Recruiting
Early Phase 1

Cannabidiol

Sponsor:

Yale University

Code:

NCT04587791

Conditions

Chronic Pain

Opioid Use Disorder

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

400 mg Cannabidiol

800 mg Cannabidiol

1200 mg Cannabidiol

Beta carotene oral solution without CBD

Study Details

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

Study ID

NCT04587791

Start date

Dec 8, 2021

Status verified date

Apr, 2026

Completion date

Aug 31, 2026

Anticipated

Primary completion date

Aug 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

34 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: CBD 400 mg

CBD 400 mg

active comparator: CBD 800 mg

CBD 800mg

active comparator: CBD 1200 mg

CBD 1200 mg

placebo comparator: Beta carotene oral solution

Beta carotene oral solution without CBD

Interventions

400 mg Cannabidiol

Participants will receive 400 mg CBD

800 mg Cannabidiol

Participants will receive 800 mg CBD

1200 mg Cannabidiol

Participants will receive 1200 mg CBD

Beta carotene oral solution without CBD

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

Primary outcome measure

  • 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 ]
  • 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) ]
  • Cognitive effects of CBD measured by the Hopkins Verbal Learning Test (HVLT) [ Time Frame: +210 minutes after the administration of CBD ]
  • Cognitive/psychomotor effects of CBD measured by the Continuous Performance Test (CPT) [ Time Frame: +210 minutes after the administration of CBD ]

Central Contacts and Locations

Central contacts

Joao De Aquino, M.D.

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

Julia Meyerovich, M.S.

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

Locations

Department of Veterans Affairs Hospital

Recruiting

West Haven, Connecticut, United States, 06516

Contacts

Joao De Aquino, M.D.

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

Principal Investigator:

Joao De Aquino, M.D.

More Information

Sponsor

Yale University

Last update posted

Apr 14, 2026

Last verified

Apr, 2026

Keywords

  • Methadone
  • Buprenorphine
  • Cannabidiol
  • Pain

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Yale University on 2026-04-14.