ABSTRACT In recent years, cannabis, and its constituents (delta-9 tetrahydrocannabinol [THC] and cannabidiol [CBD]) have been promoted as natural remedies, with chronic disease patients as prominent marketing targets. Consequently, adults with underlying medical conditions are more likely to use cannabis compared to adults without medical conditions. This is alarming given that evidence for therapeutic benefits or potential risks related to cannabis use is generally lacking. Additionally, the impact of cannabis use on the clinical course of chronic diseases, which could be significant, is unknown. Here, we propose to recruit a prospective cohort of adult patients with early-stage high blood pressure (BP). This sizable population (30% of all United States adults) are at a heightened risk for cardiovascular disease (CVD). We will recruit patients from primary care clinics in Michigan, where cannabis is legal for adult consumption, and use data from detailed questionnaires, physical exams and biospecimen collections across the 30-month study to a) characterize cannabis use trajectories among patients, b) estimate the association between cannabis use trajectories and cardiovascular risk status and c) estimate the association between cannabis use trajectories and underlying mechanisms of CVD including systemic inflammation, platelet aggregation and arterial vasospasm. We hypothesize that persistent or escalating high THC cannabis smoking trajectories will predict worsened cardiovascular risk status in patients with high BP compared to other use trajectories (e.g., high CBD, oral ingestion, cessation) or non-use. Epidemiological studies on the cardiovascular health effects of cannabis are scarce, their results are mixed, and they lack cannabis and CVD measurements proposed here. We will study the cardiovascular health effects of cannabis use while accounting for cannabis potency and route of administration. Existing research relied heavily on controlled laboratory studies, conducted using NIDA-supplied cannabis that differs from cannabis used in the real world. Hence, generalizability and applicability to human health remain uncertain. We will adapt a mobile pharmacology laboratory approach to assess the potency of cannabis products available to patients in Michigan. This proposal is important and timely given the recent changes in cannabis policies. In 2018, Michigan became the first state in the Midwest to legalize cannabis for recreational use. On the other hand, CVD is the leading cause of death in Michigan and the state rank poorly relative to other states. Characterizing cannabis use trajectories and how they relate to cardiovascular health over time is essential for cannabis policies, to identify which trajectories are associated with fewer or greater cardiovascular risks and communicate these risks and harm reduction strategies to the public. Our results will also inform medical cannabis recommendations, not only for patients with high BP, but for a diverse group of patients who need cannabis for the management of anorexia, pain, anxiety, or sleep problems, and are at increased risk of CVD (e.g., patients with HIV, depression, post- traumatic stress disorder and neuropathies).

PROJECT NARRATIVE The prevalence of cannabis use is increasing among United States adults with chronic medical conditions. Cannabis use may trigger acute cardiovascular complications, and this effect can be more pronounced among individuals at a heightened risk for cardiovascular disease. The goal of this proposal is to recruit a cohort of adult patients with early-stage high blood pressure (i.e., hypertension) and study the prospective association between cannabis use trajectories and cardiovascular health.