Brain/Craving Response to Smoking Cues After Oral Nicotine Pouch Use

July 7, 2026 updated by: John Robert Monterosso, University of Southern California

Cue-Exposure Response Evaluation: Brain Reactivity to ONPs

Oral nicotine pouches (ONPs) are non-combustible nicotine products that may reduce cigarette craving and smoking cue-induced brain activity, supporting their potential as harm-reduction tools for adults who smoke cigarettes. This within-subject, repeated-measures study will evaluate the acute effects of a single 6 mg oral nicotine pouch on subjective craving and prefrontal neural responses to smoking-related cues using functional near-infrared spectroscopy (fNIRS). Participants will complete assessments before and after nicotine pouch administration following overnight nicotine abstinence to characterize changes in craving and neural cue reactivity.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study will evaluate the acute effects of oral nicotine pouch (ONP) use on subjective cigarette craving and prefrontal neural responses to smoking-related cues among adult cigarette smokers. Although oral nicotine pouches do not involve combustion or inhalation, their effects on craving relief and neural cue reactivity following nicotine abstinence remain poorly understood. Characterizing these acute responses may improve understanding of the potential role of oral nicotine pouches as lower-risk nicotine products.

This is a single-arm, within-subject, repeated-measures study consisting of one baseline screening visit and one experimental visit. During the baseline visit, informed consent will be obtained, eligibility will be confirmed, demographic and tobacco use information will be collected, nicotine dependence will be assessed, and head circumference will be measured to determine appropriate functional near-infrared spectroscopy (fNIRS) cap sizing. Participants will also receive instructions to abstain from nicotine use for at least 12 hours before the experimental visit.

At the experimental visit, overnight nicotine abstinence will be verified before participants complete baseline assessments of subjective craving and nicotine withdrawal. Participants will then complete a standardized smoking cue reactivity task while prefrontal brain activity is recorded using functional near-infrared spectroscopy (fNIRS). Following completion of the baseline task, participants will self-administer one commercially available 6 mg oral nicotine pouch and complete a standardized 25-minute absorption period. Participants will then complete an identical post-pouch cue reactivity task with simultaneous fNIRS recording, followed by post-session assessments of craving, withdrawal, subjective product effects, and product perceptions.

The smoking cue reactivity task consists of repeated presentations of smoking-related and neutral visual cues, followed by guided imagery in which participants imagine smoking a cigarette or performing a comparable neutral behavior while holding the corresponding object. The task is administered before and after nicotine pouch administration using identical procedures to permit within-subject comparisons of neural and subjective responses.

Functional near-infrared spectroscopy is a non-invasive neuroimaging technique that measures changes in oxygenated and deoxygenated hemoglobin within cortical tissue as an indirect measure of neural activity. Brain activity will be recorded continuously throughout both cue reactivity task runs using a standardized prefrontal optode montage. Participants will be monitored throughout study procedures for discomfort, and study procedures will be discontinued if requested by the participant or if study staff determine continuation is not appropriate.

Study Type

Interventional

Enrollment (Estimated)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90089
        • Recruiting
        • University of Southern California - 3641 Watt Way (HNB B22)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age 21 years - 55 years
  • Self-reported use of cigarettes within the past 30 days

  • Biochemical confirmation of cigarette use:

    o Carbon monoxide (CO) breath sample ≥10 ppm

  • Fagerström Test for Nicotine Dependence (FTND) score ≥5, indicating moderate to high nicotine dependence
  • Fluent in English
  • Willing to try an oral nicotine pouch
  • Willing to abstain from nicotine for at least 12 hours prior to each experimental session

Exclusion Criteria:

  • Age younger than 21 years or older than 55 years

  • Biochemical evidence inconsistent with recent cigarette use:

    o CO breath sample <10 ppm

  • Expressed intent to reduce or quit nicotine use within the next 30 days
  • History of medical conditions contraindicated for nicotine use (e.g., uncontrolled hypertension, recent cardiac events)
  • Primary use of non-cigarette products (e.g., cigars, pipe tobacco, smokeless tobacco)
  • Prior use of oral nicotine products in their lifetime

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acute Oral Nicotine Pouch Administration
Adult cigarette smokers will complete one experimental session consisting of pre-pouch cue reactivity and subjective assessments, administration of a single 6 mg oral nicotine pouch, a standardized 25-minute absorption period, and identical post-pouch assessments. All participants complete the same study procedures and serve as their own control for pre- versus post-intervention comparisons.
Other: Oral Nicotine Pouch
Participants will self-administer one commercially available 6 mg oral nicotine pouch following overnight nicotine abstinence. The pouch will be used for approximately 25 minutes before participants complete the post-pouch cue reactivity assessment.
Behavioral: Smoking Cue Reactivity Task
Participants will complete a standardized smoking cue reactivity task before and after oral nicotine pouch administration. During each task, participants will view smoking-related and neutral images, complete guided imagination trials while holding either a cigarette or a neutral object, and undergo simultaneous functional near-infrared spectroscopy (fNIRS) to measure prefrontal brain activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Prefrontal Neural Cue Reactivity to Smoking-Related Cues Measured by Functional Near-Infrared Spectroscopy (fNIRS)
Time Frame: Baseline (pre-pouch) and approximately 25 minutes after administration of a 6 mg oral nicotine pouch (post-pouch) during the experimental session.
Prefrontal neural responses to smoking-related and neutral cues will be assessed using functional near-infrared spectroscopy (fNIRS). The primary outcome will be the within-subject change in oxygenated (HbO) and deoxygenated (HbR) hemoglobin concentration from the pre-pouch assessment to the post-pouch assessment. Larger positive HbO responses to smoking-related cues indicate greater neural cue reactivity.
Baseline (pre-pouch) and approximately 25 minutes after administration of a 6 mg oral nicotine pouch (post-pouch) during the experimental session.
Change in Subjective Cigarette Craving Measured by the Questionnaire of Smoking Urges-Brief (QSU-Brief)
Time Frame: Baseline (pre-pouch) and approximately 25 minutes after administration of a 6 mg oral nicotine pouch (post-pouch) during the experimental session.
Subjective cigarette craving will be assessed using the Questionnaire of Smoking Urges-Brief (QSU-Brief). The QSU-Brief consists of 10 items, each rated on a 7-point Likert scale (1 = strongly disagree to 7 = strongly agree). Total scores range from 10 to 70, with higher scores indicating greater cigarette craving (worse outcome). The primary outcome will be the within-subject change in total QSU-Brief score from the pre-pouch assessment to the post-pouch assessment.
Baseline (pre-pouch) and approximately 25 minutes after administration of a 6 mg oral nicotine pouch (post-pouch) during the experimental session.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southern California

Investigators

  • Principal Investigator: Natalia Peraza, University of Southern California
  • Study Chair: John Monterosso, University of Southern California

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2026

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

June 26, 2025

First Submitted That Met QC Criteria

July 7, 2026

First Posted (Actual)

July 13, 2026

Study Record Updates

Last Update Posted (Actual)

July 13, 2026

Last Update Submitted That Met QC Criteria

July 7, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UP-25-00525

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) that underlie the results reported in any future publications (e.g., self-reported craving scores, task performance metrics, and fNIRS-derived signal outputs) will be shared. The data will be stripped of all personally identifying information in accordance with HIPAA guidelines and made available upon reasonable request for academic and research purposes. A data dictionary and codebook will be provided to facilitate reuse. Access will be granted upon request to the corresponding author.

IPD Sharing Time Frame

Data will be made available within a target of 1 year after study completion.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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