Oral Cannabidiol for Opioid Withdrawal

Johns Hopkins University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Opioid Withdrawal; Opioid Craving; Opioid Use Disorder

Treatments: Drug: Epidiolex; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04238754

IRB00232412

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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3 participants in 2 patient groups, including a placebo group

Epidiolex (CBD) Then Placebo

Experimental group

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.

Treatment:

Drug: Placebo

Drug: Epidiolex

Placebo Then Epidiolex

Placebo Comparator group

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.

Treatment:

Drug: Placebo

Drug: Epidiolex