Trial Outcomes & Findings for Cannabidiol on Reward- and Stress-related Neurocognitive Processes in Individuals With Opioid Use Disorder (NCT NCT04982029)
NCT ID: NCT04982029
Last Updated: 2023-10-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
15 participants
Primary outcome timeframe
Visit 2 and 3 (at least 1 week apart)
Results posted on
2023-10-05
Participant Flow
This study took place from April 2022 - December 2022 at Brigham and Women's Hospital in Boston and Rutland Medical Clinic in Rutland VT. Participants were recruited through clinics and patient registries.
Participant milestones
| Measure |
Cannabidiol 600mg First, Placebo Second
In this condition, 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
In their second intervention visit, participants will receive a matched placebo. Following administration, a battery of tests will be conducted to examine reward- and stress-related neurocognitive processes.
This group received CBD first and placebo second.
|
Placebo First, Cannabidiol 600mg Second
Participants in this condition will receive a matched placebo in their first visit. Following administration, a battery of tests will be conducted to examine reward- and stress-related neurocognitive processes.
In their second intervention visit, 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
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
8
|
|
Overall Study
Baseline
|
7
|
8
|
|
Overall Study
First Intervention
|
5
|
5
|
|
Overall Study
Second Intervention
|
5
|
5
|
|
Overall Study
COMPLETED
|
5
|
5
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Cannabidiol 600mg First, Placebo Second
In this condition, 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
In their second intervention visit, participants will receive a matched placebo. Following administration, a battery of tests will be conducted to examine reward- and stress-related neurocognitive processes.
This group received CBD first and placebo second.
|
Placebo First, Cannabidiol 600mg Second
Participants in this condition will receive a matched placebo in their first visit. Following administration, a battery of tests will be conducted to examine reward- and stress-related neurocognitive processes.
In their second intervention visit, 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
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
3
|
Baseline Characteristics
Cannabidiol on Reward- and Stress-related Neurocognitive Processes in Individuals With Opioid Use Disorder
Baseline characteristics by cohort
| Measure |
Cannabidiol 600mg First and Placebo Second
n=5 Participants
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 CBD first and placebo second.
|
Placebo First and Cannabidiol 600mg Second
n=5 Participants
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.
|
Not Randomized
n=5 Participants
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
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
44.2 years
STANDARD_DEVIATION 6.98 • n=5 Participants
|
46 years
STANDARD_DEVIATION 11.40 • n=7 Participants
|
33.6 years
STANDARD_DEVIATION 3.78 • n=5 Participants
|
41.75 years
STANDARD_DEVIATION 9.33 • n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
5 participants
n=5 Participants
|
15 participants
n=4 Participants
|
|
Patient Health Questionnaire
|
7.2 units on a scale
STANDARD_DEVIATION 6.18 • n=5 Participants
|
5.6 units on a scale
STANDARD_DEVIATION 2.61 • n=7 Participants
|
10.4 units on a scale
STANDARD_DEVIATION 8.35 • n=5 Participants
|
8.07 units on a scale
STANDARD_DEVIATION 6.17 • n=4 Participants
|
|
Generalized Anxiety Disorder 7
|
9.2 units on a scale
STANDARD_DEVIATION 6.87 • n=5 Participants
|
3.4 units on a scale
STANDARD_DEVIATION 3.21 • n=7 Participants
|
10.2 units on a scale
STANDARD_DEVIATION 6.46 • n=5 Participants
|
7.6 units on a scale
STANDARD_DEVIATION 6.16 • n=4 Participants
|
|
Brief Pain Inventory
Severity
|
3 units on a scale
STANDARD_DEVIATION 2.5 • n=5 Participants
|
3.8 units on a scale
STANDARD_DEVIATION 2.69 • n=7 Participants
|
1.95 units on a scale
STANDARD_DEVIATION 1.87 • n=5 Participants
|
2.82 units on a scale
STANDARD_DEVIATION 2.97 • n=4 Participants
|
|
Brief Pain Inventory
Interference
|
3.51 units on a scale
STANDARD_DEVIATION 3.57 • n=5 Participants
|
3.2 units on a scale
STANDARD_DEVIATION 3.28 • n=7 Participants
|
3.69 units on a scale
STANDARD_DEVIATION 3.16 • n=5 Participants
|
3.60 units on a scale
