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

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.

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

The principal investigator, Brook Henry PhD (blhenry@ucsd.edu), will supply individual participant data to other researchers after the project is completed.

Adverse event data were collected during the 6 hours following each drug administration.

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.