Clinical pharmacology of oral nicotine pouches

The National Institutes of Health Office of the Director awarded The Regents of the University of California, San Francisco $1,639,996 on August 1, 2026, under the Family Smoking Prevention and Tobacco Control Act Regulatory Research program (CFDA 93.077).

The award funds a clinical pharmacology study of oral nicotine pouches (ONPs)—small microfiber sachets filled with purified or synthetic nicotine and typically flavored. The research will examine nicotine exposure and subjective effects from ONP use at 0 mg, 3 mg, and 6 mg nicotine doses compared to cigarette smoking and vaping, and determine acute cardiovascular effects including hemodynamic, vascular, and immunological responses. The study addresses a gap in independent research on ONP safety; most prior human pharmacology studies have been industry-conducted single-dose investigations, yet regular ONP users consume multiple pouches daily and can titrate intake by removing pouches when desired effects are achieved. The work is particularly relevant following FDA authorization of 20 ZYN ONP products on January 16, 2025, and will assess absolute risks of ONP use in never-smokers compared to nonuse.

The period of performance runs August 1, 2026, through July 31, 2029. Performance occurs in San Francisco, California.

Abstract

Oral nicotine pouches (ONPS), which are small microfiber sachets, filled with nicotine purified from tobacco or with synthetic nicotine but no tobacco leaves, and usually flavored, have wide appeal among adults and youth and are growing in popularity in the U.S. On january 16, 2025, FDA authorized the marketing of 20 ZYN ONP products, which were judged to be appropriate for the protection of public health with the rationale that they are likely to provide greater benefits than risks to the general population, based on the potential benefit of supporting switching to ONP from cigarettes outweighing the risk to never smokers using ONPS. While oral nicotine use is likely to be much less harmful compared to use of combustible tobacco products, and probably safer than using E-cigarettes, there are questions about absolute risks of non-inhaled nicotine use, especially among those who are never-smokers. Most studies of the human pharmacology of ONPS to date have been conducted by the tobacco industry, with only a few by independent researchers. These have all been single dose studies in which pharmacokinetics and subjective effects have been examined. However, regular users of ONP use several pouches per day. Importantly, users can titrate their nicotine intake by removing pouches when the desired nicotine effects or flavor effects are experienced. While ONPS may offer harm reduction benefit to smokers, there is concern about absolute harm of ONP use in never-nicotine users. Thus, IT is important to assess the absolute risks of ONPS compared to not using any nicotine product. Therefore, we propose a clinical pharmacology study of ONPS with the following specific aims: (1) examine differences in nicotine exposure and subjective effects from use of oral nicotine pouches (0 MG, 3 MG and 6 MG nicotine) VS cigarette smoking or vaping; and, (2) determine the acute cardiovascular effects (hemodynamic, vascular and immunological) of oral nicotine pouches (0 MG, 3 MG , 6 MG nicotine) and compare to the effect of smoking or vaping after a single and multiple dose conditions. The proposed within-subject (CROSSOVER) study will compare nicotine exposure and subjective and acute cardiovascular effects of two strengths of oral nicotine pouches (3 MG and 6 MG nicotine) and one zero nicotine pouch to cigarette smoking or E-cigarette use, over 7 hours on four separate days. This will be the first examination of nicotine intake, subjective effects and cardiovascular effects of ONPS after multiple administrations during the day. Findings will inform public health and regulatory policy in the context of rapid population uptake of oral nicotine pouches.