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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
Participants will receive 400mg
Participants will receive 800mg
Participants will receive 1200mg
Department of Veterans Affairs Hospital
West Haven, Connecticut, United States
RECRUITINGPrimary Outcome Variable #1: Safety and tolerability of CBD
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.
Time frame: Baseline and up to 6 hours
Primary Outcome Variable #2: Pain Sensitivity
We will measure pain sensitivity using a comprehensive QST battery at baseline and approximately hourly for 6 hours.
Time frame: Baseline and up to 6 hours
Primary Outcome Variable #3: Abuse potential of CBD (DEQ)
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".
Time frame: Baseline and up to 6 hours
Primary Outcome Variable #4A: Cognitive/psychomotor effects (CPT)
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).
Time frame: +210 minutes post dose
Primary Outcome Variable #4B: Cognitive/psychomotor effects (HVLT)
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.
Time frame: +210 minutes post dose
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Participants will receive saline
Secondary Outcome Variable #1: Opioid Craving
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.
Time frame: Baseline and +150 minutes post dose