Back to resultsSafety and Tolerability of Cannabidiol Among Persons With Opioid Use Disorder Receiving Methadone or Buprenorphine
Primary Purpose
Addiction
Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
CBD Day 1
CBD Day 2
CBD Day 3
Sponsored by
About this trial
This is an interventional treatment trial for Addiction
Eligibility Criteria
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.
Sites / Locations
- Veteran Affairs HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
CBD 400mg
CBD 800mg
CBD 1200mg
Arm Description
CBD 400mg
CBD 800mg
CBD 1200mg
Outcomes
Primary Outcome Measures
Agitation Calmness Evaluation Scale (ACES)
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.
Mini Mental Status Examination (MMSE)
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.
Systematic Assessment of Side Effects (SAFTEE)
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
Quantitative Sensory Testing (QST)
Pain will be assessed using a comprehensive QST battery
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05076370
Brief Title
Safety and Tolerability of Cannabidiol Among Persons With Opioid Use Disorder Receiving Methadone or Buprenorphine
Official Title
Cannabidiol Pharmacotherapy for Comorbid Opioid Addiction and Chronic Pain
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 8, 2021 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
October 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Addiction
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
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)
Allocation
Non-Randomized
Enrollment
6 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CBD 400mg
Arm Type
Active Comparator
Arm Description
CBD 400mg
Arm Title
CBD 800mg
Arm Type
Active Comparator
Arm Description
CBD 800mg
Arm Title
CBD 1200mg
Arm Type
Active Comparator
Arm Description
CBD 1200mg
Intervention Type
Drug
Intervention Name(s)
CBD Day 1
Intervention Description
CBD 400mg
Intervention Type
Drug
Intervention Name(s)
CBD Day 2
Intervention Description
CBD 800mg
Intervention Type
Drug
Intervention Name(s)
CBD Day 3
Intervention Description
CBD 1200mg
Primary Outcome Measure Information:
Title
Agitation Calmness Evaluation Scale (ACES)
Description
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.
Time Frame
8 hours
Title
Mini Mental Status Examination (MMSE)
Description
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.
Time Frame
8 hours
Title
Systematic Assessment of Side Effects (SAFTEE)
Description
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".
Time Frame
8 hours
Secondary Outcome Measure Information:
Title
Quantitative Sensory Testing (QST)
Description
Pain will be assessed using a comprehensive QST battery
Time Frame
8 hours
Other Pre-specified Outcome Measures:
Title
The Heroin Craving Questionnaire - Short Form 14 (HCQ-SF-14)
Description
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).
Time Frame
8 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joao De Aquino, M.D.
Phone
203-932-5711
Ext
2916
Email
Joao.deaquino@yale.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Mehmet Sofuoglu, M.D.,Ph.D.
Phone
203-932-5711
Ext
4809
Email
mehmet.sofuoglu@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joao De Aquino, M.D.
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Veteran Affairs Hospital
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brendan Sullivan
Phone
203-932-5711
Ext
3350
Email
brendan.sullivan@va.gov
First Name & Middle Initial & Last Name & Degree
Joao De Aquino, M.D.
12. IPD Sharing Statement
Learn more about this trial
Safety and Tolerability of Cannabidiol Among Persons With Opioid Use Disorder Receiving Methadone or Buprenorphine
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