Clinical trial NCT04587791: Cannabidiol in Opioid Use Disorder and Chronic Pain
Official title: Cannabidiol Pharmacotherapy for Co-occurring Opioid Use Disorder and Chronic Pain
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Chronic Pain
Opioid Use Disorder
Keywords: Methadone
Buprenorphine
Cannabidiol
Pain
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: VA Connecticut Healthcare System
name: National Institute on Drug Abuse (NIDA)
First posted: 2020-10-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: participants will receive CBD (400 mg, 800 mg, 1200 mg) or placebo.
Primary purpose: TREATMENT

Brief summary: This is a double-blind, randomized, placebo-controlled cross-over human laboratory study with a duration of approximately 4 weeks, during which participants will come to the testing site for a total of five times: one initial screening session, and four experimental sessions where study medication, Cannabidiol (CBD) will be administered, separated by at least 72 hours to limit carryover effects.

Detailed description: Thirty-six male and female (ages 18-70) participants with comorbid opioid use disorder (OUD) and non-cancer chronic pain for at least 6 months, currently receiving methadone (n= 22) or buprenorphine (n= 12), will be enrolled. Prior to their daily methadone or buprenorphine dose and thus at trough plasma levels of opioid, participants will receive oral CBD (400 mg, 800 mg, 1200 mg) or placebo. Subsequently, all participants will undergo laboratory testing of opioid-related outcomes.

Pain sensitivity will be measures including the well-validated, Quantitative Sensory Testing (QST), the Pain Catastrophizing Scale (PCS), and a pain Visual Analog Scale (VAS). Attentional bias and cue-induced opioid craving will be measured using a visual probe task and the Heroin Craving Scale (HCQ-14). Abuse potential will be measured using the Drug Effects Questionnaire (DEQ). Negative affect will be measured using the Positive and Negative Affect Schedule (PANAS). Cognitive performance will be measured by a comprehensive cognitive battery that includes the Continuous Performance Test (CPT) and the Hopkins Verbal Learning Test (HVLT). Safety will be thoroughly measured with the Systematic Assessment for Treatment Emergent Events (SAFTEE) for adverse effects.

The order of study medication administration will be counterbalanced order to minimize carryover effects. On the initial screening day and at the end of medication treatment, blood will be drawn to determine serum drug levels. Participants will be thoroughly evaluated by a physician prior to discharge on each experimental session. One week after the last study medication dose, participants will be conducted by phone for a follow-up session.

Eligibility criteria: Inclusion Criteria:

* Males and females, Veterans and non-Veterans, aged between 18 and 70 years old.
* Diagnosed with OUD and currently enrolled in methadone or buprenorphine maintenance treatment.
* Having chronic pain, uniformly operationalized as grade II (high-intensity) non-cancer musculoskeletal pain for ≥ 6 months 49
* Capable of providing informed consent in English.
* Compliant in opioid maintenance treatment and on a stable dose for two weeks or longer.
* Not meeting DSM-5 criteria for substance use disorders other than OUD or tobacco use disorder within the last 12 months.
* No current medical problems deemed contraindicated for participation by principal investigator.
* For women, not pregnant as determined by pregnancy screening; not breast-feeding; using acceptable birth control methods.

Exclusion Criteria:

* Other current major psychiatric disorders deemed clinically unstable by the principal investigator, such as severe depression and/or active suicidal ideation.
* Having experienced major psychosocial stressors recently (≤ 6 weeks before enrollment), at the discretion of the principal investigator.
* Having received inpatient psychiatric treatment recently (≤ 60 days before enrollment).
* A study physician will determine if participants receiving products containing THC or CBD products may participate in the study.
* Current use benzodiazepines or platelet inhibitors (e.g., clopidogrel, apixaban, ticagrelor).
* Current weight of less of 60 kg.

Primary outcomes:
measure: Primary Outcome Variable #1: Safety and tolerability of CBD
timeFrame: Baseline and up to 6 hours
measure: Primary Outcome Variable #2: Pain Sensitivity
timeFrame: Baseline and up to 6 hours
measure: Primary Outcome Variable #3: Abuse potential of CBD (DEQ)
timeFrame: Baseline and up to 6 hours
measure: Primary Outcome Variable #4A: Cognitive/psychomotor effects (CPT)
timeFrame: +210 minutes post dose
measure: Primary Outcome Variable #4B: Cognitive/psychomotor effects (HVLT)
timeFrame: +210 minutes post dose
Secondary outcomes:
measure: Secondary Outcome Variable #1: Opioid Craving
timeFrame: Baseline and +150 minutes post dose
Other outcomes:
measure: Influence of sex
timeFrame: Up to 6 hours
Locations:
city: West Haven
country: United States
facility: Department of Veterans Affairs Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Joao De Aquino, M.D.
role: PRINCIPAL_INVESTIGATOR
References: