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Cannabidiol in Opioid Use Disorder and Chronic Pain

Early Phase 1
Recruiting
Conditions
Chronic Pain
Opioid Use Disorder
Interventions
Drug: 400mg Cannabidiol
Drug: 800mg Cannabidiol
Drug: 1200mg Cannabidiol
Drug: Saline
Registration Number
NCT04587791
Lead Sponsor
Yale University
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
40
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
CBD 400mg400mg CannabidiolCBD 400 mg
CBD 800mg800mg CannabidiolCBD 800mg
CBD 1200mg1200mg CannabidiolCBD 1200mg
SalineSalinesaline
Primary Outcome Measures
NameTimeMethod
Primary Outcome Variable #1: Safety and tolerability of CBDBaseline and up to 6 hours

To monitor adverse events from the study medications, the Systematic Assessment for Treatment Emergent Events (SAFTEE) will be administered before and after each experimental session. This is a symptom checklist that has been used successfully in our previous studies to assess possible side effects of study medications. It includes information regarding severity of any presenting side effects, as well as the course of action taken by study staff in response.

Primary Outcome Variable #2: Pain SensitivityBaseline and up to 6 hours

We will measure pain sensitivity using a comprehensive QST battery at baseline and approximately hourly for 6 hours.

Primary Outcome Variable #3: Abuse potential of CBD (DEQ)Baseline and up to 6 hours

The abuse potential of CBD will be assessed using the Drug Effects Questionnaire (DEQ) administered at baseline and every 30 minutes. The primary DEQ outcome is the Stimulatory Effects subscale, obtained by averaging participants responses to the items: "Feel High"; "Feel Stimulated"; and "Feel the Drug Strength".

Primary Outcome Variable #4A: Cognitive/psychomotor effects (CPT)+210 minutes post dose

The cognitive/psychomotor effects of CBD will be assessed using the Continuous Performance Test (CPT). For the CPT, the primary outcome will be the throughput score, which indexes attention/working memory accuracy (i.e. percent of correct responses) and speed (i.e. reaction time).

Primary Outcome Variable #4B: Cognitive/psychomotor effects (HVLT)+210 minutes post dose

The cognitive/psychomotor effects of CBD will be assessed using the Hopkins Verbal Learning Test (HVLT). The primary outcome for the HVLT will be immediate and delayed recall, which index verbal memory.

Secondary Outcome Measures
NameTimeMethod
Secondary Outcome Variable #1: Opioid CravingBaseline and +150 minutes post dose

We will measure opioid craving using the short form Heroin Craving Questionnaire (HCQ-14) given to participants before and after a watching a visual probe task used to induce craving.

Trial Locations

Locations (1)

Department of Veterans Affairs Hospital

🇺🇸

West Haven, Connecticut, United States

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