Cannabis, HIV Infections, Neuropathic Pain
Conditions
Brief summary
This study will examine how medical cannabis use affects neuropathic pain, inflammation and adverse events in people living with HIV (PLWH) with neuropathic pain. The investigators will observe how varying ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD) in medical cannabis impact neuropathic pain, inflammation and adverse events.
Detailed description
This study will examine how medical cannabis use affects neuropathic pain in PLWH with neuropathic pain. The investigators will enroll adults with HIV who have a) neuropathic pain, b) are actively certified for medical cannabis, and c) intend to have soft gel capsule products dispensed at Vireo (medical cannabis dispensary). The investigators will observe how pain and inflammation change in participants after they are randomized to receive high THC:low CBD product, an equal THC:CBD product, a low THC:high CBD product, or placebo by our collaborator in a separate study. Over 14 weeks, data sources will include questionnaires, blood samples, urine samples; medical, pharmacy, and Prescription Monitoring Program (PMP) records. The primary independent variable will be type of medical cannabis product dispensed at dispensary, and the primary outcome will be self-reported pain.
Interventions
OTHERReceipt of Coupon for Placebo Soft-Gel Capsule
The investigators will follow participants who were randomized to receive a coupon for placebo soft-gel capsule medical cannabis products by our collaborators at Vireo medical cannabis dispensary in a separate study Placebo (0:0) Softgel, 0mg THC and 0mg CBD per cap, Bottle of 30 caps
OTHERReceipt of Coupon for High THC Soft-Gel Capsule
The investigators will follow participants who were randomized to receive a coupon for high THC soft-gel capsule medical cannabis products by our collaborators at Vireo medical cannabis dispensary in a separate study Vireo Yellow (6:1) Softgel, 4.29mg THC and 0.72mg CBD per cap, Bottle of 30 caps
OTHERReceipt of Coupon for Equal THC and CBD Soft-Gel Capsule
The investigators will follow participants who were randomized to receive a coupon for equal THC and CBD soft-gel capsule medical cannabis products by our collaborators at Vireo medical cannabis dispensary in a separate study Vireo Green (1:1) Softgel, 2.5mg THC and 2.5mg CBD per cap, Bottle of 30 caps
OTHERReceipt of Coupon for High CBD Soft-Gel Capsule
The investigators will follow participants who were randomized to receive a coupon for high CBD soft-gel capsule medical cannabis products by our collaborators at Vireo medical cannabis dispensary in a separate study Vireo Indigo (1:19) Softgel, 0.25mg THC and 4.75mg CBD per cap, Bottle of 30 caps
Sponsors
National Institute on Drug Abuse (NIDA)
University of Colorado, Boulder
University of Pittsburgh
Vireo Health
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
We will observe participants who are enrolled in one of 4 arms in a partnering study over 14 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
-\>=18 years old * Diagnosis of HIV * Fluency in English * Active certification for medical cannabis * ICD-10 diagnosis code for neuropathic pain, OR Neuropathic pain in problem list of electronic medical record, OR Neuropathic pain per medical cannabis certification form, OR Neuropathic Pain Questionnaire-Short Form\>0
Exclusion criteria
* Inability to provide informed consent * Inability to complete 14 weeks of study visits * Medical cannabis use within 14 days of enrollment, and no medical cannabis dispensed within 30 days of enrollment * Unique pain symptoms (e.g., multiple sclerosis, rheumatoid arthritis) * Terminal illness * Current or prior psychotic disorder * Unregulated cannabis use in the past 14 days; opioid or cocaine use in the past 30 days * Dispensed opioids within 30 days * Non-steroidal anti-inflammatory use within 7 days prior to enrollment * Steroid use within the past 14 days with duration of therapy \>=21 days * COVID vaccination or booster within 14 days of screening * Active or acute cardiac disease based on clinician chart review.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Severity Score | At weekly intervals from Baseline to 14 weeks | Change in self-reported Pain Severity was measured at weekly intervals from baseline through 14 weeks using the Brief Pain Inventory (BPI) pain severity subscale. The BPI Pain Severity subscale uses a 0-10 numerical rating scale where 0 = No pain at all and 10 = Pain as bad as you can imagine; completely interferes such that higher scores were associated with increased Pain Severity. Participants were asked to assign a score to their pain, on average, over the prior week. Scores were summarized by study arm. For purposes of this study change in Pain Severity scores from baseline to 14 weeks following intervention were summarized and reported with positive values being indicative of increased pain severity