NCT04982029

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

Completed Phase 2 Results posted Last updated 5 October 2023

What this trial tests

Phase 2 trial testing Cannabidiol 100 MG/ML [Epidiolex] in Opioid-use Disorder in 15 participants. Completed in 2 December 2022.

Timeline

14 April 2022

Primary endpoint
2 December 2022

2 December 2022

Quick facts

Lead sponsor	Brigham and Women's Hospital
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	treatment
Enrollment	15
Start date	14 April 2022
Primary completion	2 December 2022
Estimated completion	2 December 2022
Sites	2 locations across United States

Drugs / interventions tested

• Cannabidiol 100 MG/ML [Epidiolex] — full drug profile →
• Placebo

Conditions studied

• Opioid-use Disorder — all drugs for Opioid-use Disorder →

Sponsor

Brigham and Women's Hospital

Who can join

Adults 18 to 65, any sex, with Opioid-use Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Cue-reactivity Primary · 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.

Pre-cue

Group	Value	95% CI
Cannabidiol 600mg	0.7	± 1.3
Placebo	1.1	± 2.0

Post-drug cue

Group	Value	95% CI
Cannabidiol 600mg	0.9	± 1.1
Placebo	2.4	± 1.7

Post-neutral cue

Group	Value	95% CI
Cannabidiol 600mg	0.5	± 1.3
Placebo	1.1	± 2.0

Cue-induced craving

Group	Value	95% CI
Cannabidiol 600mg	0.2	± 0.79
Placebo	1.3	± 1.9

Delayed Discount Secondary · 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.

Group	Value	95% CI
Cannabidiol 600mg	0.020	± 0.024
Placebo	0.039	± 0.075

Decision Making Secondary · 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

Group	Value	95% CI
Cannabidiol 600mg.	2.2	± 9.3
Placebo	-6.4	± 18.9

Attentional Bias Secondary · 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 pressi

Automatic orienting

Group	Value	95% CI
Cannabidiol 600mg	-80.4	± 298.8
Placebo	100.3	± 123.5

Controlled attention

Group	Value	95% CI
Cannabidiol 600mg	145.2	± 392.3
Placebo	-93.1	± 268.5

Stress-reactivity Secondary · 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.

Group	Value	95% CI
Cannabidiol 600mg	59.00	± 37.75
Placebo Session	99.83	± 100.78

Stress-Reactivity (Physiological) Secondary · 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.

Pre-Paradigm

Group	Value	95% CI
Cannabidiol 600mg	0.0855	± 0.0579
Placebo Session	0.1542	± 0.179

Post-Paradigm

Group	Value	95% CI
Cannabidiol 600mg	0.0745	± 0.272
Placebo Session	0.0816	± 0.045

20 Minutes Post Paradigm

Group	Value	95% CI
Cannabidiol 600mg	0.0828	± 0.060
Placebo Session	0.0806	± 0.0429

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. The therapeutic potential of purified cannabidiol.
   O'Sullivan SE, Jensen SS, Nikolajsen GN, Bruun HZ, et al · · 2023 · cited 33× · PMID 37312194 · DOI 10.1186/s42238-023-00186-9
2. Impact of cannabidiol on reward- and stress-related neurocognitive processes among individuals with opioid use disorder: A pilot, double-blind, placebo-controlled, randomized cross-over trial.
   Suzuki J, Prostko S, Szpak V, Chai PR, et al · · 2023 · cited 8× · PMID 37065899 · DOI 10.3389/fpsyt.2023.1155984