User:QuackGuru/Sand 14

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https://hub.jhu.edu/2024/03/08/zyn-nicotine-pouch-tory-spindle/

https://en.wikipedia.org/wiki/Veev

https://en.wikipedia.org/wiki/Iqos

https://en.wikipedia.org/wiki/Zyn_(nicotine_pouches)

https://tobaccotactics.org/wiki/nicotine-pouches/

https://commons.wikimedia.org/wiki/File:Size_of_nicotine_pouch_(cropped).png Slightly less crop

https://pubmed.ncbi.nlm.nih.gov/34034614/ wait for review

https://pubmed.ncbi.nlm.nih.gov/32998027/ wait for review

https://pubmed.ncbi.nlm.nih.gov/34233354/ wait for review

https://www.mdpi.com/2297-8739/8/6/77/htm wait for review

https://www.tandfonline.com/doi/full/10.1080/01480545.2021.1925691

[1]

https://www.sciencedirect.com/science/article/pii/S0278691520306037?via%3Dihub

[2]

https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntab030/6285126

[3]

https://www.mdpi.com/2297-8739/8/6/77/htm

[4]

https://pubmed.ncbi.nlm.nih.gov/?term=Nicotine+pouch&filter=years.2021-2021&size=200

https://en.wikipedia.org/w/index.php?title=Nicotine_pouch&oldid=1115455413 15:11, 11 October 2022 Nicotine pouch

https://pubmed.ncbi.nlm.nih.gov/36355951/ See "Cited by" for reviews.

Bronchial

Bronchial Epithelial Cells

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002198/

A 2022 in vitro study shows nicotine pouch extracts cause a toxic response in gingival epithelial cells directly.[6]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937772/


Size of nicotine pouch (nearly 3 centimeters).
Size of nicotine pouch (nearly 3 cms).
Schematic demonstration of the effect of oral nicotine pouches on oral/lung epithelial cells. Chewing of oral nicotine pouches could lead to oral epithelial injury by releasing reactive oxygen species via activation of inflammatory cytokines such as TNF-α, IL-6, and IL-8 which could further lead to oral and lung-related problems.
Schematic demonstration of the effect of oral nicotine pouches on oral/lung epithelial cells.[7] Chewing of oral nicotine pouches could lead to oral epithelial injury by releasing reactive oxygen species via activation of inflammatory cytokines such as TNF-α, IL-6, and IL-8 which could further lead to oral and lung-related problems.[7]

A nicotine pouch is a white powder preportioned pouch containing nicotine and other ingredients that do not contain tobacco leaf.[8] They use nicotine salts, while some contain synthetic nicotine.[9] The level of nicotine content is greater than nicotine replacement products.[9] A nicotine pouch is typically provided in a small pouch that is put in the mouth like snus, but unlike snus it does not contain moistened finely ground tobacco.[10] The user puts a pouch between the lip and gum and typically left there for around 30 minutes and then removed as an intact item.[11] No combustion is involved[8] and it is not swallowed.[10] The user does not need to spit.[8] The pouches do not need refrigeration.[8] Nicotine pouches primarily contain nicotine, water, flavorings, sweeteners, and fibers from plants.[10] The pouches are sold in an array of fruit flavors and other flavors.[8]

In contrast to US Food and Drug Administration (FDA)-approved nicotine replacement products, nicotine gum, and lozenges,[10] nicotine pouches are not approved as a quitting smoking tool in the US.[9] The least harmful nicotine products tend to be US FDA-approved nicotine replacement products.[12] Although nicotine pouches have the possibility of being a reduced risk nicotine product, there is no independent testing of their constituents, exposure or biomarkers of effects.[8]

Side effects can involve hiccups, mouth sore, and upset stomach.[10] The long-term effects of nicotine pouch use are unknown.[13] Studies have also indicated an association between nicotine pouches usage and risks for various diseases, including Parkinson’s disease, cancer, birth defects, type II diabetes, oral submucosal fibrosis, periodontal diseases, and cardiovascular diseases.[5] Nicotine pouches provide nicotine to the user for approximately an hour.[14] The pouches contain the addictive chemical nicotine.[10] The International Agency for Research on Cancer does not consider nicotine to be a carcinogen, though several studies demonstrate it is carcinogenic.[15] Because it can form nitrosamine compounds (particularly N-Nitrosonornicotine (NNN) and nicotine-derived nitrosamine ketone (NNK)) through a conversion process, nicotine itself exhibits a strong potential for causing cancer.[16] Nitrosamine carcinogenicity is thought to be a result of enhanced DNA methylation and may lead to an agonist response on the nicotinic acetylcholine receptors, which acts to encourage tumors to grow, stay alive, and penetrate into neighboring tissues.[16]

The first snus product that contained no tobacco was sold in 2014.[17] In 2019, five big tobacco companies offered nicotine pouch products.[8] Various major tobacco companies, including Altria, Swedish Match, and RJ Reynolds, are presently marketing nicotine pouches.[5] Since there entrance into the market, sales have grown exponentially.[9] The degree to which nicotine pouches are being used among minors and adults in the US is uncertain.[3] As seen with vaping products such as Juul in the US, novel nicotine products have the possibility for increased use by young adults and underage minors.[8] Nicotine pouches can be used recreationally.[18] Nicotine pouches may entice youth as well as young adult never-smokers because they are available in an array of fruit flavors and may be used unobtrusively.[8] They are marketed as containing no tobacco leaf.[8] These products are marketed online as they may be used anywhere as well as they do not require batteries or devices.[8]

Usage

Prevalence

Flavor distribution of snus versus synthetic nicotine pouches
Flavor distribution of snus versus synthetic nicotine pouches[5]

As seen with vaping products such as Juul in the US, novel nicotine products have the possibility for increased use by young adults and underage minors.[8] Nicotine pouches may be used for other reasons apart from quitting smoking[9] such as for recreational use.[18] Most people who use them are young adults who used combustible, or combustible-free tobacco products, normally with the underlying belief that these products are safer than other tobacco products.[13]

The diagrams show the wheel-based classification/categorization of natural/synthetic oral nicotine pouches (ONPs)/products that are commonly sold in the US. (A) Flavor wheel for natural/snus oral nicotine pouch (B) Flavor wheel for synthetic oral nicotine pouch. The nicotine concentration of all smoke-free nicotine-based pouches ranges from 3 mg to 8 mg per pouch; mint/menthol and fruit are two of the most widely sold flavors in the US. The flavors of each pouch product in the diagram are color-coded by flavor category, bright green color represents ONPs of mint/menthol flavors, light blue for fruit flavors, red color mixed flavors, pink color ONPs available in drink flavors, yellow color for tobacco flavors ONPs, parrot green color ONPs available in dessert flavors, sky blue ONPs in aroma flavors and orange represents ONPs available in flavor of spices. The inner wheel represents the most common flavors, and the outer wheel represents specific flavors.
The diagrams show the wheel-based classification/categorization of natural/synthetic oral nicotine pouches (ONPs)/products that are commonly sold in the US.[7] (A) Flavor wheel for natural/snus oral nicotine pouch (B) Flavor wheel for synthetic oral nicotine pouch.[7] The nicotine concentration of all smoke-free nicotine-based pouches ranges from 3 mg to 8 mg per pouch; mint/menthol and fruit are two of the most widely sold flavors in the US.[7] The flavors of each pouch product in the diagram are color-coded by flavor category, bright green color represents ONPs of mint/menthol flavors, light blue for fruit flavors, red color mixed flavors, pink color ONPs available in drink flavors, yellow color for tobacco flavors ONPs, parrot green color ONPs available in dessert flavors, sky blue ONPs in aroma flavors and orange represents ONPs available in flavor of spices.[7] The inner wheel represents the most common flavors, and the outer wheel represents specific flavors.[7]

Nicotine pouches may possibly be utilized as an alternative to smokeless tobacco products.[12] No studies are available to determine if smokers would switch to nicotine pouches or if they would continue to smoke and use nicotine pouches, resulting in dual use.[8] Nicotine pouches gives rise to the possibility for a nicotine fix in public areas where smoking is unacceptable.[19]

Canada

In Canada, 4 mg nicotine pouches became available for sale in gas stations and convenience stores in 2023 as a form of nicotine replacement therapy for adults under the brand Zonnic.[20] Although, children and teens were able to buy these products in Canada in 2023, as there were no laws preventing who could buy them.[20] Nicola Mercer, the CEO of Wellington-Dufferin-Guelph, stated in 2023 that Zonnic nicotine pouches have been seen at local high schools in Canada.[21]

Canada youth

In 2023, 17-year-old Ottawa student states that flavored nicotine pouches are being used at his high school.[22]

United States

The magnitude of using nicotine pouches among adults in the US is uncertain.[3] Nicotine pouches are available in a multitude of flavors such as fruit, dessert, citrus, mint, coffee, berry, and wintergreen, which contributes to the prevalence of nicotine pouch utilization in the US.[5]

United States youth

The magnitude their use among minors in the US is uncertain.[3] In 2022, less than one of every 100 middle school students (0.5%) and about 1 of every 100 high school students (1.4%) reported using nicotine pouches in the past 30 days in the US.[23]

In the US in 2021 the National Youth Tobacco Survey conducted online found that among high school students, e-cigarettes were the most commonly used tobacco product (11.3%; 1.72 million), followed by cigars (2.1%), cigarettes (1.9%), hookahs and smokeless tobacco (both 1.2%), nicotine pouches (1.1%), heated tobacco products (0.8%), and pipe tobacco (0.4%).[24] In the US in 2021 the National Youth Tobacco Survey conducted online found that among middle school students, e-cigarettes were the most commonly used tobacco product (2.8%; 320,000), followed by cigarettes (1.0%), cigars and smokeless tobacco (both 0.6%), hookahs and HTPs (both 0.4%), nicotine pouches (0.3%), and pipe tobacco (0.2%).[24] In the US in 2021 the National Youth Tobacco Survey conducted online found that among students who currently used each respective tobacco product, frequent use (on ≥20 days of the past 30 days) ranged from 17.2% for nicotine pouches to 39.4% for e-cigarettes.[24]

United Kingdom

In the UK in 2021, among past and present smokers or e-cigarette users, 15.9% of participants were aware of nicotine pouches, among which 2.7% were present users and 4.4% were ever consumers.[5] In the UK, the use of nicotine pouches among adults more than doubled from 0.14% in November 2020 to 0.32% in October 2021.[25]

