Reducing Pain and Opioid Use With CBD

Study Overview
=================
Brief Summary
-----------------
This is a double-blind, placebo-controlled, parallel group study designed to assess the tolerability and efficacy of fsCBD and bsCBD, compared to a placebo control, to reduce opioid use, anxiety, and pain and improve sleep and cognitive function. If eligible for the study, subjects will be randomized to receive one of the conditions for 12 weeks.

Detailed Description
-----------------
To better understand the effects of hemp-derived CBD with and without a small amount of THC, the investigators propose a Phase II randomized clinical trial (RCT) to examine the safety, tolerability, and clinical effects of Full Spectrum CBD (fsCBD, contains less than 0.3% THC) vs. Broad Spectrum CBD (bsCBD, does not contain THC), vs. a matching placebo in a population of opioid users. This is a double-blind, placebo-controlled, parallel group study designed to assess the tolerability and efficacy of fsCBD and bsCBD, compared to a placebo control, to reduce opioid use, anxiety, and pain and improve sleep and cognitive function. If eligible for the study, subjects will be randomized to receive one of the conditions for 12 weeks. The initial Week 0 / Baseline visit will take place at the University of Colorado Anschutz Medical Campus. There will be in-person visits at Weeks 1, 6, and 12. Participants will be contacted by Zoom each remaining week during the 12-week period. A follow up Zoom interview will occur in Week 16, approximately 4 weeks after the end of dosing.

