Research to inform comprehensive regulation of oral nicotine pouches

The National Institutes of Health Office of the Director awarded The Ohio State University $773,576 on August 1, 2026, under the Family Smoking Prevention and Tobacco Control Act Regulatory Research program (CFDA 93.077) to conduct research on oral nicotine pouches and their abuse liability.

The research will investigate how freebase nicotine fraction and moisture content in oral nicotine pouches affect the speed of nicotine delivery to users and how acute laboratory measures of abuse liability predict long-term switching outcomes from cigarettes. The study will conduct a double-blind trial among 240 cigarette smokers across two phases, using investigational oral nicotine pouches with equivalent flavors and total nicotine content but varying freebase nicotine fraction (70 percent low) and percent moisture (35 percent low). Researchers will measure both objective markers such as plasma nicotine delivery and subjective measures such as craving relief, and will test whether standardized versus ad libitum use patterns predict switching success. The findings are intended to inform federal regulation of oral nicotine pouches by identifying which abuse liability measures best translate to prospective switching behaviors.

Work is performed at The Ohio State University in Columbus, Ohio. The period of performance runs from August 1, 2026, through July 31, 2031.

Abstract

Oral nicotine pouches (ONPS) could reduce cancer risk for cigarette smokers, but they deliver nicotine too slowly to rapidly relieve cravings. Two factors are expected to drive the speed of nicotine delivery in ONPS: (1) freebase nicotine (FBN) and (2) moisture. While one federally funded study investigates the role of FBN fraction in the abuse liability of ONPS (our study), ONP moisture and its synergistic effects with FBN fraction are unstudied. We found that increasing an ONP's FBN fraction led to significantly greater plasma nicotine concentration within the first 5 minutes of use, and increasing moisture is likely to further boost nicotine delivery speed. As one of the greatest reinforcing effects of smoking is the rapid nicotine delivery from cigarettes, increasing the speed of nicotine delivery could position ONPS as a more successful substitute for cigarettes. Beyond moisture, a second GAP in the ONP research portfolio is a lack of studies measuring how acute-use measures of ONPS' abuse liability predict switching outcomes in the long term. For example, do objective (e.g., plasma nicotine delivery) or subjective (e.g., craving relief) measures of abuse liability best predict switching success? IT is also unknown how these measures differ when ONP use is standardized VS. Ad libitum, nor is II known whether standardized or ad libitum use measures of abuse liability best predict switching. Understanding how abuse liability measures translate to prospective switching behaviors would maximize the utility of prior and ongoing human laboratory studies for developing ONP regulations. Using investigational ONPS with equivalent flavors and total nicotine, but varying FBN fraction (low: 70%) and percent moisture (low: 35%), we will conduct a double-blind trial among N=240 cigarette smokers in 2 phases. AL visit 1, participants will be randomized to 1 of 4 study ONPS to use for an ad libitum use session (phase 1) and in the switching phase of the study (phase 2). Phase 1 nisits 2-7): participants will use each study ONP via a standardized use protocol (4/6 visits), their study ONP ad libitum (1/6 visits), or smoke a usual brand cigarette ad libitum (1/6 visits). Prior to each ONP visit, participants will receive the respective ONP to sample at home for >3 days. Phase 2 nisit 8): participants will switch to their study ONP for 12 weeks and complete two remote surveys. They will return for visit 8 in-person. We will measure plasma nicotine, withdrawal and craving relief, subjective effects, and behavioral economic demand indices at visits 2-7. We will biochemically confirm smoking status (visit 1) and abstinence (visits 2-8) using expired carbon monoxide and assess changes in biomarkers of toxicant exposure from cigarettes using urinary cema(8-HR half-life) and nnal (10-18 day half-life) (visits 1 and 8). This project is significant and innovative because IT will be the first to examine the independent and joint effects of moisture and FBN fraction on ONP acute-use abuse liability and longer-term substitutability of ONPS for cigarettes. Leveraging this design, this will also be the first study to provide a bridge between acute-use objective and subjective measures of ONP abuse liability and long-term switching outcomes and changes in biomarkers of exposure.