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Liisa-Ly Pakosta Eesti Vabariigi valitsuse justiits- ja digiasjade minister E-posti teel: [email protected] / [email protected]

24. juuli 2026 Lugupeetud minister

Kommentaar tubakaseaduse ja riigitasude seaduse kavandatavate muudatuste kohta – JDM/26-0826

Minu nimi on Clive Bates, Ühendkuningriigis tegutsev rahvatervise ja tubakakontrolli spetsialist. Olen endine Action on Smoking and Health UK direktor, endine kõrgem riigiametnik ning juhin nüüd Counterfactual Consultingut, keskendudes jätkusuutlikule arengule ja rahvatervisele. Mul ei ole huvide konflikte tubaka-, nikotiini- ega farmaatsiatööstuse osas.1

Olen näinud uudiseid Eesti valitsuse ettepanekutest kehtestada uued piirangud suitsuvabadele nikotiinitoodetele (aurutid, suukaudne nikotiin, kuumutatud tubakas jne).2 Kirjutan, et lugupidavalt üles kutsuda ettevaatlikkusele ja juhtida tähelepanu selliste meetmete tõenäolistele perverssetele ja ettenägematutele tagajärgedele.

Kokkuvõtteks võib öelda, et pakutud meetmetel on tõenäoliselt kolm laiemat kahjulikku mõju:

1. Suitsetamisega kaasnevate isiklike, sotsiaalsete ja majanduslike koormate pikendamine. WHO andmetel suitsetab rohkem kui üks neljast täiskasvanud eestlasest. Need piirangud takistavad seadusliku nikotiinituru liikumist kõrge riskiga toodetelt madala riskiga toodetele (protsess, mis toimub üle maailma), kaitstes olemasolevat sigaretikaubandust konkurentsivõimeliste ja ohutumate toodete eest. See tähendab, et vähem suitsetajaid vahetab üle ja rohkem kannatab selle tõttu asjatult, mis toob kaasa veelgi tootlikkuse ja tervishoiu kulusid. Paljud noored, kes täna aurustavad, oleksid suitsetanud ka ilma aurutamiseta; Nende jaoks on noorte aurutamine rahvatervise võit.

2. Kasvata suurt ebaseaduslikku turgu. Legaalsete toodete piirangud vähendavad nõudlust vähe. Tarbijad otsivad soovitud tooteid nii mitteametlikelt kui ka kuritegelikelt turgudelt. See loob suuremaid võimalusi piiratud toodete suurele ebaseaduslikule turule. Fraunhoferi Instituut hindas, et 2025. aastal toimus Eestis 41% ebaregulaarsest e-sigarettide kaubandusest, millest 32% oli must turg ja 9% piiriülesed.3 Hollandis, kus on juba kasutusele võetud sarnased meetmed nagu praegu Eestis ette nähtud, leidis Bureau Beke, et 87% aurutajatest kasutab ebaseadusliku müügikanali kaudu saadud vape'e. Hollandi tarbijad kulutavad vape'ile umbes 280 miljonit eurot aastas, kuid sellest umbes 257 miljonit eurot kulutatakse ebaseaduslikele toodetele.4

3. Käivita riskantseid lahendusi. Tarbijad püüavad saada soovitud tooteid innovatsiooni või lahenduste kaudu. Näiteks saavad inimesed ise vedelikke valmistada ja lisada kommertstoidu maitseid või isegi aroomiteraapia vedelikke. Nikotiini piirangutest saab mööda hiilida, lisades nikotiini ebaseaduslikult ostetud kontsentraatidest. Võib esineda käitumuslikke kohanemisi; Näiteks võivad inimesed hakata korraga kasutama kahte või enamat nikotiinipakki. Tootjad saavad regulatsioonidele loominguliselt reageerida: 4 mg/g täiteaine piirang viiks suuremate ja tihedamate täitematerjalide kasutamiseni.

1 Vaata clivebates.com: Teave Täpsemalt. 2 ERR. EE Justiitsministeerium soovib karmistada nikotiinitoodete müügipiiranguid, 20. juuli 2026 [link] 3 Fraunhoferi Instituut. (2026). E-sigarettide ebaregulaarne turg Euroopas. Fraunhofer IIS koostöös MRU GmbH-ga.

https://www.scs.fraunhofer.de/en/publications/the-irregular-market-for-e-cigarettes-in-europe.html 4 Emily Berger, Emma Derksen, Christa Dinnissen ja Juno van Esseveldt. (2026). Dark Clouds: Eelnev uurimus ebaseaduslikust

vape-kaubandusest Hollandis. Bureau Beke. https://bureaubeke.nl/geen-categorie/dark-clouds/

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• Poliitikakujundamine nõuab suhtelise riski mõistmist. On kahtlustamatu, et suitsuvabad nikotiinitooted, mis ei hõlma tubakasuitsu põlemist ega sissehingamist, on palju ohutumad kui suitsetamistooted. Nende suitsuvabade toodete hulka kuuluvad e-sigaretid (e-sigaretid), nikotiinipakid ja muud suukaudsed tooted, kuumutatud tubakas ning suitsuvaba tubakas. Järgmine diagramm, mis annab umbkaudsed hinnangud riskile seoses sigarettide suitsetamisega, pärineb Rahvusvahelise Valuutafondi ekspertide poolt läbi viidud uuringust optimaalse maksustamise kohta.5

• Poliitikakujundajad ei saa oodata kindlust, vaid peavad tegema toimivaid ligikaudseid hinnanguid. Neid suhtelisi riske ei ole võimalik kindlalt teada, kuid on võimalik teada piisavalt kindlalt, et luua alus poliitikakujundamiseks. Suitsetamise ja suitsuvabade toodete vahel on tõenäoliselt üks kuni kaks suurusjärgu erinevus riskides. Nikotiinipakkidel on tõenäoliselt riskid, mis on võrreldavad nikotiini asendusraviga. See viitab suurele rahvatervise potentsiaalile nikotiini tarvitamise üleminekul kõrge riskiga toodetest madala riskiga toodetele.

• Madala riskiga tooted asendavad kõrge riskiga tooteid. Samuti on vähe kahtlust, et need tooted asendavad suitsetamist järk-järgult kahe peamise mehhanismi kaudu: (1) olemasolevad suitsetajad lähevad üle ohutumatele suitsuvabadele toodetele ja (2) uued nikotiini kasutajad, sealhulgas noored, suunduvad suitsetamisest ohutumatele toodetele alustamise hetkel ning vananevad seejärel elanikkonna hulka ilma kunagi suitsetamata. Enamik noori, kes täna regulaarselt e-sigarette tarvitavad, on saanud suitsetajaks maailmas, kus e-sigarette pole. Peamine probleem suures osas Euroopas ei ole see, et noored hakkavad suitsetamise asemel aurutama, vaid see, et vanemad täiskasvanud jäävad sigarettide juurde.

• Suitsetamisprobleem püsib ja on koondunud vanematele nikotiinikasutajatele. Eestis on endiselt märkimisväärne täiskasvanute elanikkond, kes on suitsetamisega seotud suremuse ja haigestumise, sealhulgas vähi, südame-veresoonkonna ja hingamisteede haiguste riskiga, kusjuures üle ühe neljanda täiskasvanu suitsetab (26,1% täiskasvanutest, 30,9% meestest ja 21,4% naistest – WHO andmed).6 Selle Eesti elanikkonna segmendi jaoks on need tooted potentsiaalsed päästjad, kuid ainult siis, kui kasutajad leiavad need atraktiivseks ja on kindlad, et need on palju ohutumad.

5 MF, Van Oordt ja Rosenberg,Kahjulike harjumuste maksustamine, 2026. Graafika tuletatudMurkett jt 2022 6 Maailma Terviseorganisatsioon (2025). WHO ülemaailmne aruanne tubaka tarvitamise levimuse trendidest 2000–2024 ja

prognoosid aastateks 2025–2030 (6. väljaanne). https://www.who.int/publications/i/item/9789240116276

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• Rootsi kogemus näitab õiget suunda. Euroopa Liidu riik, mis on saavutanud suitsetamisega seotud haiguste vähendamise ja suitsetamisega seotud haiguste vähendamise kõige olulisema edu, on Rootsi. Kui võtta meeste kopsuvähi esinemissagedus suitsetamisega seotud kahjude mõistliku näitajana, näeme, et Rootsis on tasemed palju madalamad kui Eestis – umbes kolmandik.7

Vanuse standardiseeritud vähiesinemissagedus, mehed vanuses 40–84 Kopsuvähk Huulte, suuõõne ja neeluvähk

Rahvusvaheline Vähiuuringute Agentuur (IARC): Globaalne Vähiobservatoorium

• Nikotiini kasutamine on vältimatu, kuid kõrge haiguse tase mitte. Põhjus on selles, et nikotiini kasutatakse Rootsis erinevalt, peamiselt suitsuvaba suukaudse tubaka või snusi kaudu. Ajalooliselt on Rootsis olnud kõrged nikotiinitarbimise tasemed (kõrgemad kui Eestis), kuid palju madalam suitsetamise tase. Selle tulemusena on Rootsis suitsetamisega seotud haiguste (sh suuvähi) tase madalam.8

• EL-i keeld snusile oli suur poliitiline läbikukkumine. Euroopa Liit keelas snusi 1992. aastal, välja arvatud Rootsi puhul. Alates 1992. aastast on suitsetamisega seotud haigustesse surnud üle 20 miljoni eurooplase (Eestis umbes 60 000).9 Kui EL oleks edendanud snusi alternatiivina

7 IARC Globaalne Vähiobservatoorium, Vähk aja jooksul https://gco.iarc.who.int/en 8 Ramstrom, L. M. (2024). Kui Rootsis poleks olnud snus'i: snus'i mõju suitsetamisest tingitud suremusele. Kahjude vähendamise

ajakiri, 21(1), 176. https://doi.org/10.1186/s12954-024-01095-7 9 Tervisemõõdikute ja Hindamise Instituut, GBD Compare 2023, https://vizhub.healthdata.org/gbd-compare/

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sigarettidele, selle asemel et keelustada, oleks siseturg võinud aidata vähendada suitsetamisega seotud haigusi kõigis riikides. Oht seisneb selles, et Euroopa Komisjon ja mitmed liikmesriigid ei ole snus'i keelustamisest õppetunde saanud ning näivad olevat valmis seda viga kordama, piirates nikotiinipakke ja e-sigarette. Eesti pakutud meetmed võivad korrata Euroopa Liidu 1992. aasta vigu, mida on hiljem ja hiljem ning hiljem ka Hollandi ja teiste poolt säilitatud.

• Vape-maitsete keelustamine võib suitsetamise suurenemise tõttu tõenäoliselt tagasilöögi anda. On märkimisväärseid tõendeid, et vape-maitse keelud suurendavad sigarettide suitsetamist. See on tingitud sellest, et e-sigaretid ja sigaretid on majanduslikud asendused. Muutes ühe vähem atraktiivseks nii kasutajatele kui potentsiaalsetele kasutajatele, muutub teine suhteliselt atraktiivsemaks. Piirava aurutamise või kotikese maitse keelu korral kaitstakse kahjulikke alternatiivtooteid, näiteks sigarette, tõhusama konkurentsi eest. Kvasi- eksperimentaalne majandusuuringud on näidanud, et vape-maitse keelud on suurendanud suitsetamist osariigi tasandil Ameerika Ühendriikides; Friedman jt (2026) näitavad:10

Meie tulemused näitavad, et ENDS-i maitsepiirangud toovad kaasa märkimisväärseid ENDS-i müügi vähenemisi, peamiselt tänu maitsestatud ENDS-i müügi märkimisväärsele langusele ning maitsestamata ENDS-i müügi mitteolulistele kasvudele. Täiendavad analüüsid näitavad, et ENDS-i maitsepiirangud suurendavad põlevate sigarettide müüki, mis on kahjulikum toode: nende poliitikate tõttu ostetakse iga müüdud 0,7 ml ENDS kapsli kohta 11 kuni 15 lisasigaretti. [rõhuasetus lisatud]

• ... ja ebaseaduslikku kaubandust. Lisaks pääsevad e-sigarettide kasutamise soovijad ligi suurele mustale turule reguleerimata toodetes, mis on lõpuks seotud organiseeritud kuritegelike rühmitustega.

• Maitse reguleerimine peaks keskenduma maitse kirjeldajatele. Maitset võib iseloomustada keemilise retseptina, aistinguna ("õun", "münt") või kirjeldajana – nime ja brändinguna, mida kasutatakse tarbijatele, et anda tarbijatele teada, millist maitset ja tunnet nad peaksid ootama. See on tooteinfo vorm, aga ka turunduse vorm. Regulatsioon peaks keskenduma sellele, et vältida lastele meeldivate teemadega turundust ning tagada, et maitsekirjeldused annavad toote sõnasõnalise kirjelduse ilma tühiste kaunistusteta.

• Madal nikotiini piirang kotikestes võib tõenäoliselt tagasi lüüa. Täiteaine piirang 4mg/g muudab peaaegu kõik praegu Euroopas saadaval olevad tooted mittenõuetele vastavaks. Kehtestades piirangu, mis ei vasta paljudele suitsetajatele või nikotiini tarvitajatele, soodustab see musta turu nikotiinipakkides, mida inimesed otsivad. See toob tõenäoliselt kaasa muutusi varustuses – suuremad kotikesed tihedamast materjalist ja julgustatakse kasutama korraga rohkem kui ühte.

• Palju kõrgemad piirangud on rahvatervise kaalutlustel õigustatud. Enamik koti reguleerimist on seni põhinenud nikotiini massil kotis (mg/kott), mitte täiteühiku (mg/g) alusel. Turul on saadaval tootevalik umbes 1 mg kuni 20 mg kotikeses. 1 118 kotisordist, mida jaemüüja Haypp Groupi poolt iseseisvalt testiti, sisaldas 921 (82%) rohkem kui 4 mg nikotiini kotis.11 Üks viis mõõta uue regulatsiooni põhjustatud häireid (ja seega mõju kasutajatele ning tõenäoliselt ettenägematuid tagajärgi) on hinnata, kui suur osa olemasolevast turust muutuks uue regulatsiooni alusel mittevastavusse. Suur veebimüüja Haypp Group esitab järgmised andmed

10 Friedman, A. S., Liber, A. C., Crippen, A. ja Pesko, M. F. (2026). E-sigarettide maitsepiirangute mõju tubakatoodete müügile.

American Journal of Health Economics, 12(2), 377–411. https://doi.org/10.1086/734689 11 Haypp Group, NicoLeaks, https://nicoleaks.com/

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oma nikotiinikotide müügi kohta. 80–95% Euroopa tarbimisest muutuks nõuetele mittevastavaks, kui piirang oleks 4 mg/kotike.12 Pane tähele, et näidatud piirpiir on piiratud 20 mg/kotikesega, kuna see on ettevõtte poolt müüdav maksimaalne nikotiinisisaldus poliitika alusel.

Haypp Groupi (veebimüüja) müügiandmed

• Pakutud piirang hävitaks olemasoleva kotituru täielikult. Ometi on Eesti ettepanek rangem. Kui määrata 4 mg täiteaine grammi kohta (mitte kotikese kohta), oleks piirang kotikese kohta madalam. Hayppi sõnul sisaldab mediaantoode veidi alla 0,5 g täiteainet, mis tähendab, et Eesti pakutav 4 mg/g täiteaine piirang tähendaks ligikaudu nikotiini piirmäära 2 mg kotis. See kaotaks peaaegu kõik praegu Euroopas kasutatavad tooted.

• Puudub tuvastatav kasulik põhjus selle piiri seadmiseks. Nikotiinikoguse piiramiseks alla 20 mg ei ole tegelikku rahvatervise õigustust. Kui suitsetaja vajab tugevamat taskutoodet, mis on põhjus, miks talle ligipääs keelata? Ületarbimisega seotud riskid tekivad võrdselt ka siis, kui inimesed kasutavad rohkem kui ühte kotikest või hoiavad neid liiga kaua suus.

• Nikotiinipakkide ebaseaduslik kaubandus võib kergesti jõuda samale tasemele kui vape'id. Ebaseadusliku kaubanduse levik on juba kogetud väga suurt vape'ide puhul. Ülemaailmne ebaseaduslik osakaal vape'i turul oli 2025. aastal 75% ja kasvab, teatas äriinfoteenuse Euromonitor.13 On igati põhjust eeldada, et nikotiinipakkide liigne reguleerimine või maksustamine viiks sarnase ebaseadusliku kaubanduse ulatuseni kotikestega.