United Kingdom youth and young adults

1% of 16-19-year-olds reported using nicotine pouches in 2019.[25]

Czech youth

The use of nicotine pouches in Czech is popular among minors.[26] Minors about 16 years of age have used nicotine pouches with hard alcohol in Czech.[26]

International

According to the International Tobacco Control Youth 2021 survey, 4% of 16-19-year-olds reported ever using nicotine pouches.[25] This considers data across the USA, Canada and England.[25] Among adolescents and Dutch adults in 2021 about 0.06% were present customers, and 0.56% were identified as ever having been customers of nicotine pouches.[5]

Youth

Nicotine pouches have become popular tobacco products among adolescents/young adults, and over 50% of young adult users of nicotine pouches use flavored nicotine pouches, such as menthol/mint, tobacco, dessert/candy, and fruity, which are the most popular flavors.[5] Using nicotine pouches is more prevalent among students who had vaped and smoked cigarettes.[13]

Motivation

Tobacco, menthol, and fruit-flavored nicotine pouches could motivate cigarette smokers to switch to using to nicotine pouches.[5] Nicotine pouches may entice youth as well as young adult never-smokers because they are available in an array of fruit flavors and may be used unobtrusively.[8] Adolescents display high interest in the latest newer smokeless non-tobacco nicotine pouches due to their resemblance with the preferred food products, such as chewing gums, and their accessibility in appealing flavors.[5] With the vaping bans in the US in 2019, teenagers are starting to use other addictive products such as nicotine pouches.[14] Concern exists that flavored nicotine pouches might entice youth.[27] "These products are attractive to youth. They come in appealing flavours. They come in containers that could well hold candy. Of course youth are going to be interested in them," Rob Cunningham stated in November 2023, who is a policy analyst with the Canadian Cancer Society..[28]

Gateway effect

Czech lieutenant Colonel Cross cautions that nicotine pouches can act as a bridge to other drugs, such as cannabis.[26] Czech military psychologist Michal Kříž states that the use of nicotine pouches among children can result in them becoming addicted to other substances.[26]

Contents

The contents of a nicotine pouch.
The contents of a nicotine pouch

A nicotine pouch is a white powder preportioned pouch containing nicotine.[8] They use nicotine salts, while some contain synthetic nicotine.[9] The level of nicotine content is greater than nicotine replacement products.[9] Some flavored nicotine pouches may be slightly off-white.[1] Because it does not contain tobacco leaf they differ from other nicotine-containing smokeless tobacco products, such as chewing tobacco, snuff, and snus.[10] Prime components of snus pouches noted are air or sun-cured tobacco, salt, water, and food-grade flavorings, whereas the nicotine pouches are plant-based fibers boosted by flavorings, nicotine, and other ingredients.[5] A nicotine pouch is typically provided in a small pouch that is put in the mouth like snus, but it does not contain moistened finely ground tobacco like snus.[10] The user puts a pouch between the lip and gum and typically left there for around 30 minutes and then removed as an intact item.[11] The user does not need to spit.[8] No combustion[8] or swallowing is involved.[10]

Nicotine pouches primarily contain nicotine, water, flavorings, sweeteners, and fibers from plants.[10] The nicotine content among nicotine pouch brands differ per pouch.[8] The nicotine content among 37 nicotine pouch brands tested from six producers varies from 1.29 mg per pouch to 6.11 mg per pouch, while free nicotine varies from 0.166 to 6.07 mg per pouch.[3] These results show that nicotine and pH levels contained in more than a few of these nicotine pouches are like that of traditional tobacco products, as for example moist snuff and snus.[3] The majority of nicotine pouches are flavored.[3] Nicotine pouches are sold in an array of fruit flavors such as citrus,[8] berry,[1] and black cherry.[8] Other flavors include honey,[9] mint,[12] peppermint,[8] coffee,[12] and cinnamon.[12]

The pouches come in tin[29] or plastic containers[1] and do not need refrigeration.[8] The small pouches kind of resemble chewing gum.[14]

Nicotine pouches typically cost about as much as a pack of regular cigarettes.[8] Velo were purchased for US$3.76, Zyn were purchased for US$5.11, Dryft were purchased for US$5.54, and On! were purchased for US$6.50 in 2019.[8]

Health effects

Positions of organizations and anti-smoking advocates

Advocacy groups opposed to the introduction of nicotine pouches in Kenya have protested that they may raise the risk of cancer, heart disease, and reproductive or developmental harms.[30] Kenya Tobacco Control Alliance (KETCA) objected to the entrance of nicotine pouches in Kenya, stating that there is no reliable research that demonstrates nicotine pouches are safer than regular cigarettes.[30] KETCA Chairman Joel Gitali said that given the higher levels of some possibly toxic chemicals, and what the US Food and Drug Administration said was a lack of medical data showing the nicotine pouches are safer than cigarettes (as claimed by British American Tobacco's managing director Beverly Spencer-Obatoyinbo), the government should not license the products.[30]

