Oral Nicotine Pouch Use and Potential Health Effects among AYAs - Project Summary Oral nicotine pouches (ONPs)- small and dissolvable microfiber sachets pre-filled with microcrystalline powder, nicotine, and other constituents - are gaining popularity among U.S. adolescents and young adults (AYAs). In 2023, ONP was the second most used tobacco product among U.S. youth, with adolescent use rising sharply between 2023 and 2024. Among young adults, past-month ONP use doubled from 1.6% in 2022 to 3.2% in 2023. Meanwhile, monthly sales of ONP units more than tripled from 327 million in July 2021 to 1046 million in May 2024. ONPs often contain high levels of nicotine, a variety of flavors (e.g., mint, fruit), and can be used discreetly without spitting, therefore appealing to young people. Given these trends—mirroring earlier e-cigarette growth— ONP use among AYAs is expected to rise substantially in the upcoming years. In January 2025, the FDA authorized marketing for 20 Zyn nicotine pouch products with varying flavors and nicotine strengths. However, the FDA’s review primarily emphasized adult product use, and the FDA indicated that marketing authorization may be revisited based on future data on youth use. Currently, there is a dearth of evidence on risk and protective factors, longitudinal transitions, and health effects related to AYAs’ ONP use in the US population. This study will harmonize the nationally representative Population Assessment of Tobacco and Health (PATH) Study Waves 7-9 (2022-2025) Interview survey data and restricted biomarker data to examine the ONP use in adolescents (age 12-17) and young adults (18-24), including longitudinal influencing factors, transitions to other tobacco and substance use behaviors, , biomarkers of exposure (BOE) to tobacco-related toxicants, and nicotine dependence. In Aim 1, we will identify risk and protective factors associated with ONP initiation across individual, marketing exposure, social, and neighborhood domains. In Aim 2, we will apply marginal structure models to assess prospective associations of ONP use with transitions to (1) other tobacco products (e.g., cigarettes, e- cigarettes) and (2) other substances (e.g., cannabis). In Aim 3, we will examine BOE differences by ONP use status, within-subjects BOE changes in transitions, and associations between ONP use and adverse health outcomes (e.g., nicotine dependence). This study is innovative in its integration of biospecimen and survey data to model longitudinal nicotine pouch ↔ other tobacco and substance use transitions and their associated health effects. It also employs state-of-the-art statistical techniques in handling multi-domain influencing factors and time-dependent exposure and time-varying confounders. This study is significant because it provides timely evidence regarding nicotine pouch use and health outcomes in AYAs, a priority population for tobacco control policies and regulatory actions. Findings from this study are poised to inform current and future priorities for pediatric nicotine use prevention and tobacco regulatory policies on emerging ONP products. 1