• Ebaseaduslike turgude negatiivsed tagajärjed on tõsised: o Piirangute või maksude eesmärk, mis põhjustas ebaseadusliku kaubanduse, nurjub o Tooted on reguleerimata ja võivad olla ohtlikud, aegunud või defektsed o Müüjad on ebaausad ärimehed ja müüvad igale vanusele o Kuritegelikud võrgustikud toimivad vägivalla, korruptsiooni ja väljapressimise kaudu o Tarbijal puuduvad kaitsed ega õiguskaitse; Vaidlused lahendatakse vägivalla kaudu o Jõustamismeetmed on kallid, sageli liialdatud ja piiravad vähe pakkumist o Karistused pakkumise ja kasutamise takistamiseks muutuvad riski suhtes ebaproportsionaalseks o Noored tõmmatakse kuritegelikesse tarneahelatesse kui madalaima taseme tarnijad o Tarbijad puutuvad kokku teiste ebaseaduslike toodete või teenustega, näiteks ebaseaduslike

narkootikumidega o Suured ebaseaduslikud kasumid rahastavad õitsevaid organiseeritud kuritegelikke rühmitusi ja

terrorismi

12 Haypp Group, isiklik suhtlus, 24. juuli 2024 13 Euromonitor, Üle 75% ülemaailmsest e-auru mahust on põhjustatud ebaseaduslikust turust, 28. august 2025. [Euromonitor]

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ÜRO Narkootikumide ja Kuritegevuse Büroo on dokumenteerinud kahjud, mis tulenevad kuritegelikust infrastruktuurist, mis toetab ebaseaduslikku narkokaubandust.14 UNODC diagramm kaardistab osalejad:

• Kõigi tubaka- ja nikotiinipoliitikate kriitiline eesmärk peab olema turg seaduslikuna. Ebaseadusliku kaubanduse tõenäolised tagajärjed piiravad Euroopa poliitikakujundajate paindlikkust kehtestada piiravaid või keelavaid poliitikaid. Selline kaubandus õõnestab poliitika algset eesmärki, jätab turu reguleerimata ja põhjustab laia valikut sotsiaalseid kahjusid. Ei ole piisav lihtsalt nõuda rangemat jõustamist ilma selgitamata, miks see pole seni suutnud peatada umbes kolmveerand maailma turust ja pool Euroopa turu aurutamise ebaseaduslikuks või ebaregulaarseks muutumist aastaks 2025.

• Mida teha: arendada riskiproportsionaalse regulatsiooni raamistik. Poliitika eesmärk peaks olema rakendada kõige karmimaid ja piiravamaid meetmeid, et tegeleda suitsetamisega seotud riskidega nii kasutajale kui ka pealtvaatajatele. Ohutumate nikotiinitoodete reguleerimine peaks keskenduma tarbijakaitsele (keemia-, elektri- ja soojusohutus ning usaldusväärne info) ning noorte vastuvõtu piiramisele meetmete kaudu, mis tagavad vastutustundliku varustuse, jaemüügi ja turunduse.

• Mida teha: keskendu tarbijakaitsele ja usaldusele. Regulatsioon peaks toetama tubaka- ja nikotiinitoodete kasutajate huve ning looma proportsionaalse heidutuse uute kasutajate vastuvõtuks. Agressiivsed katsed käitumise muutmiseks regulatsiooni kaudu toovad suuresti kaasa soovimatuid tagajärgi, nagu suitsetamise kasv, ebaseaduslikum kaubandus ja riskantsed lahendused. Peamine eesmärk peaks olema nikotiinituru ülemineku hõlbustamine kõrge riskiga toodetelt madala riskiga toodetele, kuid tarbijate nõusoleku ja valiku kaudu, mitte sundiva, karistava või stigmatiseeriva poliitika kaudu. Valitsus peaks seadma kõrge prioriteedi turu seaduslikkuse säilitamisele ning poliitikavalikuid tuleks vastavalt piirata.

14 ÜRO Narkootikumide ja Kuritegevuse Büroo, uurimisülevaade rahvusvahelisest organiseeritud kuritegevusest, november 2025

[UNODC]

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Liisa-Ly Pakosta Minister of Justice and Digital Affairs Government of the Republic of Estonia By email: [email protected] / [email protected]

24 July 2026 Dear Minister

Comment on proposed amendments to the Tobacco Act and the State Fees Act – JDM/26-0826

My name is Clive Bates, a UK-based public health and tobacco control specialist. I am a former Director of Action on Smoking and Health UK), a former senior civil servant, and I now run Counterfactual Consulting, focusing on sustainable development and public health. I do not have conflicts of interest with respect to the tobacco, nicotine or pharmaceutical industries.1

I have seen news of the government of Estonia’s proposals to impose new restrictions on smoke- free nicotine products (vapes, oral nicotine, heated tobacco, etc).2 I am writing to respectfully urge caution and to draw attention to the likely perverse unintended consequences of such measures.

To summarise, the proposed measures would likely have three broad harmful effects:

1. Prolonging the personal, social and economic burdens of smoking. More than one in four adult Estonians smoke, according to WHO. These restrictions will obstruct the migration of the lawful nicotine market from high-risk to low-risk products (a process that is underway globally), protecting the incumbent cigarette trade from competitive safer products. It will mean fewer people who smoke will switch, and more will suffer needlessly as a result, with further costs in productivity and healthcare. Many young people who are vaping today would have smoked in the absence of vapes; for them, youth vaping is a public health win.

2. Cultivate a large illicit market. Restrictions on legal products will do little to lower demand. Consumers will seek the products they want via informal and criminal markets. This will create greater opportunities for a large illicit market in the restricted products. The Fraunhofer Institute estimated that in 2025, Estonia had 41% irregular trade in e-cigarettes, of which 32% was black market and 9% was cross-border.3 In the Netherlands, which has already adopted similar measures to those now proposed for Estonia, Bureau Beke found that 87% of vapers use vapes obtained through an illegal sales channel. Dutch consumers spend around €280 million per year on vapes, but of that, approximately €257 million is spent on illegal products.4

3. Trigger risky workarounds. Consumers will try to obtain the products they want through innovation or workarounds. For example, people can make their own liquids and add commercial food flavours or even aromatherapy liquids. It is possible to work around limits on nicotine by adding nicotine from illegally purchased concentrates. There may be behavioural adaptations; for example, people may start using two or more nicotine pouches at once. Manufacturers can respond creatively to regulations: a limit of 4mg/g of filler would lead to the use of larger, denser filler materials.

1 See clivebates.com: About for more detail. 2 ERR.EE Ministry of Justice wants to tighten restrictions on the sale of nicotine products, 20 July 2026 [link] 3 Fraunhofer Institute. (2026). The irregular market for e-cigarettes in Europe. Fraunhofer IIS in cooperation with MRU GmbH.

https://www.scs.fraunhofer.de/en/publications/the-irregular-market-for-e-cigarettes-in-europe.html 4 Emily Berger, Emma Derksen, Christa Dinnissen, & Juno van Esseveldt. (2026). Dark Clouds: A preliminary exploration of the

illegal vape trade in the Netherlands. Bureau Beke. https://bureaubeke.nl/geen-categorie/dark-clouds/

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• Policymaking requires a grasp of relative risk. It is beyond reasonable doubt that smoke-free nicotine products that do not involve combustion and inhalation of tobacco smoke are far safer than smoking products. These smoke-free products include e-cigarettes (vapes), nicotine pouches and other oral products, heated tobacco and smokeless tobacco. The following chart, which provides rough estimates of risk relative to cigarette smoking, is from research on optimal taxation conducted by experts at the International Monetary Fund.5

• Policymakers cannot expect certainty but must make workable approximations. It is not possible to know these relative risks with certainty, but it is possible to know enough with confidence to provide a basis for policymaking. There is a likely one- to two-orders-of- magnitude difference in risks between smoking and smoke-free products. Nicotine pouches are likely to have risks comparable to nicotine replacement therapy. That suggests major public health potential in migrating nicotine use from high-risk to low-risk products.

• Low-risk products are displacing high-risk products. There is also little doubt that these products are steadily displacing smoking through two main mechanisms: (1) existing smokers switching to safer smoke-free products, and (2) new nicotine users, including youth, diverting from smoking to safer products at the point of initiation and then ageing into the population without ever smoking. Most young people who are vaping regularly today would have become smokers in a world without e-cigarettes. The main problem in much of Europe is not that young people are taking up vaping instead of smoking, but that older adults are sticking with cigarettes.

• The smoking problem remains and is concentrated in older nicotine users. Estonia still has a substantial adult population at risk of smoking-related mortality and morbidity, including cancer, cardiovascular and respiratory disease, with more than one in four adults smoking (26.1% of adults, 30.9% men and 21.4% of women – WHO data)6. For this segment of Estonia’s population, these products are a potential lifesaver, though only if users find them appealing and are confident that these products are much safer.

5 MF, Van Oordt & Rosenberg, Taxing harmful habits, 2026. Graphic derived from Murkett et al. 2022 6 World Health Organisation (2025). WHO global report on trends in prevalence of tobacco use 2000–2024 and projections

2025–2030 (6th Edition). World Health Organisation. https://www.who.int/publications/i/item/9789240116276

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• The Swedish experience shows the right direction to take. The European Union country with the most significant success in addressing smoking and reducing smoking-related disease is Sweden. If we take male lung cancer incidence as a reasonable indicator for smoking-related harm, we see that Sweden has far lower levels than Estonia – around one third.7

Age standardised cancer incidence, men age 40-84 Lung cancer Lip, oral cavity and pharynx cancer

International Agency for Research on Cancer (IARC): Global Cancer Observatory

• Nicotine use is inevitable, but high levels of disease are not. The reason is that nicotine is

used differently in Sweden, mostly via smokeless oral tobacco or snus. Historically, Sweden has had high levels of nicotine use (higher than Estonia), but much lower levels of smoking. As a result, Sweden has lower levels of smoking-related disease (including oral cancer).8

• The EU ban on snus was a major policy failure. The European Union banned snus in 1992 with an exception for Sweden. Since 1992, more than 20 million Europeans have died from smoking- related disease (about 60,000 in Estonia).9 Had the EU promoted snus as an alternative to

7 IARC Global Cancer Observatory, Cancer Over Time https://gco.iarc.who.int/en 8 Ramstrom, L. M. (2024). If there had been no snus in Sweden: The impact of snus on mortality attributable to smoking. Harm

Reduction Journal, 21(1), 176. https://doi.org/10.1186/s12954-024-01095-7 9 Institute of Health Metrics and Evaluation, GBD Compare 2023, https://vizhub.healthdata.org/gbd-compare/

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cigarettes instead of banning it, the internal market could have contributed to reducing smoking-related disease in all countries. The danger is that the European Commission and several member states have not learned lessons from the ban on snus and appear willing to repeat the error with excessive restrictions on nicotine pouches and e-cigarettes. Estonia’s proposed measures risk repeating the mistakes of the European Union in 1992 and maintained subsequently and, more recently, those of the Netherlands and others.

• A ban on vape flavours is likely to backfire by increasing smoking. There is substantial evidence that vape flavour bans increase cigarette smoking. This is because vapes and cigarettes are economic substitutes. By making one less attractive to its users and potential users, the other becomes relatively more attractive. In the case of a restrictive vape or pouch flavour ban, the harmful alternative products, cigarettes, are protected from more effective competition. Quasi-experimental economic research has shown that vape flavour bans have increased smoking at the state level in the United States; Friedman et al (2026) show:10

Our findings reveal that ENDS flavor restrictions yield substantial decreases in total ENDS sales, primarily owing to significant declines in flavored ENDS sales alongside nonsignificant increases in unflavored ENDS sales. Further analyses find that ENDS flavor restrictions increase sales of combustible cigarettes, a more harmful product: 11 to 15 additional cigarettes are purchased for every 1 less 0.7 mL ENDS pod sold because of these policies. [emphasis added]

• … and illicit trade. In addition, those who wish to use vapes will access a large black market in unregulated products ultimately linked to organised crime groups.

• Flavour regulation should focus on flavour descriptors. A flavour can be characterised as a chemical recipe, a sensation (“apple”, “mint”) or a descriptor – the name and branding used to convey to consumers what they should expect the product to taste and feel like. This is a form of product information, but also a form of marketing. Regulation should focus on preventing marketing with child-appealing themes and ensuring that flavour descriptors provide a literal description of the product without frivolous embellishments.

• A low limit on nicotine in pouches is likely to backfire. A limit of 4mg/g of filler will render nearly all the products currently available in Europe non-compliant. By setting a limit that would not meet the demands of many people who smoke or wish to use nicotine, it will nurture a black market in pouches with nicotine content that people are seeking. It will likely lead to changes in supply – larger pouches of denser material and encouragement to use more than one at once.

• Much higher limits are justified on public health grounds. Most pouch regulation so far has been based on the mass of nicotine in a pouch (mg/pouch), not per unit of filler (mg/g). The market shows a range of products from around 1 mg to 20 mg per pouch. Of the 1,118 pouch varieties independently tested on behalf of Haypp Group, a retailer, 921 (82%) had more than 4mg of nicotine per pouch.11 One way of measuring the disruption a new regulation would cause (and hence the impact on users and likely unintended consequences) is to assess how much of the existing market would become non-compliant under the new regulation. The major online retailer Haypp Group provides the following data for its nicotine pouch sales. 80-95% of

10 Friedman, A. S., Liber, A. C., Crippen, A., & Pesko, M. F. (2026). E-Cigarette Flavor Restrictions’ Effects on Tobacco Product

Sales. American Journal of Health Economics, 12(2), 377–411. https://doi.org/10.1086/734689 11 Haypp Group, NicoLeaks, https://nicoleaks.com/

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European consumption would become non-compliant with a limit of 4mg/pouch.12 Note that the ceiling shown is limited to 20mg/pouch as that is the maximum nicotine content sold by the company as a matter of policy.

Haypp Group (online retailer) sales data

• The proposed limit would wipe out the existing pouch market. Yet, Estonia’s proposal is more restrictive. By specifying a limit of 4mg per gram of filler (rather than per pouch), the limit per pouch would be lower. According to Haypp, the median product has just under 0.5g of filler, meaning Estonia’s proposed limit of 4mg/g of filler would equate to approximately a nicotine limit of 2mg per pouch. That would eliminate almost every product currently used in Europe.

• No identifiable beneficial reason to set this limit. There is no real public health justification for limiting nicotine content to less than 20 mg. If someone who smokes needs a stronger pouch product, what is the reason to deny them access? Risks associated with overconsumption arise equally from people using more than one pouch or keeping them in the mouth for too long.

• Illicit trade in nicotine pouches could easily reach the same levels as vapes. A very high penetration of illicit trade has already been experienced for vapes. The global illicit share of the vape market was 75% in 2025 and is growing, according to the business information service Euromonitor.13 There is every reason to expect that excessive regulation or taxation of nicotine pouches would lead to a similar scale of illicit trade in pouches.

• The negative consequences of illicit markets are severe: o The aim of the restrictions or taxes that caused the illicit trade is defeated o The products are unregulated and may be dangerous, out of date, or defective o The sellers are unscrupulous commercial operators and will sell to anyone of any age o Criminal networks operate through violence, corruption and extortion o The consumer has no protections or recourse; disputes are settled through violence o Enforcement actions are expensive, often excessive, and do little to limit supply o Penalties to deter supply and use become disproportionate to the risk o Young people are drawn into criminal supply chains as bottom-tier suppliers o Consumers are exposed to other illegal products or services, such as illicit drugs o Large illicit profits finance flourishing organised crime groups and terrorism

12 Haypp Group, personal communication, 24 July 2024 13 Euromonitor, Over 75% of global e-vapour volume is driven by illicit market, 28 August 2025. [Euromonitor]

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The UN Office on Drugs and Crime has documented the harms arising from criminal infrastructure that underpins the illicit drug trade.14 The UNODC chart maps the actors involved:

• A critical goal for all tobacco and nicotine policies must be to keep the market legal. The likely consequences of illicit trade constrain European policymakers’ flexibility to impose restrictive or prohibitive policies. Such trade undermines the policy’s original purpose, leaves the market unregulated, and causes a wide range of social harms. It is not adequate simply to call for more enforcement without explaining why this has so far failed to stop around three- quarters of the global market and half the European market in vapes becoming illicit or irregular by 2025.

• What to do: develop a framework for risk-proportionate regulation. The policy aim should be to take the toughest, most restrictive measures to address the risks of smoking to the user and bystanders. The regulation of safer nicotine products should focus on consumer protection (chemical, electrical, and thermal safety, and reliable information) and on limiting youth uptake through measures to ensure responsible supply, retailing, and marketing.

An outline of a risk-proportionate regulatory framework for tobacco and nicotine

Measure Cigarettes, hand-rolling tobacco, and other combustibles

Vaping, heated and smokeless tobacco and oral nicotine

Overall aim Reduce appeal and deter use Consumer protection

Taxation Relatively high taxes Low or zero tax (sales tax only)

Advertising Prohibit other than within trade Control themes and placement

Warnings Graphic warnings depicting disease Messages encouraging switching

Public places Legally mandated controls Up to the discretion of the owner

Plain packaging Yes No. Controls on imagery and branding

Risk communication Major risks to health A far safer alternative to smoking

Age restrictions No sales to under-21s No sales to under-18s

Flavours Ban characterising flavours Control flavour descriptors

Product standards Control risks and reduce appeal Control safety risks to the user

14 UN Office on Drugs & Crime, Research Brief on Transnational Organized Crime, November 2025 [UNODC]

Nicotine policy evidence briefings Table of Contents

1 NICOTINE FOR POLICYMAKERS ............................................................................................. 2

1.1 KEY CONCEPTS ............................................................................................................................. 2 1.2 WHAT IS NICOTINE? ....................................................................................................................... 3 1.3 NICOTINE AND ADDICTION .............................................................................................................. 4 1.4 THE CHALLENGE OF REGULATING NICOTINE EXPOSURE .......................................................................... 6 1.5 HEALTH EFFECTS OF NICOTINE ......................................................................................................... 7 1.6 CONCLUSION ............................................................................................................................... 9 1.7 REFERENCES .............................................................................................................................. 10

2 SMOKE-FREE NICOTINE IS FAR LESS HARMFUL THAN SMOKING ........................................... 18

2.1 KEY CONCEPTS ........................................................................................................................... 18 2.2 STUDIES AND ASSESSMENTS .......................................................................................................... 19 2.3 PROOF OF CONCEPT .................................................................................................................... 20 2.4 CONCERNS AND MISUNDERSTANDINGS ........................................................................................... 20 2.5 REFERENCES .............................................................................................................................. 22

3 SMOKE-FREE NICOTINE USE REDUCES SMOKING ................................................................ 27

3.1 KEY CONCEPTS ........................................................................................................................... 27 3.2 STUDIES AND ASSESSMENTS .......................................................................................................... 27 3.3 EXPERIENCE AND OUTCOMES......................................................................................................... 28 3.4 HEATED TOBACCO AND SMOKING ................................................................................................... 29 3.5 BARRIERS TO GREATER IMPACT........................................................................................................ 29 3.6 REFERENCES .............................................................................................................................. 30

4 SMOKE-FREE NICOTINE AND YOUTH ................................................................................... 33

4.1 KEY CONCEPTS ........................................................................................................................... 33 4.2 YOUTH VAPING DISPLACES YOUTH SMOKING ..................................................................................... 33 4.3 THE GATEWAY EFFECT IS DISCREDITED .............................................................................................. 34 4.4 YOUNG PEOPLE HAVE A STAKE IN THE HEALTH OF ADULTS ...................................................................... 35 4.5 REFERENCES .............................................................................................................................. 35

5 POLICIES FOR SMOKE-FREE NICOTINE PRODUCTS ....................................................................... 38

5.1 KEY CONCEPTS ........................................................................................................................... 38 5.2 PROHIBITIONS ............................................................................................................................ 39 5.3 TAXATION .................................................................................................................................. 39 5.4 BANNING FLAVOURS .................................................................................................................... 40 5.5 CONTROLS ON NICOTINE .............................................................................................................. 42 5.6 BANNING DISPOSABLE VAPES ......................................................................................................... 42 5.7 CONTROLS ON MARKETING AND BRANDING....................................................................................... 42 5.8 CONTROLS ON NICOTINE POUCHES ................................................................................................. 43 5.9 CONTROLS ON ENVIRONMENTAL EXPOSURES .................................................................................... 43 5.10 PROTECTING YOUTH ..................................................................................................................... 44 5.11 RISK PROPORTIONATE REGULATION ................................................................................................. 45 5.12 REFERENCES .............................................................................................................................. 46

1 Nicotine for policymakers

1.1 Key concepts • Nicotine is the primary psychoactive agent in tobacco and alternative nicotine delivery systems (ANDS

- vapes, pouches, heated and smokeless tobacco). It is a stimulant that produces subjective feelings of

pleasure, reduces stress and anxiety and improves aspects of cognitive function. Its use can make

people feel better and feel as though they function better. Nicotine does not cause drug effects like

intoxication, oblivion, hallucinations, or violence. It may also have therapeutic benefits, showing

promise for some inflammatory diseases, ADHD, and Parkinson’s Disease, among others.

• The subjectively perceived positive aspects of nicotine use largely explain why people use nicotine.

However, these rewards can consolidate into a physical dependence with withdrawal and craving,

reinforcing nicotine use. Nicotine may provide immediate relief from stress, but its overall impact may

increase stress levels physiologically and psychologically due to the cycle of use, relief, and

withdrawal.

• Nicotine use is disproportionately prevalent in poorer, marginalised or otherwise disadvantaged sub-

populations. Nicotine probably interacts with elevated levels of stress in these groups.

• There is no simple answer to the question, Is nicotine addictive? It depends on the characteristics of

the user, the route of administration, and the definition of “addiction”, which is an imprecise and

stigmatising term. Addiction usually refers to compulsive behaviour that persists in the face of

significant harm caused to the user. Cigarette smoking meets this definition, but ANDS use may not. It

is better to think of physical dependence or addiction as an emergent constellation of behaviours

with consequences for the individual rather than an intrinsic property of a molecule, device or liquid.

• Nicotine is not a major direct cause of smoking-related disease. Dozens of other hazardous and

potentially hazardous chemicals form through combustion and constitute the particles and toxic gases

of inhaled tobacco smoke. These are overwhelmingly the causes of smoking-related diseases.

• Nicotine in isolation is much less harmful than smoking but not entirely harmless. It does not cause

cancer, heart disease or lung illnesses but may increase risks in people with preexisting cardiovascular

conditions and can promote tumour growth in animals. Smoking causes poor pregnancy outcomes,

but nicotine is unlikely to be the primary cause. Nicotine may contribute to adverse outcomes in

pregnancy, and nicotine-induced constriction of blood vessels may aggravate peripheral arterial

disease.

• Nicotine is the primary reason people use tobacco or ANDS, and the use of these products should be

understood as nicotine-seeking behaviour. Within broad limits, the user, not the product, determines

the dose. Users generally regulate their intake to maintain desired levels of nicotine in the body.

Regulatory schemes that try to control nicotine intake through restrictions on product design are

unlikely to succeed, as users titrate their nicotine intake to preferred levels, resulting in

“compensation” (using the product more intensively) or switching nicotine products if compensation

is not possible.

• As with other psychoactive substances – alcohol, caffeine, cannabis, etc. - the demand for nicotine is

unlikely to disappear even with punitive laws. Demand is driven primarily by the real or perceived

benefits experienced by those using it and, for some people, the effort required to stop.

• The main deterrent to nicotine use, the multiple health and welfare harms arising from smoking, is

significantly reduced in smoke-free alternative nicotine delivery systems. The secondary deterrent is

the effect of policies designed to control smoking, such as high taxes. For substantially safer

alternatives, this deterrent should also significantly diminish. It is possible, therefore, that overall

societal nicotine use will increase, though the total harms associated with using nicotine will

substantially decline.

1.2 What is nicotine? What is nicotine? Nicotine1 is a naturally occurring alkaloid present in the tobacco plant, in which it

functions as a botanical insecticide. It can also be made synthetically. Nicotine is also present in tea,

peppers, tomatoes, potatoes, cauliflower and eggplant,2 though dietary exposure is far lower than

through tobacco use and does not have a noticeable psychoactive effect.3 Humans have deliberately

consumed nicotine, whether through pipes, cigars, chewing, snuffing, or cigarette smoking, for over

12,000 years.4 At the levels intentionally consumed by tobacco or ANDS users, nicotine is not poisonous.

For humans, it functions as a psychoactive substance5, working as both a stimulant and an anxiolytic (i.e.

with calming effects on anxiety). Unlike many drugs of abuse, nicotine does not lead to acute and often

harmful effects such as intoxication, violence, oblivion, paranoia, disorientation, loss of control, or

hallucinations. However, nicotine use does provide psychoactive reward and reinforcing effects. Tolerance

to initial aversive effects in naive users soon develops, which frequently leads to physical dependence and

unpleasant withdrawal symptoms following abstinence.

How does nicotine work as a drug? When tobacco is smoked, sucked or chewed, the nicotine is released

from the tobacco or ANDS product and enters the blood via the oral cavity, airways, lungs, or nasal

passages, then makes its way to the brain via the arterial circulation. Nicotine binds to receptors in the

brain to release several neurotransmitters, most notably dopamine6 and adrenaline.7 These interactions

produce feelings of pleasure,8 increased alertness,9 improved cognitive function,10 11 and mood

regulation, such as reduced stress and anxiety.12 13 For example, research conducted through the

Intramural Research Program of the U.S. National Institute on Drug Abuse concluded: 14

We found significant positive effects of nicotine or smoking on six domains: fine motor, alerting,

attention-accuracy and response time (RT), orienting attention-RT, short-term episodic memory-

accuracy, and working memory-RT.

This range of subjectively positive effects is important in explaining why there is demand for nicotine – for

some people, the use of nicotine can make them feel or function better. That observation should not be

understood as an endorsement of nicotine use or a recommendation, but it is an explanation. This range

of effects also forms the basis of reward and reinforcement that lead some users to develop physical

dependence and adverse withdrawal symptoms when they stop.15 16

Therapeutic effects of nicotine. In some circumstances, nicotine can have anti-inflammatory or stabilising

effects with potential therapeutic benefits in preventing, treating or relieving the symptoms of certain

diseases. These may include Parkinson’s,17 18 ulcerative colitis,19 20 ADHD,21 22 23 24 and psychosis.25 26 27 28 29 Smokers were significantly less likely to contract COVID-19, suggesting a possible protective effect.30 31

However, it is unclear if this was attributable to nicotine, some other component of smoke, or a statistical

artefact. Much of the discourse on therapeutic effects has been cautiously expressed because of the

justifiable concern that it might encourage smoking, and the research is often suggestive, not conclusive,

or has an ambiguous direction of causation. Tobacco and ANDS are not medications and should not be

used to treat these conditions as an alternative to medical supervision. However, some people may be

unconsciously using nicotine to self-medicate or ease symptoms arising from these conditions. This is an

explanation, not a recommendation.

Who uses nicotine and why? Tobacco or nicotine use is not uniformly distributed across the whole

population at any given age. It is driven by various genetic and psychosocial factors (characteristics of the

individual, their family, and social circumstances).32 A 2016 study identified ninety-eight distinct predictors

for smoking onset:33

An increased risk of smoking onset was consistently (i.e., in four or more studies) associated with

increased age/grade, lower SES, poor academic performance, sensation seeking or rebelliousness,

intention to smoke in the future, receptivity to tobacco promotion efforts, susceptibility to

smoking, family members’ smoking, having friends who smoke, and exposure to films.

A 2019 study considered 13 reasons for e-cigarette use and formed these into two main factors:

“alternative to cigarettes” and “larger social environment”.34 Nicotine use is disproportionately prevalent

among those experiencing some form of stress, disadvantage, minority status, other forms of

marginalisation, or challenging history such as neglect or abuse.35 36 37 38 39 40 41 The sustained use of

nicotine in these populations may be a response to the stress experienced as a result of these

disparities.42 Over time, the brain adapts to nicotine use, requiring higher doses to achieve the same

calming effect, which can lead to dependence. Additionally, the withdrawal symptoms associated with

nicotine, such as craving, irritability, anxiety, and difficulty concentrating, further contribute to stress

when nicotine levels drop in the bloodstream. Thus, while nicotine may provide immediate relief from

stress, its overall impact may increase stress levels physiologically and psychologically due to the cycle of

dependence and withdrawal. However, some people remain light or non-daily nicotine users and use

primarily for positive reinforcement without experiencing withdrawal symptoms.

1.3 Nicotine and addiction Is nicotine addictive? Not always. Nicotine addiction is a behaviour with adverse consequences for the

individual rather than a universal property of the nicotine molecule. Most of what we know about

nicotine comes from studies of smoking behaviours. In the case of smoking, there is a clear rationale for

quitting to avoid significant health and welfare detriments. Yet, many people still struggle to quit, which

creates the basis for public health intervention. However, when there is much less harm, the motivation

to quit is likely lower, and the consequences of not quitting are less. So, definitions of addiction tend to

stress compulsive and harmful use, and some care is required in defining terms like addiction (see below).

This is why we treat caffeine and our need for morning coffee differently – we may be dependent on it,

but it does not do much harm.43 Whether nicotine is addictive depends on the definition used, the

characteristics of the user (e.g. genetics, stress or other factors that increase the intensity of use), the

user’s pattern of use, and the method of nicotine administration.

Definitions of addiction. Whether nicotine is “addictive” also depends, crucially, on the chosen definition

of the term “addiction”. This is a loaded, stigmatising word and is often used imprecisely.44 Most formal

definitions of addiction not only require dependent and compulsive use but also serious net harm to the

user.45 For example, the definition of addiction used in the Addiction Ontology is as follows:46

A mental disposition towards repeated episodes of abnormally high levels of motivation to

engage in a behaviour, acquired as a result of engaging in the behaviour, where the behaviour

results in risk or occurrence of serious net harm.

The U.S. National Institute of Drug Use (NIDA) also includes adverse consequences within its definition:47

48

Addiction is a chronic disease characterised by drug seeking and use that is compulsive, or

difficult to control, despite harmful consequences.

The American Psychiatric Association prefers the more clinically precise title substance use disorder (SUD)

rather than addiction, though this terminology also stresses compulsive use despite harm.49

Substance use disorder (SUD) is a complex condition in which there is uncontrolled use of a

substance despite harmful consequences. People with SUD have an intense focus--sometimes

called an addiction--on using a certain substance(s) such as alcohol, tobacco, or other

psychoactive substances, to the point where their ability to function in day-to-day life becomes

impaired.

Substance use disorder. In professional practice, the term “addiction” has been superseded by the more

nuanced concept of substance use disorder, which considers different dimensions of harm. The American

Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) refers

to substance use disorder (SUD), including Tobacco Use Disorder.50 Substance use disorders are assessed

against eleven criteria,51 which cover four broad categories of problem: impaired control, social problems,

risky use, and physical dependence. Substance use disorder is graded from mild to severe according to the

number of criteria met. Severe substance use disorder, involving six or more criteria, is often seen as a

clinical equivalent to the more colloquial term addiction.52 53 Nicotine use does not generally cause

impaired control or social problems, and its riskiness depends heavily on the type of product used.

However, nicotine does have the potential to cause physical dependence.

Physical dependence. It is more appropriate to describe sustained nicotine use without severe harmful

effects (e.g., via low-risk alternatives to cigarettes) as potentially causing physical dependence, maintained

by the adverse effects of withdrawal. The AddictO ontology defines substance dependence as follows:54

…impaired functioning following reduction or termination of use of a psychoactive substance as a

result of long-term physiological adaptation to that substance.

Nicotine dependence is defined informally in this ontology as “A tendency to experience adverse effects

from reduction or termination of nicotine intake”.55 This definition of physical dependence contrasts with

an “addiction”, which stresses serious harm to the user through compulsive ongoing use.

The public health significance of harm. Unless there is significant harm to the user, their family,

bystanders or wider society, the case for a public health intervention to address any form of substance

use or compulsive behaviour is greatly diminished. In its definition of “addiction”, the Addiction Ontology

provides the following rationale:

This entity focuses on abnormal motivation to engage in a behaviour and includes serious net

harm as a feature. The reason is to limit the class to things that merit a treatment and public

health response.

This insight should drive resources to smoking cessation and recognition that vaping cessation is unlikely

to be a cost-effective use of public or non-profit funds, given the respective harms. All healthcare systems

ration in some way, and spending the marginal dollar on smoking cessation or other interventions with

better cost-effectiveness in terms of health outcomes per dollar spent will always be better.

Other reinforcers. Though nicotine is the essential psychoactive agent in cigarette smoke, there are

others, including, for example, monoamine oxidase inhibitors (MAOIs) found in smoke. MAOIs inhibit the

action of the enzyme monoamine oxidase, which breaks down dopamine and other monoamines such as

serotonin, causing them to build up and persist for longer, enhancing the psychoactive effects of

nicotine.56 This may be an important consideration in explaining differences in the dependence-forming

potential of different tobacco and nicotine products. Reinforcement is not just chemical; it may be driven

by behavioural rituals and triggered by cues57 58 or marketing.59 60

Nicotine and abuse liability – a regulator’s dilemma. Nicotine use tends to be more strongly reinforcing

when the levels of nicotine rise rapidly and peak at a high level in the brain, creating a rapid pike or

“bolus”. The time course of nicotine as it is absorbed in the body, carried to the brain, and then

metabolised and eliminated is known as pharmacokinetics, often abbreviated to “PK”. The PK profile is

primarily determined by three interacting factors:

(1) the route of administration (e.g., via inhalation, absorption in the mouth, or through the skin),

(2) characteristics of the product or device (e.g., nicotine concentration, particle size, pH)

(3) individual user characteristics (e.g., puffing rate and depth for inhaled products or use time for oral

products, which may reflect the strength of their drive to use nicotine).

Abuse liability is a concept used by regulators to address the concern that users could become dependent

on a therapeutic product. For nicotine, PK studies are often used to characterise abuse liability. However,

this can present a dilemma when assessing consumer-based reduced-risk alternatives to cigarettes, such

as vapes or pouches. The PK profile may also reflect their efficacy as cigarette replacements, matching the

PK profile experienced as a reward by smokers. Pharmaceutical regulators have generally required

manufacturers of nicotine replacement therapies (NRT) to keep abuse liability low, but this has likely

made NRT less effective for smoking cessation.61 62 63

1.4 The challenge of regulating nicotine exposure Users control their nicotine exposure, and this may lead to counterintuitive effects. It is not a surprise

that alcohol drinkers control the amount of alcohol they consume, drinking larger volumes of beer and

smaller volumes of whiskey for the same alcohol intake. Drinkers can do this by deeper and more

frequent gulps of beer and by sipping whiskey. To facilitate this, beer is served in larger glasses and usually

without a straw to constrict the flow. There are equivalents for nicotine: users control or “titrate” their

nicotine intake by varying their puff depth and frequency (known as “puff topography”) and by their

choice of product to facilitate the exposure they want without excessive effort. This creates an effect

known as “compensation”, in which users adjust their behaviour in response to changes in the availability

of nicotine.64 65 It means, for example, that reducing nicotine strength may cause a greater intake of

vapour aerosol to achieve the same nicotine exposure.

Attempts to measure and regulate nicotine delivery. Several ways of characterising and regulating

nicotine exposure have been proposed. As discussed below, these may be ineffective and may be

misleading or counterproductive.

• Nicotine yield. This approach was common until the 2000s, when it became no longer possible to

ignore its flaws. Nicotine yield is a measure of the nicotine that is emitted from the product during

use under standardised smoking regimes using a smoking machine.66 The nicotine yield is the mass of

nicotine trapped on a filter pad, reported in mg per cigarette, typically 0.1-3.0mg per stick.67 The

challenge is that people adjust their smoking behaviour (“compensation”) to obtain the nicotine they

want (“titration”),68 69 and this varies greatly between individuals and by race,70 genetics,71 and

deprivation.72 Further, tobacco companies designed cigarettes that would show low tar and nicotine

yields on machines but made it easy for users to compensate, for example, by including filter

ventilation holes that the user could easily block. This led to falsely reassuring “light” and “mild”

brands, which exploited smokers’ concerns about health without doing anything to reduce risk.73 74

• Nicotine content in tobacco. There are proposals to control the addictiveness of cigarettes or tobacco

by limiting the concentration of nicotine present in the tobacco itself.75 76 Denicotinisation is feasible

and can be achieved through genetic modification or by chemically lowering the nicotine to a “sub-

addictive” level or levels that are too low for compensation to work. The primary health question is

how users will respond to mandated low-nicotine standards: will they quit smoking, smoke very low-

nicotine cigarettes, switch to safer nicotine products, access illicit nicotine cigarettes, or find

workarounds? Removing most of the nicotine from cigarettes approximates to a ban on cigarettes, as

most people use them. A deliberately induced de facto ban would present a wide range of challenges

that regulators and lawmakers must consider carefully. These include public acceptability, especially

among those affected, farming and supply chain disruption, enforcement, corruption and community

effects, illicit trade and tax revenues. All policies to reduce smoking affect a range of interests over

time, but they differ in the extent and pace of disruption.

• Nicotine strength of e-liquids. The European Union sets a maximum nicotine concentration for e-

liquids of 20mg/ml (about 2% by volume),77 and this regulatory approach has been used in other

jurisdictions.78 The issue is both acceptability to consumers and user compensation; people consume

larger volumes of weaker liquids to achieve their preferred nicotine dose. However, that may increase

exposure to contaminants and toxic products of thermal decomposition, but without doing much to

change their nicotine exposure 79 80

• Nicotine flux. This measures the flow rate of nicotine emitted from a product (e.g., micrograms of

nicotine per second of puffing).81 82 While intended as a proxy for nicotine delivery, parameters

defining nicotine flux do not capture all factors that account for nicotine delivery to the user. The

main challenge is that the user controls this flow by varying the puff frequency, depth and length.

Proponents of this method propose to limit the effect of user behaviour by making ENDS devices

function as metered-dose products, delivering a fixed or limited dose of nicotine.83 However, in

practice, the idea is unworkable and ineffective. If the dose is too low or the use of the product is

frustrating or unsatisfying, users will seek alternatives, including cigarettes or vaping products that

can provide the nicotine dose the user wants.

• Nicotine “abuse liability”. This would involve placing limits on the spike (“bolus”) of nicotine

exposure in the brain–the peak level “Cmax” and time to reach the peak “Tmax” or the ratio Cmax/Tmax.84

Again, these are mainly under the user’s control, though they can be subject to device constraints.

For low-risk products, there is ambiguity about the regulatory purpose. Should it be to reduce abuse

liability to stop the products from causing dependence but risk that they will not be used as

alternatives to smoking? Or should it be to match the PK profile of a cigarette and thereby provide a

“satisfying” and viable, low-risk alternative to smoking that works for people who smoke but with a

higher risk of dependence?

The overarching point is that trying to control nicotine use by limiting the devices or liquids through which

it is consumed is likely to fail. Users will ultimately access the nicotine they want. It would be like trying to

control alcohol use by limiting the size of wine glasses or making people drink through a straw.

1.5 Health effects of nicotine Health effects of nicotine. It is now commonplace to cite Michael Russell’s 1976 insight, “People smoke

for the nicotine but die from the tar”,85 to convey the idea that it is not the nicotine that is the primary

direct cause of disease and death arising from smoking. It is the reason people smoke and, as a result,

expose themselves to thousands of toxicants in cigarette smoke. That insight still holds true today. U.S.

Food and Drug Administration leadership reiterated this point in 2017, setting out a strategic approach to

nicotine:86

Nicotine, though not benign, is not directly responsible for the tobacco-caused cancer, lung

disease, and heart disease that kill hundreds of thousands of Americans each year.

But if nicotine itself is not directly responsible for the major smoking-related diseases, what are the

residual risks? Epidemiological studies of smokeless tobacco87 88 89 90 or long-term use of nicotine

replacement therapy (pharmaceutical nicotine)91 92 suggest that serious disease risks attributable to

nicotine are low or arise in limited circumstances when nicotine consumption is decoupled from smoke

inhalation.

• All-cause mortality. Long-running surveys of American exclusive smokeless tobacco (SLT) users do not

show elevated mortality risks: “SLT users, in general, did not display a significantly increased risk for

all-cause mortality, all-cancer mortality, or diseases of the heart compared to never-tobacco users […]

Additionally, SLT use had no discernible adverse effect on any of the nine leading causes of death and

did not increase mortality risk for any of the major neoplasms often associated with SLT use”.93

• Cardiovascular disease, there is no generalised cardiovascular risk attributable to nicotine, but there

may be a nicotine-specific risk to people with preexisting cardiovascular conditions:94

“the risks of nicotine without tobacco combustion products (cigarette smoke) are low compared to

cigarette smoking but are still of concern in people with cardiovascular disease.

Studies of nicotine use without smoke exposure, for example, snus use, do not show elevated

cardiovascular risk, and that “toxic components other than nicotine appear implicated in the

pathophysiology of smoking-related ischemic heart disease”95 and “use of snus was not associated

with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of

stroke.”96 There is some suggestion of higher rates of fatality among snus users experiencing heart

attacks,97 but there are disagreements about whether this relationship is genuine and causal.98

• Cancer. The U.S. Surgeon General’s Report of 2014 concluded: 99

“The evidence is inadequate to infer the presence or absence of a causal relationship between

exposure to nicotine and risk for cancer.”

However, this report notes animal studies showing that nicotine “is a tumor promoter in some

experimental models” but cites human epidemiological data suggesting “that in humans nicotine may

not have a strong tumor-promoting effect”. To the extent that smokeless tobacco poses any cancer

risk, evidence suggests this is caused by exposure to compounds other than nicotine.100 101

• Respiratory disease. The evidence does not support a link between systemic nicotine exposure and

respiratory disease. Though there is no conclusive evidence, it is possible that direct exposure of lung

cells to nicotine102 or exposure to hazardous agents other than nicotine in an inhaled nicotine aerosol

could create respiratory risk.

• Pregnancy. Smoking is clearly associated with a range of poor birth outcomes.103 However, much of

this is likely due to exposure to toxicants other than nicotine present in tobacco smoke. The U.S.

Surgeon General concluded:104

“Evidence from studies of gene-environment interactions support the hypothesis that components

of tobacco other than nicotine may contribute to tobacco-related adverse pregnancy outcomes.”

A trial of over 1,000 pregnant women who smoked found “Regular use of e-cigarettes or nicotine

patches by pregnant smokers does not appear to be associated with any adverse outcomes.”105 While

most studies find no risk from vaping, the evidence can be of poor quality and contradictory.106

• Impacts on the adolescent brain. There has been a high level of political, media and public concern

about the effects of nicotine on the developing brain. The U.S. Surgeon General raised this as a

significant finding in the 2016 report, E-Cigarette Use Among Youth and Young Adults.107 However, the

underlying evidence base is weak, based on animal models or subject to potential confounding of

genetic and socioeconomic factors, the influence of other substance abuse, and the role of preexisting

neuropsychiatric problems associated with youth smoking.108 If there were noticeable impairments

associated with adolescent nicotine use, these would be observable in the generations of adults who

smoked as teenagers. However, there is no compelling evidence to support this: one study found that

“Past smoking was not associated with significantly poorer performance than never smokers in any

cognitive domain.”109 Recent evidence suggests a further challenge to this argument: there are signs

that differences in brain structure may predate and predict subsequent substance use initiation,110

with exposure to environmental pollution as a possible underlying cause.111

• Mental health. There are significantly higher rates of nicotine use in populations with mental health

disorders such as ADHD, anxiety disorders, and depression. It is plausible that nicotine use among

affected populations is an attempt, consciously or subconsciously, to self-medicate or regulate these

disorders.112 113 It is also possible that nicotine use could cause or intensify these disorders or that the

causal relationship is bidirectional.114 115 It is inherently challenging to isolate the direction of any

causal relationship in the association, and the evidence is currently contradictory and uncertain. 116 117

Public and professional perceptions of nicotine risks are grossly inaccurate. There is an extensive body of

literature that supports the analysis that “People smoke for the nicotine but die from the tar” or its many

variants. Yet, awareness of the basic risk concepts about nicotine is very poor. For example, in the United

States, a 2022 study found that 61.2% of smokers believe nicotine causes cancer or don’t know; the

authors called for corrective messaging.118 In New Zealand, proposals to lower the nicotine content of

cigarettes were incorrectly understood as making the products safer.119 In the UK in 2021, only 11% of

smokers recognised that ‘none’ or ‘a very small amount’ of the health risks from smoking come from

nicotine in tobacco cigarettes.120 Several surveys show that medical professionals also share these

misperceptions. For example, a 2021 U.S. study found:121

Overall, the majority of physicians “strongly agreed” that nicotine directly contributes to the

development of cardiovascular disease (83.2%), COPD (80.9%), and cancer (80.5%).

These nicotine misperceptions also underpin misperceptions of the risk of vaping and other smoke-free

nicotine options, and this creates a barrier to switching from smoking to smoke-free. The problem is that

false perceptions of harm influence behaviour and inhibit beneficial behaviour change, intent, and action.

1.6 Conclusion When used as intended, nicotine is a relatively benign psychoactive substance and does not cause

overdose, intoxication, hallucinations, oblivion or other more extreme drug effects. People use nicotine

because it makes them feel better and feel as though they function better, and this underpins the demand

for the drug. Nicotine itself does not cause the vast majority of tobacco-related harms, though it does

have some adverse health effects and risks. Nicotine use may create dependence by reinforcement

through positive rewards and adverse effects of temporary withdrawal and craving. Nicotine can be

challenging to quit. We may consider nicotine dependence to be an addiction if the user cannot stop

despite significant harm, for example, through continued smoking.

For the past 100 years, nicotine has been primarily consumed by inhaling toxic tobacco smoke. However,

that is changing as the world begins a transition to nicotine without smoke (vapes, pouches, heated and

smokeless tobacco). This opens up a range of policy challenges and opportunities. These products can

meet the nicotine demand with significantly reduced harm compared to combustible tobacco. But that

also means the loss of the main deterrent to nicotine use: the harms caused by smoking. The emergence

of nicotine as a relatively benign drug without major harms associated with its use demands a profound

re-evaluation of the position of nicotine as a legal substance (like caffeine, alcohol and, increasingly,

cannabinoids) in society.

Regulation of nicotine use is challenging because users largely control their own intake by changing

behaviour, changing products, and ultimately seeking illicit supplies of the products they want.

Policymakers should accept that the demand for nicotine is inevitable and likely to persist indefinitely. In

that case, the policy challenge is to make nicotine available in regulated markets, with lawful suppliers

meeting adult demand with safeguards to raise awareness, control marketing and branding, and limit

access.

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79 Dawkins, L., Cox, S., Goniewicz, M., McRobbie, H., Kimber, C., Doig, M., & Kośmider, L. (2018). ‘Real-world’ compensatory behaviour with low nicotine concentration e-liquid: Subjective effects and nicotine, acrolein and formaldehyde exposure. Addiction, 113(10), 1874–1882. https://doi.org/10.1111/add.14271

80 Kośmider, L., Kimber, C. F., Kurek, J., Corcoran, O., & Dawkins, L. E. (2018). Compensatory Puffing With Lower Nicotine Concentration E-liquids Increases Carbonyl Exposure in E-cigarette Aerosols. Nicotine & Tobacco Research, 20(8), 998–1003. https://doi.org/10.1093/ntr/ntx162

81 Shihadeh, A., & Eissenberg, T. (2015). Electronic Cigarette Effectiveness and Abuse Liability: Predicting and Regulating Nicotine Flux. Nicotine & Tobacco Research, 17(2), 158–162. https://doi.org/10.1093/ntr/ntu175

82 El-Hellani, A., Hanna, E., Sharma, M., Blohowiak, R., Joseph, P., Eid, T., Nadim, H., El-Hage, R., Salman, R., Karaoghlanian, N., Adeniji, A., Salam, S., Talih, F., Elbejjani, M., Breland, A., Eissenberg, T., Shihadeh, A., Baldassarri, S. R., & Talih, S. (2023). Nicotine flux as a powerful tool for regulating nicotine delivery from e- cigarettes: Protocol of two complimentary randomized crossover clinical trials. PLOS ONE, 18(9), e0291786. https://doi.org/10.1371/journal.pone.0291786

83 Patev, A. J., Combs, M., Gaitan, N., Karaoghlanian, N., Lipato, T., Eissenberg, T., & Breland, A. (2024). Constraining electronic nicotine delivery systems (ENDS) nicotine dose by controlling nicotine flux at a limited puff duration. Experimental and Clinical Psychopharmacology, 32(5), 604–614. https://doi.org/10.1037/pha0000719

84 Kolli, A. R., Veljkovic, E., Calvino-Martin, F., Esposito, M., Kuczaj, A. K., Koumal, O., Rose, J. E., & Peitsch, M. C.