STANDARD_DEVIATION 3.00 • n=4 Participants
|
|
Timeline Follow Back
Alcohol
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
4.2 Average days of substance use
STANDARD_DEVIATION 8.84 • n=7 Participants
|
0.2 Average days of substance use
STANDARD_DEVIATION 0.45 • n=5 Participants
|
1.47 Average days of substance use
STANDARD_DEVIATION 5.14 • n=4 Participants
|
|
Timeline Follow Back
Cannabis
|
6 Average days of substance use
STANDARD_DEVIATION 12.33 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=7 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
2 Average days of substance use
STANDARD_DEVIATION 7.21 • n=4 Participants
|
|
Timeline Follow Back
Crack/Cocaine
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0.4 Average days of substance use
STANDARD_DEVIATION 0.89 • n=7 Participants
|
1.4 Average days of substance use
STANDARD_DEVIATION 1.67 • n=5 Participants
|
0.6 Average days of substance use
STANDARD_DEVIATION 1.18 • n=4 Participants
|
|
Timeline Follow Back
Amphetamine
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=7 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=4 Participants
|
|
Timeline Follow Back
Opioid Analgesic
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
2.4 Average days of substance use
STANDARD_DEVIATION 5.37 • n=7 Participants
|
1 Average days of substance use
STANDARD_DEVIATION 2.24 • n=5 Participants
|
1.13 Average days of substance use
STANDARD_DEVIATION 3.95 • n=4 Participants
|
|
Timeline Follow Back
Heroin
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=7 Participants
|
6.8 Average days of substance use
STANDARD_DEVIATION 4.1 • n=5 Participants
|
2.27 Average days of substance use
STANDARD_DEVIATION 3.97 • n=4 Participants
|
|
Timeline Follow Back
Hallucinogen
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=7 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=4 Participants
|
|
Timeline Follow Back
Sedatives
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=7 Participants
|
0.2 Average days of substance use
STANDARD_DEVIATION 0.45 • n=5 Participants
|
0.07 Average days of substance use
STANDARD_DEVIATION 0.26 • n=4 Participants
|
|
Timeline Follow Back
Benzodiazepines
|
0.2 Average days of substance use
STANDARD_DEVIATION 0.45 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=7 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0.07 Average days of substance use
STANDARD_DEVIATION 0.26 • n=4 Participants
|
|
Timeline Follow Back
Inhalants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=7 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=5 Participants
|
0 Average days of substance use
STANDARD_DEVIATION 0 • n=4 Participants
|
|
COWS
|
0.4 units on a scale
STANDARD_DEVIATION 0.55 • n=5 Participants
|
0.8 units on a scale
STANDARD_DEVIATION 0.84 • n=7 Participants
|
1.6 units on a scale
STANDARD_DEVIATION 1.52 • n=5 Participants
|
.93 units on a scale
STANDARD_DEVIATION 1.19 • n=4 Participants
|
|
Positive and Negative Affect Schedule
Positive PANAS
|
26.2 units on a scale
STANDARD_DEVIATION 9.96 • n=5 Participants
|
31 units on a scale
STANDARD_DEVIATION 3 • n=7 Participants
|
22.2 units on a scale
STANDARD_DEVIATION 2.59 • n=5 Participants
|
26.47 units on a scale
STANDARD_DEVIATION 6.83 • n=4 Participants
|
|
Positive and Negative Affect Schedule
Negative PANAS
|
24.8 units on a scale
STANDARD_DEVIATION 10.64 • n=5 Participants
|
16.6 units on a scale
STANDARD_DEVIATION 2.79 • n=7 Participants
|
21.6 units on a scale
STANDARD_DEVIATION 7.80 • n=5 Participants
|
21.67 units on a scale
STANDARD_DEVIATION 7.98 • n=4 Participants
|
|
Opioid Cravings
|
1.2 units on a scale
STANDARD_DEVIATION 1.30 • n=5 Participants
|
2.4 units on a scale
STANDARD_DEVIATION 3.29 • n=7 Participants
|
8.2 units on a scale
STANDARD_DEVIATION 1.48 • n=5 Participants
|
3.31 units on a scale
STANDARD_DEVIATION 3.66 • n=4 Participants
|
|
Timeline Follow Back Alcohol Drinks
|
0 numbers of drinks per drinking day
STANDARD_DEVIATION 0 • n=5 Participants
|
2.05 numbers of drinks per drinking day
STANDARD_DEVIATION 0.22 • n=7 Participants
|
2 numbers of drinks per drinking day
STANDARD_DEVIATION 0 • n=5 Participants
|
2.05 numbers of drinks per drinking day
STANDARD_DEVIATION 0.22 • n=4 Participants
|
PRIMARY outcome
Timeframe: Visit 2 and 3 (at least 1 week apart)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.
Outcome measures
| Measure |
Cannabidiol 600mg
n=10 Participants
In this visit, patients received 600mg of Cannabidiol.