Official Title
-----------------
Reducing Pain and Opioid Use With CBD

Conditions
-----------------
Opioid Use Disorder

Intervention / Treatment
-----------------
* Drug: Cannabidiol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Self-reported desire or intent to use cannabidiol to reduce pain and/or opioid use Must be 18 years of age or older. Exclusion Criteria: Self-reported recreational drug use (other than opioids) in the past 30 days or failed urine screen for cocaine, benzodiazepines, MDMA, sedatives, or methamphetamine; Self-reported current moderate/severe alcohol use, or severe opioid use disorder on the DSM V (unless patient is medically stable and approved by personal physician as well as the Medical Director for the study); Actively seeking or in treatment for or history of any substance use disorder, other than opioid use disorder; Currently being treated for or diagnosed with a moderate, severe, or unstable medical illness (e.g., renal disease, liver disease, cardiovascular disease). If the person has had a recent operation, they must be cleared for study participation by their surgeon or primary care doctor. Study inclusion/exclusion will be evaluated by our medical director when there are questions about applying criteria; Currently taking any of the following medications: Those known to have a major interaction with Epidiolex (buprenorphine, leflunomide, levomethadyl acetate, lomitapide, mipomersen, pexidartinib, propoxyphene, sodium oxybate, and/or teriflunomide) Acute treatment with any antiepileptic medications (e.g. clobazam, sodium valproate) Report being treated for bipolar disorder, schizophrenia, dissociative disorders, eating disorders, or any other psychotic or organic mental disorder in the last year. Females of childbearing potential who are pregnant, nursing, or who are not using a reliable form of birth control. Endorsing item 2 on the C-SSRS measure of suicide risk.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Full-spectrum Cannabidiol<br>210mg/day of full-spectrum cannabidiol, containing less than 0.3%THC. | Drug: Cannabidiol<br>* The current study will directly test the hypothesis that a moderate dose of CBD leads to a reduction in opioid consumption, opioid craving, pain, peripheral markers of inflammation, and anxiety, as well as changes in sleep, AEA, and cognition.<br>* Other names: CBD;|
| Active Comparator: Broad-spectrum Cannabidiol<br>210mg/day of full-spectrum cannabidiol, containing 0%THC. | Drug: Cannabidiol<br>* The current study will directly test the hypothesis that a moderate dose of CBD leads to a reduction in opioid consumption, opioid craving, pain, peripheral markers of inflammation, and anxiety, as well as changes in sleep, AEA, and cognition.<br>* Other names: CBD;|
| Placebo Comparator: Hemp Seed Oil Placebo<br>210mg/day of hemp-seed oil with no cannabinoids present. | Drug: Placebo<br>* Placebo arm<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in opioid use | The Time Line Follow Back is a calendar-assisted measure that can be used to assess opioid use. The investigators will use this measure to create the opioid use variable. | 0-12 Weeks | 
| Change in sleep disturbance | The PROMIS Short Form v1.0 - Sleep Disturbance - 4A measure the severity of sleep disturbances. Possible scores range from 0 to 4 with lower scores indicating a worse outcome/more severe symptoms of sleep disturbance/fatigue. | 0-12 Weeks | 
| Change in fatigue | The PROMIS Short Form v1.0 - Fatigue - 4a measures subject fatigue over the past 7 days on a 4 point scale, with higher scores indicating more fatigue. | 0-12 Weeks | 
| Change in anxiety | The Depression Anxiety Stress Scale measures the severity of anxiety symptoms. Possible scores range from 0 to 41 with higher scores indicating a worse outcome/more severe symptoms of anxiety. | 0-12 Weeks | 
| Change in pain intensity | The PROMIS Numeric Rating Scale v1.0 - Pain Intensity - 1a will be used to measure pain intensity with a one question item over the past 7 days. Higher scores indicate more pain. | 0-12 Weeks | 
| Change in pain interference | The PROMIS Short Form v1.1 - Pain Interference - 6b scale will be used to assess how disruptive pain was over the past 7 days. There are six questions with a total score of 30-higher scores indicate more interference. | 0-12 Weeks | 
| Change in pain behavior | the PROMIS Pain Behavior Scale will be used to assess changes in pain behavior on seven aspects. Each is measured on a 6 point scale with a higher score indicating more pain behavior (scale 0-42). | 0-12 Weeks | 
| Change in subjective pain | The McGill Pain Questionnaire measure the severity of subjective pain. Possible scores range from 0 to 78 with higher scores indicating a worse outcome/more severe symptoms of subjective pain. | 0-12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in opioid craving | The Opioid Craving Scale will be used to assess changes in craving over time. This scale has three questions assessed using a 10-pt likert scale. Higher scores (0-30) indicate greater opioid craving. | 0-6 Weeks | 
| Change in opioid craving | The Opioid Craving Scale will be used to assess changes in craving over time. This scale has three questions assessed using a 10-pt likert scale. Higher scores (0-30) indicate greater opioid craving. | 6-12 Weeks | 
| Change in opioid craving | The Opioid Craving Scale will be used to assess changes in craving over time. This scale has three questions assessed using a 10-pt likert scale. Higher scores (0-30) indicate greater opioid craving. | 0-12 Weeks | 
| Change in opioid craving | The Opioid Craving Scale will be used to assess changes in craving over time. This scale has three questions assessed using a 10-pt likert scale. Higher scores (0-30) indicate greater opioid craving. | 0-16 Weeks | 
| Change in inflammation | Differences in inflammatory markers (e.g. IL-6) will be assessed over time as a moderating factor. | 0-6 Weeks | 
| Change in inflammation | Differences in inflammatory markers (e.g. IL-6) will be assessed over time as a moderating factor. | 6-12 Weeks | 
| Change in inflammation | Differences in inflammatory markers (e.g. IL-6) will be assessed over time as a moderating factor. | 0-12 Weeks | 
| Change in inflammation | Differences in inflammatory markers (e.g. IL-6) will be assessed over time as a moderating factor. | 0-16 Weeks | 
| Change in Anandamide (AEA) | Differences in AEA will be assessed over time as a moderating factor. | 0-6 Weeks | 
| Change in Anandamide (AEA) | Differences in AEA will be assessed over time as a moderating factor. | 6-12 Weeks | 
| Change in Anandamide (AEA) | Differences in AEA will be assessed over time as a moderating factor. | 0-12 Weeks | 
| Change in quality of life | Changes in subjective quality of life will be assessed using the PROMIS Global-10 Short Form). Scores range from 10-50, with higher scores indicating poorer quality of life. | 0-6 Weeks | 
| Change in quality of life | Changes in subjective quality of life will be assessed using the PROMIS Global-10 Short Form. Scores range from 10-50, with higher scores indicating poorer quality of life. | 6-12 Weeks | 
| Change in quality of life | Changes in subjective quality of life will be assessed using the PROMIS Global-10 Short Form. Scores range from 10-50, with higher scores indicating poorer quality of life. | 0-12 Weeks | 
| Change in quality of life | Changes in subjective quality of life will be assessed using the PROMIS Global-10 Short Form. Scores range from 10-50, with higher scores indicating poorer quality of life. | 0-16 Weeks | 
| Change in self-reported cognitive function | Changes in self-reported cognitive function will be assessed using the FACT-Cog. There are 37 questions on a 5-pt likert scale with higher scores indicating poorer cognition. | 0-6 Weeks | 
| Change in self-reported cognitive function | Changes in self-reported cognitive function will be assessed using the FACT-Cog. There are 37 questions on a 5-pt likert scale with higher scores indicating poorer cognition. | 6-12 Weeks | 
| Change in self-reported cognitive function | Changes in self-reported cognitive function will be assessed using the FACT-Cog. There are 37 questions on a 5-pt likert scale with higher scores indicating poorer cognition. | 0-12 Weeks | 
| Change in self-reported cognitive function | Changes in self-reported cognitive function will be assessed using the FACT-Cog. There are 37 questions on a 5-pt likert scale with higher scores indicating poorer cognition. | 0-16 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CBD, Opioids, Pain, Cannabidiol, Cannabis