Although nicotine pouches have been gaining popularity over the last few years, little known about how nicotine pouch users actually use these products.

This study will be comprised of adults who use nicotine pouches. If eligible, participants will be asked to complete three study visits and participate in two switching periods where participants use study-provided nicotine pouches.

This investigation expands on the parent study's Aims 1 and 2 by examining the effects of a feature that the investigators have identified varies across nicotine pouches (ONP): particle size. The investigators expect that particle size differences may translate to differences in user experience. The investigators wish to further explore this hypothesis among current ONP users. Data will be captured over the course of 3 clinic visits and across two week-long switching periods with daily diary surveys. This will inform interpretation of results from Aims 1 and 2, including how to translate those findings to commercially-available nicotine pouches.

Aim 1: Assess the effects of nicotine concentration, form, and isomer on the satisfaction and appeal of ONPs relative to cigarettes and ST. ONPs with high FBN and >99% S-nicotine will have (H1a) increased satisfaction and appeal (e.g., faster nicotine delivery, greater liking). H1b: Associations of form and isomer with addiction potential and appeal will be strongest in the high nicotine concentration arm.

Aim 2: Evaluate the effects of nicotine concentration, form, and isomer on switching from cigarettes or ST to ONPs. Over 4 weeks, participants randomized to use ONPs with high FBN and >99% S-nicotine (vs. other ONPs) will report higher prevalence of (H2a) partially switching to ONPs (use ONPs >14 days but continued usual product use) and (H2b) complete switching to ONPs by week 4. H2c: Associations of form and isomer with switching outcomes will be strongest in the high nicotine concentration arm.

Study Procedures:

Participants will complete three in-person visits. Visits involve randomized, double-blinded use of either small-particle ONPs or a distribution of particle-size ONPs (one assigned product per visit).

Visit 1

• 12-hour abstinence requirement prior to visit.
• Informed consent procedures.
• Baseline questionnaires.
• Exhaled carbon monoxide (CO) testing and pregnancy screening (if applicable).
• IV-line placement followed by four timed blood draws to assess plasma nicotine levels.
• 120-minute controlled ONP use session.

Post-use surveys assessing:

• Product appeal
• Withdrawal symptoms and relief
• Sensory scales
• Behavioral intentions

One-Week Switching Period (at-home)

Following Visit 1, participants enter a 7-day ad libitum use period using their assigned ONPs.

During this phase, participants complete online daily diary surveys (1 per day) to capture product use and switching behavior.

Visit 2

• 12-hour abstinence prior to visit.
• Exhaled CO testing and pregnancy screening (if applicable).
• IV-line placement and four timed blood draws (plasma nicotine levels).
• 120-minute controlled ONP use session.
• Post-use surveys (same as Visit 1).

One-Week Switching Period (at-home)

Following Visit 2, participants enter a 7-day ad libitum use period using their assigned ONPs.

During this phase, participants complete online daily diary surveys (1 per day) to capture product use and switching behavior.

Visit 3

• Completion of survey measures only (no product administration or IV-lines).
• Return of unused ONPs from the at-home switching period.

Inclusion Criteria:

• Age 21 or older
• Able to read and speak English
• Willing to abstain from tobacco, nicotine, and marijuana for at least 12 hours prior to study visits
• Exclusive use of ONPs (other product use <10x/mo).
• Exhaled CO reading <10 ppm
• Owns a smartphone and can receive SMS text messages with embedded survey links
• Negative pregnancy test at V1 and V2 (if applicable)
• Uses ≥1.5 cans of ONPs/week
• Daily use of ONPs for the past 3 months
• At least half of ONPs used are 6mg nicotine concentration.

Exclusion Criteria:

• Non-English speaker
• Individuals currently pregnant, planning to become pregnant, or breastfeeding are excluded due to potential risks associated with nicotine exposure and study procedures (e.g., blood draws).
• Individuals with unstable or significant psychiatric conditions are excluded to minimize risk and ensure reliable participation.
• Individuals actively attempting to quit nicotine use are excluded to avoid ethical concerns and ensure that study participation does not interfere with cessation efforts
• Non-nicotine users and regular tobacco users are excluded from the clinical trial component to ensure that participants have established use patterns appropriate for assessing ONP use behaviors.