Nicotine Pouches for Tobacco Addiction

Recruiting at 1 trial location

Overseen By Jonathan Foulds, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Milton S. Hershey Medical Center

Disqualifiers: Pregnancy, Respiratory diseases, Kidney disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

375 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new oral nicotine pouch can help people reduce cigarette smoking and improve health outcomes. Researchers will examine how different nicotine levels and flavors in the pouches influence smoking behavior and health markers. Participants will be divided into groups based on pouch strength and flavor, and they must reduce their cigarette use by 75% over 16 weeks. Those who typically smoke at least 5 cigarettes a day and wish to cut back by half may be suitable for this study. As an unphased study, this trial provides a unique opportunity to contribute to research that could lead to healthier smoking alternatives.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a serious medical condition or are on medications that might affect your safety or the study's results, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nicotine pouches might be safer than traditional cigarettes because they lack the harmful substances found in cigarette smoke. However, no tobacco product, including nicotine pouches, is completely safe.

Users place nicotine pouches under the upper lip, eliminating the need to smoke them. This method avoids inhaling smoke, potentially reducing health risks compared to smoking cigarettes. However, the FDA has not approved nicotine pouches as a smoking cessation aid.

Limited information exists on how well people tolerate nicotine pouches. Since they are not burned, they might cause fewer issues than smoking. Still, individual reactions vary, and some people might experience side effects from the nicotine.

Overall, more research is needed to fully understand the safety of nicotine pouches. Before using them, especially when considering participation in a trial, consulting a healthcare professional is advisable to ensure it is a safe choice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about nicotine pouches for tobacco addiction because they offer a smoke-free and spit-free way to deliver nicotine, which could be less harmful than smoking cigarettes or using traditional smokeless tobacco. Unlike traditional cessation aids like nicotine gum, patches, or lozenges, these pouches come in different flavors and strengths, providing more personalized options for users. This variety could help manage cravings more effectively and accommodate individual preferences, potentially increasing the chances of quitting smoking successfully. Additionally, the discreet nature of nicotine pouches makes them convenient for use in various settings, potentially increasing adherence to the treatment.

What evidence suggests that this trial's nicotine pouches could be effective for reducing tobacco addiction?

This trial will evaluate the effectiveness of nicotine pouches in helping people reduce or quit smoking. Research has shown that nicotine pouches can help people smoke fewer cigarettes. One study found that those using these pouches smoked less than those who didn't. Among the users, 41% successfully quit smoking, while 38.1% reduced their smoking. These pouches are generally easy to use, allowing most people to use them without major problems. Overall, nicotine pouches seem promising for those wanting to smoke less or quit entirely. Participants in this trial will receive nicotine pouches with varying strengths and flavors to assess their impact on smoking behavior. ^{6 7 8 9 10}

Who Is on the Research Team?

Jonathan Foulds, PhD

Principal Investigator

Penn State College of Medicine

Are You a Good Fit for This Trial?

This trial is for daily smokers with a baseline exhaled CO of ≥6 ppm, who read and write English, have internet access, and want to cut down smoking by at least 50% using nicotine pouches. Not for pregnant women, those planning pregnancy soon, people with recent severe illnesses or hospitalizations, serious respiratory diseases, kidney/liver disease or heavy illegal drug use.

Inclusion Criteria

Exhaled CO measurement of ≥ 6 parts per million at baseline

Access to e-mail and a smartphone/computer that has reliable internet connection

I understand the study and agree to participate.

Exclusion Criteria

You have been using illegal drugs regularly (every day or every week) in the past 3 months.

Recent unstable illness that may increase risks of participation or ability to participate fully (e.g. hospitalization for a mental health condition or substance use disorder in prior 6 months, stroke or myocardial infarction in the past year)

You intend to stop smoking within the next month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of six nicotine pouch groups to use over 16 weeks and asked to reduce cigarette smoking by at least 75% by substituting with nicotine pouches.

16 weeks

Multiple visits for sample collection and questionnaires

Follow-up

Participants are encouraged to quit smoking and connected to cessation services, followed-up 4 weeks later to assess the influence of nicotine content on quitting.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Pouches

Trial Overview The study tests new oral nicotine pouches in different strengths (0 mg, 3 mg, 6 mg) and flavors (Smooth and Wintergreen), aiming to reduce cigarette use by substituting these pouches over 16 weeks. Participants will be randomly assigned a product variant to see how it affects health indicators and smoking habits.

How Is the Trial Designed?

Group I: 6 mg + Wintergreen flavor Experimental Treatment 2 Interventions

Participants are provided with high strength (6 mg) nicotine pouches with wintergreen flavor.

Group II: 6 mg + Smooth flavor Experimental Treatment 2 Interventions

Participants are provided with high strength (6 mg) nicotine pouches with smooth flavor.

Group III: 3 mg + Wintergreen flavor Experimental Treatment 2 Interventions

Participants are provided with medium strength (3 mg) nicotine pouches with wintergreen flavor.

Group IV: 3 mg + Smooth flavor Experimental Treatment 2 Interventions

Participants are provided with medium strength (3 mg) nicotine pouches with smooth flavor.

Group V: 0 mg + Wintergreen flavor Experimental Treatment 2 Interventions

Participants are provided with zero strength (0 mg) nicotine pouches with wintergreen flavor.

Group VI: 0 mg + Smooth flavor Experimental Treatment 2 Interventions

Participants are provided with zero strength (0 mg) nicotine pouches with smooth flavor.

Nicotine Pouches is already approved in United States, European Union for the following indications:

Approved in United States as Nicotine Pouches for:

• Smoking cessation aid
• Nicotine replacement therapy

Approved in European Union as Nicotine Pouches for:

• Smoking cessation aid
• Nicotine replacement therapy

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Lucy, a company producing flavored nicotine products, may mislead consumers by marketing its gums, lozenges, and pouches in a way that confuses smoking cessation products with those that maintain nicotine dependence, particularly since only the lozenges are FDA approved for cessation.

The attractive packaging and marketing strategies, which emphasize flavors and downplay nicotine warnings, could appeal to youth and non-users, potentially increasing nicotine initiation rather than promoting cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lucy-Novel Flavored Nicotine Gum, Lozenges, and Pouches: Are They Misleading Consumers? Unger, JB., Barker, J., Cruz, TB., et al.[2023]

The novel tobacco-free nicotine pouch, ZYN, delivers nicotine effectively, with the 6 mg and 8 mg doses providing similar or faster nicotine absorption compared to traditional smokeless products like General snus and Longhorn moist snuff.

ZYN products showed a higher extraction fraction of nicotine (50-59%) compared to General snus (32%) and Longhorn moist snuff (19%), indicating a more efficient delivery of nicotine without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff. Lunell, E., Fagerström, K., Hughes, J., et al.[2021]

A survey of 6,131 U.S. participants aged 13-40 revealed that 33% had ever used oral nicotine products, with higher usage rates among those aged 21-40 compared to those under 21.

Marketing significantly influences the likelihood of purchasing oral nicotine products, especially among younger users, who are more likely to buy products like Zyn pouches when they perceive marketing messages about appealing flavors and social comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use, marketing, and appeal of oral nicotine products among adolescents, young adults, and adults. Gaiha, SM., Lin, C., Lempert, LK., et al.[2023]

A significant portion of young adults, particularly those who currently use nicotine products, expressed a willingness to try oral nicotine pouches, with willingness rates of 33.8% for non-combustible users and 43.9% for dual users, compared to only 14.7% for non-users.

Despite this interest, many participants (49.1%) were uncertain about whether nicotine pouches are less harmful than cigarettes, indicating a lack of clear understanding regarding the safety of these products among young adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in Young Adults' Perceptions of and Willingness to Use Nicotine Pouches by Tobacco Use Status. Vogel, EA., Barrington-Trimis, JL., Kechter, A., et al.[2023]

ZYN nicotine pouches contain no nitrosamines or polycyclic aromatic hydrocarbons (PAHs), indicating a potentially lower risk profile compared to traditional tobacco products, which often contain harmful constituents.

The levels of harmful and potentially harmful constituents (HPHCs) in ZYN were found to be similar to those in nicotine replacement therapy (NRT) products, suggesting that ZYN may be a safer alternative for nicotine delivery compared to moist snuff, which had significantly higher levels of harmful compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harmful and potentially harmful constituents (HPHCs) in two novel nicotine pouch products in comparison with regular smokeless tobacco products and pharmaceutical nicotine replacement therapy products (NRTs). Back, S., Masser, AE., Rutqvist, LE., et al.[2023]

Participants in focus groups perceived oral nicotine pouches (ONPs) as having similar or lower risks compared to traditional cigarettes and smokeless tobacco, although they acknowledged potential gastrointestinal and cardiovascular risks.

ONPs were viewed as situational substitutes rather than complete replacements for cigarettes and smokeless tobacco, which could lead to increased overall nicotine use in certain populations, particularly in Appalachia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceptions of oral nicotine pouches & their marketing among Ohio Appalachia smokers and smokeless tobacco users. Long, L., Alalwan, MA., Keller-Hamilton, B., et al.[2023]

In a study involving 63 smokers, both snus and Zonnic were preferred over nicotine gum, showing greater effectiveness in reducing smoking urges and causing fewer side effects.

Participants experienced significant reductions in smoking (33% for gum, 37% for snus, and 42% for Zonnic), indicating that snus and Zonnic could be promising alternatives for nicotine replacement therapy, warranting further research on their long-term effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover trial of the acceptability of snus, nicotine gum, and Zonnic therapy for smoking reduction in heavy smokers. Caldwell, B., Burgess, C., Crane, J.[2022]

Medicinal nicotine has significantly improved smoking cessation rates over the past 20 years, with various products like patches, gum, and inhalers available to help smokers quit.

Innovative nicotine delivery methods, such as high-dose patches and new forms like drinks and lollipops, are being developed to enhance cessation success and manage withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine delivery systems. Shiffman, S., Fant, RV., Buchhalter, AR., et al.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41001885/

Nicotine pouches and clinical outcomes related to smoking ... Conclusions: Tobacco-free nicotine pouches appear to be well tolerated and may reduce cigarette consumption compared with control, with effects ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/add.70193?af=R

Nicotine pouches and clinical outcomes related to smoking ... Nicotine pouches and clinical outcomes related to smoking cessation: A systematic review of randomized trials - Heshmati - Addiction - Wiley ...

3. nature.com nature.com/articles/s41598-025-15070-0

Prevalence, safety, and role of nicotine pouches in ... Among those who had used nicotine pouches, 41.0% reported success in quitting smoking, while 38.1% experienced partial success, and 20.9% were ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12377922/

The Effects of Oral Nicotine Pouches on Cigarette Smoking ... Together, these findings suggest that pouches may have appeal for smoking cessation and might have comparable effects on smoking-related ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2214750024001628

Beyond smoking: Risk assessment of nicotine in pouches This study aims to assess nicotine in pouches and potential risks for health damage. 31 samples of nicotine pouches were collected and analyzed.

6. cdc.gov cdc.gov/tobacco/nicotine-pouches/index.html

Nicotine Pouches | Smoking and Tobacco Use There are no safe tobacco products, including nicotine pouches. ... The FDA has not approved any nicotine pouches to help people quit smoking.

7. yalemedicine.org yalemedicine.org/news/nicotine-pouches

What Parents Should Know About Nicotine Pouches And while nicotine pouches may be a safer alternative to cigarettes or vaping because they don't contain the known carcinogens associated with ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12037535/

Oral Nicotine Pouches: Rising Popularity and State of the ... This review highlights how nicotine pouches, including ZYN, are rising in appeal and prevalence of use, particularly among adolescents and young adults.

9. mdanderson.org mdanderson.org/cancerwise/what-to-know-about-nicotine-pouches.h00-159773289.html

What to know about nicotine pouches Another important note is that right now, these nicotine pouches are only approved by the FDA for marketing – not tobacco cessation.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8887571/

The New Nicotine Pouch Category: A Tobacco Harm ... Nicotine pouches are placed under the upper lip, are non-combustible, and contain no leaf tobacco, and are being studied as a potential tool for reducing ...