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).

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.

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.

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.

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.

Cannabidiol 100 MG/ML [Epidiolex]: 600mg

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.

Placebo: Matching placebo

In this arm, participants received placebo first and CBD second.

In this condition, participants only completed the baseline visit and were lost to follow-up prior to randomization. Therefore, only baseline characteristics are reported for these individuals.

Total of all reporting groups

The Patient Health Questionnaire (PHQ-9) is a questionnaire that quantifies depressive levels in participants. The PHQ-9 provides an assessment of depression severity. The minimum value is 0 and the maximum value is 27. Lower scores indicated lower levels of depression. The reliability, validity, and clinical utility of the PHQ-9 instrument are well-established.

The Generalized Anxiety Disorder 7 or the GAD7 is a questionnaire that measures anxiety in patients. It categorizes scores into mild, moderate and severe on a scale of 0-21, where lower scores represent more milder anxiety and higher scores more severe. Each individual question is a 4-point scale ranging 0 (none of the days) to 3 (almost all of the days).

The Brief Pain Inventory or BPI assesses severity of pain and impact on daily functioning. Higher BPI scores mean greater severity and impact on functioning and lower scores mean less severity and impact on functioning. Questions are on a scale of 0-10 and final scores are averages of questions.

The Timeline Follow Back measures how many days in a specified amount of time, an individual has used an illicit substance. At Baseline, we asked individuals about the past 30 days. The data is noted in average days the substance was consumed.

The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale used to help determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. This tool can be used in both inpatient and outpatient settings. This scale has 11 questions with potential scores ranging from 0-48. Lower scores represent less severe opiate withdrawal symptoms and higher scores represent more severe symptoms.

The Positive and Negative Affect Schedule (PANAS) measures positive and negative affect in participants in how they engage with their every day life. This scale consists of 20 questions, 10 measure positive affect and 10 measure negative. Each runs on a scale from 10 to 50. Higher scores indicate higher levels of positive/negative effect and lower scores indicate lower levels.

The Opioid Craving scale is based off the validated craving scale by McHugh and colleagues (2021). Answers are on a 10-point scale where 0 represents lower symptoms of opioid cravings and 10 represents high symptoms of opioid cravings.

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.

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).

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.

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.

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.

Participants will receive a matched placebo the opposite visit they received CBD. Following administration, a battery of tests will be conducted to examine reward- and stress-related neurocognitive processes.

This arm represents the visits all participants received placebo.