Several advocacy groups in Kenya have formally requested to the national cabinet secretary of health, Mutahi Kagwe, to prohibit the sale of the Lyft nicotine pouch.[31] The advocacy groups state that Lyft is not a pharmaceutical drug and it leads to severe addiction in young people along with giving rise to non-communicable diseases in Kenya.[32] In 2020, sales in Kenya were halted as a result of Kagwe intervening in 2020, who contested the reasoning stemming from the Pharmacy and Poisons Board's decision.[31] Kagwe later told British American Tobacco that Lyft would have to comply with the regulations that Kenya has implemented for tobacco products.[31]

In 2020, Health Canada recommended that nicotine pouches should be avoided by everyone and by people who are ultrasensitive to nicotine, have not smoked or are sporadic smokers, are minors, pregnant or breastfeeding, and have had recent heart issues (such as heart attack and arrhythmia) or a stroke.[33] Although Health Canada permitted Zonnic nicotine pouches for sale in July 2023 in Canada under the Natural Health Product Regulations, medical organizations, including the Canadian Cancer Society, have recommended that Zonnic nicotine pouches to be recategorized as a prescription-only medication or to halt the sale until the loophole fixed.[21] Smoking-control proponents had recommended to the Canadian federal government to prohibit the sale of Zonnic flavored nicotine pouches that were being marketed and sold to underage minors which were authorized for sale in 2023 by Health Canada without imposing any legal restrictions.[20]

Smoking cessation

In Norwegian pharmacies, nicotine pouches are sold as a delivery mechanism for nicotine replacement products, approved by the Norwegian Medicines Agency for smoking cessation, and sold under the brand Zonnic.[18] On July 18, 2023, Health Canada authorized the selling of Zonnic nicotine pouches in Canada as a type of nicotine replacement product for quitting smoking.[34] Health Canada noted that there are risks involved with using Zonnic nicotine pouches.[35]

In contrast to US Food and Drug Administration (FDA)-approved nicotine replacement products, nicotine gum, and lozenges,[10] nicotine pouches are not approved as a quitting smoking tool in the US.[9] 6 mg for ZYN and 8 mg for On! surpass the maximum allowable concentration of nicotine at 4 mg permitted by the US FDA for nicotine gum and lozenges.[12] WebMD recommends to discuss it with a doctor first prior to using a nicotine pouch if one is trying to quit using tobacco.[10]

Harm reduction

The number and variety of alternative tobacco and nicotine products that can potentially provide reduced-risk choices for cigarette smokers who switch completely to such products instead of continued smoking have grown substantially in the prior decade to 2020.[11] Innovation and choice are likely to improve the prospects of smokers making the switch, but this provides challenges to regulators and manufacturers to ensure that changes to regulations and products promote rather than hinder contributions to tobacco harm reduction.[11]

The least harmful nicotine products tend to be US FDA-approved nicotine replacement products.[12] No research is available to determine whether nicotine pouches could assist smokers to switch from regular cigarettes to a possible reduced harm nicotine product, or if they would be result in dual-use.[8]

Safety

Schematic depicting possible modulation of signaling cascades activation by oral nicotine pouches-mediated chemical moieties
Schematic depicting possible modulation of signaling cascades activation by oral nicotine pouches-mediated chemical moieties[5]

Studies demonstrated that the regular utilization of smokeless nicotine products is related to a higher risk for diseases such as cancers, Parkinson’s disease, birth defects, oral submucosal fibrosis, periodontal diseases, cardiovascular disease, and type 2 diabetes.[5] As nicotine pouches are not directly inhaled through the lungs, the flavoring chemicals, nicotine, and the byproducts within this product might be secreted across the membrane of the buccal cavity into the systemic circulation; these byproducts can then act locally on various tissues within the human body; responses of these are associated with the cardiopulmonary system via kidneys, liver, microvasculature, esophagus, and the pancreas.[5]

Although thought to have lower cytotoxicity, nicotine pouches can still cause injuries in cells and trigger inflammatory responses.[5] A 2022 study found higher levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and inflammatory cytokines (TNF-α, IL-6, and IL-8) in human gingival epithelial cells (HGEPp), human lung epithelial cells (BEAS-2B), and human bronchial epithelial cells (16-HBE) after treatment with nicotine pouches.[5] A 2022 in vitro investigation focused on oral–pulmonary health effects of snus and nicotine pouches, indicating that the flavored nicotine pouches are risky and likely to cause local and systematic toxicological responses during chronic consumption.[5]

Side effects can involve hiccups, mouth sore, and upset stomach.[10] The long-term effects of nicotine pouch use are unknown.[13] Unauthorized nicotine pouches in Canada may result in serious threats to health.[33] For instance, unauthorized nicotine pouches in Canada could contain nicotine at levels above what is deemed safe, or contain other ingredients not disclosed on the ingredient panel.[33] The use of a product that contains unidentified ingredients increases the odds of serious health consequences.[33] WebMD recommends to contact a doctor urgently if a nicotine pouch is swallowed.[10]

Oral health

Schematic mechanism showing nicotine pouches cause oxidative stress/inflammation/immune dysfunction, dysbiosis, and miRNAs dysregulation on periodontal health
Schematic mechanism showing nicotine pouches cause oxidative stress/inflammation/immune dysfunction, dysbiosis, and miRNAs dysregulation on periodontal health[6]

