Pouch

A few days ago I posted a list of research-based findings concerning nicotine. The post was simply titled “Nicotine”.

One main point of that post was to ask, “On a scale from 0 to 10 how important is it to treat tobacco use in a patient with a substance use disorder? And why?”

That post elicited a response suggesting I do a similar look at vape. In response to that suggestion, I posted a list of research-based findings concerning vape. The post was simply titled “Vape”.

The information about vape included cellular effects of various vape ingredients, the impacts of second and third-hand vape exposure, gateway effects of vape on the prevalence of cigarette smoking, harms of vape upon eyes and oral health, a need for oversight and regulation of the content of vapes; and more. .

I really did’t see it coming, but that post on vape elicited a suggestion I do a similar style post on the pouch. Thus, I provide the content below.

What struck me while gathering this information on the pouch is the wide amount of critically important information we do not have, and the unleashing of these products on us nonetheless.

But what hit me hardest was learning that synthetic analogs of nicotine are here. I did not know that.

Hopefully the information below is helpful or interesting to someone.

“The rapid rise of ZYN^® nicotine pouches poses an emerging public health concern, particularly among adolescents and young adults.

Marketed as a discreet, tobacco-free alternative to smoking and vaping, ZYN products have gained widespread popularity, fueled by youth-targeted marketing, appealing flavors, and social media influencers.

Despite their perceived safety, ZYN pouches deliver high doses of nicotine, raising concerns about addiction, dual use with other tobacco products, and long-term health consequences.

Current regulatory frameworks lack adequate oversight, allowing widespread availability and minimal enforcement of age restrictions.

…explores the product’s marketing tactics, associated health risks, and the social and ethical implications of normalized nicotine use…

…calls for urgent action through stronger regulatory measures, public education, and expanded research to mitigate youth exposure and prevent a new wave of nicotine addiction.”

Adekeye OT, Mumba MN. Oral Nicotine Pouches: A Growing Public Health Concern. Journal of Psychosocial Nursing and Mental Health Services. 2025;63(6):7-10. doi:10.3928/02793695-20250507-04

“Nicotine pouches are noncombustible products that contain nicotine but no tobacco plant material.

With rising popularity and increased media attention surrounding ZYN and other nicotine pouch brands, questions remain about whether empirical evidence exists on the public health effects of these products.

This review highlights how nicotine pouches, including ZYN, are rising in appeal and prevalence of use, particularly among adolescents and young adults.

The use of nicotine pouches is also more prevalent among people who use other tobacco products (vs those who do not), including electronic cigarettes (e-cigarettes), and some people report using nicotine pouches to help reduce or quit the use of e-cigarettes or combustible tobacco products.

Nicotine pouches deliver amounts of nicotine similar to other tobacco products and do so at a rate similar to other oral nicotine products, including some US Food and Drug Administration (FDA)–approved nicotine replacement therapies.

In addition, nicotine pouches have the potential to be tobacco harm-reduction products if unintended harms can be minimized, although more research is needed to determine the health effect profile of nicotine pouches under naturalistic use conditions.

Overall, additional research is needed to verify the results from industry-funded studies, further understand product characteristics that influence nicotine delivery and health effects, and translate findings to real-world use behaviors.

This additional research could help determine whether nicotine pouches have a robust evidence base to meet the public health standard by which FDA evaluates new tobacco products.”

Felicione NJ, Ozga JE, Eversole A, et al. Oral Nicotine Pouches: Rising Popularity and State of the Science. Public Health Reports. 2025;0(0). doi:10.1177/00333549251313668

“Oral nicotine pouches (ONPs) are a new class of nicotine products. This scoping review summarizes evidence on ONPs and explores their potential public health impact.

nationally representative U.S. studies find current use at 1.5% and lifetime use below 2.5% through 2023.

Between 35% and 42% of U.S. adolescents and young adults have heard of ONPs, and 9-21% of tobacco-naïve youth were susceptible to trying them.

U.S. adult-use estimates varied widely (0.8%–3% current; 3%–16% lifetime use) and were limited to populations with a history of tobacco use.

The chemical composition of ONPs suggests fewer harmful/potentially harmful compounds at lower levels than cigarettes and smokeless tobacco (SLT), except formaldehyde.

Industry-funded studies find substantially less cytotoxicity compared to cigarettes and suggest that higher nicotine-strength ONPs can deliver nicotine at levels comparable to or higher than SLT or cigarettes, although with slower nicotine release than cigarettes.

ONPs appear to be less toxic than cigarettes and deliver comparable nicotine, presenting an alternative for combustible product users, although key data are mainly available from industry-funded studies.

Data from independent research is critically needed. Industry marketing of ONPs may encourage initiation in youth and situational and dual use in adults.

The review provides an initial assessment of the potential role of ONPs in harm reduction and aims to determine unintended consequences of their use (youth uptake and dual-use) and identify populations that disproportionately use the product.

This information is essential for tobacco regulatory bodies in determining the net public health impact of nicotine pouches.”

Nargiz Travis, Kenneth E Warner, Maciej L Goniewicz, Hayoung Oh, Radhika Ranganathan, Rafael Meza, Jamie Hartmann-Boyce, David T Levy, The Potential Impact of Oral Nicotine Pouches on Public Health: A Scoping Review, Nicotine & Tobacco Research, Volume 27, Issue 4, April 2025, Pages 598–610, https://doi.org/10.1093/ntr/ntae131

“In 2023, 6-methyl nicotine (6MN), a synthetic nicotine analogue, was introduced in US-marketed electronic cigarette products advertised as exempt from regulation.

It is unknown whether the use of 6MN has spread to the oral nicotine pouch product category that has become increasingly popular.

Two US-based brands, “MG” and “Hippotine” pouches, were identified in August 2024, advertised to contain “Imotine”-trademarked 6MN.

MG Pouches are marketed in four youth-appealing flavors.

“Hippotine”-branded pouches are marketed in two flavors.

Products list extensive addiction and health warnings, including warnings not to operate vehicles.

Vendors state that these are not a tobacco product, implicating that federal and state tobacco regulations do not apply.

The spread of nicotine analogues to additional product categories such as oral pouches is concerning, especially given the high 6MN contents that exceed nicotine contents in popular US-marketed oral nicotine pouch products.

Legislators and regulators need to provide certainty about the regulatory status of nicotine analogues to prevent further erosion of tobacco flavor bans and other regulations.”

Sven E. Jordt, Sairam V. Jabba. Introduction of Nicotine Analogue-Containing Oral Pouch Products in the United States, 20 September 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-5110349/v1]

“The prefrontal cortex is not fully developed in middle/high school students, therefore many substances, including nicotine, have the potential to affect it, impair learning, and hinder academic performance.

Nicotine in pouches is an emerging, heavily marketed, explicit public health concern.

Adolescents may not know of the risks associated with nicotine pouches, especially with social media and marketing claims that they help with weight loss, athletic abilities, mood, and focus.

Middle/high school students’ nicotine pouch use was associated with C/D/F grades…

Longitudinal research is needed in this new area of tobacco-derived product development.”

Wiener, R. C., Gaydos, M. S., & Bhandari, R. (2025). Nicotine Pouch Use and Adolescents’ and Children’s Grades in School, National Youth Tobacco Survey 2022–23. Substance Use & Misuse, 60(7), 1053–1059. https://doi.org/10.1080/10826084.2025.2481323

“Artificial sweeteners, sucralose and acesulfame-k, are listed as ingredients of oral nicotine pouches (ONPs), a product category with a rapidly growing market share.

The exact quantities of these sweeteners in ONPs remain unknown. Artificial sweeteners in ONPs may reduce aversion, facilitate initiation, and encourage consumption behavior.

Acesulfame-k was detected in on!, Zyn, and Velo ONPs (~0.3 to 0.9 mg/pouch), including products marketed as “Unflavored” or “Flavor ban-approved.”

In Velo ONPs, sweetened with sucralose (~0.6 to 1.2 mg/pouch), higher nicotine strength products contained higher sucralose levels. Tas1r2^−/− mice consumed less ONP extracts than wild-type mice in both sexes.

ONPs contain significant amounts of artificial sweeteners acesulfame-k and sucralose, with some brands adding more sweeteners to higher nicotine strength ONPs.

In mice, artificial sweeteners, at levels present in ONPs, increase nicotine consumption.

Increasing sweetener contents facilitates the consumption of higher nicotine strength ONPs.

Sweetness imparted by sweetener addition to ONPs likely reduces the aversive sensory effects of nicotine and other ONP constituents.

Artificial sweeteners such as acesulfame-k or sucralose reduce aversion and likely facilitate the consumption of ONPs.

The marketing of some artificially sweetened ONPs as “Unflavored” or “Flavor ban-approved” suggests that the tobacco industry rejects sweet taste as a determinant for the presence of a characterizing flavor.

Sweetness as imparted by artificial sweeteners in tobacco products needs to be addressed by regulators as a component of a characterizing flavor, with the aim to reduce product appeal and initiation by never users, and especially youth attracted to sweet flavors.”

Sairam V Jabba, Peter Silinski, Alicia Y Yang, Wenyi Ouyang, Sven E Jordt, Artificial Sweeteners in US-Marketed Oral Nicotine Pouch Products: Correlation With Nicotine Contents and Effects on Product Preference, Nicotine & Tobacco Research, 2024; ntae293, https://doi.org/10.1093/ntr/ntae293

“Oral nicotine pouches (ONPs) are tobacco-free and non-combustible products that are pouch-shaped and fit between the alveolar process and the upper lip.

Through their use, nicotine is absorbed into the body through the oral mucosa.

Their harmfulness is significantly less than that of traditional cigarettes because they do not require combustion.

Research indicates ONPs have lower cytotoxicity compared to snus and cigarettes, with some studies suggesting reduced harm-related biomarkers. However, they still pose health risks.

The unregulated status and accessibility of nicotine pouches, especially to youth, underscore the need for awareness of their potential dangers.

It is important to emphasize their potential negative effects on the oral mucosa and periodontium, as well as on the body, due to their content of nicotine and other potentially dangerous substances.

ONPs are suspected of contributing to mucosal lesions, gingival recession, alveolar bone loss, and increased mediators of periodontitis…

ONPs contain low levels of tobacco-derived carcinogens, and may include substances classified by the IARC as potentially carcinogenic.

Due to the short time the product has been on the market and narrow period of widespread use, the effects of ONP on human health cannot be predicted with certainty.

It is very important to conduct further research in several areas regarding the health effects of ONP and potential consequences that may occur in the future.”

Rusiecka, A. W., Szymacha, K., Lewkowicz, N. (2024). The safety of using oral nicotine pouche – consideration of their effects on general health, oral mucosa and periodontal diseases, comparing them to snus and other nicotine containing products. J Pre Clin Clin Res., 18(3), 224-230. https://doi.org/10.26444/jpccr/189645

“Tobacco-free nicotine pouches is a novel category of oral nicotine-delivery products. Among current tobacco users such pouches may serve as a low-risk alternative to cigarettes or conventional, tobacco-based oral products e.g., snus and moist snuff. In the United States…the market leading nicotine-pouch brand is ZYN®. However, no data on the chemical characteristics of ZYN have been published.

The tested products contained nicotine at varying levels.

The two ZYN products contained no nitrosamines or polycyclic aromatic hydrocarbons (PAHs) but low levels of ammonia, chromium, formaldehyde, and nickel.

In the NRT products we quantified low levels of acetaldehyde, ammonia, cadmium, chromium, lead, nickel, uranium-235, and uranium-238.

The largest number (27) and generally the highest levels of HPHCs were quantified in the moist snuff products. For example, they contained six out of seven tested PAHs, and seven out of ten nitrosamines (including NNN and NNK).

A total of 19 compounds, none of which were PAHs, were quantified at low levels in the snus product. NNN and NNK levels were five to 12-fold lower in snus compared to the moist snuff products.

No nitrosamines or PAHs were quantified in the ZYN and NRT products. Overall, the number of quantified HPHCs were similar between ZYN and NRT products and found at low levels.”

Back, S., Masser, A.E., Rutqvist, L.E. et al. 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). BMC Chemistry 17, 9 (2023). https://doi.org/10.1186/s13065-023-00918-1

“Oral mucosal lesions are commonly found in Swedish smokeless tobacco (snus) users where the pouch is placed. These lesions are reversible, that is, clinical and histological tissue changes return to normal following cessation. However, the exact mechanisms behind these changes are unknown.

The main aim of this study was to investigate how snus-like non-tobacco-based nicotine pouches affect the oral mucosa and the severity of pre-existing lesions.

Sixty regular users of Swedish smokeless tobacco were encouraged to substitute their snus with non-tobacco-based nicotine pouch products during a 6-week period. Meanwhile, oral mucosal lesions were assessed using a four-degree scale.

Over time, a reduction of pre-existing mucosal lesions was observed between baseline and the final visit.

Results showed significantly increased production of proinflammatory cytokines in cells exposed to regular snus compared to untreated or cells exposed to the non-tobacco-based nicotine products. This may be related to the improved clinical appearance of the oral mucosa in the participants that used the non-tobacco-based nicotine test pouches.”

Alizadehgharib S, Lehrkinder A, Alshabeeb A, Östberg A-K, Lingström P. The effect of a non-tobacco-based nicotine pouch on mucosal lesions caused by Swedish smokeless tobacco (snus). Eur J Oral Sci 2022. 130: 3e12885. https://doi.org/10.1111/eos.12885

“The single-dose pharmacokinetics (PK) of a novel, non-tobacco-based nicotine pouch, ZYN, 3 and 6 mg, were compared with 8 mg General snus (part 1) and ZYN 8 mg was compared with 18 mg Longhorn moist snuff (part 2). The present study demonstrates the characteristics of three strengths of a novel tobacco-free oral snus, ZYN, viz. the extraction of nicotine from the oral cavity and its uptake into the systemic blood circulation. Comparison is made to Swedish General snus and American Longhorn moist snuff and from literature 4 mg Nicorette gum and mean of 13 brands of e-cigarettes.

Less nicotine was extracted from ZYN 3 mg (1.5 mg) and more from ZYN 6 mg (3.5 mg) than from 8 mg General (2.4 mg). The extracted fractions of nicotine for both ZYN products (56% and 59%) were significantly larger than for 8 mg General (32%).

The extracted amount of nicotine from ZYN 8 mg (3.8 mg) was larger than the amount extracted from Longhorn Natural 18 mg (3.0 mg), but smaller than the extracted amount of nicotine from General 2 × 8 mg snus pouches (5.0 mg).

The extracted fraction of nicotine for ZYN 8 mg (50%) was larger than for Longhorn Natural (19%) and General 2 × 8 mg snus pouches (33%).

The two higher doses of ZYN (6 and 8 mg) deliver nicotine as quickly and to a similar extent as existing smokeless products…”

Erik Lunell, Karl Fagerström, John Hughes, Robert Pendrill, Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff, Nicotine & Tobacco Research, Volume 22, Issue 10, October 2020, Pages 1757–1763, https://doi.org/10.1093/ntr/ntaa068