Cannabis, HIV Neuropathy, Pain Syndrome
Conditions
Keywords
neuropathic pain, human immunovirus, vaporized cannabis
Brief summary
Acute cannabis administration is reported to alleviate HIV neuropathic pain (HIV-NP), but there is limited knowledge about the effects of cannabis constituents (delta-9 tetrahydrocannabinol/THC and cannabidiol/CBD), the consequences of long-term cannabis use, and the impact of cannabis on endocannabinoid (EC) function in people living with HIV- NP. Our objective is to address these three fundamental gaps in our knowledge by: 1) examining the acute effects of various CBD/THC products on HIV-NP, 2) utilizing a mHealth text messaging protocol, Individual Monitoring of Pain and Cannabis Taken (IMPACT) to monitor daily real-world cannabis use and changes in pain; and 3) studying the relationship between cannabinoids, EC biomarkers, and chronic neuropathic pain
Detailed description
Our objective is to assess 120 community-dwelling people living with HIV who have neuropathic pain and are currently using cannabis. These participants will be enrolled in a study that consists of two phases: Phase 1) This will involve a cross over study involving three different doses of vaporized cannabis that contain THC and varying concentrations of CBD: * Low CBD session: 8 puffs of 1.9% THC + 0.01% CBD * Medium CBD sessions: 4 puffs of 1.4% THC + 0.01% CBD plus 4 puffs of 1.4% THC + 5.1% CBD * High CBD sessions: 8 puffs of 1.4% THC + 5.1% CBD This phase will examine the acute effects of cannabis on pain intensity, blood endocannabinoid levels, and the relationship of pain with heart rate variability (HRV). Phase 2) This phase will involve the association between dispensary-obtained cannabis and changes in pain reported via IMPACT, a mHealth text messaging program that will serve as a useful tool to monitor the relationship between pain and cannabis use. Text messaging is an effective method to modify health behaviors, monitor substance use, and track pain. Our group has recently demonstrated the feasibility of using short message service (SMS) texting to promote anti-retroviral therapy adherence and monitor daily methamphetamine (METH) use in persons living with HIV neuropathy with bipolar disorder or METH dependence.
Interventions
DRUGCannabis
vaporization of cannabis
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants will receive vaporized cannabis using Volcano vaporizers (Storz and Bickel) with either 3.74% THC + 0.49% CBD, 3.49% THC + 4.17% CBD, or 3.11% THC + 15.76% CBD at each of three visits. Allocation assignment of visits will be assigned using a Web-based random number- generating program, Research Randomizer (http:// www.randomizer.org/). The allocation schedule will be kept in the pharmacy and concealed from other study personnel.
Intervention model description
Acutely administered CBD/THC will reduce HIV-neuropathic pain in a stair-step manner; the highest CBD dose will provide the greatest pain reduction (high CBD \> medium CBD \> low CBD).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. the ability to provide informed consent 2. age 18 or older 3. HIV infection documented at the HNRP or assessed by an HIV test at screening; 4. a diagnosis of HIV sensory neuropathy 5. current use of cannabis 6. the ability to describe the THC and CBD content in the products they use, i.e., obtaining cannabis from dispensaries that list THC and CBD content 7. ability to respond to daily text message
Exclusion criteria
1. meeting criteria for current substance or alcohol dependence 2. traumatic brain injury 3. dementia or Alzheimer's disease 4. psychosis 5. a respiratory condition, i.e., pulmonary disease, that would be exacerbated by inhaling vaporized cannabis 6. history of cardiovascular disease, including myocardial infarction or stroke; 7. uncontrolled hypertension, defined as a systolic blood pressure greater than 160 mm Hg or a diastolic blood pressure greater than 100 mm Hg 8. pregnancy, breastfeeding, or unwillingness to prevent pregnancy during the cannabis administration portion of the study (using birth control in female participants of child- bearing age) 9. unwillingness or inability to receive or respond to text messages
