Cannabidiol Pharmacotherapy for Co-occurring Opioid Use Disorder and Chronic Pain
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Abuse potential of CBD measured by the Drug Effects Questionnaire (DEQ)
研究概览
简要总结
This is a randomized, placebo-controlled, crossover human laboratory study investigating the dose-dependent safety and acute effects of Cannabidiol (CBD) on measures of pain and opioid craving in outpatients with opioid use disorder (OUD) receiving medication-assisted treatment with methadone or buprenorphine. With a duration of approximately 4 weeks, participants will come to the testing site for a total of five times: one initial screening session, and four experimental sessions where study medication, CBD, will be administered, separated by at least 72 hours to limit carryover effects.
详细描述
Thirty-four 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. Across four test sessions, 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 measured using 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). Subjective opioid withdrawal symptoms will be assessed using the Subjective Opiate Withdrawal Scale (SOWS). 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Participants will receive CBD (400 mg, 800 mg, 1200 mg) or placebo.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 pain for ≥ 6 months.
- •Capable of providing informed consent in English.
- •Compliant in opioid maintenance treatment and on a stable dose for four 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. Acceptable contraception for females includes oral contraceptives, contraceptive depot injections, contraceptive subdermal implants, intrauterine devices, or surgical contraception methods. Acceptable contraception for males includes condoms or surgical contraception methods.
排除标准
- •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.
- •Methadone dose under 30 mg or over 150 mg/day.
- •Buprenorphine dose over 24 mg per day.
- •Having received inpatient psychiatric treatment recently (≤ 60 days before enrollment).
- •Candidates receiving products containing either THC or CBD will be excluded. All participants will be asked to abstain from cannabinoids. Prior to receiving the study medication on the first test session, participants' cannabinoid use will be assessed using a quantitative point-of-care urine 11-nor-9-carboxy-THC concentration test with a cut-off of ≤ 50 mg/mL. If a participant tests greater than ≤50 mg/mL, they will be asked to abstain for an additional 7 to 14 days. If 14 days after their initial THC concentration test the participant continues to test positive, they will not be allowed to participate in the study.
- •A physician will carefully evaluate participants for use of over-the-counter or prescription psychoactive drugs known to affect pain threshold or pain tolerance (including NSAIDS, serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g. venlafaxine, duloxetine), gabapentinoids, tricyclic antidepressants (e.g., nortriptyline, amitriptyline), anticonvulsant medications (e.g., topiramate, carbamazepine)). Only participants who are on stable doses (i.e., consistent daily administration of the medication for at least three months at the same dose following the last dose change, either increase or decrease) of these medications, and whose dosing schedules allow participation in the study visits, thus excluding instances of single-dose or temporary dosing of the medication, will be eligible as determined by principal investigator. If possible, the morning dose will be administered after the study visit.
- •Current, regular use of benzodiazepines, other prescription opioids, or platelet inhibitors (e.g., clopidogrel, apixaban, ticagrelor).
- •Current weight of less of 60 kg.
- •Allergy to sesame seed oil, which is an ingredient of the CBD formulation used.
- •Serious medical or neurological illness or treatment for a medical disorder that could interfere with study participation as determined by principal investigator.
- •Participants who have elevation of liver enzymes (ALT and/or AST) 2x above the normal limit or higher.
- •Contraindications for exposure to cold temperatures, such as Raynaud's phenomenon and hypertension.
研究组 & 干预措施
CBD 800 mg
CBD 800mg
干预措施: 800 mg Cannabidiol (Drug)
CBD 1200 mg
CBD 1200 mg
干预措施: 1200 mg Cannabidiol (Drug)
Beta carotene oral solution
Beta carotene oral solution without CBD
干预措施: Beta carotene oral solution without CBD (Drug)
CBD 400 mg
CBD 400 mg
干预措施: 400 mg Cannabidiol (Drug)
结局指标
主要结局
Abuse potential of CBD measured by the Drug Effects Questionnaire (DEQ)
时间窗: Baseline (30 minutes before the administration of CBD), and every 30 minutes after the administration of CBD (up to +240 minutes)
The DEQ will be administered to assess the abuse potential of CBD. The DEQ is a 10-item questionnaire used to assess the subjective effects of psychoactive drugs. Each item is a visual analogue scale (VAS) ranging from 0-100. The questionnaire is used to measure whether a subject feels the drug "feels high", likes or dislikes the effects, and whether they want more of the drug. The primary DEQ outcome will be the Stimulatory Effects subscale, obtained by averaging participants responses to the items: "Feel High"; "Feel Stimulated"; and "Feel the Drug Strength".
Cognitive effects of CBD measured by the Hopkins Verbal Learning Test (HVLT)
时间窗: +210 minutes after the administration of CBD
The HVLT will be used to assess the cognitive effects of CBD. The primary outcomes will be immediate and delayed recall, which index verbal memory. The HVLT consists of a 12-item word list, composed of four words from each of the three semantic categories. The participant is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The participants' free recall of the list is recorded. The same procedure is repeated for two more trials (immediate recall). After approximately 15 minutes the participant will be asked to recall as many words from the list as they can without the list being re-read to them (delayed recall).
Cognitive/psychomotor effects of CBD measured by the Continuous Performance Test (CPT)
时间窗: +210 minutes after the administration of CBD
The cognitive/psychomotor effects of CBD will be assessed using the Continuous Performance Test (CPT). CPT is a computerized neuropsychological assessment that measures participants sustained and selective attention. 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).
Safety and tolerability of CBD measured by the Systematic Assessment for Treatment Emergent Effects (SAFTEE)
时间窗: Baseline (30 minutes before the administration of CBD) and +240 minutes after the administration of CBD
The SAFTEE is a multi-symptom checklist that has been used successfully in the investigators previous studies to assess and monitor any adverse events and possible side effects of study medications. It includes information regarding the severity of any presenting symptoms (0= none, 1= mild, 2= moderate, and 3= severe), as well as the course of action taken by the study staff in response. The SAFTEE is administered before the administration of CBD at baseline, (timepoint -30 minutes) and 4 hours after the administration of CBD (timepoint +240 minutes) during each test session. Data will be presented as the number of participants that reported symptoms on the SAFTEE.
次要结局
- Pain sensitivity measured by Quantitative Sensory Testing (QST) Pain threshold and tolerance(Baseline (30 minutes before the administration of CBD), +120 minutes and +240 minutes after the administration of CBD.)
- Pain sensitivity measured by change in Quantitative Sensory Testing (QST) Conditioned Pain Modulation (CPM)(Baseline (30 minutes before the administration of CBD), +120 minutes and +240 minutes after the administration of CBD.)
- Pain sensitivity measured by Quantitative Sensory Testing (QST) Temporal Summation of Pain (TSP)(Baseline (30 minutes before the administration of CBD), +120 minutes and +240 minutes after the administration of CBD.)
- Response to Quantitative Sensory Testing (QST) battery measured by Pain Visual Analog Scale (VAS)(Baseline (30 minutes before the administration of CBD), +120 minutes and +240 minutes after the administration of CBD.)
- Pain Catastrophizing measured by the Pain Catastrophizing Scale (PCS)(Baseline (30 minutes before the administration of CBD))
- Opioid craving measured by change in the Heroin Craving Questionnaire - Short Form 14 (HCQ-SF-14)(Average difference of scores from before cue-induced craving video (+150 minutes) and after cue-induced craving video (+155 minutes))
- Opioid craving measured by the Subjective Opiate Withdrawal Scale (SOWS)(Baseline (30 minutes before the administration of CBD), +30 minutes, +90 minutes, +150 minutes, +210 minutes, and +240 minutes after the administration of CBD)
- Negative affect measured by the Positive and Negative Affect Schedule (PANAS)(Baseline (30 minutes before the administration of CBD), and every 30 minutes after the administration of CBD (up to +240 minutes))
研究者
Joao De Aquino
Assistant Professor of Psychiatry
Yale University