Concerns about their potential harms to periodontal health have been raised.[6] Nicotine pouches are likely to have a relatively low-risk profile, similar to other forms of orally administered nicotine; however, the prolonged and regular use may give increased risk of local oral problems.[25] Although they are shown to have their toxic effects, the number of pouches used per day for a number of months/years (as with smokers with cigarettes pack/year or puffs/day for vapers) required to have potential periodontal effects are not yet clinically standardized.[5]

A 2022 study detected the existence of tobacco-specific nitrosamines in 26 of 44 nicotine pouch products.[6] The highest measured concentrations of N-Nitrosonornicotine and nicotine-derived nitrosamine ketone were 13 ng and 5.4 ng/pouch.[6] In addition to nicotine and tobacco-specific nitrosamines, toxic chromium and formaldehyde were detected in some of the nicotine pouch products.[6] Exposure to N-Nitrosonornicotine is reported to be associated with promoting esophageal tumors.[6] This raises a special concern for nicotine pouches that are used in the oral cavity.[6] Studies show that appealing flavorings contained in nicotine pouches pose harm to periodontal innate immune responses and increase penetration of nitrosamines.[6]

The most plausible hypothesis that explains the relationship between nicotine pouches and periodontal disease is that the primary toxic component of nicotine pouches, namely, nicotine, interacts with host cells and affects inflammatory responses to microbial challenges.[6] It may directly or indirectly deteriorate periodontal tissue.[6] In vitro studies show that nicotine exposure significantly activated nicotinic acetylcholine receptor (nAChR) expression, repressed periodontal ligament (PDL) fibroblasts cells, and stem cell viability, and increased the generation of cellular reactive oxygen species (ROS).[6] Increased ROS level subsequently leads to sequential activation of signals, e.g., ERK, JNK, and caspase-3, 9, followed by DNA fragmentation and cell death.[6]

Established tobacco smoker effects

In established tobacco smokers, their use may be potentially useful.[13]

Dual use effects

Flavored nicotine pouches increase the risk of dual or poly-tobacco products among young adults, stacking up detrimental effects on the periodontium.[6]

Youth and young adult effects

The use of nicotine pouches provides no benefits to students who do not smoke.[13] Their use poses significant health risks, especially for adolescents and young adults.[6] Their recreational use among miners is dangerous because they do not understand their unwelcomed effects and risks of addiction.[13]

Addiction and dependence

Nicotine pouches provide nicotine to the user for approximately an hour.[14] Research analyzing their nicotine delivery is unavailable.[8] The nicotine pouches contain the addictive chemical nicotine.[10] Nicotine pouches have lower pharmacokinetics and addictive potential compared to traditional tobacco products.[5] Recent evidence investigated the pharmacokinetic parameters of nicotine pouches and reported that oral nicotine pouches carry the potential to be an acceptable substitute for adult smokers, as the users can achieve adequate nicotine levels to deliver into the body.[5]

Tobacco extracted versus synthetic nicotine effects

An image of S-nicotine and R-nicotine nicotine enantiomers
S-nicotine and R-nicotine nicotine enantiomers[36]

The nicotine used in the manufacturing of nicotine pouches is usually extracted from the tobacco plant; thus, related alkaloids (e.g., nornicotine, anatabine, and anabasine) may be found as impurities in small quantities.[4] Moreover, due to environmental factors such as temperature, humidity, light and storage containers, the degradation of nicotine may occur, giving rise to the formation of nicotine degradation products (e.g., cotinine, nicotine-N’-oxide, myosmine. and β-nicotyrine).[4]

The production of synthetic nicotine may create a blend of equal proportions of nicotine enantiomers.[37] Nicotine in nature occurs solely as the S-nicotine enantiomer (99.3%[6]).[37] Nicotine enantiomers have similar physical and chemical properties, yet in vitro and in vivo studies have shown that they have different pharmacological and toxicological properties.[36] For instance, studies have reported that S-nicotine is more toxic than R-nicotine in multiple species.[36] Consequently, the racemic mixture of nicotine is more toxic than R-nicotine.[36] The health implications of the presence of a significant amount of R-nicotine in synthetic nicotine products is unknown.[9] Products containing synthetic nicotine is a growing concern.[38]

Nicotine effects

Possible side effects of nicotine include increased clotting tendency, atherosclerosis, enlargement of the aorta, bronchospasm, muscular tremor and pain, gastrointestinal nausea, dry mouth, dyspepsia, diarrhea, heartburn, peptic ulcer, cancer, lightheadedness, headache, sleep disturbances, abnormal dreams, irritability, dizziness, blood restriction, increased or decreased heart rate, increased blood pressure, tachycardia, more (or less) arrhythmias, coronary artery constriction, coronary artery disease, high insulin, insulin resistance, and risks to child later in life during pregnancy include type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.
Possible side effects of nicotine[39]