compared to baseline and negative values being indicative of decreased pain severity compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-4 (IL-4) | From Baseline to 14 weeks | Change in circulating test levels of recent inflammation (based on a panel of inflammatory markers) from baseline to 14 weeks was analyzed. Blood draws for circulating levels of pro- and anti-inflammatory cytokines were collected, processed, and analyzed using an O-link assay which uses normal protein expression (NPX) values expressed on a log2 scale, where a higher value indicates a higher protein level. Results for IL-4 are summarized by study arm using basic descriptive statistics. For purposes of this study change in circulating levels of IL-4 from baseline to 14 weeks following intervention were summarized and reported. Samples were collected at two time points prior to the intervention and the results from these analyses were averaged and compared to the 14-week results. |
| Change in Circulating Levels of Pro-inflammatory Cytokines - Tumor Necrosis Factor Alpha (TNFa) | From Baseline to 14 weeks | Change in circulating test levels of recent inflammation (based on a panel of inflammatory markers) from baseline to 14 weeks was analyzed. Blood draws for circulating levels of pro- and anti-inflammatory cytokines were collected, processed, and analyzed using an O-link assay which uses normal protein expression (NPX) values expressed on a log2 scale, where a higher value indicates a higher protein level. Results for TNFa are summarized by study arm using basic descriptive statistics. For purposes of this study change in circulating levels of TNFa from baseline to 14 weeks following intervention were summarized and reported. Samples were collected at two time points prior to the intervention and the results from these analyses were averaged and compared to the 14-week results. |
| Change in Circulating Levels of Pro-inflammatory Cytokines - Interleukin-6 (IL-6) | From Baseline to 14 weeks | Change in circulating test levels of recent inflammation (based on a panel of inflammatory markers) from baseline to 14 weeks was analyzed. Blood draws for circulating levels of pro- and anti-inflammatory cytokines were collected, processed, and analyzed using an O-link assay which uses normal protein expression (NPX) values expressed on a log2 scale, where a higher value indicates a higher protein level. Results for IL-6 are summarized by study arm using basic descriptive statistics. For purposes of this study change in circulating levels of IL-6 from baseline to 14 weeks following intervention were summarized and reported. Samples were collected at two time points prior to the intervention and the results from these analyses were averaged and compared to the 14-week results. |
| Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-10 (IL-10) | From Baseline to 14 weeks | Change in circulating test levels of recent inflammation (based on a panel of inflammatory markers) from baseline to 14 weeks was analyzed. Blood draws for circulating levels of pro- and anti-inflammatory cytokines were collected, processed, and analyzed using an O-link assay which uses normal protein expression (NPX) values expressed on a log2 scale, where a higher value indicates a higher protein level. Results for IL-10 are summarized by study arm using basic descriptive statistics. For purposes of this study change in circulating levels of IL-10 from baseline to 14 weeks following intervention were summarized and reported. Samples were collected at two time points prior to the intervention and the results from these analyses were averaged and compared to the 14-week results. |
| Change in HIV Viral Load Suppression | From Baseline to 14 weeks | Change in HIV viral load suppression from baseline was measured and assessed at 14 weeks. Blood draws were obtained at baseline and 14 weeks following intervention and samples were processed, analyzed, and quantified using the Abbott RealTime HIV-1 Viral Load assay. Results were summarized and HIV viral load values were reported in copies/milliliter (copies/mL). For purposes of this study change in HIV viral load from baseline to 14 weeks following intervention were summarized and reported. Positive values are indicative of increased HIV viral load levels compared to baseline and negative values are indicative of decreased/suppressed HIV viral load levels compared to baseline. A high HIV viral load in the blood is associated with increased risk of disease progression and HIV transmission. |
