Cannabidiol in the Treatment of Opioid Use Disorder

Study Overview
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Brief Summary
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The long-term goal of the project is to determine whether cannabidiol (CBD) can reduce craving and relapse in individuals with opioid use disorder (OUD). The first phase of our project was an open cross-over design study in healthy individuals to confirm the safety and pharmacokinetic (PK) effects of CBD (Brains CBD; Brains Bioceutical). This next phase is to determine whether CBD can serve as a potential adjunct treatment to reduce craving and anxiety in individuals with OUD maintained on opioid agonist therapy.

Detailed Description
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In Phase 2 of this study, we will conduct a double-blind (placebo-controlled) randomized controlled trial to evaluate whether 200mg and/or 400mg CBD (BSPG Laboratories) given twice daily (morning and evening), as compared to placebo, reduces craving and anxiety in individuals with opioid use disorder who are maintained on methadone or buprenorphine. In addition to in-lab physiological and behavioral assessments of cue-induced craving and anxiety, we will also employ ecological momentary assessment (EMA) to obtain real- time and real-world measures of symptoms including craving, anxiety, and mood as well as to track adherence to usage of the study drug. We will also explore the association between peripheral blood epigenetic change (chromatin accessibility across the genome) and lipidomic (endocannabinoid) levels with treatment outcomes leveraging blood samples already being collected for toxicology to track potential epigenetic and endocannabinoid alterations in relation to clinical outcomes.

Official Title
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Cannabidiol in the Treatment of Opioid Use Disorder

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: Cannabidiol
* Other: Placebo
* Drug: Cannabidiol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An individual who meets all of the following criteria will be eligible for study participation: Individuals between 18 and 65 years old; sex is a biological factor of interest (30% of individuals recruited will be biological females based on AIMS patient demographics, allowing sex comparisons). Ability to understand and give informed consent. Current opioid use disorder (OUD) or OUD in remission while on maintenance therapy with OAT, as determined by DSM-5 with the M.I.N.I. interview (Mini-International Neuropsychiatric Interview). Current opioid agonist maintenance treatment in an opioid treatment program with methadone or buprenorphine for at least 14 days prior to study participation. With the following more specific criteria for each of these two medications: Current methadone maintenance treatment with a dose of ≥ 40mg/day, (maximum: 200mg/day), AND urinary toxicology positive for methadone and EDDP. OR Current buprenorphine maintenance treatment with a dose of ≥ 8mg/day (maximum: 24mg/day), AND urinary toxicology positive for buprenorphine and norbuprenorphine. Exclusion: An individual who meets any of the following criteria will be excluded from participation: Participants who are non-English speaking. Psychiatric conditions under DSM-5 (examined with the MINI) that would make study participation unsafe or which would prevent adherence to study procedure; examples include: suicidal or homicidal ideation requiring immediate attention, inadequately-treated mental health disorder (e.g., active psychosis, uncontrolled bipolar disorder). Current diagnosis of a severe substance use disorder (except for opioid and nicotine/tobacco) in the past 3 months, based on the MINI interview, that would preclude safe participation in the study as determined by the study medical clinician. Alcohol intoxication when arriving at the study site (i.e., positive alcohol breathalyzer / alcohol salivary strips / urine alcohol). Signs of acute drug intoxication when arriving at the study site as determined by clinician assessment. Medical or psychiatric contraindications for CBD administration (e.g., history of hypersensitivity to cannabinoids); or any of the ingredients in the product (gelatin or sesame oil). Showing signs of acute opioid withdrawal symptoms (as determined by the result of the Clinical Opiate Withdrawal Scale (COWS). A Score of ≥ 5 or as interpreted by the investigator will be considered a positive result for withdrawal symptoms) and/or by clinician assessment. Have a medical condition that would make study participation unsafe, which would make treatment compliance difficult, or would prevent adherence to study procedure. This includes, but is not limited to the following criteria: History of impaired renal function or elevated liver enzymes at prescreening. The exclusionary lab values are: >4x the upper limit of normal (ULN) per laboratory criteria for AST or ALT, >1.5x ULN for bilirubin or <30mL/min/1.73m2 eGFR QTc Frederica > 500ms Participating in another pharmacotherapeutic trial in the past 3 months. Participants who have used any medication, dietary supplements (and/or grapefruit juice), or combination of medications and supplements known to alter the metabolism of, or interact with CBD (buproprion, rifampin, barbiturates, phenothiazines, cimetidine, etc.) 14 days prior to and during the duration of the study. For women: being pregnant (positive urine test for pregnancy) or breastfeeding. Not using an appropriate method of contraception such as hormonal contraception (oral hormonal contraceptives, Depo-Provera, Nuva-Ring), intrauterine device (IUD), sterilization, or double barrier method (combination of any two barrier methods used simultaneously, i.e. condom, spermicide, diaphragm). Participants who have been court mandated to attend treatment centers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: One group in each cohort (methadone and buprenorphine) will receive study drug and the other group will receive placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OUD, Methadone<br>Individuals with Opioid Use Disorder, maintained on Methadone | Drug: Cannabidiol<br>* Cannabidiol 200mg (twice daily)<br>* Other names: BSPG CBD;Other: Placebo<br>* Placebo (Twice Daily)<br>Drug: Cannabidiol<br>* Cannabidiol 400mg (twice daily)<br>* Other names: BSPG CBD;|
| Experimental: OUD, Buprenorphine<br>Individuals with Opioid Use Disorder, maintained on Buprenorphine | Drug: Cannabidiol<br>* Cannabidiol 200mg (twice daily)<br>* Other names: BSPG CBD;Other: Placebo<br>* Placebo (Twice Daily)<br>Drug: Cannabidiol<br>* Cannabidiol 400mg (twice daily)<br>* Other names: BSPG CBD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VASC and VASA at 4-weeks | Cue-induced Visual Analog Scale for craving (VASC) and anxiety (VASA) at 4-weeks. Proportion of subjects with positive urine toxicology for illicit opioid use at 4-weeks. Safety and drug tolerability. Safety and adverse effects with the Systematic Assessment for Treatment Emergent Events (SAFTEE). | 4-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VASC and VASA at 8-weeks | Cue-induced VASC and VASA at 8-weeks of treatment, general craving self-report, general anxiety self-report, duration of first illicit opioid abstinence, psychiatric symptomatology, physiological measures (heart rate, blood pressure, body temperature, O2, cue-induced cortisol levels), duration of sleep, cognitive function, quality of life, substance use other than opioids, concentration of methadone or buprenorphine metabolites, retention in treatment, change in opioid treatment dosage (at 8-week assessment). | 8-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid Use Disorder, Methadone, Buprenorphine