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 - Numerical Pain Rating Scale (NPRS) | Pain is measured once before they receive study medication and then 2 minutes after drug treatment. | This is a scale from 0 to 10 indicating the self-reported level of pain. 0 is the minimum score, indicating no pain. 10 is the maximum score indicating highest level of pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 - Patient Global Impression of Change (PGIC) | The PGIC was measured two minutes after drug administration. | This is a 7-point ordinal scale that asks the participant to rate improvement in their pain after drug administration compared to before drug administration. The scale range is 1 to 7. A score of 1 indicates the greatest improvement (reduction) in pain. A score of 7 indicates that pain is worse. |
| Phase 1 - Von Frey Test | The von Frey test was administered before drug administration and two minutes after drug administration. | This test measures sensitivity to pain causes by physical contact with the skin. The von Frey filament is applied to the dorsum of the more painful foot until bending is observed for 3 seconds. Pain is rated using a visual analog score (VAS). The scale is 0 to 100, where 0 indicates no pain and 100 indicates the worst pain. |
| Phase 1 - Marijuana Subscale (M-scale) of the Addiction Research Center Inventory (ARCI) | The M-scale was administered 2 minutes after drug treatment. | The M-scale has 12 true/false statements describing the subjective effects of marijuana on participants after they take the drug. Each question is scored as 0 or 1. The scale ranges from 0 (minimum score) to 12 (maximum score). A lower score indicates that the participant is experiencing fewer side effects of the drug. A higher score indicates that the participant is experiencing more side effects of the drug. Reported side effects on this scale include dry mouth, slower movements, shaking hands, and having a pleasant feeling. |
| Phase 1 - Levels of the Endocannabinoid Biomarker Anandamide (AEA) | AEA was quantified 60 minutes after drug administration. | Anandamide levels in plasma were quantified using liquid chromatography-tandem mass spectrometry (LC/MS). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cannabis Administration Sessions Participants attend three daily sessions, separated by 3- to 5-day intervals, where they inhale cannabis products. At one session (Low CBD) they inhale 8 puffs of vaporized cannabis containing 1.9% THC + 0.01 CBD. At one session (Medium CBD) they inhale 8 puffs of vaporized cannabis where 4 puffs contain 1.9% THC + 0.01 CBD and 4 puffs will contain 1.4% THC + 5.1% CBD. At one session (High CBD) they inhale 8 puffs of vaporized cannabis containing 1.4% THC + 5.1% CBD. The order of the Low CBD, Medium CBD, and High CBD sessions is randomized.
Cannabis: vaporization of cannabis | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Cannabis Administration Sessions |
|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 3.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 3 / 5 | 2 / 5 | 2 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Phase 1 - Numerical Pain Rating Scale (NPRS)
This is a scale from 0 to 10 indicating the self-reported level of pain. 0 is the minimum score, indicating no pain. 10 is the maximum score indicating highest level of pain.
Time frame: Pain is measured once before they receive study medication and then 2 minutes after drug treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low CBD Session | Phase 1 - Numerical Pain Rating Scale (NPRS) | Before Drug Administration | 2.2 units on a scale | Standard Error 0.7 |
| Low CBD Session | Phase 1 - Numerical Pain Rating Scale (NPRS) | After Cannabis Administration | 1.4 units on a scale | Standard Error 0.6 |
| Medium CBD Session | Phase 1 - Numerical Pain Rating Scale (NPRS) | Before Drug Administration | 2.6 units on a scale | Standard Error 1 |
| Medium CBD Session | Phase 1 - Numerical Pain Rating Scale (NPRS) | After Cannabis Administration | 1.2 units on a scale | Standard Error 0.6 |
| High CBD Session | Phase 1 - Numerical Pain Rating Scale (NPRS) | Before Drug Administration | 2.8 units on a scale | Standard Error 0.8 |
| High CBD Session | Phase 1 - Numerical Pain Rating Scale (NPRS) | After Cannabis Administration | 1.2 units on a scale | Standard Error 0.4 |
Secondary
Phase 1 - Levels of the Endocannabinoid Biomarker Anandamide (AEA)
Anandamide levels in plasma were quantified using liquid chromatography-tandem mass spectrometry (LC/MS).