| Change in Depression Score | From Baseline to 14 weeks | Change in Depression score was measured at baseline and 14 weeks using the Center for Epidemiologic Studies Depression (CES-D) questionnaire. The CES-D questionnaire is a 20-item screening tool used to assess the severity and frequency of depressive symptoms. Participants were asked to rate each of the 20 items using a 4-point Likert scale ranging from 0 (Rarely/none of the time) to 3 (Most/all of the time) to describe symptoms over the prior week (Questions, 4, 8, 12, and 16 were reverse-scored). Scores were summed to yield an overall possible scoring range of 0-60 with higher scores being indicative of increased severity/frequency of depressive symptoms. For purposes of this study change in depression score from baseline to 14 weeks following intervention was summarized. Positive values are indicative of increased depressive symptom severity/frequency compared to baseline and negative values are indicative of decreased depressive symptom severity/frequency compared to baseline. |
| Change in Anxiety Score | From Baseline to 14 weeks | Change in Anxiety score was measured and assessed at baseline and 14 weeks using the Generalized Anxiety Disorder-7 (GAD-7). The GAD-7 is a 7-item screening tool used to assess the severity of anxiety-related symptoms. Participants were asked to rate each of the 7 items using a 4-point Likert scale ranging from 0 (Not at all) to 3 (Nearly every day) to indicate how long they have been bothered by the problems listed over the prior 2-week period, yielding an overall possible score of 0-21, with higher scores being indicative of worsening anxiety. Scores were summarized by study arm. For purposes of this study change in anxiety score from baseline to 14 weeks following intervention was summarized and reported. Positive values are indicative of increased anxiety symptoms compared to baseline and negative values are indicative of decreased anxiety symptoms compared to baseline. |
| Change in Antiretroviral Medication Adherence Score | From Baseline to 14 weeks | Change in Antiretroviral medication adherence from baseline to 14 weeks was assessed using the Visual Analog Scale (VAS) of antiretroviral therapy (ART) adherence. This is an ordinal scale representing the percentage of medication taken to that which had been administered. Participants were presented with a visual ranging from 0% to 100% scaled at 10% increments and asked to provide a best guess as to how much medicine was taken over the prior 30 days with 0% signifying no medication, 50% signifying half of administered medication taken, and 100% signifying that every single dose of medication was taken. Higher scores were indicative of increased medication adherence. Scores were summarized by study arm. For purposes of this study change in antiretroviral adherence score from baseline to 14 weeks following intervention was summarized and reported. Positive values are indicative of increased medication adherence from baseline and negative values are indicative of decreased adherence. |
Countries
United States
Participant flow
Pre-assignment details
Thirty-five (35) participants were consented and enrolled into the study. One participant completed screening, consent and enrollment, but then did not want to be randomized into one of the coupon categories (study arms). As such, 34 patients were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Coupon for a Discounted Placebo Product Participants who were previously randomized to a coupon for discounted placebo soft-gel capsules by the collaborators, Vireo, will be observed.
Receipt of Coupon for Placebo Soft-Gel Capsule: The investigators will follow participants who were randomized to receive a coupon for placebo soft-gel capsule medical cannabis products by our collaborators at Vireo medical cannabis dispensary in a separate study | 9 |
| Coupon for a Discounted High THC Product Participants who were previously randomized to a coupon for discounted 4.3 mg THC/0.7 mg CBD soft-gel capsules by the collaborators, Vireo, will be observed.
Receipt of Coupon for High THC Soft-Gel Capsule: The investigators will follow participants who were randomized to receive a coupon for high THC soft-gel capsule medical cannabis products by our collaborators at Vireo medical cannabis dispensary in a separate study | 8 |
| Coupon for a Discounted Equal THC and CBD Product Participants who were previously randomized to a coupon for discounted 2.5 mg THC/2.5 mg CBD soft-gel capsules by the collaborators, Vireo, will be observed.
Receipt of Coupon for Equal THC and CBD Soft-Gel Capsule: The investigators will follow participants who were randomized to receive a coupon for equal THC and CBD soft-gel capsule medical cannabis products by our collaborators at Vireo medical cannabis dispensary in a separate study | 9 |
| Coupon for a Discounted High CBD Product Participants who were previously randomized to a coupon for discounted 0.2 mg THC/4.8 mg CBD soft-gel capsules by the collaborators, Vireo, will be observed.