Nicotine poses an array of health risks[15] such as the stimulation of cancer development and growth.[40] The International Agency for Research on Cancer does not consider nicotine to be a carcinogen, though several studies demonstrate it is carcinogenic.[15] Because it can form nitrosamine compounds (particularly N-Nitrosonornicotine (NNN) and nicotine-derived nitrosamine ketone (NNK)) through a conversion process, nicotine itself exhibits a strong potential for causing cancer.[16] About 10% of breathed in nicotine is estimated to convert to these nitrosamine compounds.[16] Nitrosamine carcinogenicity is thought to be a result of enhanced DNA methylation and may lead to an agonist response on the nicotinic acetylcholine receptors, which acts to encourage tumors to grow, stay alive, and penetrate into neighboring tissues.[16]

Various research studies disclosed the involvement of nicotine in activating several signaling cascades.[5] A 2015 study demonstrated that nicotine exposure decreased the reduction in T24 cells via elevating pAkt and pS6 expressions in vitro and in vivo via stimulating the PI3K/Akt/mTOR signaling in bladder cancer.[5] Another study showed that the involvement of nicotine in the progression and development of colon cancer is responsible for cell proliferation regulation and the suppression of apoptosis.[5] A 2012 study found that nicotine stimulates the levels of apoptotic markers, such as cleaved caspase-3, via increasing oxidative stress and enhancing the number of apoptotic cells upon podocyte injury.[5]

Nicotine in nicotine pouches could possibly engage the class-Ia PI3K, which stands for heterodimer constructed of the p110 catalytic and p85 regulatory subunits.[5] This further leads to the recruitment AKT and NF-kB, further activating the apoptotic proteins Bcl, Bax, and Caspase-3, triggering the apoptosis process.[5] Additionally, nicotine pouches elevate the reactive oxygen species, which can stimulate the levels of TGF-β1, triggering the activation of SMAD pathway via modulating the procollagen CTGF, augmenting inflammation, and ultimately activating the process of epithelial mesenchymal transition.[5]

Brands

Overview of companies

Velo nicotine pouches.
Velo nicotine pouches
Zone X nicotine pouches.
Zone X nicotine pouches

Nicotine pouches are mainly produced by the same businesses that produce snus.[41] In 2019, five big tobacco companies offered nicotine pouch products.[8] Large tobacco companies are selling them in the US.[9] Some tobacco businesses are selling them without stating they are nicotine replacement products.[9] No less than seven tobacco-free nicotine pouches (containing synthetic nicotine) had entered the US market in 2021.[9] These were Bidi, Fre, FR3SH, Lucy, NIIN, Rush, and 2one.[9]

Epok

Epok is owned by British American Tobacco and was for sale in Norway from 2014 to 2018.[17] It was described as being a tobacco-free snus.[17] In June 2018 the Norwegian Directorate of Health warned the company to remove Epok from sale or face fines of 4% of its revenue.[42] The Norwegian Directorate of Health stated that since Epok did not contain any tobacco it was a new form of nicotine product, distinct from the other forms of snus approved in Norway.[42] The company removed the tobacco-free product from Norwegian stores.[42] Epok was re-introduced to the Norwegian market after it was banned with tobacco added in order for it to be permitted to be sold again.[43] It is sold in Norwegian grocery stores.[43]

Lucy

Lucy nicotine pouches are sold in the US with more enticing flavors, such as mango and cool cider, than nicotine replacement products.[9] The nicotine content of 8 mg Lucy kapsel pouches, twice the amount of other Lucy nicotine products, and stated their nicotine pouches use tobacco-free nicotine, which differs from that of Lucy gum and lozenges.[9]

Lyft

Lyft is owned by British American Tobacco and it is sold in the UK and Sweden.[8] The nicotine content for Lyft is 4 and 6 mg.[8] In 2019, British American Tobacco started selling nicotine pouches in Kenya.[30] Dryft was owned by Kretek International and it was sold in the US.[8] The nicotine content for Dryft was 2 and 7 mg.[8] British American Tobacco which is a subsidiary of Reynolds American bought the brand Dryft in 2020 and announced at that time it will be rebranded under their US brand, Velo.[44] Velo is owned by Reynolds American and it is sold in the US.[44] The nicotine content for Velo is 2 and 4 mg.[8] Velo states that the contents in their products consist of nicotine obtained from the tobacco plant, microcrystalline cellulose, water, salt, sucralose, citric acid, and artificial flavor.[8] Zone X is part of Imperial Tobacco Canada, a subsidiary of British American Tobacco.[45]

Nordic Spirit

Nordic Spirit is owned by Japan Tobacco International and it is sold in Switzerland[46] and Sweden.[8] The Nordic Spirit pouches contain plant-based fibers, nicotine, additives, and flavorings and are intended to be put beneath the upper or lower lip and are absorbed through the gums.[47]

Altria purchased 80% of the On! nicotine pouch company in 2019.[8] In December 2020 and April 2021, its subsidiaries completed agreements to buy the remaining 20% of the company for about $250 million.[48] It is sold in Sweden, Japan, and the US.[8]

Rogue

Rogue nicotine pouches hit the market in November 2019 in the US[49] and is owned by the Floridian company, Swisher.[50]

Zonnic

Zonnic is owned by NicoNovum.[51] In Norway Zonnic is sold as a smoking cessation product.[52] Zonnic comes in a flavored nicotine small pouch in microcrystalline cellulose beads.[53] It is available in 4 mg of nicotine.[53] A user puts it between the upper lip and gum.[53] It releases approximately 3 mg of nicotine in 30 minutes.[51] Mouth irritation and throat irritation were frequently reported adverse effects.[51] Less commonly reported effects were nausea.[51] Zonnic should not be used during breastfeeding as nicotine may harm children.[52]

