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Safety and Tolerability of Cannabidiol Among Persons With Opioid Use Disorder Receiving Methadone or Buprenorphine

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ClinicalTrials.gov Identifier: NCT05076370
Recruitment Status : Recruiting
First Posted : October 13, 2021
Last Update Posted : October 17, 2022
Information provided by (Responsible Party):
Joao De Aquino, Yale University

Brief Summary:
The overarching goal of this study is to evaluate the potential of Cannabidiol (CBD) as an adjunctive treatment for comorbid opioid use disorder (OUD) and chronic pain. This is a randomized, placebo-controlled, crossover human laboratory study investigating the dose-dependent safety and acute effects of CBD on measures of pain and opioid craving in outpatients with OUD receiving medication-assisted treatment (MAT) with methadone or buprenorphine.

Condition or disease Intervention/treatment Phase
Addiction Drug: CBD Day 1 Drug: CBD Day 2 Drug: CBD Day 3 Early Phase 1

Detailed Description:
An initial safety pilot phase will recruit six participants: three receiving treatment with methadone and three receiving treatment with buprenorphine. If the results of the pilot study support the safety of CBD administration in this clinical sample, the general study will recruit 48 participants with comorbid OUD and chronic pain, for a total of 24 completers - 12 subjects (6 men and 6 women) receiving methadone and 12 subjects (6 men and 6 women) receiving buprenorphine. Both sub-studies will enroll participants who do not currently require an inpatient hospitalization.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Initial safety pilot phase of 6 participants,(3 methadone and 3 on Buprenorphine) The general study is a randomized, placebo-controlled, crossover human laboratory study investigating the dose-dependent safety and acute effects of CBD on measures of pain and opioid craving in outpatients with OUD receiving medication-assisted treatment (MAT) with methadone or buprenorphine.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cannabidiol Pharmacotherapy for Comorbid Opioid Addiction and Chronic Pain
Actual Study Start Date : December 8, 2021
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : July 30, 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: CBD 400mg
CBD 400mg
Drug: CBD Day 1
CBD 400mg

Active Comparator: CBD 800mg
CBD 800mg
Drug: CBD Day 2
CBD 800mg

Active Comparator: CBD 1200mg
CBD 1200mg
Drug: CBD Day 3
CBD 1200mg

Primary Outcome Measures :
  1. Agitation Calmness Evaluation Scale (ACES) [ Time Frame: 8 hours ]
    The ACES consists of a single item that rates overall agitation and sedation of the participant at the time of evaluation, where 1 indicates marked agitation; 2: moderate agitation; 3: mild agitation; 4: normal behavior; 5: mild calmness; 6: moderate calmness; 7: marked calmness; 8: deep sleep; and 9: unarousable. Clinically significant sedation was a priori defined as an ACES score of 7 (marked calmness) or higher at any point during the session.

  2. Mini Mental Status Examination (MMSE) [ Time Frame: 8 hours ]
    The MMSE is a 30-point scale that measures five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The MMSE is used extensively in clinical and research settings to measure cognitive impairment. A score of 23 or lower is indicative of cognitive impairment.

  3. Systematic Assessment of Side Effects (SAFTEE) [ Time Frame: 8 hours ]
    The SAFTEE is a multi-symptom checklist that has been used successfully in our 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 was administered before the administration of CBD at baseline, (timepoint -30 minutes) and 4.5 hours after the administration of CBD (timepoint +240 minutes) during each test session. We did not observe evidence of "confusion", "fatigue", "inability to respond to things", "slowed thinking", "dizziness/lightheadedness", "weakness", "slowed movements", or "lack of coordination".

Secondary Outcome Measures :
  1. Quantitative Sensory Testing (QST) [ Time Frame: 8 hours ]
    Pain will be assessed using a comprehensive QST battery

Other Outcome Measures:
  1. The Heroin Craving Questionnaire - Short Form 14 (HCQ-SF-14) [ Time Frame: 8 hours ]
    The HCQ-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).

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 49.
  • 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 60mg or over 100mg
  • Buprenorphine over 24mg.
  • Having received inpatient psychiatric treatment recently (≤ 60 days before enrollment).
  • Candidates receiving products containing either THC or CBD will be excluded.
  • Current use regular use other prescription opioids, gabapentinoids (pregabalin, gabapentin), antidepressants (SSRIs, SNRIs, TCAs), benzodiazepines, platelet inhibitors (e.g., clopidogrel, apixaban, ticagrelor), or NSAIDs.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05076370

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Contact: Joao De Aquino, M.D. 203-932-5711 ext 2916 Joao.deaquino@yale.edu
Contact: Mehmet Sofuoglu, M.D.,Ph.D. 203-932-5711 ext 4809 mehmet.sofuoglu@yale.edu

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United States, Connecticut
Veteran Affairs Hospital Recruiting
West Haven, Connecticut, United States, 06516
Contact: Brendan Sullivan    203-932-5711 ext 3350    brendan.sullivan@va.gov   
Principal Investigator: Joao De Aquino, M.D.         
Sponsors and Collaborators
Yale University
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Principal Investigator: Joao De Aquino, M.D. Yale University
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Responsible Party: Joao De Aquino, Principal Investigator, Yale University
ClinicalTrials.gov Identifier: NCT05076370    
Other Study ID Numbers: 2000029286
First Posted: October 13, 2021    Key Record Dates
Last Update Posted: October 17, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Behavior, Addictive
Compulsive Behavior
Impulsive Behavior