Marijuana Use, Opioid Use, Pain
Conditions
Keywords
Opioid, Marijuana, Pain, neurocognition, Dependence, Behavioral treatment
Brief summary
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
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.
Interventions
DRUGCannabis
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.
BEHAVIORALPrescription 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.
Sponsors
Massachusetts General Hospital
Cambridge Health Alliance
MaineHealth
National Institute on Drug Abuse (NIDA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Difference in Prescription Monitoring Program Verified Opioid Dose at Baseline and Week 24 | Week 24 | Median opioid dose verified by the Prescription Monitoring Program, in morphine milligram equivalents (MME) per day, over monthly interval preceding study visit. |
| Mean Difference in Pain, Enjoyment, General Activity (PEG) Scale Summed Score Over Post-baseline to Week 24 Interval | Every post-baseline day until week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Difference in Self-Reported Opioid Dose Over Post-baseline to Week 24 Interval | Every post-baseline day until week 24 | 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. |
| Mean Difference in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form Summed Score at Weeks 4, 8, 12, 16, 20, 24 | Week 4, week 8, week 12, week 16, week 20, week 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. |
| Mean Difference in PROMIS-29 Depression Subscale Summed Score at Weeks 4, 8, 12, 16, 20, 24 | Week 4, week 8, week 12, week 16, week 20, week 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. |
| Mean Difference in PROMIS-29 Anxiety Subscale Summed Score at Weeks 4, 8, 12, 16, 20, 24 | Week 4, week 8, week 12, week 16, week 20, week 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. |
| Mean Difference in Opioid Use Disorder Symptoms at Weeks 4, 8, 12, 16, 20, 24 | Week 4, week 8, week 12, week 16, week 20, week 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. |
| Mean Difference in Cannabis Use Disorder Symptoms at Weeks 12 and 24 | Week 12, Week 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJodi Gilman, PhD
Massachusetts General Hospital
PRINCIPAL_INVESTIGATORA. Eden Evins, MD
Massachusetts General Hospital
Participant flow
Recruitment details
Recruitment took place at three academic medical centers in the Northeastern United States (Massachusetts General Hospital, Boston, MA; Cambridge Health Alliance, Cambridge, MA; Maine Medical Center, Portland, ME).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56.4 Years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Opioid use disorder (OUD) symptoms | 1.6 Number of symptoms STANDARD_DEVIATION 1.5 |
| Pain, Enjoyment, and General Activity (PEG) Scale Score | 5.68 Score STANDARD_DEVIATION 1.82 |
| Prescription Monitoring Program-verified daily opioid dose | 96.8 Morphine milligram equivalents (MME)/day STANDARD_DEVIATION 113 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 75 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 45 |
| other Total, other adverse events | 36 / 42 | 35 / 45 |
| serious Total, serious adverse events | 7 / 42 | 5 / 45 |
Outcome results
None listed