ZYN

In 2022, Philip Morris International paid $16 billion to purchase the company Swedish Match.[54] ZYN is owned by Swedish Match and it is sold in Europe and the US.[8] Zyn states that the contents in their products consist of pharmaceutical-grade nicotine salt, hydroxypropyl cellulose, microcrystalline cellulose, maltitol, gum arabic, sodium carbonate, sodium bicarbonate, acesulfame K, and food-grade flavorings.[8] It is packaged in a child resistant container, according to the company.[55] ZYN is sold in over 4,000 retailers in the US.[56] G.4 All White is owned by Swedish Match.[43] It contains the same formula as ZYN but with a few grams of tobacco added.[43] It is permitted to be sold in Norway.[43] The nicotine content for ZYN is 3, 6, and 8 mg.[57] 49.9 million cans were sold in the first quarter of 2022, whereas 73.2 million cans were sold in the first quarter of 2023.[58] It is estimated they will ship 520 million Zyn cans in 2024.[59]

https://www.fda.gov/tobacco-products/ctp-newsroom/fda-issues-warning-letters-and-files-civil-money-penalty-complaints-against-retailers-underage-sales

Society and culture

Social media

A nicotine pouch shop in Helsinki, Uusimaam Finland.
A nicotine pouch shop in Helsinki, Uusimaa, Finland

A large number of teens are finding out about Zyn nicotine pouches for the first time on social media.[60] Proponents on TikTok, typically young men, speak about their favorite Zyn flavors, or attempt to put as many pouches as they can into their mouths.[60] As of 2024, there are 29,700 TikTok's using the hashtag #Zyn, and one of them is from conservative political commentator Tucker Carlson who says they are "a powerful work enhancer."[60] On his show, Joe Rogan has spoken about the Zyn brand.[60] Prominent YouTube pranksters have supported the use of Zyn nicotine pouches.[60] Children are seeing social media influencers use Zyn nicotine pouches.[60] Compared to other nicotine pouch brands in the US, Zyn has attracted the most attention.[60] This is because it comprises nearly 60% of the sales of nicotine pouches in the US.[60]

Marketing

Companies that sell nicotine pouches are involved in advertising and marketing strategies, digital marketing campaigns, and marketing themes that project minimal harm, especially to attract the youth population.[29] Over time, marketing of nicotine pouches has increased substantially in the US.[5] There is no warning label on their packaging.[29] Zyn advertisements do not have a warnings conerning oral cancer and gum disease that is mandatory for other smoke-free tobacco products.[41] They are extensively advertised as 'harmless tobacco-free alternatives' on the Internet, on billboards, and on buses.[29] Companies use marketing terms such as 'tobacco-free' or 'tobacco leaf free'.[8]

They are marketed online as they may be used anywhere as well as they do not require batteries or devices.[8] Nicotine pouches are being marketed as a safe means to obtain a 'nicotine hit' without the dangers involved with the use of tobacco or snus products.[29] Some brands that manufacture nicotine pouches are marketing these products as a safer substitute to smoking and dipping.[10] British American Tobacco Kenya had marketed Lyft as substitute to cigarettes for smokers.[32] Lyft is being pushed in certain regions in Africa as a 'modern oral nicotine pouch without tobacco'.[9] Nordic Spirit handed out free samples of its nicotine pouches at top festivals in the UK in the summer of 2022.[61]

Canadian Cancer Society's Rob Cunningham stated in 2023 that Imperial Tobacco Canada's advertising approach and various flavors for its nicotine pouch brand, Zonnic, are aimed at youth and need to be dealt with.[20] Imperial Tobacco Canada's web posts show images of young people and emphasize the Zonnic's flavors like berry frost and tropic breeze.[20] The Zonnic website promotes the pouches as a nicotine replacement product, but health proponents state it is merely the efforts of the tobacco industry to create a new generation of addicted young people that evade the laws on the marketing and the selling of tobacco.[20]

Corporate sponsorship

Zyn was a sponsor at the IndyCar's Music City Grand Prix in Nashville, Tennessee in August 2023.[59]

Economics

Originating from Scandinavia, the selling of nicotine pouches quickly spread to many other countries, including the European Union, the UK, the US, and Japan.[5] Since 2016, the US market has consisted of nicotine pouches that do not contain tobacco leaves in the final product, and since 2018, they have been in Europe.[5] During the January 29, 2020 discussion at the Las Vegas Convention Center, Thomas Ericsson, a scientist who helped develop a handful of the nicotine pouches in the marketplace, stated that any product must meet the user's tastes.[62] Nicotine pouches are probably snatching away sales from dipping tobacco.[50]

Since there entrance into the market, sales have grown exponentially.[9] During the last five years leading up to 2023, their sales have grown considerably.[13] In the US, sales of nicotine pouches reached $642,000 in 2016, $13.9 million in 2017, and $52 million in 2018.[3] The commercial market share of nicotine pouches in the US jumped from 0.9% in 2018 to 4.0% in 2019.[5] Sales of nicotine pouches in convenience stores in the US increased 470% from January 2020 to July 2020.[19] From 2021 to 2022, the nicotine pouch share of the market increased to 21.9% of the US oral tobacco segment, a rise of 6.5% compare with the previous year.[63] As of 2022, tobacco-free nicotine products are offered on Amazon, which does not allow the sale of either tobacco or vaping products in the US.[9]

