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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Cannabidiol on reward-and Stress-related Neurocognitive Processes in Individuals With Opioid Use Disorder: A Double-blind, Placebo-controlled, Cross-over Trial

Conditions
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Opioid-use Disorder

Intervention / Treatment
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* Drug: Cannabidiol 100 MG/ML [Epidiolex]
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study is a double-blind, placebo-controlled, cross-over trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol 600mg<br>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. | Drug: Cannabidiol 100 MG/ML [Epidiolex]<br>* 600mg<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Visit 2 and 3 (at least 1 week apart) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Visit 2 and 3 (at least 1 week apart) | 
| 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). | Visit 2 and 3 (at least 1 week apart) | 
| 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. | Visit 2 and 3 (at least 1 week apart) | 
| 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. | Visit 2 and 3 (at least 1 week apart) | 
| 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. | Visit 2 and 3 (at least 1 week apart) |