Chronic PainEarly Phase 1NCT07886606
Cannabidiol in Opioid Use Disorder and Chronic Pain With Buprenorphine
A Early Phase 1 study testing 400 mg Cannabidiol, 800 mg Cannabidiol and 1200 mg Cannabidiol in people with Chronic Pain and Opioid Use Disorder, run by Yale University at 1 site in United States.
Trial summary
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 buprenorphine. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Pain, Opioid Use Disorder
- What is being tested?
- 400 mg Cannabidiol, 800 mg Cannabidiol and 1200 mg Cannabidiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Dec 2021to 31 Dec 2027
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females, Veterans and non-Veterans, aged between 18 and 70 years old.
- Diagnosed with OUD and currently enrolled in 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.
Who cannot join
- 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.
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Department of Veterans Affairs Hospital
West Haven, Connecticut, 06516
Joao De Aquino, M.D., 203-932-5711 ext. 12916, joao.deaquinolima@yale.edu
Joao De Aquino, M.D.
About this study
Official title: Cannabidiol Pharmacotherapy for Co-occurring Opioid Use Disorder and Chronic Pain
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 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.
Read the detailed description
Participants with comorbid opioid use disorder (OUD) and non-cancer chronic pain for at least 6 months, currently receiving buprenorphine will be enrolled. Across four test sessions, prior to their daily 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.
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.
- Conditions
- Chronic Pain, Opioid Use Disorder
- Being tested
- 400 mg Cannabidiol, 800 mg Cannabidiol, 1200 mg Cannabidiol, Beta carotene oral solution without CBD
- Keywords
- Buprenorphine, Cannabidiol, Pain
- Medical subject headings
- Chronic Pain, Opioid-Related Disorders, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
400 mg CannabidiolDrug
Also called CBD, Epidiolex
Participants will receive 400 mg CBD
800 mg CannabidiolDrug
Also called CBD, Epidiolex
Participants will receive 800 mg CBD
1200 mg CannabidiolDrug
Also called CBD, Epidiolex
Participants will receive 1200 mg CBD
Beta carotene oral solution without CBDDrug
Also called Placebo
Participants will receive beta carotene oral solution without CBD (placebo)
| Study group | Role | What they receive |
|---|---|---|
| CBD 400 mg | Active comparator | CBD 400 mg Receives: Drug: 400 mg Cannabidiol |
| CBD 800 mg | Active comparator | CBD 800mg Receives: Drug: 800 mg Cannabidiol |
| CBD 1200 mg | Active comparator | CBD 1200 mg Receives: Drug: 1200 mg Cannabidiol |
| Beta carotene oral solution | Placebo comparator | Beta carotene oral solution without CBD Receives: Drug: Beta carotene oral solution without CBD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of CBD measured by the Systematic Assessment for Treatment Emergent Effects (SAFTEE)
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.
Measured: Baseline (30 minutes before the administration of CBD) and +240 minutes after the administration of CBD
Abuse potential of CBD measured by the Drug Effects Questionnaire (DEQ)
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".
Measured: Baseline (30 minutes before the administration of CBD), and every 30 minutes after the administration of CBD (up to +240 minutes)
Cognitive effects of CBD measured by the Hopkins Verbal Learning Test (HVLT)
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).
Measured: +210 minutes after the administration of CBD
Cognitive/psychomotor effects of CBD measured by the Continuous Performance Test (CPT)
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).
Measured: +210 minutes after the administration of CBD
Secondary outcomes (8)
Pain sensitivity measured by Quantitative Sensory Testing (QST) Pain threshold and tolerance
Pain threshold and tolerance will be assessed using a comprehensive QST battery. This is a reliable, dynamic, and computerized method of quantifying distinct mechanisms of the pain experience. QST measures are sensitive to the effects of cannabinoids, important biomarkers of chronic pain, and predictors of the pain treatment response. Threshold: the temperature the participant first begins to feel pain (average pain threshold). Tolerance: the temperature when the participant can no longer tolerate the stimuli. The temperature ranges from 37° Celsius to 50° Celsius. A lower temperature represents a lower pain threshold/tolerance and a higher temperature represents a higher pain threshold/tolerance.