The majority of supermarkets in the UK are selling the pouches.[64]

Regulations

Overview

As they are neither tobacco products nor medicinal products, regulatory approaches have varied.[11] It is not clear how they are classified in most countries.[8]

Africa

The majority of tobacco regulations in Africa do not address nicotine products.[9]

Asia

The Ministry of Health, Labour and Welfare in Japan has decided to regulate tobacco-free nicotine pouches as pharmaceutical drugs.[9]

Canada

A nicotine pouch may be considered a prescription drug in Canada.[33] This depends on the amount of nicotine delivered.[33] In Canada, tobacco-free oral use nicotine pouches with a dosage exceeding 4 milligrams are considered a prescription drug, therefore personal imports of nicotine pouches containing over 4 milligrams of nicotine per pouch are prohibited.[65] Exceptions for up to a 90-day supply do exist for tobacco-free oral use nicotine pouches containing over 4 milligrams of nicotine per pouch for those being of these criteria: a health practitioner or medical practitioner, a pharmacist, or while visiting Canada.[65] In Canada, tobacco-free oral use nicotine pouches with a dosage of 4 milligrams or less is only permitted for personal use, therefore personal imports of nicotine pouches containing 4 milligrams or less of nicotine per pouch is allowed for up to a 90-day supply.[65]

All nicotine pouches must receive approval from Health Canada to be lawfully sold in Canada.[33] On July 18, 2023, a sister company of Imperial Tobacco was granted market permission to sell flavored nicotine pouches in pursuant of the Natural Health Product Regulations,[66] laws which are classified under the Food and Drugs Act.[34] These nicotine products do not contain tobacco.[66] Health Canada previously authorized the sale of Zonnic flavored nicotine pouches from Imperial Tobacco Canada with no advertising or sales restrictions.[67] Since July 18, 2023, it was totally lawful for retailers to sell them to anyone of any age including children.[66] On October 12, 2023, Imperial Tobacco Canada reported that it had started offering for sale the Zonnic nicotine pouches.[34] Mark Holland, the minister of health in Canada states that he will swiftly take action to close the loophole following Health Canada authorizing the selling of these nicotine flavored nicotine pouches without any advertising or sales restrictions.[22]

United States

The US FDA amended the official definition of tobacco products in 2022 into "any product made or derived from tobacco or containing nicotine from any source, that is intended for human consumption" which includes tobacco-free nicotine products.[5] As a result, nicotine pouches are completely under the regulation of the US FDA, whether the nicotine content is tobacco-derived nicotine or tobacco-free (synthetic) nicotine.[5]

European Union

As of 2021, they ae not regulated in the European Union.[29] In 2023 nicotine pouches are regulated in the UK by default under the General Product Safety Regulations.[25] The Tobacco and Related Product Regulations currently regulates all categories of tobacco products, with parts 6-8 of the Tobacco and Related Product Regulations regulating e-cigarettes.[25] However, the Tobacco and Related Product Regulations does not cover nicotine pouches.[25]

Because nicotine pouches contain nicotine instead of tobacco, they do not fall under tobacco regulations which makes them unregulated in Czech.[26] Anyone under 18 years of age can purchase them in Czech.[26]

In Finland, nicotine pouches are regulated under the Medicines Act and Medicines Decree.[68] Imports for personal use and selling them in Finland are permitted.[68] In Finland, until April 2023, nicotine pouches were categorized for medicinal use.[69] The Finnish Medicines Agency stated that nicotine pouches cannot be categorized as medicinal products unless they are explicitly marketed for a medicinal purpose or it can be shown in another way that they are commonly used in a way that is similar to medicinal products.[69]

Nicotine pouches without containing tobacco are not permitted to be sold in Norway.[43]

Untied Kingdom

As nicotine pouches are only currently marketed as consumer products in the UK, they do not fall under the Jurisdiction of the Medicines and Healthcare Regulatory Agency.[25] The pouches are not part of tobacco or medical laws in the UK.[64] In 2022, the Action on Smoking and Health group called for a regulatory framework covering all nicotine products.[64]

Other names

A nicotine pouch[70] is variously known as nicotine buccal pouch,[33] non-medicinal nicotine pouch,[29] tobacco-free snus,[29] tobacco-less nicotine pouch,[33] nicotine-containing tobacco-free oral pouch,[4] tobacco-free nicotine product,[9] tobacco-free ‘modern’ oral nicotine product,[2] oral smokeless product,[3] modern oral nicotine pouch,[71] oral nicotine pouch,[33] "snus" nicotine pouches,[72] nicotine bag,[26] or all white tobacco.[71]

Other products

A nicotine-free snus called Choice was launched in Swedish in 2003 and another nicotine-free snus brand called Onico was launched in 2016.[73] Boldt Runners sells cannabidiol dipping pouches called Cannadips CBD that do not contain nicotine or tobacco.[74]

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Further reading

External links