Evaluation of Medical Cannabis and Prescription Opioid Taper Support for Reduction of Pain and Opioid Dose in Patients With Chronic Non-Cancer Pain

Study Overview
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Brief Summary
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This study will use a randomized controlled design to test whether medical marijuana use by adults on high-dose chronic opioid therapy (COT) for chronic non-cancer pain is associated with reduced opioid dose and improved pain intensity and interference when added to a 24-week behavioral intervention (POTS).

Detailed Description
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This trial is a randomized, six-month study of medical marijuana (MM) on opioid use that will: (1) evaluate whether adults with chronic, non-cancer pain on COT assigned to MM+POTS, compared with those assigned to WL+POTS, have greater reduction in opioid dose and/or pain intensity and interference, (2) assess whether participants assigned to MM+POTS, compared with those assigned to WL+POTS, have improved quality of life, depression, and anxiety; and reduced self-reported opioid dose, (3) evaluate whether those assigned to MM+POTS develop symptoms of CUD and have a reduced number of OUD symptoms over the 24-week intervention, as well as at the 12-month time point. Participants will be randomly assigned to either an active MM arm (n = 125), or to a waitlist control arm (WLC) (n = 125). Participants will be assessed at baseline, every 4 weeks for 6 months, and at a 12-month follow-up for opioid use, development of CUD, development or resolution of OUD, and neurocognitive performance. Urine collected will be assessed with quantitative assays.

Official Title
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Evaluation of Medical Cannabis and Prescription Opioid Taper Support for Reduction of Pain and Opioid Dose in Patients With Chronic Non-Cancer Pain

Conditions
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Opioid Use, Pain, Marijuana Use