Measured: 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)
CPM indexes top-down pain inhibition, by leveraging the "pain inhibits pain phenomena". In CPM, a test stimulus is rated on a -100 to +100 Numeric Rating Scale (NRS) for pain both alone and during a concurrent conditioning stimulus applied elsewhere on the body. The CPM Score is the difference between these two ratings. CPM score is a Difference (Delta): Pain rating (test stimulus alone) - Pain rating (test stimulus with conditioning stimulus) Interpretation: Higher (more positive) values indicate greater pain inhibition.
Measured: 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)
TSP involves the repeated administration of noxious stimuli, indexing bottom-up pain facilitation. Therefore, TSP measures the increase in pain perception with repeated noxious stimuli, calculated as the area under the curve (AUC) of pain ratings over time during repeated stimulation. Higher TSP scores indicate worse outcomes (greater pain facilitation/central sensitization), while lower TSP scores indicate better outcomes (less pain facilitation/central sensitization). The TSP AUC values represent the cumulative pain experience during repeated stimulation (VAS units*seconds), where larger values reflect greater temporal summation of pain, which is associated with central nervous system sensitization and chronic pain conditions.
Measured: 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)
The pain VAS will be used by participants as a secondary rating scale for pain severity pain testing. This scale ranges from 0 to 100 and contains of a horizontal line, anchored by verbal descriptors of "no pain" and "pain as bad as it could be". Participants will place a vertical line at the point that best indicates their present pain.
Measured: 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)
The PCS is a 13-item self-report scale designed to measure negative thoughts and feelings associated with pain. Each item is rated on a 5-point scale: 0 (Not at all) to 4 (all the time). Total scores range from 0 to 52, with higher scores indicating greater catastrophizing. The PCS contains three subscales: magnification (scores ranging from 0-12), rumination (scores ranging from 0-16), and helplessness (scores ranging from 0-24).
Measured: Baseline (30 minutes before the administration of CBD)
Opioid craving measured by change in the Heroin Craving Questionnaire - Short Form 14 (HCQ-SF-14)
The HCQ-SF-14 consists of 14 statements about the respondent's feelings and thoughts about using heroin as he or she is completing the questionnaire (i.e., right now). Each of the 14 items is scored on a scale from 1 (Strongly Disagree) to 7 (Strongly Agree). The HCQ-SF-14 score is obtained by adding the scores of all 14 statements and dividing the total by 14. Higher scores on the HCQ-SF-14 indicate a stronger craving for heroin. The HCQ-14 was administered before (+150 minutes) and after (+155 minutes) participants watched a cue-induced craving video. The difference of the two HCQ-14 scores (post - pre) will be used to index cue-elicited craving.
Measured: 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)
The SOWS is a 16-item, participant-administered questionnaire designed to rate the intensity of opioid withdrawal symptoms. It assesses symptoms on a 0-4 scale ("not at all" to "extremely"), with total scores of 1-10 indicating mild, 11-20 moderate, and 21-30 severe withdrawal.
Measured: 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)
The PANAS is a 20-item self-report questionnaire listing adjectives relating to Positive Affect (PA) (e.g., excited, inspired) and Negative Affect (NA) (e.g., distressed, afraid). Items are rated on a Likert scale ranging from 1 "Very slightly or not at all" to 5 "extremely". The PANAS yields separate PA and NA scores, each ranging from 10 to 50. Higher PA scores indicate more positive feelings, while higher NA scores indicate more negative feelings. These scores are used to track emotional states over time. The PANAS will be used to measure the effects of CBD on mood.
Measured: Baseline (30 minutes before the administration of CBD), and every 30 minutes after the administration of CBD (up to +240 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2026
- Study start8 Dec 2021
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will receive CBD (400 mg, 800 mg, 1200 mg) or placebo.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Connecticut Healthcare System, National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Joao De Aquino, Yale University
- Investigators
- Joao De Aquino, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07886606
- Sponsor's protocol ID
- JD001_a
- Other IDs
- 2000029286
- Status last verified
- Oct 2026
- First submitted
- 6 Oct 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No