Time frame: AEA was quantified 60 minutes after drug administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low CBD Session | Phase 1 - Levels of the Endocannabinoid Biomarker Anandamide (AEA) | 0.52 nanograms per milliliter (ng/ml) | Standard Error 0.08 |
| Medium CBD Session | Phase 1 - Levels of the Endocannabinoid Biomarker Anandamide (AEA) | 0.53 nanograms per milliliter (ng/ml) | Standard Error 0.16 |
| High CBD Session | Phase 1 - Levels of the Endocannabinoid Biomarker Anandamide (AEA) | 0.49 nanograms per milliliter (ng/ml) | Standard Error 0.13 |
Secondary
Phase 1 - Marijuana Subscale (M-scale) of the Addiction Research Center Inventory (ARCI)
The M-scale has 12 true/false statements describing the subjective effects of marijuana on participants after they take the drug. Each question is scored as 0 or 1. The scale ranges from 0 (minimum score) to 12 (maximum score). A lower score indicates that the participant is experiencing fewer side effects of the drug. A higher score indicates that the participant is experiencing more side effects of the drug. Reported side effects on this scale include dry mouth, slower movements, shaking hands, and having a pleasant feeling.
Time frame: The M-scale was administered 2 minutes after drug treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low CBD Session | Phase 1 - Marijuana Subscale (M-scale) of the Addiction Research Center Inventory (ARCI) | 1.4 score on a scale | Standard Error 0.5 |
| Medium CBD Session | Phase 1 - Marijuana Subscale (M-scale) of the Addiction Research Center Inventory (ARCI) | 3.2 score on a scale | Standard Error 0.6 |
| High CBD Session | Phase 1 - Marijuana Subscale (M-scale) of the Addiction Research Center Inventory (ARCI) | 1.8 score on a scale | Standard Error 0.4 |
Secondary
Phase 1 - Patient Global Impression of Change (PGIC)
This is a 7-point ordinal scale that asks the participant to rate improvement in their pain after drug administration compared to before drug administration. The scale range is 1 to 7. A score of 1 indicates the greatest improvement (reduction) in pain. A score of 7 indicates that pain is worse.
Time frame: The PGIC was measured two minutes after drug administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low CBD Session | Phase 1 - Patient Global Impression of Change (PGIC) | 2.8 score on a scale | Standard Error 0.6 |
| Medium CBD Session | Phase 1 - Patient Global Impression of Change (PGIC) | 2.6 score on a scale | Standard Error 0.4 |
| High CBD Session | Phase 1 - Patient Global Impression of Change (PGIC) | 3.4 score on a scale | Standard Error 0.7 |
Secondary
Phase 1 - Von Frey Test
This test measures sensitivity to pain causes by physical contact with the skin. The von Frey filament is applied to the dorsum of the more painful foot until bending is observed for 3 seconds. Pain is rated using a visual analog score (VAS). The scale is 0 to 100, where 0 indicates no pain and 100 indicates the worst pain.
Time frame: The von Frey test was administered before drug administration and two minutes after drug administration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low CBD Session | Phase 1 - Von Frey Test | Before Drug Administration | 28 units on a scale | Standard Error 11.1 |
| Low CBD Session | Phase 1 - Von Frey Test | After Cannabis Administration | 7.4 units on a scale | Standard Error 3.8 |
| Medium CBD Session | Phase 1 - Von Frey Test | Before Drug Administration | 13.4 units on a scale | Standard Error 9.4 |
| Medium CBD Session | Phase 1 - Von Frey Test | After Cannabis Administration | 10.8 units on a scale | Standard Error 5.7 |
| High CBD Session | Phase 1 - Von Frey Test | Before Drug Administration | 14.5 units on a scale | Standard Error 6.4 |
| High CBD Session | Phase 1 - Von Frey Test | After Cannabis Administration | 8.8 units on a scale | Standard Error 5.1 |