Receipt of Coupon for High CBD Soft-Gel Capsule: The investigators will follow participants who were randomized to receive a coupon for high CBD soft-gel capsule medical cannabis products by our collaborators at Vireo medical cannabis dispensary in a separate study | 8 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | No longer interested in participating | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Coupon for a Discounted Placebo Product | Coupon for a Discounted High THC Product | Coupon for a Discounted Equal THC and CBD Product | Coupon for a Discounted High CBD Product | Total |
|---|---|---|---|---|---|
| Age, Continuous | 50.1 years STANDARD_DEVIATION 10.9 | 52.5 years STANDARD_DEVIATION 9.65 | 55.9 years STANDARD_DEVIATION 10.7 | 61.8 years STANDARD_DEVIATION 6.96 | 55.0 years STANDARD_DEVIATION 9.63 |
| Antiretroviral Medication Adherence Score | 9.25 score on a scale STANDARD_DEVIATION 1.5 | 10 score on a scale STANDARD_DEVIATION 0 | 8 score on a scale STANDARD_DEVIATION 3.46 | 8.25 score on a scale STANDARD_DEVIATION 2.36 | 8.93 score on a scale STANDARD_DEVIATION 1.72 |
| Anxiety Score | 12.43 score on a scale STANDARD_DEVIATION 6.85 | 5.71 score on a scale STANDARD_DEVIATION 3.09 | 9.62 score on a scale STANDARD_DEVIATION 6.14 | 7.38 score on a scale STANDARD_DEVIATION 6.59 | 8.77 score on a scale STANDARD_DEVIATION 5.71 |
| CD4 Count | 658.63 cells/uL STANDARD_DEVIATION 414.89 | 699.12 cells/uL STANDARD_DEVIATION 185.88 | 828.78 cells/uL STANDARD_DEVIATION 444.96 | 621.43 cells/uL STANDARD_DEVIATION 458.37 | 708.47 cells/uL STANDARD_DEVIATION 375.61 |
| Circulating levels of Pro-Inflammatory and Anti-inflammatory Cytokines Interleukin-10 (IL-10) | 4.01 NPX value STANDARD_DEVIATION 0.53 | 3.7 NPX value STANDARD_DEVIATION 0.3 | 3.98 NPX value STANDARD_DEVIATION 0.68 | 3.69 NPX value STANDARD_DEVIATION 0.35 | 3.84 NPX value STANDARD_DEVIATION 0.47 |
| Circulating levels of Pro-Inflammatory and Anti-inflammatory Cytokines Interleukin-4 (IL-4) | 0.94 NPX value STANDARD_DEVIATION 0.77 | 0.47 NPX value STANDARD_DEVIATION 0.25 | 0.55 NPX value STANDARD_DEVIATION 0.49 | 0.81 NPX value STANDARD_DEVIATION 1.22 | 0.66 NPX value STANDARD_DEVIATION 0.65 |
| Circulating levels of Pro-Inflammatory and Anti-inflammatory Cytokines Interleukin-6 (IL-6) | 4.2 NPX value STANDARD_DEVIATION 0.73 | 4.17 NPX value STANDARD_DEVIATION 1.11 | 4.42 NPX value STANDARD_DEVIATION 0.67 | 4.52 NPX value STANDARD_DEVIATION 1.19 | 4.33 NPX value STANDARD_DEVIATION 0.92 |
| Circulating levels of Pro-Inflammatory and Anti-inflammatory Cytokines Tumor Necrosis Factor Alpha (TNFa) | 4.32 NPX value STANDARD_DEVIATION 0.89 | 3.95 NPX value STANDARD_DEVIATION 0.31 | 4.11 NPX value STANDARD_DEVIATION 0.49 | 3.97 NPX value STANDARD_DEVIATION 0.24 | 4.08 NPX value STANDARD_DEVIATION 0.46 |
| Depression Score | 24.14 score on a scale STANDARD_DEVIATION 11.61 | 23 score on a scale STANDARD_DEVIATION 9.93 | 16.37 score on a scale STANDARD_DEVIATION 7.93 | 17.88 score on a scale STANDARD_DEVIATION 11.19 | 20.13 score on a scale STANDARD_DEVIATION 10.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 1 Participants | 6 Participants | 4 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 7 Participants | 3 Participants | 4 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HIV Viral Load Suppression | 9560.33 copies/mL STANDARD_DEVIATION 29836.6 | 0 copies/mL STANDARD_DEVIATION 0 | 4.67 copies/mL STANDARD_DEVIATION 13.2 | 18193.38 copies/mL STANDARD_DEVIATION 5000.73 | 6812.71 copies/mL STANDARD_DEVIATION 9078.06 |
| Pain Severity Score | 6.22 score on a scale STANDARD_DEVIATION 2.54 | 7.63 score on a scale STANDARD_DEVIATION 1.18 | 8.56 score on a scale STANDARD_DEVIATION 1.13 | 7.5 score on a scale STANDARD_DEVIATION 1.85 | 7.47 score on a scale STANDARD_DEVIATION 1.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 5 Participants | 4 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants |
| Region of Enrollment United States | 9 participants | 8 participants | 9 participants | 8 participants | 34 participants |
| Sex: Female, Male Female | 0 Participants | 5 Participants | 7 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 2 Participants | 4 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 1 / 9 | 1 / 8 | 0 / 9 | 0 / 8 |
| serious Total, serious adverse events | 1 / 9 | 2 / 8 | 0 / 9 | 0 / 8 |
Outcome results
Primary
Change in Pain Severity Score
Change in self-reported Pain Severity was measured at weekly intervals from baseline through 14 weeks using the Brief Pain Inventory (BPI) pain severity subscale. The BPI Pain Severity subscale uses a 0-10 numerical rating scale where 0 = No pain at all and 10 = Pain as bad as you can imagine; completely interferes such that higher scores were associated with increased Pain Severity. Participants were asked to assign a score to their pain, on average, over the prior week. Scores were summarized by study arm. For purposes of this study change in Pain Severity scores from baseline to 14 weeks following intervention were summarized and reported with positive values being indicative of increased pain severity compared to baseline and negative values being indicative of decreased pain severity compared to baseline.
