns Hopkins Univeristy

cberge21@jhmi.edu

410-550-1979

Study Officials

• Cecilia L Bergeria, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Epidiolex is flavor masked with cherry syrup.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 17, 2020
• First Posted: January 23, 2020
• Study Start: November 1, 2020
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: August 29, 2023
• Results First Posted: August 29, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)