Nicotine Pouches for Nicotine Addiction

Recruiting at 1 trial location

Overseen By Adam Leventhal, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Southern California

Disqualifiers: Pregnancy, Stroke, Seizures, Hypertension, others

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

Compensation: Varies

Number of Visits: 3

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how different levels of nicotine and pH affect the appeal and sensory experience of nicotine pouches, especially for those who already use both nicotine pouches and e-cigarettes or traditional cigarettes. Researchers seek to determine how these factors might encourage increased use of nicotine pouches. Participants will try pouches with varying nicotine strengths and pH levels to gather this data. Individuals who have used nicotine pouches in the last 30 days and are not looking to quit nicotine use would be a good fit for this study. As an unphased trial, this study offers participants the opportunity to contribute to a deeper understanding of nicotine pouch use and its potential appeal.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a history of certain health conditions like stroke, seizures, or heart problems, you may not be eligible to participate.

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

In a previous study, the FDA found that nicotine pouches might help adults who smoke by providing a smoke-free option. However, these products are not without risks. Research has shown that nicotine pouches can be addictive and may contain other harmful chemicals. The FDA warns of serious health risks, especially for young people. While nicotine pouches do not contain tobacco, they do contain nicotine, which is harmful in any form. This is particularly concerning for youth, young adults, and pregnant women. Although some adults may use nicotine pouches without issues, the potential for addiction and other health risks should be carefully considered. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these nicotine pouches because they offer a unique way to tackle nicotine addiction by altering the nicotine delivery and pH levels. Unlike traditional treatments like nicotine gums, patches, or lozenges, which provide a steady release of nicotine, these pouches are designed for users to self-administer and potentially adjust their nicotine intake. The experimental pouches include variations with both high nicotine content (6-8mg) and low pH levels, which may enhance nicotine absorption and satisfaction, potentially helping users manage cravings more effectively. Additionally, the placebo comparator pouches with high pH or lower nicotine content (3-4mg) offer insights into how different nicotine concentrations and pH levels affect user experience and addiction management, paving the way for more personalized nicotine replacement therapies.

What evidence suggests that this trial's treatments could be effective for nicotine addiction?

This trial will evaluate different nicotine pouches for their effectiveness in reducing cigarette cravings. Participants will be assigned to one of several treatment arms: a nicotine pouch with high nicotine (6-8mg), a pouch with high pH (8.5 or greater), a pouch with low nicotine (3-4mg), or a pouch with low pH (less than 8.5). Research has shown that nicotine pouches can help reduce cigarette cravings by providing sufficient nicotine. Studies indicate these pouches are less harmful than smoking and can deliver nicotine in a manner similar to cigarettes. Many users continue using them due to their addictive nature, with about 73% of young users continuing after trying them. Although there is limited information on the long-term health effects, they are considered a safer option for those switching from cigarettes. Their appeal partly lies in not requiring lighting or smoking, making them more discreet than other nicotine products. ^{5 6 7 8 9}

Who Is on the Research Team?

Dae Hee Han, PhD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for young adults who have used nicotine pouches and e-cigarettes or combustible cigarettes in the past 30 days. Participants should not be looking to quit nicotine use. The study specifically targets current dual users of these products.

Inclusion Criteria

I am between 21 and 35 years old.

Positive cotinine test via saliva test strip

I have used nicotine pouches in the last 30 days.

Exclusion Criteria

Intention to quit nicotine use in the next 30 days

I have a history of stroke, seizures, high blood pressure, heart or lung problems.

Current pregnancy or breastfeeding (urine pregnancy test will be conducted during the orientation session)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Orientation

Participants confirm age, provide informed consent, and complete verification of nicotine use status by cotinine test strip

1 day

1 visit (in-person)

Experimental Session

Participants self-administer 4 different nicotine pouches varied by nicotine concentration and pH, and rate appeal and sensory attributes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any immediate effects post-experimental session

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Pouch

Trial Overview The study is testing how different levels of nicotine concentration (3 mg vs 6 mg) and pH values (8.5 or higher vs lower than 8.5) in nicotine pouches affect their appeal and sensory experience among users, using a double-blind randomized design.

How Is the Trial Designed?

Group I: Nicotine pouch with low pH (less than 8.5) Experimental Treatment 1 Intervention

Participants will self-administer a nicotine pouch with low pH (less than 8.5).

Group II: Nicotine pouch containing high nicotine (6-8mg) Experimental Treatment 1 Intervention

Participants will self-administer a nicotine pouch containing 6-8mg nicotine.

Group III: Nicotine pouch with high pH (8.5 or greater) Placebo Group 1 Intervention

Participants will self-administer a nicotine pouch with high pH (8.5 or greater).

Group IV: Nicotine pouch containing low nicotine (3-4mg) Placebo Group 1 Intervention

Participants will self-administer a nicotine pouch containing 3-4mg nicotine.

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

Approved in United States as Nicotine Pouch for:

• Smoking cessation aid

Approved in European Union as Nicotine Pouch for:

• Smoking cessation aid

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study of 30 adult smokers, the 4-mg nicotine pouch significantly reduced withdrawal cravings by 23 points within the first hour, outperforming nicotine gum and placebo, which showed reductions of 15 and 8 points, respectively.

Participants rated the nicotine pouch as more helpful and pleasant to use compared to gum, indicating a preference that could enhance its effectiveness as a smoking cessation aid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single-blind, randomized, crossover trial of the effects of a nicotine pouch on the relief of tobacco withdrawal symptoms and user satisfaction. Thornley, S., McRobbie, H., Lin, RB., et al.[2015]

In a study of 314 daily smokers, starting nicotine polacrilex gum treatment 4 weeks before the quit date did not significantly improve smoking abstinence rates compared to starting on the quit date.

Both groups showed similar self-reported and biochemically verified abstinence rates after 12 months, indicating that the timing of nicotine gum initiation may not impact long-term quitting success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine gum treatment before smoking cessation: a randomized trial. Etter, JF., Huguelet, P., Perneger, TV., et al.[2018]

In a study involving adult smokers, nicotine pouches (NPs) showed lower peak nicotine levels (Cmax) and longer time to peak (tmax) compared to traditional cigarettes, indicating a slower nicotine delivery.

Participants reported lower cravings for cigarettes when using NPs, suggesting that these products may have a lower abuse potential and could serve as a safer alternative for smokers looking to switch from cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine pharmacokinetics and subjective response among adult smokers using different flavors of on!® nicotine pouches compared to combustible cigarettes. Rensch, J., Liu, J., Wang, J., et al.[2021]

In a study involving 30 adult smokers, 6-mg oral nicotine pouches (ONPs) delivered more nicotine to the bloodstream at 30 minutes compared to both 3-mg ONPs and cigarettes, suggesting they can be effective for nicotine delivery.

However, neither concentration of ONPs provided as much relief from cravings at 5 minutes as cigarettes did, indicating that while ONPs may be less harmful, they might not satisfy cravings as effectively, which could influence their potential for misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study. Keller-Hamilton, B., Alalwan, MA., Curran, H., 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]

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]

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]

Nicotine pouches, a new product category, are being marketed with minimal research and regulatory oversight, highlighting significant gaps in understanding their potential harms and benefits.

The commentary suggests a comprehensive assessment approach to inform regulatory policies, aiming to enhance public health outcomes while reducing unintended negative effects associated with nicotine pouch use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The New Nicotine Pouch Category: A Tobacco Harm Reduction Tool? Patwardhan, S., Fagerström, K.[2023]

Introducing the nicotine pouch ZYN in the US in 2000 could potentially lead to 249 fewer deaths among a simulated cohort of 100,000 smokers by 2050, translating to approximately 700,000 fewer deaths nationwide.

The model suggests that even with conservative estimates of ZYN's reduced risk compared to smoking, switching to ZYN could significantly lower product-related mortality, highlighting its potential as a safer alternative for smokers not intending to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimating the public health impact had tobacco-free nicotine pouches been introduced into the US in 2000. Lee, PN., Fry, JS., Ljung, T.[2022]

Citations

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

The New Nicotine Pouch Category: A Tobacco Harm ... The authors suggest that users can draw adequate nicotine from the pouches to overcome cravings from cigarettes. The only published pharmacokinetics study on NP ...

2. truthinitiative.org truthinitiative.org/research-resources/emerging-tobacco-products/what-zyn-and-what-are-oral-nicotine-pouches

What is Zyn and what are oral nicotine pouches? Current oral nicotine pouch use among 10th and 12th graders doubled from 1.3% in 2023 to 2.6% in 2024. · According to JAMA Network Open research, 5.4% of 10th ...

3. keck.usc.edu keck.usc.edu/news/use-of-nicotine-pouches-increases-significantly-among-u-s-teens/

Use of nicotine pouches increases significantly among ... The long-term health effects of nicotine pouches are unknown, but they carry the risk of nicotine addiction, and some users report symptoms ...

4. lung.org lung.org/blog/zyn-nicotine-addiction

ZYN 101: What to Know About Big Tobacco's Latest ... A concerning trend is that nicotine pouches are so addicting, 73% of young people who have tried nicotine pouches are currently still using them. This could be ...

5. academic.oup.com academic.oup.com/ntr/article/27/4/598/7693924

Potential Impact of Oral Nicotine Pouches on Public Health ONPs appear to be less toxic than cigarettes and deliver comparable nicotine, presenting an alternative for combustible product users.

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. · Youth, young adults, and women who are pregnant should not use nicotine pouches ...

7. fda.gov fda.gov/news-events/press-announcements/fda-authorizes-marketing-20-zyn-nicotine-pouch-products-after-extensive-scientific-review

FDA Authorizes Marketing of 20 ZYN Nicotine Pouch ... Additionally, the FDA found that the applicant showed these nicotine pouch products have the potential to provide a benefit to adults who smoke ...

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

What to know about nicotine pouches Nicotine pouches are a smokeless, spitless product. While nicotine pouches are considered a tobacco product, they don't actually contain tobacco.

9. cancer.org cancer.org/cancer/latest-news/what-to-know-about-nicotine-pouches-and-cancer-risk.html

What to Know About Nicotine Pouches and Cancer Risk However, the FDA warns that pouches can be addictive, may include other harmful chemicals, and carry serious health risks. “Nicotine pouches don ...