Time frame: At weekly intervals from Baseline to 14 weeks
Population: Number of participants analyzed is summarized for each arm/group at each week in the table below. Reasons for variability in the number of participants analyzed is attributable to missed virtual visits or incomplete data collection during specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 10 | 4.22 score on a scale | Standard Deviation 3.73 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 7 | 4.11 score on a scale | Standard Deviation 3.62 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 1 | 6.44 score on a scale | Standard Deviation 2.07 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 8 | 4.25 score on a scale | Standard Deviation 3.11 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 13 | 3.55 score on a scale | Standard Deviation 3.21 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 3 | 5.22 score on a scale | Standard Deviation 3.15 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 9 | 3.44 score on a scale | Standard Deviation 2.92 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 4 | 3.87 score on a scale | Standard Deviation 2.64 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 2 | 5.87 score on a scale | Standard Deviation 3.09 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 14 | -3 score on a scale | Standard Deviation 2.39 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 12 | 3.78 score on a scale | Standard Deviation 3.67 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 5 | 4 score on a scale | Standard Deviation 2.87 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 6 | 4.37 score on a scale | Standard Deviation 2.72 |
| Coupon for a Discounted Placebo Product | Change in Pain Severity Score | Week 11 | 3.88 score on a scale | Standard Deviation 3.72 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 6 | 5.14 score on a scale | Standard Deviation 3.43 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 3 | 5.86 score on a scale | Standard Deviation 2.23 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 4 | 6.28 score on a scale | Standard Deviation 2.63 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 7 | 5.57 score on a scale | Standard Deviation 2.29 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 8 | 4.86 score on a scale | Standard Deviation 3.67 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 9 | 5.5 score on a scale | Standard Deviation 4.63 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 11 | 4.75 score on a scale | Standard Deviation 2.96 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 12 | 6.37 score on a scale | Standard Deviation 3.89 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 13 | 5 score on a scale | Standard Deviation 3.21 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 10 | 5 score on a scale | Standard Deviation 3.16 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 1 | 6.86 score on a scale | Standard Deviation 2.27 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 2 | 6.67 score on a scale | Standard Deviation 2.58 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 5 | 3 score on a scale | Standard Deviation 2.34 |
| Coupon for a Discounted High THC Product | Change in Pain Severity Score | Week 14 | -2.625 score on a scale | Standard Deviation 2.77 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 14 | -3.28 score on a scale | Standard Deviation 2.36 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 13 | 5.43 score on a scale | Standard Deviation 3.15 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 2 | 7.37 score on a scale | Standard Deviation 1.76 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 5 | 7 score on a scale | Standard Deviation 2.23 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 4 | 7.14 score on a scale | Standard Deviation 2.73 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 7 | 6 score on a scale | Standard Deviation 2.2 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 1 | 8 score on a scale | Standard Deviation 2.38 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 8 | 6 score on a scale | Standard Deviation 2.56 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 9 | 5.28 score on a scale | Standard Deviation 3.03 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 12 | 5.87 score on a scale | Standard Deviation 3.18 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 11 | 6.83 score on a scale | Standard Deviation 3.37 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 10 | 7.6 score on a scale | Standard Deviation 2.07 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 3 | 7.57 score on a scale | Standard Deviation 2.25 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Pain Severity Score | Week 6 | 6.25 score on a scale | Standard Deviation 2.37 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 2 | 6.75 score on a scale | Standard Deviation 2.43 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 11 | 5.37 score on a scale | Standard Deviation 2.97 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 4 | 6.375 score on a scale | Standard Deviation 2.92 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 12 | 6.14 score on a scale | Standard Deviation 2.61 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 13 | 5.63 score on a scale | Standard Deviation 2.5 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 8 | 6.57 score on a scale | Standard Deviation 2.69 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 3 | 6.37 score on a scale | Standard Deviation 2.92 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 14 | -1.88 score on a scale | Standard Deviation 2.1 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 5 | 6.17 score on a scale | Standard Deviation 2.71 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 7 | 5.5 score on a scale | Standard Deviation 3.07 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 1 | 7.37 score on a scale | Standard Deviation 2.5 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 9 | 4.14 score on a scale | Standard Deviation 2.97 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 6 | 5.37 score on a scale | Standard Deviation 2.77 |
| Coupon for a Discounted High CBD Product | Change in Pain Severity Score | Week 10 | 5.33 score on a scale | Standard Deviation 2.8 |
Comparison: The study team hypothesized that participants randomized to coupons for high THC products would have greater reduction in self-reported pain severity than high CBD, equal parts THC and CBD, or placebo.p-value: 0.030395% CI: [-4.98, -0.25]Mixed Models Analysis
Comparison: The study team hypothesized that participants randomized to coupons for high THC products would have greater reduction in self-reported pain severity than high CBD, equal parts THC and CBD, or placebo.p-value: 0.4851Mixed Models Analysis
Comparison: The study team hypothesized that participants randomized to coupons for high THC products would have greater reduction in self-reported pain severity than high CBD, equal parts THC and CBD, or placebo.p-value: 0.6165Mixed Models Analysis
Secondary
Change in Antiretroviral Medication Adherence Score
Change in Antiretroviral medication adherence from baseline to 14 weeks was assessed using the Visual Analog Scale (VAS) of antiretroviral therapy (ART) adherence. This is an ordinal scale representing the percentage of medication taken to that which had been administered. Participants were presented with a visual ranging from 0% to 100% scaled at 10% increments and asked to provide a best guess as to how much medicine was taken over the prior 30 days with 0% signifying no medication, 50% signifying half of administered medication taken, and 100% signifying that every single dose of medication was taken. Higher scores were indicative of increased medication adherence. Scores were summarized by study arm. For purposes of this study change in antiretroviral adherence score from baseline to 14 weeks following intervention was summarized and reported. Positive values are indicative of increased medication adherence from baseline and negative values are indicative of decreased adherence.
