Effect of Product Characteristics on the Abuse Liability of Nicotine Pouches

The goal of this study is to assess the effects of nicotine concentration and its interplay with pH on sensory experience, product appeal, and abuse liability of NPs among young adults NP users.

Primary objective is to assess the effect of variation in nicotine concentration in nicotine pouches (NPs) and its interaction effect with pH level on three proximal outcomes of relevance to regulation: (1) sensory experience, (2) product appeal, and (3) abuse liability of NPs.

Study Overview

• Status: Recruiting
• Conditions: Nicotine Addiction
• Intervention / Treatment: Other: Nicotine pouch: Low dose; Other: Nicotine pouch: High dose; Other: Low pH; Other: High pH

Detailed Description

Oral nicotine pouches (NPs) are a rapidly growing segment of nicotine products regulated by the U.S. Food and Drug Administration (FDA). These microfiber pouches contain nicotine but no tobacco leaf, and they dissolve in the mouth without requiring spitting. Between late 2019 and early 2022, NP sales surged from 126 million to 808 million units. Their sleek packaging, concealability, and "tobacco-free" claims have made them particularly appealing to young adults, with recent studies showing that over 10% of young adults reported using NPs in the past 30 days. However, this popularity raises health concerns. NPs deliver nicotine efficiently through buccal absorption, leading to rapid increases in blood nicotine levels, which may contribute to oral toxicity, cardiovascular effects, and nicotine dependence. These factors also elevate the abuse liability of NPs-defined as the likelihood of non-medical use leading to harmful consequences.

The FDA has the authority to impose stricter regulations on products with characteristics that enhance appeal and sensory experience, especially among youth. For instance, the agency has proposed banning menthol cigarettes due to their ability to mask irritation and encourage deeper inhalation of nicotine. Similar regulatory scrutiny is now being applied to emerging products like NPs. One key factor influencing product appeal is nicotine formulation. Free-base nicotine, commonly used in non-combustible products like e-cigarettes (ECs), has aversive effects such as bitterness and airway irritation, especially at high concentrations. To counter this, manufacturers began adding organic acids to convert nicotine into a protonated salt, lowering the product's pH and improving its palatability. This shift not only enhances the sensory experience but also increases the abuse liability of high-nicotine products. Evidence suggests that regulating acid additives or setting minimum pH levels could reduce the appeal of these products. Since NPs also use acid additives to lower pH, they share similar characteristics with ECs that attract young users, underscoring the need for targeted regulatory action.

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dae Hee Han, PhD; Phone Number: 404-727-8742; Email: dae.hee.han@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Rollins School of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Current established users of nicotine pouches (have used nicotine pouches in the past 30 days & currently use nicotine pouches every day or someday)
• Positive cotinine test via saliva test strip
• Those who are unmotivated to quit nicotine use
• Read and speak English.
• Poly-users of nicotine pouches, e-cigarettes (e.g., vape ≥20 days/month), and tobacco (e.g., ≥4 cigarettes/day for ≥2 years) will be eligible for participation

