Project Summary Cannabis hyperemesis syndrome (CHS) is a frequently under-recognized syndrome of cyclic nausea and vomiting occurring in the context of daily chronic cannabis use. The characterization of CHS and rise in CHS cases treated in emergency departments correlates with increasing availability of medical and recreational cannabis. In Colorado medical cannabis liberalization led to a twofold increase in emergency department visits for cyclic vomiting; in New Mexico - when cannabis was legalized - incident CHS cases increased by 400%. Patients with CHS frequently have multiple Emergency Department (ED) visits, hospital admissions, and undergo non-diagnostic advanced imaging, such as CT and endoscopy, which are high cost practices that can be harmful to patients and result in unnecessary healthcare expenditure. Patients often have no choice but to visit the ED as there are extremely limited outpatient treatment resources available for CHS. Despite the increasing prevalence of CHS, there is no medical consensus on the root cause and there is a lack of understanding as to why this syndrome only recently emerged or why CHS occurs in some people who use cannabis daily, but not others. Since the 1970s the average potency (THC concentration) of cannabis preparations has steadily increased while concentrations of other cannabinoids, such as CBD, declined. Additionally, consumers can choose from a growing list of high THC concentration products, such as oils and waxes, with a THC content that can be >75%. High potency cannabis products are associated with increased levels of physiologic dependence, affective disturbances, and development of cannabis use disorder (CUD). CHS occurs in daily cannabis users at high risk of CUD, leading to the hypothesis that CHS may be associated with chronic exposure to higher potency cannabis. Given the large, demographic of young people with chronic cannabis use in the US and rising prevalence of CHS, there is an urgent need to better understand CHS causation and disease progression. A quantitative and qualitative mixed method study in a cohort of 40 patients recruited from the ED with active CHS symptoms will be performed. Over the 180-day period surrounding an index ED visit we will characterize cannabis product and use patterns in relation to symptoms and disease progression and explore motivations and barriers to change cannabis use and treatment engagement. This will be complimented with a toxicological assessment of whole blood cannabinoids and metabolites to evaluate differences in the toxicological cannabinoid profile in patients with CHS on separate occasions when experiencing versus not experiencing a cyclic vomiting episode. This foundational work will guide future cannabis policy and support the development of a patient-centered ED-based behavioral intervention focused on prevention and treatment options.