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Cannabidiol on Reward- and Stress-related Neurocognitive Processes in Individuals With Opioid Use Disorder

Primary Purpose

Opioid-use Disorder

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cannabidiol 100 MG/ML [Epidiolex]
Placebo
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid-use Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • English speaking
  • DSM5 diagnosis of opioid use disorder
  • Receiving buprenorphine or methadone for treatment of opioid use disorder
  • Agreeable to abstaining from using any cannabis or CBD products for the duration of the trial.

Exclusion Criteria:

  • Any self-reported use of cannabis or CBD products in the past 30 days
  • Baseline depression (PHQ9) or anxiety (GAD7) scores of greater than 10
  • Currently pregnant
  • Hepatic liver enzymes greater than 3x upper normal limit
  • Hypersensitivity to cannabinoids or sesame oil (CBD solution comes in sesame oil emulsion)
  • Currently taking any medications with known significant pharmacokinetic interactions with CBD

Sites / Locations

  • Brigham and Women's Hospital
  • Rutland Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cannabidiol 600mg

Placebo

Arm Description

All subjects will receive 600mg of oral cannabidiol in a double-blind fashion. Cannabidiol will be provided using Epidiolex™ oral solution 100mg/mL. Following administration, a battery of tests will be conducted to examine reward- and stress-related neurocognitive processes.

All subjects will receive a matching placebo in a double-blind fashion. Following administration, a battery of tests will be conducted to examine the impact on reward- and stress-related neurocognitive processes.

Outcomes

Primary Outcome Measures

Change in Cue-reactivity
The primary outcomes is cue-induced cravings (Opioid Craving Scale). This was measured with a single 10-point likert scale asking about cravings, where 0 represented lower levels of craving and 10 indicated higher levels of cravings. This was given at 3 different time points, pre-cue, post-neutral, and post-drug images. Cue-induced craving is the difference between drug cue and pre-cue scores.

Secondary Outcome Measures

Delayed Discount
Monetary Choice Questionnaire will be used to calculate impulse decision making. This is a 27-item self-administered questionnaire where participants choose between a smaller, immediate monetary reward and a larger, delayed monetary reward. A participants score is between one of the two endpoints (0.25 or 0.00016). If an individual is more likely to prefer the delayed versus immediate reward, their score is more likely to be closer to the 0.00016 endpoint. Please note the rate of delayed discounting is not the same for each question.
Decision Making
Iowa Gambling Task will be used to assess impulsive decision-making. The larger the number, the more "safer" options were chosen. This is measured by taking the total number of "risky" choices and subtracting it from the "less risky" choices. The lower the number, the more "high risky" options were chosen. If participants chose the less risky option, they received a positive point, if individuals picked the riskier choice, they received a negative point. Negative values indicate a participant chose more riskier decisions than less-risky, whereas positive values indicate participants chose the less riskier decision more often. The lowest score an individual could receive is -100 (very risk) to 100 (least risky).
Attentional Bias
Visual probe task will be used to assess attentional bias to drug-related cues. Opioid-related and neutral images will be used. Each trial will begin with a fixation point lasting 500ms. A pair of images then will appear on the left and right of the screen for either a short (200ms) or long (500ms) stimulus duration to assess automatic orientating and controlled attention processing, respectively. Image pairs will be replaced by a probe in the location of either the opioid-related or neutral image. The probe will remain until the participant responds to identify the probe orientation by pressing the response keys as quickly as possible. Attentional bias is calculated as the difference in reaction time (RT) between when the probe replaced the neutral compared with the opioid-related images (i.e. RTneutral - RTopioid). Therefore the more positive the number, the less attentional bias toward drug cue, and a negative number represents more attentional bias toward the drug cue.
Stress-reactivity
Physiologic and subjective stress will be assessed. Stress-reactivity was measured by participants mirror tracing an image on a compute screen where a loud beeping noise would occur if a participant took too long or went outside the lines. It's measured in ms and the longer someone stayed on the task, the better ability they have to react stress.
Stress-Reactivity (Physiological)
For this outcome, participants received a salivary cortisol test prior to, immediately after, and 20 minutes after the cue-reactivity paradigm. Lower levels indicate lower levels of salivary cortisol in the sample.

Full Information

First Posted
June 19, 2021
Last Updated
September 14, 2023
Sponsor
Brigham and Women's Hospital
Collaborators
Harvard Medical School (HMS and HSDM)
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1. Study Identification