Please note this includes all study visits in which participants received CBD.
|
Placebo
n=10 Participants
In this visit, patients received matching placebo.
Please note this includes all visits in which participants received placebo.
|
|---|---|---|
|
Change in Cue-reactivity
Pre-cue
|
0.7 score on a scale
Standard Deviation 1.3
|
1.1 score on a scale
Standard Deviation 2.0
|
|
Change in Cue-reactivity
Cue-induced craving
|
0.2 score on a scale
Standard Deviation 0.79
|
1.3 score on a scale
Standard Deviation 1.9
|
|
Change in Cue-reactivity
Post-drug cue
|
0.9 score on a scale
Standard Deviation 1.1
|
2.4 score on a scale
Standard Deviation 1.7
|
|
Change in Cue-reactivity
Post-neutral cue
|
0.5 score on a scale
Standard Deviation 1.3
|
1.1 score on a scale
Standard Deviation 2.0
|
SECONDARY outcome
Timeframe: Visit 2 and 3 (at least 1 week apart)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.
Outcome measures
| Measure |
Cannabidiol 600mg
n=10 Participants
In this visit, patients received 600mg of Cannabidiol.
Please note this includes all study visits in which participants received CBD.
|
Placebo
n=10 Participants
In this visit, patients received matching placebo.
Please note this includes all visits in which participants received placebo.
|
|---|---|---|
|
Delayed Discount
|
0.020 units on a scale
Standard Deviation 0.024
|
0.039 units on a scale
Standard Deviation 0.075
|
SECONDARY outcome
Timeframe: Visit 2 and 3 (at least 1 week apart)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).
Outcome measures
| Measure |
Cannabidiol 600mg
n=10 Participants
In this visit, patients received 600mg of Cannabidiol.
Please note this includes all study visits in which participants received CBD.
|
Placebo
n=10 Participants
In this visit, patients received matching placebo.
Please note this includes all visits in which participants received placebo.
|
|---|---|---|
|
Decision Making
|
2.2 units on a scale
Standard Deviation 9.3
|
-6.4 units on a scale
Standard Deviation 18.9
|
SECONDARY outcome
Timeframe: Visit 2 and 3 (at least 1 week apart)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.
Outcome measures
| Measure |
Cannabidiol 600mg
n=10 Participants
In this visit, patients received 600mg of Cannabidiol.
Please note this includes all study visits in which participants received CBD.
|
Placebo
n=10 Participants
In this visit, patients received matching placebo.
Please note this includes all visits in which participants received placebo.
|
|---|---|---|
|
Attentional Bias
Automatic orienting
|
-80.4 miliseconds
Standard Deviation 298.8
|
100.3 miliseconds
Standard Deviation 123.5
|
|
Attentional Bias
Controlled attention
|
145.2 miliseconds
Standard Deviation 392.3
|
-93.1 miliseconds
Standard Deviation 268.5
|
SECONDARY outcome
Timeframe: Visit 2 and 3 (at least 1 week apart)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.
Outcome measures
| Measure |
Cannabidiol 600mg
n=10 Participants
In this visit, patients received 600mg of Cannabidiol.
Please note this includes all study visits in which participants received CBD.
|
Placebo
n=10 Participants
In this visit, patients received matching placebo.
Please note this includes all visits in which participants received placebo.
|
|---|---|---|
|
Stress-reactivity
|
59.00 miliseconds
Standard Deviation 37.75
|
99.83 miliseconds
Standard Deviation 100.78
|
SECONDARY outcome
Timeframe: Visit 2 and 3 (at least 1 week apart)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.
Outcome measures
| Measure |
Cannabidiol 600mg
n=10 Participants
In this visit, patients received 600mg of Cannabidiol.
Please note this includes all study visits in which participants received CBD.
|
Placebo
n=10 Participants
In this visit, patients received matching placebo.
Please note this includes all visits in which participants received placebo.
|
|---|---|---|
|
Stress-Reactivity (Physiological)
Pre-Paradigm
|
0.0855 mcg/dL
Standard Deviation 0.0579
|
0.1542 mcg/dL
Standard Deviation 0.179
|
|
Stress-Reactivity (Physiological)
Post-Paradigm
|
0.0745 mcg/dL
Standard Deviation 0.272
|
0.0816 mcg/dL
Standard Deviation 0.045
|
|
Stress-Reactivity (Physiological)
20 Minutes Post Paradigm
|
0.0828 mcg/dL
Standard Deviation 0.060
|
0.0806 mcg/dL
Standard Deviation 0.0429
|
Adverse Events
Cannabidiol 600mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place