Effect of Product Characteristics on the Abuse Liability of Nicotine Pouches

Emory University

Status: Not yet enrolling

Conditions: Nicotine Addiction

Treatments: Other: Nicotine pouch: High dose; Other: Nicotine pouch: Low dose; Other: High pH; Other: Low pH

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07165808

2025P012303 (Other Identifier)

STUDY00009622

R00DA058241-03 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 84 estimated patients

Sex: All

Ages: 21 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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84 participants in 1 patient group

Nicotine Pouches group

Experimental group

Description:

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.

Treatment:

Other: Low pH

Other: High pH

Other: Nicotine pouch: Low dose

Other: Nicotine pouch: High dose