NCT04587791 · Yale University
Cannabidiol in Opioid Use Disorder and Chronic Pain
What this study is about
This is a randomly assigned, compared against an inactive treatment, 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.
View original scientific description
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.
Interventions
DRUG
400 mg Cannabidiol
Participants will receive 400 mg CBD
DRUG
800 mg Cannabidiol
Participants will receive 800 mg CBD
DRUG
1200 mg Cannabidiol
Participants will receive 1200 mg CBD
DRUG
Beta carotene oral solution without CBD
Participants will receive beta carotene oral solution without CBD (placebo)
Primary outcome measures
Safety and tolerability of CBD measured by the Systematic Assessment for Treatment Emergent Effects (SAFTEE)
Time frame: 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.
Abuse potential of CBD measured by the Drug Effects Questionnaire (DEQ)
Time frame: 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)
Time frame: +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)
Time frame: +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).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 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.
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.
- 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.
Where
- West Haven, Connecticut
Collaborators
VA Connecticut Healthcare System, National Institute on Drug Abuse (NIDA)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 14, 2026 · Source of record for eligibility and locations