Effect of Cannabis and Endocannabinoids on HIV Neuropathic Pain

Study Overview
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Brief Summary
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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
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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 1.6% THC + 0.09 CBD Medium CBD sessions: 4 puffs of 1.6% THC + 0.09 CBD plus 4 puffs of 1.73% THC + 5.4% CBD High CBD sessions: 8 puffs of 1.73% THC + 5.4% 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.

Official Title
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Effect of Cannabis Administration and Endocannabinoids on HIV Neuropathic Pain Primary Study - Phase 2

Conditions
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Cannabis, HIV Neuropathy, Pain Syndrome

Intervention / Treatment
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* Drug: Cannabis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: the ability to provide informed consent age 18 or older HIV infection documented at the HNRP or assessed by an HIV test at screening; a diagnosis of HIV sensory neuropathy current use of cannabis 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 ability to respond to daily text message Exclusion Criteria: meeting criteria for current substance or alcohol dependence traumatic brain injury dementia or Alzheimer's disease psychosis a respiratory condition, i.e., pulmonary disease, that would be exacerbated by inhaling vaporized cannabis history of cardiovascular disease, including myocardial infarction or stroke; uncontrolled hypertension, defined as a systolic blood pressure greater than 160 mm Hg or a diastolic blood pressure greater than 100 mm Hg 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) unwillingness or inability to receive or respond to text messages

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Interventional 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).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low CBD session<br>In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.6% THC + 0.09 CBD. They will then undergo experimental testing as described below under Outcome Measures. | Drug: Cannabis<br>* vaporization of cannabis<br>* Other names: marijuana;|
| Active Comparator: Medium CBD session<br>In the morning, participants will inhale 8 puffs of vaporized cannabis 4 puffs will contain 1.6% THC + 0.09 CBD and 4 puffs will contain 1.73% THC + 5.4% CBD. They will then undergo experimental testing as described below under Outcome Measures. | Drug: Cannabis<br>* vaporization of cannabis<br>* Other names: marijuana;|
| Active Comparator: High CBD session<br>In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.73% THC + 5.4% CBD. They will then undergo experimental testing as described below under Outcome Measures. | Drug: Cannabis<br>* vaporization of cannabis<br>* Other names: marijuana;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 - numerical 11-point Pain Intensity Scale | an ordinal scale | participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day | 
| Phase 2 - numerical 11-point Pain Intensity Scale | participants receive interactive text questions sent once a day to their cell phone asking them to indicate their average pain level for the day on a 0 to 10 scale | participants will be queried on a daily basis for six months using text messaging | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 - Patient Global Impression of Change (PGIC) | a 7 point ordinal scale reflective of improvement in pain | participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and this outcome will be measured 3 times after study medication is provided during the treatment day | 
| Phase 1 - von Frey test | The von Frey filament will be applied on the dorsum of the more painful foot until bending is observed for 3 seconds, followed by a VAS pain rating | participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day | 
| 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 | participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day | 
| Phase 1 - Neuropsychological Assessment Battery | Testing will include the Wechsler Adult Intelligence Scale (WAIS-III) Digit Symbol, Hopkins Verbal Learning Test-Revised and Grooved Pegboard Test (motor) | participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day | 
| Phase 1 - heart rate variability | Heart Rate Variability (HRV) correlates with the level of pain intensity. Persons with effective analgesic treatment of chronic pain exhibited improved HRV relative to pain sufferers with ineffective treatment suggesting HRV may serve as a pain biomarker | participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day | 
| Phase 1 - store plasma samples for evaluation of THC, CBD, and endocannabinoid system biomarkers | Cannabinoid and endocannabinoid levels in plasma will be quantified using a liquid chromatography-tandem mass spectrometry (LC/MS) | participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuropathic pain, human immunovirus, vaporized cannabis