Clinical trial NCT04238754: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Opioid Withdrawal
Opioid Craving
Opioid Use Disorder
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Dalio Foundation
First posted: 2020-01-23
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety as Assessed by Number of Adverse Events
timeFrame: through completion of the two study sessions, an average of 17 days
measure: Number of Participants Whose Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) Levels >3x Upper Limit of Normal
timeFrame: End of residential stay, prior to discharge
measure: Change in Withdrawal Scores From Baseline AfterReceiving Placebo
timeFrame: Baseline, during residential session up to 57 hours
Secondary outcomes:
measure: Initial Efficacy of Study Drug as Assessed by Area Under the Curve for the Subjective Opiate Withdrawal Scale (SOWS) Scores
timeFrame: After first administration of study drug and up to 48 hours
measure: Acceptability Assessed by Number of Participants Who Would Recommend the Medication to a Family Member or Friend
timeFrame: at the end of the 57-hour residential session, prior to discharge
measure: Acceptability Assessed by Visual Analog Ratings
timeFrame: at the end of the 57-hour residential session, prior to discharge
measure: Acceptability Assessed by Rating of Medication Acceptance on a 5-point Acceptance Rating Scale
timeFrame: at the end of the 57-hour residential session, prior to discharge
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Cecilia L Bergeria, PhD
role: PRINCIPAL_INVESTIGATOR
References: