User:QuackGuru/Sand 3

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https://pubmed.ncbi.nlm.nih.gov/?term=nicotine+salt&filter=pubt.meta-analysis&filter=pubt.review&filter=pubt.systematicreview&filter=years.2020-2021&size=200

https://pubmed.ncbi.nlm.nih.gov/?term=nicotine+salts&filter=pubt.meta-analysis&filter=pubt.review&filter=pubt.systematicreview&filter=years.2020-2021&size=200

https://en.wikipedia.org/w/index.php?title=Nicotine_salt&oldid=1023679167 18:39, 17 May 2021

QuackGuru/Sand 3
Identifiers
3D model (JSmol)
ChEMBL
EC Number
  • sulfate: 200-606-7
RTECS number
  • sulfate: QS9625000
UNII
UN number 1658
  • benzoate: CN1CCC[C@H]1C2=CN=CC=C2.C1=CC=C(C=C1)C(=O)O
  • sulfate: CN1CCC[C@H]1C2=CN=CC=C2.CN1CCC[C@H]1C2=CN=CC=C2.OS(=O)(=O)O
  • hydrochloride: CN1CCC[C@H]1C2=CN=CC=C2.Cl
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Nicotine salts are salts formed from nicotine and an acid.[1] They are found naturally in tobacco leaves.[2] Research on nicotine salts is limited.[3] Possible health risks of persistent inhalation of high levels of nicotine salts are not known.[3] The International Agency for Research on Cancer does not consider nicotine to be a carcinogen, though several studies demonstrate it is carcinogenic.[4] A conjugated nicotine base and a weak acid such as benzoic acid or levulinic acid is used to create a nicotine salt.[1]

The speed of nicotine salts uptake into the body with the use of electronic cigarettes is close to the speed of nicotine uptake from traditional cigarettes.[5] Nicotine salts are less harsh and less bitter, and as a consequence e-liquids that contain nicotine salts are more tolerable even with high nicotine concentrations.[6] Advertisements state nicotine salt liquids contain 2 to 10 times more nicotine than those found in the majority of regular e-cigarette products.[7]

Health effects

Limited research

Research on nicotine salts is limited.[3] The effects of nicotine salt liquids is not well understood.[8] Possible health risks of persistent inhalation of high levels of nicotine salts are not known.[3]

Toxicology

Nicotine salts used for vaping permeates the cell membrane and induces cytotoxic effects.[9]

Nicotine carcinogenicity

Nicotine poses an array of health risks[4] such as the stimulation of cancer development and growth.[10] The International Agency for Research on Cancer does not consider nicotine to be a carcinogen, though several studies demonstrate it is carcinogenic.[4] 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.[11] About 10% of breathed in nicotine is estimated to convert to these nitrosamine compounds.[11] 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.[11]

Lung effects

A 2021 study suggested that protonated nicotine is more likely to result in acute lung damage, as this is the form that binds to nicotinic acetylcholine receptors (which activate inflammatory immune responses) lining the lung epithelium.[12] These receptors are also expressed on macrophages; accordingly, alveolar macrophage production of inflammatory cytokines is enhanced in the presence of nicotine-containing e-cigarette aerosol condensate compared to nicotine-free e-cigarette aerosol condensate.[12]

Brain effects

See also: Effects of nicotine and electronic cigarettes on human brain development

"Juul products use nicotine salts, which can lead to much more available nicotine," Principal Deputy Director Dr. Anne Schuchat of the Centers for Disease Control and Prevention stated in September 2019.[13] She also stated that the nicotine salts "cross the blood brain barrier and lead to potentially more effect on the developing brain in adolescents."[13]

Types

A nicotine base and a weak acid such as benzoic acid or levulinic acid is used to form a nicotine salt.[1] Across a sample of 23 nicotine salts available for public purchase in 2019, the three most common acids used in the formation of nicotine salts were lactic acid, benzoic acid and levulinic acid.[14] Benzoic acid is the most used acid to create a nicotine salt.[6] Nicotine pyruvate is another form of nicotine salt.[15] A chemical reaction with a pyruvic acid is used to aerosolize nicotine.[16]

