Cannabidiol in Opioid Use Disorder and Chronic Pain

NCT04587791 | Recruiting Early Phase 1 DMC FDA Drug

• 3 other identifiers: JD00120000292861K23DA052682-01
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Chronic Pain; Opioid Use Disorder

Keywords

Methadone; Buprenorphine; Cannabidiol; Pain

Outcome Measures

Primary Outcomes (4)

• 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.

  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".

  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).

  +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).

  +210 minutes after the administration of CBD

Secondary Outcomes (8)

• 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)

Other Outcomes (1)

• Influence of sex

  Up to 6 hours

Study Arms (4)

CBD 400 mg

ACTIVE COMPARATOR

CBD 400 mg

Drug: 400 mg Cannabidiol

CBD 800 mg

ACTIVE COMPARATOR

CBD 800mg

Drug: 800 mg Cannabidiol

CBD 1200 mg

ACTIVE COMPARATOR

CBD 1200 mg

Drug: 1200 mg Cannabidiol

Beta carotene oral solution

PLACEBO COMPARATOR

Beta carotene oral solution without CBD

Drug: Beta carotene oral solution without CBD

Interventions

Beta carotene oral solution without CBD DRUG

Participants will receive beta carotene oral solution without CBD (placebo)

Also known as: Placebo

Beta carotene oral solution

400 mg Cannabidiol DRUG

Participants will receive 400 mg CBD

Also known as: CBD, Epidiolex

CBD 400 mg

800 mg Cannabidiol DRUG

Participants will receive 800 mg CBD

Also known as: CBD, Epidiolex

CBD 800 mg

1200 mg Cannabidiol DRUG

Participants will receive 1200 mg CBD

Also known as: CBD, Epidiolex

CBD 1200 mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• VA Connecticut Healthcare System: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Department of Veterans Affairs Hospital

West Haven, Connecticut, 06516, United States

RECRUITING

MeSH Terms

Conditions

Chronic Pain; Opioid-Related Disorders; Pain

Interventions

Cannabidiol; beta Carotene

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Pigments, Biological; Biological Factors

Study Officials

• Joao De Aquino, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joao De Aquino, M.D.

CONTACT

203-932-5711; joao.deaquinolima@yale.edu

Julia Meyerovich, M.S.

CONTACT

203-932-5711; julia.meyerovich@yale.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants will receive CBD (400 mg, 800 mg, 1200 mg) or placebo.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Model Details: Participants will receive CBD (400 mg, 800 mg, 1200 mg) or placebo.

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 14, 2020
• Study Start: December 8, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

US (1)