(2024). Nicotine flux and pharmacokinetics-based considerations for early assessment of nicotine delivery systems. Drug and Alcohol Dependence Reports, 11, 100245. https://doi.org/10.1016/j.dadr.2024.100245

85 Russell, M. A. (1976). Low-tar medium-nicotine cigarettes: A new approach to safer smoking. British Medical Journal, 1(6023), 1430–1433. 10.1136/bmj.1.6023.1430

86 Gottlieb, S., & Zeller, M. (2017) A Nicotine-Focused Framework for Public Health The New England Journal of Medicine; Massachusetts Medical Society. https://doi.org/10.1056/NEJMp1707409

87 Fisher, M. T., Tan-Torres, S. M., Gaworski, C. L., Black, R. A., & Sarkar, M. A. (2019). Smokeless tobacco mortality risks: An analysis of two contemporary nationally representative longitudinal mortality studies. Harm Reduction Journal, 16, 27. https://doi.org/10.1186/s12954-019-0294-6

88 Rodu, B., & Plurphanswat, N. (2019). Mortality among male smokers and smokeless tobacco users in the USA. Harm Reduction Journal, 16(1), 50. https://doi.org/10.1186/s12954-019-0321-7

89 Lee, P. N. (2011). Summary of the epidemiological evidence relating snus to health. Regulatory Toxicology and Pharmacology, 59(2), 197–214. [link]

90 Lee, P. N. (2013). Epidemiological evidence relating snus to health – an updated review based on recent publications. Harm Reduction Journal, 10(1), 36. [link]

91 Food and Drug Administration (United States) Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use. (2013, April 2). Federal Register. 78 FR 19718

92 Murray, R. P., Connett, J. E., & Zapawa, L. M. (2009). Does nicotine replacement therapy cause cancer? Evidence from the Lung Health Study. Nicotine & Tobacco Research, 11(9), 1076–1082. https://doi.org/10.1093/ntr/ntp104

93 Fisher, M. T., Tan-Torres, S. M., Gaworski, C. L., Black, R. A., & Sarkar, M. A. (2019). Smokeless tobacco mortality risks: An analysis of two contemporary nationally representative longitudinal mortality studies. Harm Reduction Journal, 16(1), 27. https://doi.org/10.1186/s12954-019-0294-6

94 Benowitz, N. L., & Burbank, A. D. (2016). Cardiovascular Toxicity of Nicotine: Implications for Electronic Cigarette Use. Trends in Cardiovascular Medicine, 26(6), 515–523. https://doi.org/10.1016/j.tcm.2016.03.001

95 Hansson, J., Galanti, M. R., Hergens, M.-P., Fredlund, P., Ahlbom, A., Alfredsson, L., Bellocco, R., Eriksson, M., Hallqvist, J., Hedblad, B., Jansson, J.-H., Nilsson, P., Pedersen, N., Trolle Lagerros, Y., Östergren, P.-O., & Magnusson, C. (2012). Use of snus and acute myocardial infarction: Pooled analysis of eight prospective observational studies. European Journal of Epidemiology, 27(10), 771–779. https://doi.org/10.1007/s10654-012- 9704-8

96 Hansson, J., Galanti, M. R., Hergens, M.-P., Fredlund, P., Ahlbom, A., Alfredsson, L., Bellocco, R., Engström, G., Eriksson, M., Hallqvist, J., Hedblad, B., Jansson, J.-H., Pedersen, N. L., Trolle Lagerros, Y., Östergren, P.-O., & Magnusson, C. (2014). Snus (Swedish smokeless tobacco) use and risk of stroke: Pooled analyses of incidence and survival. Journal of Internal Medicine, 276(1), 87–95. https://doi.org/10.1111/joim.12219

97 Arefalk, G., Hambraeus, K., Lind, L., Michaëlsson, K., Lindahl, B., & Sundström, J. (2014). Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction. Circulation, 130(4), 325–332. https://doi.org/10.1161/CIRCULATIONAHA.113.007252

98 Rodu, B., & Phillips, C. V. (2015). Letter by Rodu and Phillips Regarding Article, “Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction”. Circulation, 131(17), e422–e422. https://doi.org/10.1161/CIRCULATIONAHA.114.012038

99 National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. (2014). Nicotine (Chapter 5). In The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Centers for Disease Control and Prevention (US). https://www.ncbi.nlm.nih.gov/books/NBK294308/

100 Valen, H., Becher, R., Vist, G. E., Holme, J. A., Mdala, I., Elvsaas, I.-K. Ø., Alexander, J., Underland, V., Brinchmann, B. C., & Grimsrud, T. K. (2023). A systematic review of cancer risk among users of smokeless tobacco (Swedish snus) exclusively, compared with no use of tobacco. International Journal of Cancer, 153(12), 1942–1953. https://doi.org/10.1002/ijc.34643

101 Warnakulasuriya, S., & Straif, K. (2018). Carcinogenicity of smokeless tobacco: Evidence from studies in humans & experimental animals. The Indian Journal of Medical Research, 148(6), 681–686. https://doi.org/10.4103/ijmr.IJMR_149_18

102 Mo, R., Zhang, J., Chen, Y., & Ding, Y. (2022). Nicotine promotes chronic obstructive pulmonary disease via

inducing pyroptosis activation in bronchial epithelial cells. Molecular Medicine Reports, 25(3), 92. https://doi.org/10.3892/mmr.2022.12608

103 Tarasi, B., Cornuz, J., Clair, C., & Baud, D. (2022). Cigarette smoking during pregnancy and adverse perinatal outcomes: A cross-sectional study over 10 years. BMC Public Health, 22(1), 2403. https://doi.org/10.1186/s12889-022-14881-4

104 National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. (2014). Reproductive Outcomes. In The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Centers for Disease Control and Prevention (US). https://www.ncbi.nlm.nih.gov/books/NBK294307/

105 Pesola, F., Smith, K. M., Phillips-Waller, A., Przulj, D., Griffiths, C., Walton, R., McRobbie, H., Coleman, T., Lewis, S., Whitemore, R., Clark, M., Ussher, M., Sinclair, L., Seager, E., Cooper, S., Bauld, L., Naughton, F., Sasieni, P., Manyonda, I., & Hajek, P. (2024). Safety of e-cigarettes and nicotine patches as stop-smoking aids in pregnancy: Secondary analysis of the Pregnancy Trial of E-cigarettes and Patches (PREP) randomized controlled trial. Addiction, 119(5), 875–884. https://doi.org/10.1111/add.16422

106 Ussher, M., Fleming, J., & Brose, L. (2024). Vaping during pregnancy: A systematic review of health outcomes. BMC Pregnancy and Childbirth, 24(1), 435. https://doi.org/10.1186/s12884-024-06633-6

107 National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. (2016). Health Effects of E-Cigarette Use Among U.S. Youth and Young Adults. In E-Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General [Internet]. Centers for Disease Control and Prevention (US). https://www.ncbi.nlm.nih.gov/books/NBK538688/

108 Balfour, D. J. K., Benowitz, N. L., Colby, S. M., Hatsukami, D. K., Lando, H. A., Leischow, S. J., Lerman, C., Mermelstein, R. J., Niaura, R., Perkins, K. A., Pomerleau, O. F., Rigotti, N. A., Swan, G. E., Warner, K. E., & West, R. (2021). Balancing Consideration of the Risks and Benefits of E-Cigarettes. American Journal of Public Health, 111(9), 1661–1672. https://doi.org/10.2105/AJPH.2021.306416

109 Corley, J., Gow, A. J., Starr, J. M., & Deary, I. J. (2012). Smoking, childhood IQ, and cognitive function in old age. Journal of Psychosomatic Research, 73(2), 132–138. https://doi.org/10.1016/j.jpsychores.2012.03.006

110 Miller, A. P., Baranger, D. A. A., Paul, S. E., Garavan, H., Mackey, S., Tapert, S. F., LeBlanc, K. H., Agrawal, A., & Bogdan, R. (2024). Neuroanatomical Variability and Substance Use Initiation in Late Childhood and Early Adolescence. JAMA Network Open, 7(12), e2452027. https://doi.org/10.1001/jamanetworkopen.2024.52027

111 Kardan, O., Weigard, A. S., Cope, L. M., Martz, M. M., Angstadt, M., McCurry, K. L., Michael, C., Hardee, J. E., Hyde, L. W., Sripada, C., & Heitzeg, M. M. (2024). Functional Brain Connectivity Predictors of Prospective Substance Use Initiation and Their Environmental Correlates. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. https://doi.org/10.1016/j.bpsc.2024.10.002

112 Newhouse, P., And, A. S., & Potter, A. (n.d.). Nicotine and Nicotinic Receptor Involvement in Neuropsychiatric Disorders. Current Topics in Medicinal Chemistry, 4(3), 267–282. https://doi.org/10.2174/1568026043451401

113 Mihailescu, S., & Drucker-Colı́ n, R. (2000). Nicotine, Brain Nicotinic Receptors, and Neuropsychiatric Disorders. Archives of Medical Research, 31(2), 131–144. https://doi.org/10.1016/S0188-4409(99)00087-9

114 Lechner, W. V., Janssen, T., Kahler, C. W., Audrain-McGovern, J., & Leventhal, A. M. (2017). Bi-directional associations of electronic and combustible cigarette use onset patterns with depressive symptoms in adolescents. Preventive Medicine, 96, 73–78. https://doi.org/10.1016/j.ypmed.2016.12.034

115 Kutlu, M. G., Parikh, V., & Gould, T. J. (2015). Chapter Seven—Nicotine Addiction and Psychiatric Disorders. In M. De Biasi (Ed.), International Review of Neurobiology (Vol. 124, pp. 171–208). Academic Press. https://doi.org/10.1016/bs.irn.2015.08.004

116 Fluharty, M., Taylor, A. E., Grabski, M., & Munafò, M. R. (2017). The Association of Cigarette Smoking With Depression and Anxiety: A Systematic Review. Nicotine & Tobacco Research, 19(1), 3–13. https://doi.org/10.1093/ntr/ntw140

117 Farooqui, M., Shoaib, S., Afaq, H., Quadri, S., Zaina, F., Baig, A., Liaquat, A., Sarwar, Z., Zafar, A., & Younus, S. (2023). Bidirectionality of smoking and depression in adolescents: A systematic review. Trends in Psychiatry and Psychotherapy, 45, e20210429. https://doi.org/10.47626/2237-6089-2021-0429

118 Weiger, C., Moran, M. B., Kennedy, R. D., Limaye, R., & Cohen, J. (2022). Beliefs and Characteristics Associated With Believing Nicotine Causes Cancer: A Descriptive Analysis to Inform Corrective Message Content and Priority Audiences. Nicotine & Tobacco Research, 24(8), 1264–1272. https://doi.org/10.1093/ntr/ntac060

119 Gendall, P., Popova, L., Thrasher, J., & Hoek, J. (2024). Nicotine beliefs and perceptions of low nicotine labels and

mitigating statements among people who do and do not smoke: A cross-sectional study from Aotearoa New Zealand. Tobacco Control, tc-2023-058353. https://doi.org/10.1136/tc-2023-058353

120 McNeill, A, Simonavičius, E, Brose, LS, Taylor, E, East, K, Zuikova, E, Calder, R and Robson, D (2022). Nicotine vaping in England: an evidence update including health risks and perceptions, September 2022. A report commissioned by the Office for Health Improvement and Disparities. London: Office for Health Improvement and Disparities. https://bit.ly/3Gj5NhV

121 Steinberg, M. B., Bover Manderski, M. T., Wackowski, O. A., Singh, B., Strasser, A. A., & Delnevo, C. D. (2021). Nicotine Risk Misperception Among US Physicians. Journal of General Internal Medicine, 36(12), 3888–3890. https://doi.org/10.1007/s11606-020-06172-8

2 Smoke-free nicotine is far less harmful than smoking

2.1 Key concepts Smoking is a uniquely harmful consumer behaviour, creating major risks for cancer and cardiovascular and respiratory disease.1 Nearly all the risks from tobacco use arise from smoking: inhaling thousands of chemical agents, many toxic or carcinogenic, produced during the combustion of tobacco leaves in the burning tip of a cigarette.2 Smoking dominates (99.4%) the global tobacco-related death toll: the Global Burden of Disease study shows 7.69 million deaths attributable to smoking annually, 1.30 million attributable to secondhand smoke, and just 55,600 attributable to smokeless tobacco.3 This annual smoking-related death toll exceeds the annual

excess mortality attributable to COVID-19 in 2020 and 2021.4

The imperative to stop smoking. Stopping smoking at any time reduces the risks of serious disease and premature death. Nearly all excess mortality risk is eliminated by stopping before age 40.5 It is beyond reasonable doubt that vaping (e-cigarette or ENDS use) and the use of other smoke-free nicotine products (oral nicotine pouches, smokeless and heated tobacco) are far safer than cigarette smoking. Smoke-free products do not involve combustion or produce products of combustion. Switching from smoking to smoke-free nicotine use leads to greatly reduced exposure to the main toxicants associated with serious disease.

Four main categories of smoke-free nicotine products.

Though each non-combustion product category has a different risk profile, they are clustered closely together on a continuum of risk that has cigarettes at the opposite extreme. Most hazardous chemical agents in cigarette smoke are either not present in vape aerosol at detectable levels or at much lower levels. Similar findings apply to all the smoke-free alternatives to smoking.6

Chemical basis for reduced risk. Combustion of tobacco creates thousands of chemical reactions and new toxic chemicals not found in the tobacco. Tobacco smoke contains around 7,000 identifiable chemical agents, of which at least 158 are known to be toxic or carcinogenic.7 The switch to non-combustible, smoke-free nicotine radically changes the chemical risks and demands a rethink of our whole approach to nicotine. According to independent American experts, these alternative products have “the potential to disrupt the 120-year dominance of the cigarette”.8

2.2 Studies and assessments Major assessments. Several high-quality, independent reviews conclude that exclusive ENDS use poses a small fraction of the risks of cigarettes and is likely to be at least 95% lower risk than smoking:

● Laboratory tests of e-cigarette ingredients, in vitro toxicological tests, and short-term human studies suggest that e-cigarettes are likely to be far less harmful than combustible tobacco cigarettes. National Academies of Sciences, Engineering, and Medicine, United States (2018).9

● Based on the reviewed evidence, we believe that the ’at least 95% less harmful estimate’ (that is, smoking is at least 20 times more harmful to users than vaping) remains broadly accurate, at least over short- and medium-term periods, but it might now be more appropriate and unifying to summarise our findings using our other firm statement: that vaping poses only a small fraction of the risks of smoking. Office for Health Improvement and Disparities, England (2022).10

● Vaping poses only a small fraction of the risks of smoking and switching completely from smoking to vaping conveys substantial health benefits over continued smoking. Based on current knowledge, stating that vaping is at least 95% less harmful than smoking remains a good way to communicate the large difference in relative risk unambiguously so that more smokers are encouraged to make the switch from smoking to vaping. It should be noted that this does not mean e-cigarettes are safe. Public Health England (2018).11

● Although it is not possible to quantify the long-term health risks associated with e-cigarettes precisely, the available data suggest that they are unlikely to exceed 5% of those associated with smoked tobacco products, and may well be substantially lower than this figure. Royal College of Physicians, London (2016). 12

● Vaping exposes vapers to a far narrower range of toxins than does smoking cigarettes, and levels of toxins absorbed from vaping are generally low. It is therefore likely that vaping poses only a small fraction of the risk of smoking. Royal College of Physicians, London (2024). 13

This suggestion that vaping is at least 95% less risky than smoking has often been misunderstood: it is intended as a clear and actionable way of communicating the scale of risk reduction to consumers and professionals.14

Toxicants in the body. The most persuasive evidence comes from biomarker data.15 These are measures of toxicants found in users’ blood, saliva, or urine. Switching from cigarettes to ENDS,16 17 18 19 20 21 heated tobacco,22 23 24 25 26 27 snus,28 29 30 or nicotine pouches31 32 33 34 dramatically reduces the exposure to hazardous chemicals associated with smoking. Many biomarkers of exposure fall to background levels or below the limit of detection, and most others are radically reduced.35

Emissions toxicity. Similar findings arise from well-conducted studies of the chemical composition of aerosol emissions, including tests for cytotoxicity, mutagenicity and genotoxicity.36 However, these studies are prone to exaggerating risk because no humans are involved. The exaggeration of risk arises because the devices can be operated in unrealistic, overheated conditions that would be

intolerable for human users. This makes the liquid prone to pyrolysis, generating excessive levels of thermal decomposition products.37

Health indicators. Other supportive data show improvements in health and welfare for those who switch from smoking to ENDS use completely. Studies show improvements in asthma38, chronic obstructive pulmonary disease (COPD),39 blood pressure,40 lung function,41 42 respiratory conditions, 43 44 45 cardiovascular risk factors,46 47 and gum disease.48 One study showed that ENDS typically has a cancer potency of just 0.4% of cigarette smoke.49

Public health advice. The National Health Service of the UK provides straightforward advice to smokers: “Also known as vapes or e-cigs, they’re far less harmful than cigarettes, and can help you quit smoking for good”,50 and English authorities advertise vaping on TV as a smoking cessation strategy. New Zealand, which has seen an extremely impressive decline in smoking, has similar advice to the public: “Vaping is not harmless, but it is much less harmful than smoking.”51

2.3 Proof of concept Snus as proof-of-concept for tobacco harm reduction. The data for snus (oral tobacco) provide a powerful proof of concept for tobacco harm reduction: epidemiological evidence “provides scant support for any major adverse health effect of snus”52 53 and also that switching from cigarettes to snus reduces the risk of cancer and heart disease, and the risk in switchers being similar to that in those who quit cigarettes.54 Through the use of snus, Sweden has the lowest smoking prevalence in the European Union (7% compared to the EU average of 23% in 2021),55 and this is attributable to snus use displacing smoking,56 with similar effects in Norway.57 One estimate suggests that snus in Sweden has avoided about 3,000 deaths per year.58 Another suggests among men over the age of 30, 355,000 lives per year could have been saved if the other European Union countries had matched Sweden’s tobacco-related mortality rate.59 The ban on snus in the European Union has no basis in science or ethics.60 61 Policy decisions about nicotine pouches must be informed by the experience gained with snus. We have known since at least the early 1990s that modern smokeless tobacco carries a negligible mortality penalty.62 Yet opposition to the idea of using snus as an alternative to smoking was immediate: “I’m not in favor of advocating use of smokeless tobacco as an approach to dealing with tobacco addiction.” (M. Fiore, 1994)63 The opposition has persisted for thirty years and remains undimmed, denying or diverting millions of smokers from safer tobacco use and causing thousands, maybe millions, of avoidable deaths.

2.4 Concerns and misunderstandings Common concerns. Critics of tobacco harm reduction raise a range of concerns, but these are often based on misunderstandings or poor methods.

1. Correlation and causation. Many studies find an association between vaping and specific health effects, yet most are deeply flawed.64 Almost everyone who uses ENDS and is old enough to suffer serious illness has been smoking for decades. Few studies can isolate the effect of vaping from the impact of a long smoking history; some studies even counted effects associated with vaping that happened before users took up vaping.65 66 As noted above, studies which avoid these issues by following within-person changes when switching from smoking to ENDS show substantial reductions in harmful biomarkers and disease symptoms.

2. “EVALI”. In 2019-2020, there was an outbreak of severe lung injuries in the United States that was misleadingly named E-cigarette or Vaping Associated Lung Injury.67 It was not caused by ENDS, which are electronic nicotine delivery systems. It was caused by a thickener, Vitamin E Acetate, added to illicit cannabis (THC) liquids.68 Nicotine vaping was not and could not have been involved in EVALI.69 70 The US EVALI crisis was confined in time and geography primarily to late 2019 in the United States, and it was fixed by the removal of thickeners from THC vapes. No changes were made (or necessary) to nicotine vapes. There were EVALI sufferers who claimed not to use THC. However, there have always been strong incentives not to disclose cannabis use due to consequences with law enforcement, probation, employment, education, visas and parents.

3. “No long-term data”. It is often asserted that we just do not know the long-term effects. While technically accurate, the point is also misleading. Toxicology has advanced dramatically since the discovery of the health risks of smoking in the 1950s, and we now know a great deal from occupational and environmental health disciplines. We cannot know everything about ENDS risks, but we already know enough to be confident that the risks from using smoke-free products will be far less than those from smoking. Also, the much simpler chemistry will more easily allow remedial action if needed (for example, removing ingredients, changing materials, or controlling temperatures). Discouraging or restricting ENDS use while we wait for detailed evidence on long-term outcomes – given that we already know they are much lower risk than smoking – allows the harms of smoking to continue.

We should be mindful of the wise words of the great tobacco epidemiologist Austin Bradford Hill:71

All scientific work is incomplete – whether experimental or observational. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time.

4. “Dual use”. Some people use both cigarettes and ENDS (“dual use”) and experience lower benefits or no benefits as they continue to smoke. However, many are in a gradual transition to exclusive ENDS use or to dual use with only occasional smoking. Most dual use should be seen as progress from exclusive smoking. Dual use is not the most common form of ENDS use: in the United States, just 29% of adult ENDS users were dual users in 2021.72 In Britain, the proportion of vapers also using cigarettes has come down from around two-thirds to around one-third over the last ten years.73 It does not appear to reduce quitting intentions.74 More likely, it includes people who do not want to quit smoking at all but go on to become “accidental quitters”.75 76 Some argue that dual use makes smokers worse off, as if the exposures are additive. This arises from a misrepresentation of cross-sectional studies comparing current smokers and current dual users and, therefore, does not account for differences in dependence and intensity of smoking. Studies that track individuals through smoking to dual-use show benefits.77

False risk perceptions. Though high-quality scientific assessments suggest vapes and other smoke-free products are much less risky than cigarettes, the public understanding of these risks is very different, and the gap between scientific evidence and public perception is deteriorating over time. In the United States, the “Perceptions of E-cigarettes as more harmful than cigarettes doubled year on year, increasing most between 2019 and 2020 (2018: 6.8%, 2019: 12.8%, 2020: 28.3%)”,78

with similar findings in the UK.79 In 2023 in the UK, an ASH survey showed that 43% of adults believed “E-cigarettes are a lot more, more or equally harmful as cigarettes”, but only 34% believed that “E-cigarettes are less or a lot less harmful than cigarettes” and “only 8% correctly state that e- cigarette use is a lot less harmful than smoking”.80 Similar trends are evident among smokers. In all cases, the trend since 2013 has shown a deterioration.

Myth-busting. Several excellent resources have been created to tackle myths about product safety and other common concerns about ENDS use. These include:

● A consumer-orientated myth buster by the UK National Health Service81 and myth-busting

advice to health professionals from Public Health England.82 ● A detailed myth buster by Action on Smoking and Health (UK) verified by practising

scientists.83

● An analysis of multiple false and misleading claims made in a WHO fact sheet on ENDS.84 ● Academic responses to flawed assessments, notably those produced in Australia85 86 or

responses to the flawed position statements of medical associations.87 ● Detailed methodological criticisms of misleading research on specific topics, such as

carbonyl formation,88 heavy metals migration,89 or flawed epidemiology.90 91 ●

2.5 References

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4 Msemburi, W., Karlinsky, A., Knutson, V., Aleshin-Guendel, S., Chatterji, S., & Wakefield, J. (2023). The WHO estimates of excess mortality associated with the COVID-19 pandemic. Nature, 613(7942), Article 7942. [link]

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19 Dai, H., et al. (2022). Exposure to Toxicants Associated With Use and Transitions Between Cigarettes, e-

Cigarettes, and No Tobacco. JAMA Network Open, 5(2). [link]

20 Holt, N. M., et al. (2023). Comparison of biomarkers of exposure among US adult smokers, users of electronic

nicotine delivery systems, dual users and nonusers, 2018–2019. Scientific Reports 2023 13:1, 13(1), 1–11. [link]

21 Committee On Toxicity - UK (2020). Statement on the potential toxicological risks from electronic nicotine (and non-nicotine) delivery systems (E(N)NDS – e-cigarettes). [link]

22 McEwan, M., et al. (2021). A randomized controlled study in healthy participants to explore the exposure

continuum when smokers switch to a tobacco heating product or an E-cigarette relative to cessation. Toxicology Reports, 8, 994–1001. [link]

23 Gale, N., et al. (2021). Changes in biomarkers after 180 days of tobacco heating product use: a randomised trial.

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24 Sakaguchi, C., et al. (2021). Differences in Levels of Biomarkers of Potential Harm Among Users of a Heat-Not-

Burn Tobacco Product, Cigarette Smokers, and Never-Smokers in Japan: A Post-Marketing Observational Study. Nicotine & Tobacco Research, 2021, 1–10. [link]

25 Committee On Toxicity - UK (2017). Statement on the toxicological evaluation of novel heat not-burn tobacco products. [link]

26 Cordery, S., et al. (2024). The Product Science of Electrically Heated Tobacco Products: An Updated Narrative Review of the Scientific Literature. Cureus, 16. [link]

27 Cordery, S. et al. (2024). The Product Science of Electrically Heated Tobacco Products: An Updated Narrative Review of the Scientific Literature. Cureus, 16(5). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209752/

28 Krautter, G. R., Chen, P. X., & Borgerding, M. F. (2015). Consumption patterns and biomarkers of exposure in

cigarette smokers switched to Snus, various dissolvable tobacco products, Dual use, or tobacco abstinence. Regulatory Toxicology and Pharmacology: RTP, 71(2), 186–197. [link]

29 Hatsukami, D. K., et al. (2016). Randomised clinical trial of snus versus medicinal nicotine among smokers

interested in product switching. Tobacco Control, 25(3), 267–274. [link]

30 Naufal, Z. S., et al. (2011). Differential exposure biomarker levels among cigarette smokers and smokeless

tobacco consumers in the National Health and Nutrition Examination Survey 1999–2008. Biomarkers, 16(3), 222–235. [link]

31 Azzopardi, D., et al. (2023). Assessment of biomarkers of exposure and potential harm, and physiological and

subjective health measures in exclusive users of nicotine pouches and current, former and never smokers. Biomarkers, 28(1), 118–129. [link]

32 Rensch, J., et al. (2023). A Randomized, Controlled Study to Assess Changes in Biomarkers of Exposures Among

Adults Who Smoke That Switch to Oral Nicotine Pouch Products Relative to Continuing Smoking or Stopping All Tobacco Use. The Journal of Clinical Pharmacology, 63(10), 1108–1118. [link]

33 Health Risk Assessment of Nicotine Pouches: Updated BfR Opinion No. 023/2022 of 7 October 2022. (2022). BfR- Stellungnahmen, 2022(023). [link]

34 Murkett, R., et al. (2022). Nicotine products relative risk assessment: An updated systematic review and meta- analysis. [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2022, 9:1225 [link]

35 Hartmann-Boyce et al. (2023). Biomarkers of potential harm in people switching from smoking tobacco to

exclusive e-cigarette use, dual use or abstinence: secondary analysis of Cochrane systematic review of trials of e-cigarettes for smoking cessation. Addiction, 118(3), 539–545. [link]

36 Emma, R., et al. (2023). Cytotoxicity, mutagenicity and genotoxicity of electronic cigarettes emission aerosols

compared to cigarette smoke: the REPLICA project. Scientific Reports 2023 13:1, 13(1), 1–12. [link]

37 Soulet, S., & Sussman, R. A. (2022). Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette

Aerosol Emissions. In Toxics (Vol. 10, Issue 12, p. 714). Multidisciplinary Digital Publishing Institute. [link]

38 Polosa, R., et al. A. (2016). Persisting Long Term Benefits of Smoking Abstinence and Reduction in Asthmatic

Smokers Who Have Switched to Electronic Cigarettes. Discovery Medicine, 21(114), 99–108. [link]

39 Polosa, R., et al. (2020). COPD smokers who switched to e-cigarettes: health outcomes at 5-year follow up.

Therapeutic Advances in Chronic Disease, 11. [link]

40 Farsalinos, K., C et al. (2016). Effect of continuous smoking reduction and abstinence on blood pressure and

heart rate in smokers switching to electronic cigarettes. Internal and Emergency Medicine, 11(1), 85–94. [link]

41 Cibella, F., et al. (2016). Lung function and respiratory symptoms in a randomized smoking cessation trial of

electronic cigarettes. Clinical Science, 130(21), 1929–1937. [link]

42 Polosa, R., et al. (2021). Impact of exclusive e-cigarettes and heated tobacco products use on muco-ciliary

clearance. Therapeutic Advances in Chronic Disease, 12. [link]

43 Miler, J. A., et al. (2016). Changes in the Frequency of Airway Infections in Smokers Who Switched To Vaping:

Results of an Online Survey. Journal of Addiction Research & Therapy 2016 7:4, 7(4), 1–3. [link]

44 Hajek, P., et al. (2019). A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy. New England

Journal of Medicine, 380(7), 629–637. [link]

45 Lucchiari, C. et al. (2020). Benefits of e-cigarettes in smoking reduction and in pulmonary health among chronic

smokers undergoing a lung cancer screening program at 6 months. Addictive Behaviors, 103, 106222. [link]

46 George, J. et al. (2019). Cardiovascular Effects of Switching From Tobacco Cigarettes to Electronic Cigarettes.

Journal of the American College of Cardiology, 74(25), 3112–3120. [link]

47 Berlowitz, J. B., et al. (2022). E-Cigarette Use and Risk of Cardiovascular Disease: A Longitudinal Analysis of the

PATH Study (2013-2019). Circulation, 145(20), 1557–1559. [link]

48 Yang, I., et al. (2020). The oral health impact of electronic cigarette use: a systematic review. Critical Reviews in

Toxicology, 50(2), 97–127. [link]

49 Stephens, W. E. (2018). Comparing the cancer potencies of emissions from vapourised nicotine products

including e-cigarettes with those of tobacco smoke. Tobacco Control, 27(1), 10–17. [link]

50 National Health Service (UK). Using E-cigarettes to Stop Smoking. Accessed 1 Nov 2023 [link] and Better Health

& NHS: Vaping to Quit Smoking. Accessed 15 January 2024 [link]

51 Ministry of Health, New Zealand. Vaping Facts: vaping versus smoking. Accessed 1 Nov 2023 [link]

52 Lee, P. N. (2011). Summary of the epidemiological evidence relating snus to health. Regulatory Toxicology and Pharmacology, 59(2), 197–214. [link]

53 Lee, P. N. (2013). Epidemiological evidence relating snus to health – an updated review based on recent publications. Harm Reduction Journal, 10(1), 36. [link]

54 Lee, P. N. (2013). The effect on health of switching from cigarettes to snus – A review. Regulatory Toxicology and Pharmacology, 66(1), 1–5. [link]

55 European Commiassion, Special Eurobarometer 506: Attitudes of Europeans towards tobacco and electronic cigarettes—Data Europa EU. (2021). [link]

56 Ramström, L., Borland, R., & Wikmans, T. (2016). Patterns of smoking and SNUS use in Sweden: Implications for public health. International Journal of Environmental Research and Public Health, 13(11). [link]

57 Lund, I., & Lund, K. E. (2014). How has the availability of snus influenced cigarette smoking in Norway? [link] 58 Ramstrom, L. M. (2024). If there had been no snus in Sweden: The impact of snus on mortality attributable to

smoking. Harm Reduction Journal, 21(1), 176. https://doi.org/10.1186/s12954-024-01095-7 59 Reports of the Snus Commission: Snus Kommissionen. Accessed 18 January 2024, [link] 60 Jarvis, M. J. (2016). Jarvis M. Expert Report—Report of Professor Martin Jarvis for the High Court of Justice,

Queen’s Bench Division, Administrative Court. Vol London: Department of Epidemiology & Public Health, University College London, [link]

61 Axéll T. and 17 others, Letter from experts in tobacco science and policy regarding the European Union snus prohibition, 1 Letter to European Commissioner Frans Timmermans, June 2017. [link]

62 Rodu, B., & Cole, P. (1994). Tobacco-related mortality. Nature, 370(6486), 184–184. [link] 63 Washington Post (Don Colburn), Study casts new light on smokeless tobacco. 15 August 1994 [link] 64 Hajat, C., et al. (2022). Analysis of common methodological flaws in the highest cited e-cigarette epidemiology

research. Internal and Emergency Medicine, 17(3), 887–909. [link]

65 Bhatta, D. N., & Glantz, S. A. (2019). Electronic Cigarette Use and Myocardial Infarction Among Adults in the US

Population Assessment of Tobacco and Health. Journal of the American Heart Association, 8(12). [link]

66 Rodu, B., & Plurphanswat, N. (2020). A re‐analysis of e‐cigarette use and heart attacks in PATH wave 1 data. Addiction, 115(11), 2176–2179. [link]

67 Pesko, M. F. et al. (2022). United States public health officials need to correct e-cigarette health misinformation.

Addiction. [link]

68 Blount, B. C et al. (2019). Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI. New England

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69 Bates, C. (2021). The outbreak of lung injuries often known as “EVALI” was nothing to do with nicotine vaping.

Qeios.

70 Mendelsohn, C. P et al. (2023). Nicotine vaping was not the cause of e-cigarette, or vaping, product use-

associated lung injury in the United States. Drug and Alcohol Review, 42(2), 258–261. [link]

71 Hill, A. B. (1965). The Environment and Disease: Association or Causation? Proceedings of the Royal Society of

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72 Kramarow, E., & Elgaddal, N. (2023). Current Electronic Cigarette Use in Adults Aged 18 and Over: United States,

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73 ASH (UK) & YouGov. Use of e-cigarettes (vapes) among adults in Great Britain. 2023. [link] see Figure 1: Smoking

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74 Jackson, S. E., et al. (2020). Is dual use of nicotine products and cigarettes associated with smoking reduction

and cessation behaviours? A prospective study in England. BMJ Open, 10(3), e036055. [link]

75 Kasza, K. A., et al. (2021). Association of e-Cigarette Use With Discontinuation of Cigarette Smoking Among Adult

Smokers Who Were Initially Never Planning to Quit. JAMA Network Open, 4(12), e2140880–e2140880. [link]

76 Foulds, J. et al. (2022). Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers With

No Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial. Nicotine & Tobacco Research, 24(7), 955–961. [link]

77 Lee, P. N. et al. (2021). Cigarette consumption in adult dual users of cigarettes and e-cigarettes: a review of the

evidence, including new results from the PATH study. F1000Research 2021 9:630, 9, 630. [link]

78 Bandi, P et al. (2022). Relative Harm Perceptions of E-Cigarettes Versus Cigarettes, U.S. Adults, 2018–2020. American Journal of Preventive Medicine, 63(2), 186–194. [link]

79 Jackson, S. E., et al. (2024). Trends in Harm Perceptions of E-Cigarettes vs Cigarettes Among Adults Who Smoke in England, 2014-2023. JAMA Network Open, 7(2), e240582. [link]

80 Action on Smoking and Health (UK) with YouGov. Use of e-cigarettes among adults in Great Britain, August 2023. Figure 8 & 9 for risk perceptions in all adults and adult smokers respectively [link]

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Aerosol. Toxics, 10(9), 510. [link]

90 Hajat, C., et al. (2022). Analysis of common methodological flaws in the highest cited e-cigarette epidemiology

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91 Rodu, B., & Plurphanswat, N. (2022). Cross-sectional e-cigarette studies are unreliable without timing of

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3 Smoke-free nicotine use reduces smoking

3.1 Key concepts The best way to assess the evidence that ENDS use reduces smoking is to look at all the different types of

evidence together. It all points towards ENDS having a powerful effect on suppressing adult smoking via

five main effects:

1. The people who use e-cigarettes are more likely to quit smoking, and success rates increase over

time as smokers become familiar with e-cigarettes as an alternative.

2. More people are willing to try ENDS to quit smoking because it does not require them to give up

nicotine and several other aspects of smoking to secure significant health, welfare, and economic

gains. Moving from smoking to vaping is easier than moving from smoking to nicotine abstinence.

3. People who would not otherwise try to quit are drawn into smoking cessation via ENDS uptake and

gradual migration away from smoking. These are known as “accidental quitters”.

4. Young adults who would otherwise have become smokers are diverted into ENDS use and never

started smoking.

5. Adults who may otherwise have relapsed to smoking use vaping instead.

3.2 Studies and assessments Randomised controlled trials show ENDS to be more effective than nicotine replacement therapies and at

least as good as pharmacotherapies at achieving smoking cessation in trial conditions.

• The January 2024 Cochrane review examined 88 studies and, based on seven studies that met its

strict inclusion criteria, concluded that vaping nicotine was 59% more effective for quitting than

nicotine patches and gum.1

• A review of 363 studies by the UK National Institute for Health Research found that vaping was the most effective single quitting aid.2

• A 2023 Cochrane review of all smoking cessation therapies concluded that nicotine ENDS and varenicline were the two most effective treatments for quitting smoking.3

Observational and population studies. Smokers switching to ENDS are replacing cigarettes with a much lower-risk way of taking nicotine – they are making a different consumer choice rather than taking a smoking cessation medication. Smoking cessation rates using vaping increase over time as smokers adjust to exclusive e-cigarette use.4 In contrast, conventional quit approaches have declining quit rates over time as abstinence gives way to relapse back to smoking.5 Vaping is associated with increased quitting in observational studies,4 6 7 and population studies.8-22 Significant use of ENDS policy is reflected in national smoking rates.23 24 25

Economic data. There is also substantial evidence from economic data that ENDS function as a cigarette substitute. In a paper for FCTC COP-7, WHO concluded, “ENDS/ENNDS and cigarettes are substitutes”.26 Economic evidence supports WHO’s claim. There are pronounced substitution effects between combustibles such as cigarettes and smoke-free alternatives. 27-35 Substitution should be expected: both meet user demands for nicotine in a similar way, though ENDS with much

lower risk.

“Accidental quitters.” Vaping is also the only quitting aid to assist smokers with no intention of quitting

(‘accidental quitters’).36 37 38 That is important because this group is most likely to continue smoking and,

therefore, is most at risk of serious disease and premature death.

3.3 Experience and outcomes Impact versus efficacy. Controlled trials can give insights into “efficacy” (how likely someone using the

product is to quit smoking). But they can’t say much about how many people will use the product. ENDS

have the potential for a substantial positive public health impact, a function of individual effectiveness

multiplied by the number of people willing to try. Switching to ENDS has become by far the most popular

assisted method to quit smoking in the United States39, England,40 41 and Canada.42 There is evidence that

ENDS have made such an impact at the population level in terms of sharper declines in cigarette smoking

than originally expected. For example, US adult smoking prevalence is now lower than anticipated from

pre-ENDS era trends – with the most significant decreases in smoking occurring in the age groups with

higher uptake of ENDS (i.e., adults under 44 years of age).43 44 In Britain, the most significant decline in

smoking between 2011 and 2023 was among young adults (age 18-24); smoking prevalence fell from

25.7% to 9.8%, and this group also had the highest uptake of vaping, reaching 15.8% by 2023 from

negligible levels in 2011.45 The most compelling example of a radical transformation of the tobacco and

nicotine market is from New Zealand, in which a rapid rise in vaping has displaced smoking, including in

the Māori population.

New Zealand Smoking and Vaping

Total & Māori 2011-24

Source: New Zealand Ministry of Health, Ben Youdan46

The impact on New Zealand Māori women was especially pronounced: between 2019-20 and 2023-24,

current smoking prevalence fell by more than half from 35.0% to 16.6%, while vaping prevalence

increased from 7.2% to 33.7%.47

Guidance for healthcare providers and the public. The UK National Centre for Smoking Cessation and

Training produces high-quality guidance in the use of vaping products to quit smoking for good.48

Academic analysis in the United States is beginning to endorse ENDS for smoking cessation in clinical

settings.49 50 The Ministry of Health in New Zealand51 National Health Service (England) provides plain-

speaking advice to the public.52

User testimony. Thousands of users provide eloquent testimony of their success in quitting smoking using

ENDS. These provide compelling accounts of tobacco harm reduction at the individual level.53 Though often

dismissed as anecdotes, these first-person accounts of experience are, in fact, rich in detail and a compelling

strand of evidence that triangulates well with trials, observational data, trends and economic analysis.

3.4 Heated tobacco and smoking Heated tobacco products. A comprehensive review of the behavioural science related to HTPs undertaken

by Imperial Brands and its consultants concluded:54

This evaluation suggests that HTP use is almost exclusively observed among those with a history of

cigarette smoking, and there is a growing body of evidence for the ability of HTPs to provide support

for adult smokers to transition away from cigarette smoking, in the absence of any significant

“gateway” into tobacco use initiation. Many studies have reported a significant degree of dual use

of cigarettes and HTPs, and efforts to assess the reasons for such patterns of use, whether these

provide overall exposure reductions, and whether dual use acts as a bridge towards a complete

transition away from cigarette smoking, requires further investigation.

Heated tobacco products have been a spectacular success in reducing cigarette consumption in Japan.55 56 A

2024 study confirmed that cigarette sales had fallen by around half, with an accelerated downward trend

since the introduction of heated tobacco products in Japan in 2016. 57

Japan: Cigarette and Heated Tobacco Sales

Per capita, 2011-2023

Cummings et al. (2024)

3.5 Barriers to greater impact Are ENDS as effective for smoking cessation as they could be? Since 2011, there has been significant innovation, much of which will improve the impact of vaping and smoking, and earlier data may be less relevant. However, the effect of vaping on smoking is not just a function of product design and innovation. It results from multiple influences on behaviour, including product appeal, perceptions of risk, and expected benefits and costs.

• If people believe (incorrectly) that vaping is no less harmful than smoking, they have diminished incentives to switch, and dual users would be indifferent to moving to exclusive vaping.

• If people believe (incorrectly) that nicotine vaping caused an outbreak of severe lung injuries or that “popcorn lung” is a risk, then they may be irrationally fearful about switching.

• If taxes make vapes more expensive relative to smoking, then fewer people will respond to the diminished economic incentive to switch.

• If nicotine limits, flavour bans, or plan packaging make the product less satisfying or

appealing, expect less smoking cessation. • If doctors hesitate to recommend vaping or provide misleading information, or official

healthcare advice warns against switching, then less switching will be the result. • If ENDS advertising is banned, fewer people will be aware of the option and encouraged to

switch to trusted products.

The real-world impact of ENDS on smoking is not just a function of product design but also the regulatory, fiscal, commercial, communications, and healthcare environment in which they are available to people who smoke. This environment is modifiable by governments, regulators, academics and tobacco control activists in ways that protect the cigarette trade or in ways that enhance the downward pressure on smoking and cigarettes.

3.6 References

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39 Foxon, F., & Niaura, R. (2025). Use of nicotine products, prescription drug products, and other methods to stop smoking by US adults in the 2022 National Health Interview Survey. Internal and Emergency Medicine. https://doi.org/10.1007/s11739-024-03847-6

40 Vera Buss, Robert West, Loren Kock, Dimitra Kale, Jamie Brown. (2024, November). Smoking Toolkit (England) monthly tracker. Smoking in England https://smokinginengland.info/graphs/monthly-tracking-kpi

41 Jackson, S. E., Brown, J., Buss, V., & Shahab, L. (2025). Prevalence of Popular Smoking Cessation Aids in England and Associations With Quit Success. JAMA Network Open, 8(1), e2454962. https://doi.org/10.1001/jamanetworkopen.2024.54962

42 Gravely, S., Sweanor, D., Driezen, P., Levy, D. T., Fong, G. T., Quah, A. C. K., Craig, L. V., Chung-Hall, J., Kaai, S. C., & Cummings, K. M. (2025). Use of nicotine vaping products during an attempt to quit smoking by Canadian adults who smoke or recently quit: Findings from the 2022 Canada International Tobacco Control Four Country Smoking and Vaping Survey. Health Promotion and Chronic Disease Prevention in Canada: Research, Policy and Practice, 45(1), 54–60. https://doi.org/10.24095/hpcdp.45.1.04

43 David T. Levy, et al., US Nicotine Vaping Product SimSmoke Simulation Model: The Effect of Vaping and Tobacco Control Policies on Smoking Prevalence and Smoking-Attributable Deaths, INT. J. ENVIRON. RES. PUBLIC HEALTH 2021, 18, 4876, Results at 8, [link]

44 Foxon, F., et al. (2024). Increased e-cigarette use prevalence is associated with decreased smoking prevalence among US adults. Harm Reduction Journal, 21(1), 136. [link]

45 Office of National Statistics (UK), released 1 October 2024, ONS website, statistical bulletin, Adult smoking habits in the UK: 2023

46 Ben Youdan (ASH New Zealand), Disruptor, disaster, or distraction? Vaping and smokefree Aotearoa New Zealand, UK E-cigarette Summit 2024 [PDF] based on New Zealand Health Survey. 2011-2024. https://minhealthnz.shinyapps.io/nz-health-survey-2023-24-annual-data-explorer/

47 New Zealand Ministry of Health, 2023-24 Data Explorer: smoking and vaping indicators, accessed 12 January 2025 https://bit.ly/425TqPe

48 National Centre for Smoking Cessation and Training. Vaping: a guide for health and social care professionals, November 2023 [link][PDF]

49 Warner, K. E., Benowitz, N. L., McNeill, A., & Rigotti, N. A. (2023). Nicotine e-cigarettes as a tool for smoking cessation. Nature Medicine 2023 29:3, 29(3), 520–524. [link]

50 Rigotti, N. A. (2024). Electronic Cigarettes for Smoking Cessation—Have We Reached a Tipping Point? New England Journal of Medicine, 390(7), 664–665. [link]

51 Ministry of Health (New Zealand — Manatū Hauora and Health NZ. Vaping Facts: Vaping to Quit Smoking, Accessed 20 August 2024. [link] and Te Whatu Ora, Health New Zealand, Vaping & E-cigarettes, accessed 20 August 2024 [link]

52 National Health Service (England), Using e-cigarettes to stop smoking, accessed 20 August 2024 [link] 53 CASAA (U.S. consumer organisation). Real stories. Real lives. User testimonials, 13,523 testimonials at 25

October 2023 [link] 54 Fearon, I. M., et al. (2024). A Scoping Review of Behavioural Studies on Heated Tobacco Products. Cureus, 16.

[link] 55 Stoklosa, M., Cahn, Z., Liber, A., Nargis, N., & Drope, J. (2020). Effect of IQOS introduction on cigarette sales:

evidence of decline and replacement. Tobacco Control, 29(4), 381–387. [link] 56 Cummings, K. M., Roberson, A., Levy, D. T., Meza, R., Warner, K. E., Fong, G. T., Xu, S. S., Gravely, S., Dhungel, B.,

Borland, R., O’Connor, R. J., Goniewicz, M. L., & Sweanor, D. T. (2024). Transformation of the tobacco product market in Japan, 2011–2023. Tobacco Control. https://doi.org/10.1136/tc-2024-058734

57 Cummings, K. M., Roberson, A., Levy, D. T., Meza, R., Warner, K. E., Fong, G. T., Xu, S. S., Gravely, S., Dhungel, B., Borland, R., O’Connor, R. J., Goniewicz, M. L., & Sweanor, D. T. (2024). Transformation of the tobacco product market in Japan, 2011–2023. Tobacco Control. https://doi.org/10.1136/tc-2024-058734

4 Smoke-free nicotine and youth

4.1 Key concepts ENDS use as a youth risk behaviour. No one concerned with public health recommends or welcomes youth nicotine use. The same applies to alcohol and illicit drug use, premature or risky sexual practices, dangerous driving, and a range of other youth risk behaviours.1 Nevertheless, such behaviours are a real part of society and require a response to reduce the harm they cause. Many are concerned about youth ENDS use, especially regarding potential “gateway” effects and signs of nicotine dependence. However, it is essential to place ENDS use in the broader context of youth risk behaviours, including smoking. For most adolescents, ENDS use would not be particularly harmful, and for some, it would be an alternative to smoking and, therefore, beneficial.

Causes of youth tobacco use. Evidence suggests that a wide range of psycho-social factors drive nicotine uptake. These factors are characteristics of the individual (genetic, mental health, rebellious outlook, delinquency, etc.) and their circumstances (household, peer group, marketing, etc). One systematic review identified ninety-eight conceptually different predictors of smoking onset.2 Studies of ENDS users suggest use arises from seeking an “alternative to cigarettes”, the “wider social environment”,3 and curiosity.4

The danger for policymakers. It is not possible (or desirable) to make straightforward cause-and- effect claims about youth smoking or vaping, such as attribution of youth use to factors such as flavours, packaging, or marketing to vaping uptake. The danger of designing policy based on a simplistic understanding of causes will leave the underlying demand intact and cause users to find alternative ways to use nicotine, including switching to smoking.5 6 ENDS use is one of a range of youth risk behaviours that a subset of young people will engage in, even if adults disapprove, related to substance use, violence, sexual behaviour, and risk-taking.7 The public health challenge is to reduce the risks to these young people to the greatest possible extent, including the risks arising from the unintended consequences of poorly designed policies.

4.2 Youth vaping displaces youth smoking Understanding youth vaping. The annotated chart below provides a basis for understanding youth ENDS use. It is based on US data from the National Youth Tobacco Survey as it developed over the last 12 years, peaking in 2019.8 Many of the same dynamics will be common to other populations.

