Effect of Cannabis and Endocannabinoids on HIV Neuropathic Pain

Phase 2

Completed

Conditions: HIV Neuropathy
Pain Syndrome
Cannabis

Interventions: Drug: Cannabis

Registration Number: NCT03099005

Lead Sponsor: University of California, San Diego

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 5

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Medium CBD session	Cannabis	In the morning, participants will inhale 8 puffs of vaporized cannabis 4 puffs will contain 1.9% THC + 0.01% CBD and 4 puffs will contain 1.4% THC + 5.1% CBD. They will then undergo experimental testing as described below under Outcome Measures.
High CBD session	Cannabis	In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.4% THC + 5.1% CBD. They will then undergo experimental testing as described below under Outcome Measures.
Low CBD session	Cannabis	In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.9% THC + 0.01% CBD. They will then undergo experimental testing as described below under Outcome Measures.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).