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 this project was an open cross-over design study in healthy individuals to confirm the safety and pharmacokinetic (PK) effects of CBD (BSPG CBD; Brains Bioceutical). The second phase was a double-blinded randomized controlled trial to determine whether CBD reduces craving and anxiety in individuals with OUD maintained on opioid agonist therapy. This phase 3 trial will determine whether CBD can serve as a potential adjunct treatment to reduce illicit opioid use in individuals with OUD maintained on opioid agonist therapy.
Responding to the urgent calls for developing non-opioid therapeutics to address the opioid addiction epidemic, we have been investigating the therapeutic potential of cannabidiol (CBD), a non-intoxicating cannabinoid as a possible strategy. Our preclinical animal studies demonstrated that CBD decreases cue-induced heroin seeking behavior during drug abstinence, associated with the incubation of craving. Moreover, the effects of CBD to reduce heroin-seeking behavior was still evident even in animals that were maintained on methadone. We also showed in randomized, double-blind placebo- controlled design human clinical trials that acute CBD (Epidiolex) administration (400 mg and 800mg) decreased craving and anxiety associated with heroin cues in abstinent individuals with heroin use disorder, an effect that persisted even a week after the last CBD dose (given daily for 3 days). Moreover, another of our human studies showed that CBD was safe even in combination with a potent opioid agonist (fentanyl) to address a potential relapse condition suggesting negligible negative interaction with opioids. Building on those studies, we next set out to investigate the potential for CBD as an adjunctive treatment to methadone or buprenorphine in opioid use disorder (OUD). To that end, we first conducted Phase 1 pharmacokinetic studies with a CBD formulation in oral capsules (BSPG CBD; Brains Bioceutical) in healthy participants that showed that oral administration of BSPG CBD (400 mg) led to comparable pharmacokinetic parameters of the CBD plasma levels and its active metabolite as Epidiolex (400 mg), an FDA-approved comparator CBD product that previously reduced craving. In the Phase 2 clinical trial, we evaluated the effect of 200mg CBD (vs placebo) twice daily for 4 weeks and an additional 4 weeks of 400 mg CBD, twice daily, on cue-induced craving and anxiety in individuals with OUD who are maintained on methadone or buprenorphine. In the next phase of this IND application, we will extend the Phase 2 study to evaluate the effects of 200mg CBD, 400 mg CBD and placebo, taken twice daily, over a 24-week period in the OUD individuals maintained on methadone or buprenorphine. Our goals in this double-blinded randomized controlled clinical trial (RCT) are to investigate the potential of CBD to 1) decrease illicit opioid use and 2) reduce craving.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
450
1 capsule CBD 200mg
Bovine Gel Placebo capsule
Icahn School of Medicine at Mount Sinai
New York, New York, United States
RECRUITINGCODA Treatment Recovery
Portland, Oregon, United States
RECRUITINGPercentage of study participants with negative urine toxicology for illicit opioid use
Percentage of study participants with negative urine toxicology for illicit opioid use over the course of 24 weeks.
Time frame: 24 weeks
Concentration of illicit opioids
Concentration of illicit opioids in quantitative plasma toxicology (plasma every four weeks)
Time frame: Duration of the trial, 24 weeks
Weeks of abstinence
Weeks of abstinence of illicit opioid use
Time frame: Duration of the trial, 24 weeks
Use of non-opioid illicit substances
Number of weeks using other non-opioid illicit substances
Time frame: Duration of the trial, 24 weeks
Duration of first opioid abstinence
Duration of first opioid abstinence, defined as the number of weeks from randomization to first opioid test positive or urine test missed.
Time frame: Duration of the trial, 24 weeks
Cue-induced Visual Analog Scale for craving (VASC)
Cue-induced Visual Analog Scale for craving (VASC) Cue-induced Visual Analog Scale for craving is used to measure subjective craving responses to a drug and neutral video cues evaluated in the clinic. Total scale ranges from 0-10, with higher scores indicating extreme cravings.
Time frame: At 12 and 24-week time points
Cue-induced Visual Analog Scale for anxiety (VASA)
Cue-induced Visual Analog Scale for anxiety (VASA) Cue-induced Visual Analog Scale Anxiety is used to measure subjective anxiety responses to a drug and neutral video cue evaluated in the clinic. Total scale from 0-10, with higher score indicating extreme anxiety.
Time frame: At 12 and 24-week time points
Change in illicit opioids in plasma toxicology
Change in illicit opioids in plasma toxicology
Time frame: 24 weeks
Change in illicit opioids in urine toxicology
Change in illicit opioids in urine toxicology
Time frame: 24 weeks
Study Retention
Number of participants remaining in the study
Time frame: 24 weeks
Opioid Craving Questionnaire (OCQ)
General craving self-report using Opioid Craving Questionnaire (OCQ) Total scale from 0-9, with higher score indicating more severe craving
Time frame: Every 4 weeks up to 24 weeks
Generalized Anxiety Disorder Scale (GAD7)
General anxiety self-report using the Generalized Anxiety Disorder Scale (GAD7). The General Anxiety Disorder 7-item questionnaire (GAD-7) is a 7-item questionnaire that asks user to rank how often they have been bothered by seven problems over the past two weeks from "0" (not at all) to "3" (nearly every day). The items that users are asked to rank levels of nervousness, anxiousness, relaxing, restlessness, irritability and fearfulness. Full scale from 0-21, with higher score indicating more symptoms.
Time frame: Every 4 weeks up to 24 weeks
Substance use other than opioids
Proportion of substance use other than opioids
Time frame: Duration of the trial, 24 weeks
Methadone plasma concentrations
Methadone plasma concentrations
Time frame: Duration of the trial, 24 weeks
Buprenorphine and metabolite plasma concentrations
Buprenorphine and metabolite plasma concentrations
Time frame: Duration of the trial, 24 weeks
Retention in opioid agonist therapy
Proportion of participants who remained in treatment with opioid agonist therapy
Time frame: Duration of the trial, 24 weeks
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