Time frame: From Baseline to 14 weeks
Population: A number of participants bypassed this question stating that they did not want to answer and skipped over it in the baseline questionnaire. No change from baseline results data was able to be reported from these participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coupon for a Discounted Placebo Product | Change in Antiretroviral Medication Adherence Score | -1 score on a scale | Standard Deviation 2.708 |
| Coupon for a Discounted High THC Product | Change in Antiretroviral Medication Adherence Score | 0 score on a scale | Standard Deviation 0 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Antiretroviral Medication Adherence Score | 2 score on a scale | Standard Deviation 3.46 |
| Coupon for a Discounted High CBD Product | Change in Antiretroviral Medication Adherence Score | 1 score on a scale | Standard Deviation 2 |
Comparison: The study team hypothesized that participants randomized to coupons for high THC products would have poorer Antiretroviral (ARV) medication adherence than those randomized to coupons for high CBD, equal parts THC and CBD, or placebo.p-value: 0.39ANOVA
Secondary
Change in Anxiety Score
Change in Anxiety score was measured and assessed at baseline and 14 weeks using the Generalized Anxiety Disorder-7 (GAD-7). The GAD-7 is a 7-item screening tool used to assess the severity of anxiety-related symptoms. Participants were asked to rate each of the 7 items using a 4-point Likert scale ranging from 0 (Not at all) to 3 (Nearly every day) to indicate how long they have been bothered by the problems listed over the prior 2-week period, yielding an overall possible score of 0-21, with higher scores being indicative of worsening anxiety. Scores were summarized by study arm. For purposes of this study change in anxiety score from baseline to 14 weeks following intervention was summarized and reported. Positive values are indicative of increased anxiety symptoms compared to baseline and negative values are indicative of decreased anxiety symptoms compared to baseline.
Time frame: From Baseline to 14 weeks
Population: 4 participants did not complete the Anxiety questionnaire during baseline visit. No change from baseline results data was able to be reported from these participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coupon for a Discounted Placebo Product | Change in Anxiety Score | -5.71 score on a scale | Standard Deviation 4.07 |
| Coupon for a Discounted High THC Product | Change in Anxiety Score | -1.43 score on a scale | Standard Deviation 2.57 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Anxiety Score | -1.75 score on a scale | Standard Deviation 4.68 |
| Coupon for a Discounted High CBD Product | Change in Anxiety Score | -1.12 score on a scale | Standard Deviation 6.03 |
Comparison: The study team hypothesized that participants randomized to coupons for high THC products would have greater anxiety than those randomized to coupons for high CBD, equal parts THC and CBD, or placebo.p-value: 0.22ANOVA
Secondary
Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-10 (IL-10)
Change in circulating test levels of recent inflammation (based on a panel of inflammatory markers) from baseline to 14 weeks was analyzed. Blood draws for circulating levels of pro- and anti-inflammatory cytokines were collected, processed, and analyzed using an O-link assay which uses normal protein expression (NPX) values expressed on a log2 scale, where a higher value indicates a higher protein level. Results for IL-10 are summarized by study arm using basic descriptive statistics. For purposes of this study change in circulating levels of IL-10 from baseline to 14 weeks following intervention were summarized and reported. Samples were collected at two time points prior to the intervention and the results from these analyses were averaged and compared to the 14-week results.
