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

NCT07698470 | Recruiting

• 1 other identifier: UP-25-00525
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nicotine Dependence

Keywords

Oral Nicotine Pouches; Oral Nicotine Products; Smoking; Cigarettes; Harm Reduction

Outcome Measures

Primary Outcomes (2)

• Change in Prefrontal Neural Cue Reactivity to Smoking-Related Cues Measured by Functional Near-Infrared Spectroscopy (fNIRS)

  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)

  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.

Study Arms (1)

Acute Oral Nicotine Pouch Administration

EXPERIMENTAL

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; Behavioral: Smoking Cue Reactivity Task

Interventions

Smoking Cue Reactivity Task BEHAVIORAL

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.

Acute Oral Nicotine Pouch Administration

Oral Nicotine Pouch OTHER

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.

Acute Oral Nicotine Pouch Administration

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

University of Southern California - 3641 Watt Way (HNB B22)

Los Angeles, California, 90089, United States

RECRUITING

Related Publications (18)

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  PMID: 3954551 BACKGROUND

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  PMID: 1932883 BACKGROUND

• Rest EC, Brikmanis KN, Mermelstein RJ. Preferred flavors and tobacco use patterns in adult dual users of cigarettes and ENDS. Addict Behav. 2022 Feb;125:107168. doi: 10.1016/j.addbeh.2021.107168. Epub 2021 Oct 30.

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• Pang RD, Goldenson NI, Kirkpatrick M, Barrington-Trimis JL, Cho J, Leventhal AM. Sex differences in the appeal of flavored e-cigarettes among young adult e-cigarette users. Psychol Addict Behav. 2020 Mar;34(2):303-307. doi: 10.1037/adb0000548. Epub 2020 Jan 20.

  PMID: 31961168 BACKGROUND

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  PMID: 26687485 BACKGROUND

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  PMID: 22708884 BACKGROUND

• Keijsers M, Vega-Corredor MC, Hoermann S, Tomintz M. Cue Reactivity to Electronic Cigarettes: A Systematic Review. Subst Abuse. 2022 Jul 28;16:11782218221114971. doi: 10.1177/11782218221114971. eCollection 2022.

  PMID: 35923180 BACKGROUND

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  PMID: 12359667 BACKGROUND

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  PMID: 26806774 BACKGROUND

• Killen JD, Fortmann SP. Craving is associated with smoking relapse: findings from three prospective studies. Exp Clin Psychopharmacol. 1997 May;5(2):137-42. doi: 10.1037//1064-1297.5.2.137.

  PMID: 9234050 BACKGROUND

• FDA. FDA Authorizes Marketing of 20 ZYN Nicotine Pouch Products after Extensive Scientific Review. Accessed May 14, 2025. https://www.fda.gov/news-events/press-announcements/fda-authorizes-marketing-20-zyn-nicotine-pouch-products-after-extensive-scientific-review

  BACKGROUND

• Azzopardi D, Liu C, Murphy J. Chemical characterization of tobacco-free "modern" oral nicotine pouches and their position on the toxicant and risk continuums. Drug Chem Toxicol. 2022 Sep;45(5):2246-2254. doi: 10.1080/01480545.2021.1925691. Epub 2021 May 25.

  PMID: 34034614 BACKGROUND

• Azzopardi D, Haswell LE, Frosina J, McEwan M, Gale N, Thissen J, Meichanetzidis F, Hardie G. Assessment of biomarkers of exposure and potential harm, and physiological and subjective health measures in exclusive users of nicotine pouches and current, former and never smokers. Biomarkers. 2023 Feb;28(1):118-129. doi: 10.1080/1354750X.2022.2148747. Epub 2022 Dec 13.

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• Han DH, Cho J, Harlow AF, Tackett AP, Vogel EA, Wong M, Barrington-Trimis JL, Lerman C, Unger JB, Leventhal AM. Young adults' beliefs about modern oral nicotine products: Implications for uptake in nonvapers, dual use with e-cigarettes, and use to reduce/quit vaping. Exp Clin Psychopharmacol. 2023 Apr;31(2):455-463. doi: 10.1037/pha0000595. Epub 2022 Sep 1.

  PMID: 36048111 BACKGROUND

• NIDA. What is the scope of tobacco, nicotine, and e-cigarette use in the United States? . Accessed June 4, 2025. https://nida.nih.gov/publications/research-reports/tobacco-nicotine-e-cigarettes/what-scope-tobacco-use-its-cost-to-society

  BACKGROUND

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking; Harm Reduction

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior

Study Officials

• Natalia Peraza

  University of Southern California

  PRINCIPAL INVESTIGATOR

• John Monterosso

  University of Southern California

  STUDY CHAIR

Central Study Contacts

USC Nicotine and Tobacco Studies

CONTACT

213-821-0807; USCONPStudy@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor - Department of Psychology

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 13, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be made available within a target of 1 year after study completion.

Locations

US (1)