Oral Cannabidiol for Opioid Withdrawal

NCT ID: NCT04238754

Last Updated: 2023-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-01
• Study Completion Date: 2022-06-30

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.

Conditions

Opioid Withdrawal; Opioid Craving; Opioid Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Epidiolex (CBD) Then Placebo

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.

Group Type: EXPERIMENTAL

Epidiolex

Intervention Type: DRUG

Epidiolex 100 mg/mL Oral Solution

Placebo

Intervention Type: DRUG

Cherry syrup oral solution

Placebo Then Epidiolex

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.

Group Type: PLACEBO_COMPARATOR

Epidiolex

Intervention Type: DRUG

Epidiolex 100 mg/mL Oral Solution

Placebo

Intervention Type: DRUG

Cherry syrup oral solution

Interventions

Epidiolex

Epidiolex 100 mg/mL Oral Solution

Intervention Type: DRUG

Placebo

Cherry syrup oral solution

Intervention Type: DRUG

Other Intervention Names

Cannabidiol

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dalio Foundation

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cecilia L Bergeria, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00232412

Identifier Type: -

Identifier Source: org_study_id