Exclusion Criteria

• Planning to cut down or quit using nicotine in the next 30 days
• Currently pregnant or breastfeeding
• History of stroke, seizures, high blood pressure, heart disease/problems, or cardiovascular disease contraindications for nicotine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotine Pouches group; Participants will self-administer NPs that differ along two experimental factors: nicotine concentration (low [e.g., 3-4 mg] vs. high [e.g., 6-8 mg]) and pH level (low [<8.5] vs. high [≥8.5]). Each participant will be exposed to all four NP conditions in randomized order, with one condition administered per visit.	Other: Nicotine pouch: Low dose; Nicotine pouch: 3-4 mg; Other: Nicotine pouch: High dose; Nicotine pouch: 6-8 mg; Other: Low pH; Nicotine pouch with low pH level [<8.5]; Other: High pH; Nicotine pouch with high pH level [>8.5]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abuse liability: Amount of time with Nicotine product	Total amount of time with Nicotine Pouches in mouth (excluding periods in between NPs after disposal)	Visit 1, Visit 2, Visit 3, Visit 4 (all visits within 2-4 weeks)
Abuse liability: Number of Nicotine Pouches used	Total number of Nicotine Pouches used (i.e., larger number and longer time with Nicotine Pouches, higher abuse ability.	Visit 1, Visit 2, Visit 3, Visit 4 (all visits within 2-4 weeks)
Subjective effects measures: Drug Effects Questionnaire	During the session, participants will also repeatedly (every 30 min) complete the subjective effects measures of abuse liability of NP (using VAS), which will be developed based on the Drug Effects Questionnaire (DEQ). A modified version of the DEQ will be used to rate acute responses to the NP on the Visual Analogue Scale (range, 0-100). Items assess liking/wanting (e.g., "I enjoy nicotine buzz," "I feel good effects from the NP," "I want more," "I feel the NP strength," and "I like the NP effect").	Visit 1, Visit 2, Visit 3, Visit 4 (all visits within 2-4 weeks)
Subjective effects measures: Modified Cigarette Evaluation Questionnaire	Modified Cigarette Evaluation Questionnaire will also be used to measure domains of subjective reinforcing effects (product satisfaction, psychological reward; e.g., "NP is satisfying" on a 7-point scale (0-7).	Visit 1, Visit 2, Visit 3, Visit 4 (all visits within 2-4 weeks)
Product appeal	After each administration, participants will use visual analogue scales (VAS, 0-100 range) to rate the product they just used: (1) "How much did you like the product?" (liking); (2) "How much did you dislike the product?" (disliking); and (3) "Would you use the product again?" (use again). A composite appeal score will also be calculated by averaging the 3 appeal ratings (Cronbach's α will be estimated to assess scale reliability; disliking will be reverse-scored).	Visit 1, Visit 2, Visit 3, Visit 4 (all visits within 2-4 weeks)
Sensory Attribute	Participants will answer following sensory quality questions: (1) "How sweet was the product?"; (2) smooth?; (3) bitter?; and (4) harsh? (VAS 0-100, "Not at all" to "Extremely". Burning and tingling sensation will be measured at each trial.	Visit 1, Visit 2, Visit 3, Visit 4 (all visits within 2-4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine product use history: Number of days	Information will be collected on past 30-day number of days used nicotine pouches (NPs)	past 30-day
Nicotine product use history: Number of Nicotine product	Number of Nicotine product used per day	past 30-day
Nicotine product use history: Amount of time with Nicotine product	Amount of time with Nicotine product in mouth per episode	past 30-day
Nicotine Pouches brand	Data on brand names of NPs will be collected	past 30-day
Number of e- cigarettes	Number of e- cigarettes used in past 30 days.	past 30-day
Tobacco use	Number of tobacco products used in last 30 days	past 30-day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary cotinine	Test strips that provide a semiquantitative index of salivary cotinine will be collected to provide descriptive data on nicotine exposure.	Baseline

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Dae Han, PhD, Rollins School of Public Health

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: September 3, 2025
• First Submitted That Met QC Criteria: September 3, 2025
• First Posted (Actual): September 10, 2025

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Nicotine Addiction; Oral Nicotine Pouches; Behavioral Responses
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Tobacco Use Disorder; pHLIP protein
• Other Study ID Numbers: STUDY00009622; R00DA058241-03 (U.S. NIH Grant/Contract); 2025P012303 (Other Identifier: Emory IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual-level data collected as part of the R00 study, including baseline demographics, behavioral measures, and experimental outcome variables.
• IPD Sharing Time Frame: Data will become available within 12 months after publication of the primary study results and will remain available for at least 3 years thereafter.
• IPD Sharing Access Criteria: Data will be shared through a secure, controlled-access repository. Researchers must submit a data use request, obtain approval from the principal investigator, and sign a data use agreement to ensure protection of participant confidentiality and compliance with IRB and NIH policies
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No