Time frame: From Baseline to 14 weeks
Population: Samples were not obtained from a number of participants at baseline and there were quality control issues with a couple of the samples. Accordingly, no change from baseline results data are available for these patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coupon for a Discounted Placebo Product | Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-10 (IL-10) | 0.15 NPX value | Standard Deviation 1.12 |
| Coupon for a Discounted High THC Product | Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-10 (IL-10) | 0.41 NPX value | Standard Deviation 0.83 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-10 (IL-10) | 0.11 NPX value | Standard Deviation 0.44 |
| Coupon for a Discounted High CBD Product | Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-10 (IL-10) | 0.65 NPX value | Standard Deviation 0.85 |
Comparison: The study team hypothesized that anti-inflammatory cytokines (IL-4 and IL-10) would have greater increase in participants randomized to coupons for high CBD products than the other arms.p-value: 0.6ANOVA
Secondary
Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-4 (IL-4)
Change in circulating test levels of recent inflammation (based on a panel of inflammatory markers) from baseline to 14 weeks was analyzed. Blood draws for circulating levels of pro- and anti-inflammatory cytokines were collected, processed, and analyzed using an O-link assay which uses normal protein expression (NPX) values expressed on a log2 scale, where a higher value indicates a higher protein level. Results for IL-4 are summarized by study arm using basic descriptive statistics. For purposes of this study change in circulating levels of IL-4 from baseline to 14 weeks following intervention were summarized and reported. Samples were collected at two time points prior to the intervention and the results from these analyses were averaged and compared to the 14-week results.
Time frame: From Baseline to 14 weeks
Population: Samples were not obtained from a number of participants at baseline and there were quality control issues with a couple of the samples. Accordingly, no change from baseline results data are available for these patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coupon for a Discounted Placebo Product | Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-4 (IL-4) | -0.33 NPX value | Standard Deviation 0.57 |
| Coupon for a Discounted High THC Product | Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-4 (IL-4) | -0.21 NPX value | Standard Deviation 0.48 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-4 (IL-4) | 0.02 NPX value | Standard Deviation 0.5 |
| Coupon for a Discounted High CBD Product | Change in Circulating Levels of Anti-inflammatory Cytokines - Interleukin-4 (IL-4) | 0.07 NPX value | Standard Deviation 0.54 |
Comparison: The study team hypothesized that anti-inflammatory cytokines (IL-4 and IL-10) would have greater increase in participants randomized to coupons for high CBD products than the other arms.p-value: 0.49ANOVA
Secondary
Change in Circulating Levels of Pro-inflammatory Cytokines - Interleukin-6 (IL-6)
Change in circulating test levels of recent inflammation (based on a panel of inflammatory markers) from baseline to 14 weeks was analyzed. Blood draws for circulating levels of pro- and anti-inflammatory cytokines were collected, processed, and analyzed using an O-link assay which uses normal protein expression (NPX) values expressed on a log2 scale, where a higher value indicates a higher protein level. Results for IL-6 are summarized by study arm using basic descriptive statistics. For purposes of this study change in circulating levels of IL-6 from baseline to 14 weeks following intervention were summarized and reported. Samples were collected at two time points prior to the intervention and the results from these analyses were averaged and compared to the 14-week results.
Time frame: From Baseline to 14 weeks
Population: Samples were not obtained from a number of participants at baseline and there were quality control issues with a couple of the samples. Accordingly, no change from baseline results data are available for these patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coupon for a Discounted Placebo Product | Change in Circulating Levels of Pro-inflammatory Cytokines - Interleukin-6 (IL-6) | 0.24 NPX value | Standard Deviation 0.73 |
| Coupon for a Discounted High THC Product | Change in Circulating Levels of Pro-inflammatory Cytokines - Interleukin-6 (IL-6) | 0.11 NPX value | Standard Deviation 1.58 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Circulating Levels of Pro-inflammatory Cytokines - Interleukin-6 (IL-6) | -0.18 NPX value | Standard Deviation 0.83 |
| Coupon for a Discounted High CBD Product | Change in Circulating Levels of Pro-inflammatory Cytokines - Interleukin-6 (IL-6) | -0.09 NPX value | Standard Deviation 0.33 |
Comparison: The study team hypothesized that pro-inflammatory cytokines (TNFa and IL-6) would have greater reduction in participants randomized to coupons for high CBD products than the other arms.p-value: 0.88ANOVA
Secondary
Change in Circulating Levels of Pro-inflammatory Cytokines - Tumor Necrosis Factor Alpha (TNFa)
Change in circulating test levels of recent inflammation (based on a panel of inflammatory markers) from baseline to 14 weeks was analyzed. Blood draws for circulating levels of pro- and anti-inflammatory cytokines were collected, processed, and analyzed using an O-link assay which uses normal protein expression (NPX) values expressed on a log2 scale, where a higher value indicates a higher protein level. Results for TNFa are summarized by study arm using basic descriptive statistics. For purposes of this study change in circulating levels of TNFa from baseline to 14 weeks following intervention were summarized and reported. Samples were collected at two time points prior to the intervention and the results from these analyses were averaged and compared to the 14-week results.
