Cannabidiol in Opioid Use Disorder and Chronic Pain

Cannabidiol Pharmacotherapy for Co-occurring Opioid Use Disorder and Chronic Pain

This is a double-blind, randomized, placebo-controlled cross-over human laboratory study with a duration of approximately 3 weeks, during which participants will come to the testing site for a total of five times: one initial screening session, and four experimental sessions where study medication, Cannabidiol (CBD) will be administered, separated by at least 72 hours to limit carryover effects.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain
• Intervention / Treatment: Drug: 400mg Cannabidiol; Drug: 800mg Cannabidiol; Drug: 1200mg Cannabidiol; Drug: Saline

Detailed Description

Twenty two 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 or buprenorphine, will be enrolled. 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 measures including the well-validated Cold Pressor Test (CPT), Quantitative Sensory Testing (QST), the Short-Form McGill Pain Questionnaire (SF-MPQ) 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). 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). 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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Joao De Aquino, M.D.; Phone Number: 2916 203-5711; Email: joao.dequino@yale.edu
• Study Contact Backup: Name: Ellen Mitchell, R.N.; Phone Number: 3012 203-932-5711; Email: ellen.mitchell@yale.edu

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Recruiting
      • Department of Veterans Affairs Hospital
      • Contact: Joao De'Aquino, M.D.; Phone Number: 3012 203-932-5711; Email: joao.dequino@yale.edu
      • Principal Investigator: Joao De Aquino, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 musculoskeletal pain for ≥ 6 months 49
• Capable of providing informed consent in English.
• Compliant in opioid maintenance treatment and on a stable dose for two 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.

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.
• Having received inpatient psychiatric treatment recently (≤ 60 days before enrollment).
• A study physician will determine if participants receiving products containing THC or CBD products may participate in the study.
• Current use benzodiazepines or platelet inhibitors (e.g., clopidogrel, apixaban, ticagrelor).
• Current weight of less of 60 kg.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CBD 400mg; CBD 400 mg	Drug: 400mg Cannabidiol; Participants will receive 400mg; Other Names: CBD
Active Comparator: CBD 800mg	Drug: 800mg Cannabidiol; Participants will receive 800mg; Other Names: CBD
Active Comparator: CBD 1200mg	Drug: 1200mg Cannabidiol; Participants will receive 1200mg; Other Names: CBD
Placebo Comparator: Saline; saline	Drug: Saline; Participants will receive saline; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systematic Assessment for Treatment Emergent Events (SAFTEE)	The safety and tolerability of CBD will be assessed using the SAFTEE	up to 4 weeks
Quantitative Sensory Testing (QST)	Pain will be measured by a comprehensive QST battery	up to 4 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA); VA Connecticut Healthcare System
• Investigators: Principal Investigator: Joao De Aquino, M.D., Yale University

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2021
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): March 30, 2025

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Pain; Neurologic Manifestations; Narcotic-Related Disorders; Chronic Pain; Opioid-Related Disorders; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: JD001; 2000029286 (Other Identifier: Yale HRPP); 1K23DA052682-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No