Unique Protocol Identification Number
NCT04982029
Brief Title
Cannabidiol on Reward- and Stress-related Neurocognitive Processes in Individuals With Opioid Use Disorder
Official Title
Cannabidiol on reward-and Stress-related Neurocognitive Processes in Individuals With Opioid Use Disorder: A Double-blind, Placebo-controlled, Cross-over Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
April 14, 2022 (Actual)
Primary Completion Date
December 2, 2022 (Actual)
Study Completion Date
December 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Harvard Medical School (HMS and HSDM)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine the impact of cannabidiol on reward- and stress-related neurocognitive processes among individuals with opioid use disorder on buprenorphine or methadone treatment.
Detailed Description
Individuals with opioid use disorder (OUD) demonstrate reward- and stress-related neurocognitive changes compared to individuals without OUD, including cravings for opioids in response to exposure to triggers, tendency to make impulsive and disadvantageous decisions, and a strong attentional bias towards drug-related cues. Together, these deficits are significant contributors to relapse and discontinuation of treatment. Cannabidiol (CBD) has been shown to impact some of these cognitive deficits but studies of CBD among individuals with OUD are mostly lacking. Therefore, this study aims to answer whether CBD has any impact on reward-related neurocognitive deficits in individuals with OUD. If successful, this line of research will lay the groundwork for future studies to evaluate CBD's impact on OUD treatment outcomes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid-use Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
The study is a double-blind, placebo-controlled, cross-over trial.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
This is a double-blind cross-over trial, in which the research staff and participants will be blinded.
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cannabidiol 600mg
Arm Type
Experimental
Arm Description
All subjects will receive 600mg of oral cannabidiol in a double-blind fashion. Cannabidiol will be provided using Epidiolex™ oral solution 100mg/mL. Following administration, a battery of tests will be conducted to examine reward- and stress-related neurocognitive processes.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
All subjects will receive a matching placebo in a double-blind fashion. Following administration, a battery of tests will be conducted to examine the impact on reward- and stress-related neurocognitive processes.
Intervention Type
Drug
Intervention Name(s)
Cannabidiol 100 MG/ML [Epidiolex]
Intervention Description
600mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Primary Outcome Measure Information:
Title
Change in Cue-reactivity
Description
The primary outcomes is cue-induced cravings (Opioid Craving Scale). This was measured with a single 10-point likert scale asking about cravings, where 0 represented lower levels of craving and 10 indicated higher levels of cravings. This was given at 3 different time points, pre-cue, post-neutral, and post-drug images. Cue-induced craving is the difference between drug cue and pre-cue scores.
Time Frame
Visit 2 and 3 (at least 1 week apart)
Secondary Outcome Measure Information:
Title
Delayed Discount
Description
Monetary Choice Questionnaire will be used to calculate impulse decision making. This is a 27-item self-administered questionnaire where participants choose between a smaller, immediate monetary reward and a larger, delayed monetary reward. A participants score is between one of the two endpoints (0.25 or 0.00016). If an individual is more likely to prefer the delayed versus immediate reward, their score is more likely to be closer to the 0.00016 endpoint. Please note the rate of delayed discounting is not the same for each question.
Time Frame
Visit 2 and 3 (at least 1 week apart)
Title
Decision Making
Description
Iowa Gambling Task will be used to assess impulsive decision-making. The larger the number, the more "safer" options were chosen. This is measured by taking the total number of "risky" choices and subtracting it from the "less risky" choices. The lower the number, the more "high risky" options were chosen. If participants chose the less risky option, they received a positive point, if individuals picked the riskier choice, they received a negative point. Negative values indicate a participant chose more riskier decisions than less-risky, whereas positive values indicate participants chose the less riskier decision more often. The lowest score an individual could receive is -100 (very risk) to 100 (least risky).
Time Frame
Visit 2 and 3 (at least 1 week apart)
Title
Attentional Bias
Description
Visual probe task will be used to assess attentional bias to drug-related cues. Opioid-related and neutral images will be used. Each trial will begin with a fixation point lasting 500ms. A pair of images then will appear on the left and right of the screen for either a short (200ms) or long (500ms) stimulus duration to assess automatic orientating and controlled attention processing, respectively. Image pairs will be replaced by a probe in the location of either the opioid-related or neutral image. The probe will remain until the participant responds to identify the probe orientation by pressing the response keys as quickly as possible. Attentional bias is calculated as the difference in reaction time (RT) between when the probe replaced the neutral compared with the opioid-related images (i.e. RTneutral - RTopioid). Therefore the more positive the number, the less attentional bias toward drug cue, and a negative number represents more attentional bias toward the drug cue.
Time Frame
Visit 2 and 3 (at least 1 week apart)
Title
Stress-reactivity
Description
Physiologic and subjective stress will be assessed. Stress-reactivity was measured by participants mirror tracing an image on a compute screen where a loud beeping noise would occur if a participant took too long or went outside the lines. It's measured in ms and the longer someone stayed on the task, the better ability they have to react stress.
Time Frame
Visit 2 and 3 (at least 1 week apart)
Title
Stress-Reactivity (Physiological)
Description
For this outcome, participants received a salivary cortisol test prior to, immediately after, and 20 minutes after the cue-reactivity paradigm. Lower levels indicate lower levels of salivary cortisol in the sample.
Time Frame
Visit 2 and 3 (at least 1 week apart)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria English speaking DSM5 diagnosis of opioid use disorder Receiving buprenorphine or methadone for treatment of opioid use disorder Agreeable to abstaining from using any cannabis or CBD products for the duration of the trial. Exclusion Criteria: Any self-reported use of cannabis or CBD products in the past 30 days Baseline depression (PHQ9) or anxiety (GAD7) scores of greater than 10 Currently pregnant Hepatic liver enzymes greater than 3x upper normal limit Hypersensitivity to cannabinoids or sesame oil (CBD solution comes in sesame oil emulsion) Currently taking any medications with known significant pharmacokinetic interactions with CBD
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Rutland Medical Center
City
Rutland
State/Province
Vermont
ZIP/Postal Code
05701
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Cannabidiol on Reward- and Stress-related Neurocognitive Processes in Individuals With Opioid Use Disorder

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