Time frame: From Baseline to 14 weeks
Population: Samples were not obtained from a number of participants at baseline and there were quality control issues with a couple of the samples. Accordingly, no change from baseline results data are available for these patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coupon for a Discounted Placebo Product | Change in Circulating Levels of Pro-inflammatory Cytokines - Tumor Necrosis Factor Alpha (TNFa) | -0.02 NPX value | Standard Deviation 0.64 |
| Coupon for a Discounted High THC Product | Change in Circulating Levels of Pro-inflammatory Cytokines - Tumor Necrosis Factor Alpha (TNFa) | 0.03 NPX value | Standard Deviation 0.37 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Circulating Levels of Pro-inflammatory Cytokines - Tumor Necrosis Factor Alpha (TNFa) | 0.05 NPX value | Standard Deviation 0.18 |
| Coupon for a Discounted High CBD Product | Change in Circulating Levels of Pro-inflammatory Cytokines - Tumor Necrosis Factor Alpha (TNFa) | -0.18 NPX value | Standard Deviation 0.24 |
Comparison: The study team hypothesized that pro-inflammatory cytokines (TNFa and IL-6) would have greater reduction in participants randomized to coupons for high CBD products than the other arms.p-value: 0.66ANOVA
Secondary
Change in Depression Score
Change in Depression score was measured at baseline and 14 weeks using the Center for Epidemiologic Studies Depression (CES-D) questionnaire. The CES-D questionnaire is a 20-item screening tool used to assess the severity and frequency of depressive symptoms. Participants were asked to rate each of the 20 items using a 4-point Likert scale ranging from 0 (Rarely/none of the time) to 3 (Most/all of the time) to describe symptoms over the prior week (Questions, 4, 8, 12, and 16 were reverse-scored). Scores were summed to yield an overall possible scoring range of 0-60 with higher scores being indicative of increased severity/frequency of depressive symptoms. For purposes of this study change in depression score from baseline to 14 weeks following intervention was summarized. Positive values are indicative of increased depressive symptom severity/frequency compared to baseline and negative values are indicative of decreased depressive symptom severity/frequency compared to baseline.
Time frame: From Baseline to 14 weeks
Population: 4 participants did not complete the Depression questionnaire during baseline visit. No change from baseline results data was able to be reported from these participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coupon for a Discounted Placebo Product | Change in Depression Score | -9.71 score on a scale | Standard Deviation 6.6 |
| Coupon for a Discounted High THC Product | Change in Depression Score | -9 score on a scale | Standard Deviation 9.39 |
| Coupon for a Discounted Equal THC and CBD Product | Change in Depression Score | -3.56 score on a scale | Standard Deviation 7.07 |
| Coupon for a Discounted High CBD Product | Change in Depression Score | -2.25 score on a scale | Standard Deviation 5.52 |
Comparison: The study team hypothesized that participants randomized to coupons for high THC products would have greater depression than those randomized to coupons for high CBD, equal parts THC and CBD, or placebo.p-value: 0.13ANOVA
Secondary
Change in HIV Viral Load Suppression
Change in HIV viral load suppression from baseline was measured and assessed at 14 weeks. Blood draws were obtained at baseline and 14 weeks following intervention and samples were processed, analyzed, and quantified using the Abbott RealTime HIV-1 Viral Load assay. Results were summarized and HIV viral load values were reported in copies/milliliter (copies/mL). For purposes of this study change in HIV viral load from baseline to 14 weeks following intervention were summarized and reported. Positive values are indicative of increased HIV viral load levels compared to baseline and negative values are indicative of decreased/suppressed HIV viral load levels compared to baseline. A high HIV viral load in the blood is associated with increased risk of disease progression and HIV transmission.
Time frame: From Baseline to 14 weeks
Population: Samples were unable to be obtained from several participants at baseline. No change from baseline results data was able to be reported from these participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coupon for a Discounted Placebo Product | Change in HIV Viral Load Suppression | -12270.43 copies/mL | Standard Deviation 32267.19 |
| Coupon for a Discounted High THC Product | Change in HIV Viral Load Suppression | 7.7 copies/mL | Standard Deviation 20.4 |
| Coupon for a Discounted Equal THC and CBD Product | Change in HIV Viral Load Suppression | -5 copies/mL | Standard Deviation 14.9 |
| Coupon for a Discounted High CBD Product | Change in HIV Viral Load Suppression | 3737 copies/mL | Standard Deviation 9891.17 |
Comparison: The study team hypothesized that participants randomized to coupons for high THC products would have less suppressed HIV viral load than those randomized to coupons for high CBD, equal parts THC and CBD or placebo.p-value: 0.31ANOVA