Level and rate of delivery

Nicotine salts used in later-generation vaping devices may also have altered pharmacodynamics and acute effects relative to e-liquids containing free-base nicotine (conventionally used in e-liquids).[12] For instance, a 2021 study found that nicotine salt-based e-liquid had a more acidic pH (protonated) relative to more basic conventional (unprotonated) e-liquid; they postulated that this reduces systemic bioavailability because protonated nicotine has poorer membrane permeability.[12]

A free-base nicotine solution with an acid reduces the pH, which makes it possible to provide higher levels of nicotine without irritating the throat.[17] Nicotine salts are thought to amplify the level and rate of nicotine delivery to the user.[3] The speed of nicotine salts uptake into the body with the use of electronic cigarettes is close to the speed of nicotine uptake from traditional cigarettes.[5] Traditional cigarettes provide high levels of nicotine, but with the undesirable taste of smoking.[7] Pod mods, however, can provide the high levels of nicotine without the negative smoking experience.[7] Nicotine pouches also use nicotine salts.[18]

Nicotine salts are less harsh and less bitter, and as a consequence e-liquids that contain nicotine salts are more tolerable even with high nicotine concentrations.[6] Nicotine salts in aerosol form do not generate the sensation of irritation in the chest and lungs that regular cigarettes do.[5] Protonated nicotine salt is easier for less experienced users to inhale.[19]

Brands

The latest generation of e-cigarettes, "pod products," such as Juul, have the highest nicotine content (59 mg/mL), in protonated salt, rather than the free-base nicotine form found in earlier generations.[19] In June 2015, Juul introduced a pod mod device containing nicotine salt.[20] British American Tobacco stated that they have been using nicotine salts in their US Vuse e-liquid brand since 2012.[21]

Nicotine salts are more tolerable to the lungs when inhaled, leading to delivery of higher concentrations of nicotine.[22] It is possible that users of these products would get even more nicotine than from a traditional tobacco cigarette.[22] For this reason as well as their small compact design, there has been a dramatic increase in the use of Juul, particularly by youth, since their introduction in June 2015 to the market.[22] There has been a proliferation of pod-based products with high nicotine concentration, triggered by Juul's financial success.[6] As of September 2018, there were no less than 39 similar Juul devices as well as 15 Juul-compatible pods being offered.[6] Tested show that the pod mods Juul, Bo, Phix, and Suorin contain nicotine salts in a solution with propylene glycol and glycerin.[3]

Building on their initial success of disposable devices offered in a multitude of flavors in 2019, Puff Bar added a range of flavored pods named Puff Krush.[23] Disposable Elf Bar e-cigarettes can contain as high as 20 mg/ml (2%) of liquid nicotine salts one can obtain in the UK.[24] In 2022, Elf Bars has gained popularity among never-smoking college students in the UK.[24]

Regulation

See also: Regulation of electronic cigarettes

In the UK, the maximum nicotine concentration allowed by law for an e-cigarette or refillable liquid is 20 mg/ml.[25]

Marketing

Advertisements state nicotine salt liquids contain 2 to 10 times more nicotine than those found in the majority of regular e-cigarette products.[7]

Other names

Nicotine salt solutions are also known as salt nic.[18]

