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

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).

Study Overview

• Status: Completed
• Conditions: Pain; Marijuana Use; Opioid Use
• Intervention / Treatment: Drug: Cannabis; Behavioral: Prescription Opioid Taper Support (POTS)

Detailed Description

This trial is a randomized, six-month study of cannabis (CB) on opioid use that will: (1) evaluate whether adults with chronic, non-cancer pain on COT assigned to CB, compared with those assigned to a waitlist control condition (WL), have greater reduction in opioid dose and/or pain intensity and interference, (2) assess whether participants assigned to CB, compared with those assigned to WL, have improved quality of life, depression, and anxiety; and reduced self-reported opioid dose, (3) evaluate whether those assigned to CB 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 CB arm (n = 60), or to a waitlist control arm (WL) (n = 60). 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.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2523
      • Massachusetts General Hospital
    • Cambridge, Massachusetts, United States, 02139
      • Cambridge Health Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women aged 18-75, inclusive.
2. Endorsing > 6 months of chronic, non-cancer pain.
3. On stable prescription opioid doses of 25 MME or greater for >90 days, verified by the Prescription Monitoring Program.
4. Either no prior use or current light cannabis use (weekly or less in the past 12 months).
5. Plans to use medical cannabis for pain to control pain and/or reduce opioid dose.
6. Competent and willing to provide written informed consent in English.
7. Potential participants of childbearing potential must not be pregnant at enrollment. They will be asked to self-report pregnancy status and the start date of their most recent menstrual period and agree to use effective contraception: abstinence; hormonal contraception; intra-uterine device, sterilization; or double barrier contraception, during the study.

Exclusion Criteria:

1. 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).
2. Current cannabis use disorder; current moderate to severe substance use disorder for any substance by structured interview, EXCEPT nicotine and opioids (OUD).
3. Current uncontrolled major medical illness, such as cancer, symptomatic hypothyroidism/hyperthyroidism or severe respiratory compromise.
4. Use of non-prescribed opioids, by self-report.
5. Dose change or initiation of medications with significant analgesic effects (e.g., tricyclic antidepressants, SSRIs, gabapentin, NSAIDs) in the past 4 weeks.
6. 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.
7. Actively suicidal and/or suicide attempt or psychiatric hospitalization in past year, or current suicidal ideation with specific plan or intent.
8. History of intellectual disability (e.g., Down's syndrome) or other severe developmental disorder or IQ < 70.
9. 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.
10. Surgery within the past month or planned during the next 6 months.
11. Pregnant or trying to get pregnant or breastfeeding.
12. In the opinion of the investigator or study physicians, not able to complete study procedures or safely participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cannabis (CB); Participants assigned to the cannabis group were allowed to initiate cannabis use immediately. Participants selected cannabis product type(s), dose(s), and frequency of use from commercial sources. All study participants were offered weekly group Prescription Opioid Taper Support (POTS), a behavioral intervention promoting pain self-management and gradual, voluntary opioid tapering, for 24 weeks.	Drug: Cannabis; Participants assigned to the cannabis group were allowed to initiate cannabis use immediately. Participants selected cannabis product type(s), dose(s), and frequency of use from commercial sources.; Behavioral: Prescription Opioid Taper Support (POTS); All participants were offered weekly group Prescription Opioid Taper Support (POTS) sessions for 24 weeks. POTS is behavioral intervention promoting pain self-management and gradual, voluntary opioid tapering. This intervention was adapted for this trial to include group-based delivery. Sessions are one hour delivered via teleconference and incorporated cognitive behavioral, mindfulness-based, and motivational interviewing strategies.
Active Comparator: Waitlist (WL); Participants assigned to the waitlist control group agreed to delay cannabis use for 24 weeks. All study participants were offered weekly group Prescription Opioid Taper Support (POTS), a behavioral intervention promoting pain self-management and gradual, voluntary opioid tapering, for 24 weeks.	Behavioral: Prescription Opioid Taper Support (POTS); All participants were offered weekly group Prescription Opioid Taper Support (POTS) sessions for 24 weeks. POTS is behavioral intervention promoting pain self-management and gradual, voluntary opioid tapering. This intervention was adapted for this trial to include group-based delivery. Sessions are one hour delivered via teleconference and incorporated cognitive behavioral, mindfulness-based, and motivational interviewing strategies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Difference in Prescription Monitoring Program Verified Opioid Dose at Baseline and Week 24	Median opioid dose verified by the Prescription Monitoring Program, in morphine milligram equivalents (MME) per day, over monthly interval preceding study visit.	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 assesses pain intensity and interference. The scale ranges from 0 to 10, with a higher score indicating greater pain intensity and interference. PEG score was assessed daily through week 24 via daily self-report survey. From model fit to all post-baseline timepoints, adjusted marginal means at week 24 were computed as a summary measure.	Every post-baseline day until week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Difference in Self-Reported Opioid Dose Over Post-baseline to Week 24 Interval	Self-reported opioid dose in morphine milligram equivalents (MME) per day. Self-reported opioid dose was assessed daily through week 24 via daily self-report survey. From model fit to all post-baseline timepoints, adjusted marginal means at week 24 were computed as a summary measure.	Every post-baseline day until week 24
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 assesses changes in quality of life measures. The scale ranges from 14 - 70, with a lower score indicating greater dissatisfaction with life. Q-LES-SF score was assessed at weeks 4, 8, 12, 16, 20, and 24. From model fit to all post-baseline timepoints, adjusted marginal means at week 24 were computed as a summary measure.	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. PROMIS-29 depression subscale score was assessed at weeks 4, 8, 12, 16, 20, and 24. From model fit to all post-baseline timepoints, adjusted marginal means at week 24 were computed as a summary measure.	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. PROMIS-29 anxiety subscale score was assessed at weeks 4, 8, 12, 16, 20, and 24. From model fit to all post-baseline timepoints, adjusted marginal means at week 24 were computed as a summary measure.	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	Number of opioid use disorder (OUD) symptoms present was assessed via the Diagnostic and Statistical Manual- 5th Edition (DSM-V) checklist. As all participants were taking prescribed opioids under the supervision of a clinician, symptom counts exclude tolerance and withdrawal. Number of symptoms range from 0 to 9. A score of 2 or more indicates a current opioid use disorder diagnosis. Number of opioid use disorder symptoms were assessed at weeks 4, 8, 12, 16, 20, and 24. From model fit to all post-baseline timepoints, adjusted marginal means at week 24 were computed as a summary measure.	Week 4, week 8, week 12, week 16, week 20, week 24
Mean Difference in Cannabis Use Disorder Symptoms at Weeks 12 and 24	Number of cannabis use disorder (CUD) symptoms present was assessed via the Diagnostic and Statistical Manual- 5th Edition (DSM-V) checklist. Number of symptoms range from 0 to 11. A score of 2 or more indicates a current cannabis use disorder diagnosis. The number of cannabis use disorder symptoms were assessed at weeks 12 and 24. From model fit to all post-baseline timepoints, adjusted marginal means at week 24 were computed as a summary measure.	Week 12, Week 24