Intervention / Treatment
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* Drug: Medical Marijuana
* Behavioral: Prescription Opioid Taper Support (POTS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18-75, inclusive. Endorsing > 6 months of chronic, non-cancer pain. On stable prescription opioid doses of 25 MME or greater for >90 days, verified by the Prescription Monitoring Program. Either no prior use or current light cannabis use (weekly or less in the past 12 months). Plans to use medical cannabis for pain to control pain and/or reduce opioid dose. Competent and willing to provide written informed consent in English. Potential participants of childbearing potential must have a negative urine pregnancy test at enrollment and agree to use effective contraception: abstinence; hormonal contraception; intra-uterine device, sterilization; or double barrier contraception, during the study. Exclusion Criteria: Current cannabis use (including inhaled or ingested CBD products) of greater than weekly on average in the past 12 months, assessed via self-report (no more than 10 times in the past 90 days). Current cannabis use disorder; current moderate to severe substance use disorder for any substance by structured interview, EXCEPT nicotine and opioids (OUD). Current uncontrolled major medical illness, such as cancer, symptomatic hypothyroidism/hyperthyroidism or severe respiratory compromise. Use of non-prescribed opioids, by self-report. Dose change or initiation of medications with significant analgesic effects (e.g., tricyclic antidepressants, SSRIs, gabapentin, NSAIDs) in the past 4 weeks. Concomitant medications will be discussed at each study visit, and any medications that may interact with cannabinoids (e.g., warfarin) will be discussed with a study clinician prior to enrollment or continued participation. Actively suicidal and/or suicide attempt or psychiatric hospitalization in past year, or current suicidal ideation with specific plan or intent. History of intellectual disability (e.g., Down's syndrome) or other severe developmental disorder or IQ < 70. Current diagnosis of delirium, dementia, amnestic, or other cognitive disorder; current diagnosis of bipolar II disorder; lifetime diagnosis of bipolar I disorder, schizophrenia spectrum, or other psychotic disorder. Surgery within the past month or planned during the next 6 months. Pregnant or trying to get pregnant or breastfeeding. In the opinion of the investigator or study physicians, not able to complete study procedures or safely participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medical Marijuana + Prescription Opioid Taper Support (POTS) behavioral treatment<br>This group can begin using medical marijuana immediately and will participate in the POTS treatment groups. | Drug: Medical Marijuana<br>* Patients in this group can choose what type, how much, and when to use medical marijuana to use.<br>* Other names: Cannabis;Behavioral: Prescription Opioid Taper Support (POTS)<br>* Prescription Opioid Taper Support (POTS), a manualized behavioral prescription opioid taper support intervention developed by consultant, will be offered weekly to all participants to support behavioral self-management of pain and structured, voluntary taper of COT dose.<br>|
| Active Comparator: Prescription Opioid Taper Support (POTS) treatment alone<br>This group must abstain from marijuana use and will participate in the POTS behavioral treatment alone. | Behavioral: Prescription Opioid Taper Support (POTS)<br>* Prescription Opioid Taper Support (POTS), a manualized behavioral prescription opioid taper support intervention developed by consultant, will be offered weekly to all participants to support behavioral self-management of pain and structured, voluntary taper of COT dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Difference in Prescription Monitoring Program verified opioid dose at baseline and week 24 | Opioid dose verified by the Prescription Monitoring Program, in morphine milligram equivalents (MME) per day. If participants decide to reduce dose at week 24, we will use the reduced dose even if the new dose cannot be immediately implemented (e.g., due to delays in refilling prescription) to ensure accurate representation of change. | Baseline and week 24 | 
| Mean Difference in Pain, Enjoyment, General Activity (PEG) Scale Summed Score over post-baseline to week 24 interval | The Pain, Enjoyment, General Activity (PEG) scale will assess pain intensity and interference. The scale ranges from 0-30, with a higher score indicating greater pain intensity and interference. Collected daily by a self-reported online survey. | Every post-baseline day until week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Difference in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form Summed Score at weeks 4, 8, 12, 16, 20, 24 | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form will assess changes in quality of life measures. The scale ranges from 14 - 70, with a lower score indicating greater dissatisfaction with life. | Week 4, week 8, week 12, week 16, week 20, week 24 | 
| Mean Difference in PROMIS-29 Depression Subscale Summed Score at weeks 4, 8, 12, 16, 20, 24 | The 8-item depression subscale of the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 will be used to assess depression symptoms. The scale uses a t-score metric (mean of 50, SD of 10). Higher scores indicate worse depression. | Week 4, week 8, week 12, week 16, week 20, week 24 | 
| Mean Difference in PROMIS-29 Anxiety Subscale Summed Score at weeks 4, 8, 12, 16, 20, 24 | The 7-item anxiety subscale of the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 will be used to assess anxiety symptoms. The scale uses a t-score metric (mean of 50, SD of 10). Higher scores indicate worse anxiety. | Week 4, week 8, week 12, week 16, week 20, week 24 | 
| Mean Difference in Opioid Use Disorder Symptoms at weeks 4, 8, 12, 16, 20, 24 | The DSM-5 Opioid Use Disorder Checklist will evaluate symptoms of Opioid Use Disorder (number of symptoms). The scale ranges from 0 - 11, with a higher score indicating more severe Opioid Use Disorder. | Week 4, week 8, week 12, week 16, week 20, week 24 | 
| Mean Difference in Cannabis Use Disorder Symptoms at weeks 4, 8, 12, 16, 20, 24 | The DSM-5 Cannabis Use Disorder Checklist will evaluate symptoms of Cannabis Use Disorder (number of symptoms). The scale ranges from 0 - 11, with a higher score indicating more severe Cannabis Use Disorder. | Week 4, week 8, week 12, week 16, week 20, week 24 | 
| Mean Difference in Self-Reported Opioid Dose at weeks 4, 8, 12, 16, 20, 24 | Self-reported opioid dose in morphine milligram equivalents (MME) per day. This is collected daily by a self-reported online survey and averaged over each 4-week interval. | Week 4, week 8, week 12, week 16, week 20, week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid, Marijuana, Pain, neurocognition, Dependence, Behavioral treatment