References

  1. ↑ 1.0 1.1 1.2 Voos, Natalie; Goniewicz, Maciej L.; Eissenberg, Thomas (2 November 2019). "What is the nicotine delivery profile of electronic cigarettes?". Expert Opinion on Drug Delivery. 16 (11): 1193–1203. doi:10.1080/17425247.2019.1665647. ISSN 1742-5247. PMC 6814574. PMID 31495244.
  2. ↑ Fraga, John-Anthony Fraga (November 2019). "The Dangers of Juuling". National Center for Health Research.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Goniewicz, Maciej Lukasz; Boykan, Rachel; Messina, Catherine R; Eliscu, Alison; Tolentino, Jonatan (2018). "High exposure to nicotine among adolescents who use Juul and other vape pod systems ('pods')". Tobacco Control. 28 (6): tobaccocontrol–2018–054565. doi:10.1136/tobaccocontrol-2018-054565. ISSN 0964-4563. PMC 6453732. PMID 30194085.
  4. ↑ 4.0 4.1 4.2 Chaturvedi, Pankaj; Mishra, Aseem; Datta, Sourav; Sinukumar, Snita; Joshi, Poonam; Garg, Apurva (2015). "Harmful effects of nicotine". Indian Journal of Medical and Paediatric Oncology. 36 (1): 24. doi:10.4103/0971-5851.151771. ISSN 0971-5851. PMC 4363846. PMID 25810571.
  5. ↑ 5.0 5.1 5.2 "JUUL®: An Electronic Cigarette You Should Know About". American Academy of Family Physicians. 2019. Archived from the original on 2019-09-30. Retrieved 2019-11-18.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 Jackler, Robert K; Ramamurthi, Divya (2019). "Nicotine arms race: JUUL and the high-nicotine product market". Tobacco Control. 28 (6): tobaccocontrol–2018–054796. doi:10.1136/tobaccocontrol-2018-054796. ISSN 0964-4563. PMID 30733312. S2CID 73433596.
  7. ↑ 7.0 7.1 7.2 7.3 Barrington-Trimis, Jessica L.; Leventhal, Adam M. (2018). "Adolescents' Use of "Pod Mod" E-Cigarettes — Urgent Concerns". New England Journal of Medicine. 379 (12): 1099–1102. doi:10.1056/NEJMp1805758. ISSN 0028-4793. PMC 7489756. PMID 30134127.
  8. ↑ Soto, Brian; Costanzo, Louis; Puskoor, Anoop; Akkari, Nada; Geraghty, Patrick (2023). "The implications of Vitamin E acetate in E-cigarette, or vaping, product use-associated lung injury". Annals of Thoracic Medicine. 18 (1): 1. doi:10.4103/atm.atm_144_22. PMID 36968330.
  9. ↑ Jonas, Andrea (18 July 2022). "Impact of vaping on respiratory health". BMJ: e065997. doi:10.1136/bmj-2021-065997. PMID 35851281.
  10. ↑ Mravec, Boris; Tibensky, Miroslav; Horvathova, Lubica; Babal, Pavel (2020). "E-Cigarettes and Cancer Risk". Cancer Prevention Research. 13 (2): 137–144. doi:10.1158/1940-6207.CAPR-19-0346. ISSN 1940-6207. PMID 31619443.
  11. ↑ 11.0 11.1 11.2 Bracken-Clarke, Dara; Kapoor, Dhruv; Baird, Anne Marie; Buchanan, Paul James; Gately, Kathy; Cuffe, Sinead; Finn, Stephen P. (2021). "Vaping and lung cancer – A review of current data and recommendations". Lung Cancer. 153: 11–20. doi:10.1016/j.lungcan.2020.12.030. ISSN 0169-5002. PMID 33429159.
  12. ↑ 12.0 12.1 12.2 12.3 Snoderly, Hunter T.; Nurkiewicz, Timothy R.; Bowdridge, Elizabeth C.; Bennewitz, Margaret F. (18 November 2021). "E-Cigarette Use: Device Market, Study Design, and Emerging Evidence of Biological Consequences". International journal of molecular sciences. MDPI AG. 22 (22): 12452. doi:10.3390/ijms222212452. ISSN 1422-0067. PMC 8619996. PMID 34830344. This article incorporates text by Hunter T. Snoderly, Timothy R. Nurkiewicz, Elizabeth C. Bowdridge, and Margaret F. Bennewitz available under the CC BY 4.0 license.