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute on Drug Abuse (NIDA); Cambridge Health Alliance; MaineHealth
• Investigators: Principal Investigator: Jodi Gilman, PhD, Massachusetts General Hospital; Principal Investigator: A. Eden Evins, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Jashinski J, Grossman E, Quaye A, Cather C, Potter K, Schoenfeld DA, Evins AE, Gilman JM. Randomised, pragmatic, waitlist controlled trial of cannabis added to prescription opioid support on opioid dose reduction and pain in adults with chronic non-cancer pain: study protocol. BMJ Open. 2022 Jun 9;12(6):e064457. doi: 10.1136/bmjopen-2022-064457.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2021
• Primary Completion (Actual): May 1, 2025
• Study Completion (Actual): October 31, 2025

Study Registration Dates

• First Submitted: March 29, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pain; Opioid; Dependence; Marijuana; Behavioral treatment; neurocognition
• Additional Relevant MeSH Terms: Neurologic Manifestations; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Marijuana Use; Pain; Marijuana Abuse; Pharmaceutical Preparations; nabiximols
• Other Study ID Numbers: 2021P000871; R01DA051540 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data, code, and materials used in the analyses can be provided by Jodi Gilman and Massachusetts General Hospital pending scientific review and a completed data use agreement/material transfer agreement beginning one year after publication of the results. Requests for all materials should be submitted to Jodi Gilman at jgilman1@mgh.harvard.edu.
• IPD Sharing Time Frame: Data will become available beginning one year after publication of the results.
• IPD Sharing Access Criteria: Data will be provided pending a scientific review and a completed data use agreement/material transfer agreement. Requests should be submitted to Jodi Gilman at jgilman1@mgh.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No