ABSTRACT Dr. Deepika Slawek’s overall goal is to improve health outcomes in people living with HIV (PLWH), with a focus on determining the impact of medical cannabis. PLWH have a high burden of pain, and most commonly experience neuropathic pain. It is associated with significant disability, including functional impairment, poor antiretroviral adherence, and virologic failure. Neuropathic pain in PLWH is related to persistent systemic inflammation despite virologic suppression and is deeply interrelated with psychological symptoms. It is frequently managed with opioids, despite a high risk of misuse and use disorder, prompting interest in alternative therapies for pain like medical cannabis. Medical cannabis use is explosively increasing in the United States, and pain and HIV are qualifying conditions in most states. Though medical cannabis successfully reduced pain in the few randomized control trials completed to date, there remain gaps in our understanding of how medical cannabis affects neuropathic pain in PLWH. No studies have evaluated how the main active components of medical cannabis, ?9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact neuropathic pain in PLWH; none have occurred with products comparable to those dispensed at medical cannabis dispensaries; none have examined the impact medical cannabis has on inflammation; and none have studied how medical cannabis impacts adverse events (e.g., psychological symptoms, antiretroviral adherence, and virologic failure). Federal policies make conducting a randomized trial of medical cannabis for the management of chronic pain in PLWH infeasible. Therefore, this study will employ two coupons that provide deep discounts to medical cannabis products that are legally dispensed in New York. This K23 mentored patient-oriented career development award will train Dr. Slawek in skills necessary to be successful in the fields of HIV and cannabis research. These are: 1) design and conduct of randomized trials, 2) translational cannabis research, 3) causal inference, and 4) mediation analysis. These skills will be applied to an innovative study to test how coupons that provide deep discounts for high THC medical cannabis products or high CBD medical cannabis products affect neuropathic pain, inflammation, and adverse events in PLWH. Through a multidisciplinary mentorship team, formal coursework, and the proposed research project, Dr. Slawek will achieve the professional growth needed to become an independent investigator contributing critical findings that will be integral to the care of PLWH.

PUBLIC HEALTH RELEVANCE People living with HIV (PLWH) have a high burden of pain, and most commonly experience neuropathic pain, for which there are few treatments. Medical cannabis has emerged as a possible treatment even though there is a dearth of information about its mechanism of analgesia and potential adverse events. This proposal will shed light on these gaps in our knowledge by examining how medical cannabis affects pain, inflammation, and adverse events in PLWH with chronic pain.