  13. ↑ 13.0 13.1 LaVito, Angelica; Shama, Elijah (24 September 2019). "CDC warns of dangers of nicotine salts used by vaping giant Juul in e-cigarettes". CNBC.
  14. ↑ Benowitz, Neal L; Jacob, Peyton; Havel, Christopher M; Harvanko, Arit M (June 2020). "Characterization of Nicotine Salts in 23 Electronic Cigarette Refill Liquids". Nicotine & Tobacco Research. 22 (7): 1239–1243. doi:10.1093/ntr/ntz232. ISSN 1469-994X. PMC 7291795. PMID 31821492.
  15. ↑ "New smoking cessation therapy proves promising". American Association for the Advancement of Science. 27 February 2010.
  16. ↑ Etter, Jean-François (2015). "E-cigarettes: methodological and ideological issues and research priorities". BMC Medicine. 13 (1): 32. doi:10.1186/s12916-014-0264-5. ISSN 1741-7015. PMC 4330977. PMID 25856794.
  17. ↑ Jenssen, Brian P.; Wilson, Karen M. (2019). "What is new in electronic-cigarettes research?". Current Opinion in Pediatrics. 31 (2): 262–266. doi:10.1097/MOP.0000000000000741. ISSN 1040-8703. PMC 6644064. PMID 30762705.
  18. ↑ 18.0 18.1 Ling, Pamela M.; Kim, Minji; Egbe, Catherine O.; Patanavanich, Roengrudee; Pinho, Mariana; Hendlin, Yogi (1 March 2022). "Moving targets: how the rapidly changing tobacco and nicotine landscape creates advertising and promotion policy challenges". Tobacco Control. 31 (2): 222–228. doi:10.1136/tobaccocontrol-2021-056552. PMID 35241592.
  19. ↑ 19.0 19.1 Jenssen, Brian P.; Boykan, Rachel (2019). "Electronic Cigarettes and Youth in the United States: A Call to Action (at the Local, National and Global Levels)". Children. 6 (2): 30. doi:10.3390/children6020030. ISSN 2227-9067. PMC 6406299. PMID 30791645. This article incorporates text by Brian P. Jenssen and Rachel Boykan available under the CC BY 4.0 license.
  20. ↑ McKelvey, Karma; Baiocchi, Mike; Halpern-Felsher, Bonnie (2018). "Adolescents' and Young Adults' Use and Perceptions of Pod-Based Electronic Cigarettes". JAMA Network Open. 1 (6): e183535. doi:10.1001/jamanetworkopen.2018.3535. ISSN 2574-3805. PMC 6324423. PMID 30646249.
  21. ↑ Rachel Becker (21 November 2018). "Juul's nicotine salts are dominating the market — and other companies want in". The Verge.
  22. ↑ 22.0 22.1 22.2 Traboulsi, Hussein; Cherian, Mathew; Abou Rjeili, Mira; Preteroti, Matthew; Bourbeau, Jean; Smith, Benjamin M.; Eidelman, David H.; Baglole, Carolyn J. (2020). "Inhalation Toxicology of Vaping Products and Implications for Pulmonary Health". International Journal of Molecular Sciences. 21 (10): 3495. doi:10.3390/ijms21103495. ISSN 1422-0067. PMC 7278963. PMID 32429092. This article incorporates text by Hussein Traboulsi, Mathew Cherian, Mira Abou Rjeili, Matthew Preteroti, Jean Bourbeau, Benjamin M. Smith, David H. Eidelman, and Carolyn J. Baglole available under the CC BY 4.0 license.
  23. ↑ Kaplan, Sheila (2 June 2020). "Lawmakers Say Puff Bar Used Pandemic to Market to Teens". The New York Times.
  24. ↑ 24.0 24.1 SWNS reporter (23 December 2022). "'A lot of them never smoked': How Elf Bars took over Britain's universities". Yahoo!.
  25. ↑ "The Tobacco and Related Products Regulations 2016". legislation.gov.uk. 2024.

External links

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