• Youth ENDS use has peaked, then declined or plateaued in many countries. In the US, the proportion of high school-aged youth who used ENDS in the past 30 days peaked in 2019 at 27.5%9 but has since declined by almost two-thirds to 10.0%.10 In the UK, occasional or weekly ENDS use plateaued between 2021 and 2022,11 as did past-30-day ENDS use in Canada.12 There may be different types of use. Firstly, relatively frivolous use based on youthful experimentation, fads, and fashion is unlikely to persist – this is of little public health consequence. Secondly, more intensive and longer-term use – but this is most likely to be displacing smoking. There is reasonable evidence to support this model.

● Most youth ENDS use is experimental and temporary. Most youth who ever try ENDS do not persist in using them currently. In both the US and the UK, just under half of youth who had ever tried ENDS continued to use them 1+ times in the past 30 days. 11 13 Similarly, in the UK, over 60% of youth who used ENDS had either used them only once or twice or had used them more but discontinued them. 10 These patterns of temporary experimentation align with youths’ stated reasons for ever using ENDS, which are most often curiosity/experimentation, boredom, and social reasons.14 15 16

● ENDS use is concentrated in youth who had (or would have) used other nicotine products. US youth with an established history of other nicotine product use were over five times as likely to have used ENDS in the past 30 days.17 70% of UK youth who were currently using ENDS had a history of cigarette smoking.10 ENDS use that is frequent and/or is accompanied by nicotine dependence is even more strongly concentrated in those who had already used cigarettes or other nicotine products: approximately 98% of US youth who used ENDS frequently had used another nicotine product.16 Youth who vape have risk factors that also predispose them to smoke cigarettes,18 suggesting that they would have otherwise been cigarette smokers.19

● Higher youth ENDS use is accompanied by larger declines in smoking, suggesting displacement rather than gateway. If ENDS were a gateway to cigarette smoking, then youth smoking trends would be higher than otherwise expected as ENDS use increases. However, population-level studies show the opposite: youth and young adult smoking prevalence declined faster after ENDS use became common,20 and this pattern is remarkably consistent across countries, including the US,19 21 22 UK,23 24 Canada,25 and New Zealand.26 27 These declines have been drastic and unexpected: in the US, youth smoking in 2020 was far lower (3.3%)28 than what was thought possible in 2010, according to the US Healthy People target for 2020 (16%).29 These trends are consistent with ENDS diverting youth with a predisposition for nicotine use away from more harmful combustible cigarettes.21 25

4.3 The gateway effect is discredited Evidence for the gateway hypothesis is better explained by a “common liability” to nicotine use. Claims that ENDS are a gateway to smoking are based on a misunderstanding of the evidence (i.e. that youth who use ENDS are also more likely to smoke cigarettes). Rather than ENDS causing youth to also smoke cigarettes (which confuses correlation and causation), it is more likely that ENDS use and smoking are both explained by pre-existing characteristics which predispose some youth to use nicotine. There are dozens of these “common liability” factors (e.g., other substance use, poor mental health, risk-seeking personality) which are not accounted for in most studies. 17 The apparent gateway association becomes successively weaker as more common liability factors are accounted for30 31 – in some cases becoming not statistically significant29 32 – suggesting that it is better explained by a pre-existing propensity to use nicotine. A 2024 analysis of the gateway effect concluded:33

Evidence offered in support of the gateway hypothesis does not establish that ENDS use causes youth to also smoke cigarettes. Instead, this evidence is better interpreted as resulting from a common liability to use both ENDS and cigarettes. Population-level trends are inconsistent with the gateway hypothesis, and instead are consistent with (but do not prove) ENDS displacing cigarettes. Policies based on misinterpreting a causal gateway effect may be ineffective at best, and risk the negative unintended consequence of increased cigarette smoking.

4.4 Young people have a stake in the health of adults Young people have a stake in adult health. Young people are often discussed as if they constitute a separate population, unconnected to the adults in their lives. However, the welfare of young people is strongly connected to adults.

• Young people suffer if their parents or other significant adults are made ill or die prematurely through smoking – sadness and grief, caring burdens, and a diminished experience of parenting.34 35

• Parental smoking is a strong predictor of youth smoking initiation: there may be intergenerational benefits from parents switching from smoking to vaping.36

• Young people are usually economically dependent on adults and are fed and clothed from a household budget that is depleted by the costs of smoking.37

• Secondhand smoke exposure is harmful.38 Children may avoid secondhand smoke exposure if their parents and significant adults switch to vaping or pouches and smoking becomes denormalised in their homes and communities.

• When ENDS use displaces smoking, there are also reduced risks of household fires and resulting injuries and property loss. In March 2016, it was reported that there had been 113 fires caused by e-cigarettes in the UK over three years. There were over 16,000 smoking-related fires over the same period. 39

• Young people grow up to be adults. ENDS create “options value” for youth who smoke – they offer the means to switch later in life before the disease risks start to build up after the 40s.40 The availability of ENDS to adults reduces the life consequences of poor choices made as a teenager.

Adolescents account for a small minority of tobacco and nicotine users. Though much of the political and media focus is on youth vaping, the total number of adult nicotine users is likely much larger in most countries. For example, in the United States, the National Youth Tobacco Survey (2024) gives the total number of past-30-day tobacco and nicotine users in middle and high school at 2.25 million persons (2024).41 In contrast, Altria’s Adult Tobacco Consumer Tracker gives 54.8 million persons using tobacco and nicotine products (past-30-day users aged 21 or over, November 2024)42 twenty-four times as many adults. It is often asserted without evidence that ENDS manufacturers “target youth”. However, the addressable adult market of existing nicotine users is far larger, and adults are likely to be more intense users with more money to spend. This ratio between youth and adult users will vary between countries in response to many factors, notably demography – low- and middle-income countries have a higher proportion of younger people. However, this ratio should be a consideration in policymaking and sense-checking claims about targeting and marketing.

4.5 References

1 See, for example, the U.S. Centers for Disease Control and Prevention (CDC) Youth Risk Behavioral Surveillance

System [link].

2 Wellman, R. J et al. (2016). Predictors of the Onset of Cigarette Smoking: A Systematic Review of Longitudinal Population-Based Studies in Youth. In American Journal of Preventive Medicine (Vol. 51, Issue 5, pp. 767–778). Elsevier Inc. [link]

3 Nicksic, N. E., Snell, L. M., & Barnes, A. J. (2019). Reasons to use e-cigarettes among adults and youth in the Population Assessment of Tobacco and Health (PATH) study. Addictive Behaviors, 93, 93–99. [link]

4 Wang TW, Gentzke AS, Creamer MLR, et al. Tobacco product use and associated factors among middle and high school students-United States, 2019. MMWR Surveill Summ 2019;68(12):1–22. [link]

5 Posner, H., et al. (2022). Reactions to Sales Restrictions on Flavored Vape Products or All Vape Products Among Young Adults in the United States. Nicotine & Tobacco Research, 24(3), 333–341. [link]

6 Friedman, A. S. (2021). A Difference-in-Differences Analysis of Youth Smoking and a Ban on Sales of Flavored Tobacco Products in San Francisco, California. JAMA Pediatrics, 175(8), 863–865. [link]

7 US Youth Risk Behavior Surveillance Survey, 2021. Data explorer. [link]

8 Centers for Disease Control and Prevention (CDC). National Youth Tobacco Survey, 2011-23. [link]

9 Wang, T. W., et al. (2019). Tobacco Product Use and Associated Factors Among Middle and High School Students — United States, 2019. MMWR. Surveillance Summaries, 68(12). [link]

10 Birdsey, J. et al. (2023). Tobacco Product Use Among U.S. Middle and High School Students — National Youth Tobacco Survey, 2023. MMWR. Morbidity and Mortality Weekly Report, 72(44), 1173-1182 [link]

11 Use of e-cigarettes among young people in Great Britain (Action on Smoking and Health) (2023). [link]

12 Canadian Tobacco and Nicotine Survey, 2022 (Statisics Canada) [link]

13 Park-Lee E, et al. Tobacco Product Use Among Middle and High School Students - United States, 2022. MMWR Morb Mortal Wkly Rep. Nov 11 2022;71(45):1429-1435. [link]

14 Gentzke AS, et al. Tobacco Product Use and Associated Factors Among Middle and High School Students— National Youth Tobacco Survey, United States, 2021. MMWR Surveillance Summaries. 2022;71(5):1. [link]

15 Evans-Polce RJ, et al. Reasons for Vaping Among U.S. 12th Graders. Journal of Adolescent Health. 2018;62(4):457-462. [link]

16 Patrick ME, et al. Self-reported reasons for vaping among 8th, 10th, and 12th graders in the US: Nationally- representative results. Drug and Alcohol Dependence. 2016/08/01/ 2016;165:275-278. [link]

17 Jarvis M, et al. Epidemic of youth nicotine addiction? What does the National Youth Tobacco Survey 2017-2019 reveal about high school e-cigarette use in the USA? Qeios. 2020/09/02 2020 [link]

18 Lee P, et al. Considerations related to vaping as a possible gateway into cigarette smoking: an analytical review [version 3; peer review: 2 approved]. F1000Research. 2019;7(1915) [link]

19 Sokol NA, et al. High School Seniors Who Used E-Cigarettes May Have Otherwise Been Cigarette Smokers: Evidence From Monitoring the Future (United States, 2009-2018). Nicotine Tob Res. Oct 7 2021;23(11):1958- 1961. [link]

20 Levy DT, et al. Examining the relationship of vaping to smoking initiation among US youth and young adults: a reality check. Tob Control. Nov 2019;28(6):629-635. [link]

21 Meza R, et al. Trends in Tobacco Use Among Adolescents by Grade, Sex, and Race, 1991-2019. JAMA Network Open. 2020;3(12):e2027465-e2027465. [link]

22 Selya AS, et al. Trends in electronic cigarette use and conventional smoking: quantifying a possible ‘diversion’ effect among US adolescents. Addiction. 2021;116(7):1848-1858. [link]

23 Levy DT, et al. England SimSmoke: the impact of nicotine vaping on smoking prevalence and smoking-

attributable deaths in England. Addiction. 2021;116(5):1196-1211. [link]

24 Tattan-Birch H, et al. Rapid growth in disposable e-cigarette vaping among young adults in Great Britain from 2021 to 2022: a repeat cross-sectional survey. Addiction. Feb 2023;118(2):382-386. [link]

25 Levy DT, et al. Comparison of smoking prevalence in Canada before and after nicotine vaping product access using the SimSmoke model. Canadian Journal of Public Health. 2023/08/04 2023. [link]

26 Walker N, et al. Use of e-cigarettes and smoked tobacco in youth aged 14-15 years in New Zealand: findings from repeated cross-sectional studies (2014-19). Lancet Public Health. Apr 2020;5(4):e204-e212. [link]

27 ASH (New Zeakand) Year 10 Snapshot Survey 2023 Topline – Youth Smoking and Vaping, [link]

28 Gentzke AS, et al. Tobacco Product Use Among Middle and High School Students - United States, 2020. MMWR Morb Mortal Wkly Rep. Dec 18 2020;69(50):1881-1888. [link]

29 Healthy People 2020. Tobacco Use Objectives. [link]

30 Leventhal AM, et al. Association of Electronic Cigarette Use With Initiation of Combustible Tobacco Product Smoking in Early Adolescence. JAMA. 2015;314(7):700-707. [link]

31 Sun R, et al. Is Adolescent E-Cigarette Use Associated With Subsequent Smoking? A New Look. Nicotine Tob Res. Mar 26 2022;24(5):710-718. [link]

32 Kim S, et al. The Relationship Between Electronic Cigarette Use and Conventional Cigarette Smoking Is Largely Attributable to Shared Risk Factors. Nicotine Tob Res. Jun 12 2020;22(7):1123-1130. [link]

33 Selya, A. (2024). The “Gateway” hypothesis: Evaluation of evidence and alternative explanations. Harm Reduction Journal, 21(1), 113. [link]

34 Aguirre, L. V. C., Jaramillo, A. K., Saucedo Victoria, T. E., & Botero Carvajal, A. (2024). Mental health consequences of parental death and its prevalence in children: A systematic literature review. Heliyon, 10(2), e24999. [link]

35 Kaasbøll, J., Skokauskas, N., Lydersen, S., & Sund, A. M. (2021). Parental Chronic Illness, Internalizing Problems in Young Adulthood and the Mediating Role of Adolescent Attachment to Parents: A Prospective Cohort Study. Frontiers in Psychiatry, 12, 807563. [link]

36 Mays, D., Gilman, S. E., Rende, R., Luta, G., Tercyak, K. P., & Niaura, R. S. (2014). Parental Smoking Exposure and Adolescent Smoking Trajectories. Pediatrics, 133(6), 983–991. [link]

37 Belvin, C., Britton, J., Holmes, J., & Langley, T. (2015). Parental smoking and child poverty in the UK: An analysis of national survey data. BMC Public Health, 15, 507. [link]

38 Centers for Disease Control & Prevention (CDC) United States. Health Problems Caused by Secondhand Smoke. Access 18 June 2024. [link]

39 National Fire Chiefs Council (UK) Smoking, Vaping & Tobacco Position Statement. Retrieved 18 June 2024; [link] 40 Cho, E. R., Brill, I. K., Gram, I. T., Brown, P. E., & Jha, P. (2024). Smoking Cessation and Short- and Longer-Term

Mortality. NEJM Evidence. [link] 41 Jamal, A. (2024). Tobacco Product Use Among Middle and High School Students—National Youth Tobacco

Survey, United States, 2024. MMWR. Morbidity and Mortality Weekly Report, 73. https://doi.org/10.15585/mmwr.mm7341a2

42 Altria Client Services. (2024). Adult Tobacco Consumer Tracker. Altria Science. Retrieved 14 January 2025, from https://sciences.altria.com/science and data/survey data/adult tobacco consumer tracker

5 Policies for smoke-free nicotine products

5.1 Key concepts Policymaking for novel and emerging smoke-free tobacco products is shaped by the following:

• Non-combustible nicotine products are far safer than the dominant tobacco products (cigarettes).1

• These products function as substitutes for the dominant high-risk tobacco products

(cigarettes).2

• Policies to address youth vaping can cause more harm than good, including to young people.3

• Policy must be based on insights into the dependence-forming psychoactive effects but relatively minor health impacts of nicotine, why people use nicotine, and why its use is likely to persist.4

• Regulatory interventions can trigger unintended responses that the regulator may not expect or want, such as users switching back to smoking, expanding illicit trade, or the use of risky workarounds.

Five questions every public health official should ask when a new nicotine policy is proposed:

1. What problem is this policy trying to address? Policymakers should focus on the objectives of the FCTC,5 the SDGs,6 and their own public health goals, such as those of the E.U.7 or the U.K.8 That will usually mean tackling the non-communicable disease burden, which is primarily driven by smoking. Strategic targets for tobacco and nicotine policy should focus on smoking and achieving smoke-free status, not on tobacco use, nicotine use or vaping. Non-combustible tobacco and nicotine products can help to attain smoke-free status, and reaching smoke-free status is the overriding public health priority.

2. What evidence supports the proposed policy? The WHO routinely supports prohibitions on novel and emerging tobacco and nicotine products.9 However, there has been no reputable evaluation of this policy and its likely unintended consequences by those promoting it. Yet obvious concerns arise about illicit trade and the protection of the cigarette trade. Do flavour bans work? Do ENDS marketing restrictions protect the cigarette trade? Have the standard policymaking disciplines been applied, including impact assessment, cost-benefit analysis, risk assessment, and equity assessment?10

3. What trade-offs are created by this policy? If the policy is designed to protect youth from nicotine uptake, does it harm adults by reducing smoking cessation? Is the policy aimed at safeguarding adolescents who would never use nicotine at the expense of adolescents who would otherwise smoke? Does the policy punish disadvantaged people who continue to smoke or use nicotine, aggravating inequities? Do efforts to control access to ENDS make it relatively easier to access cigarettes?

4. What are the foreseeable unintended consequences? Policies do not always achieve the changes policymakers hope for, and they can make matters worse. Will the policy cause some ENDS users to return to smoking,11 some smokers never to switch, and some young people to

smoke instead of vaping?12 Will it trigger black-market supply13 and draw young people into criminal networks? Will it punish people for looking after their own health at their own expense? Will it cause users or suppliers to adopt workarounds that might introduce novel risks?14

5. Are distracting arguments used to justify the policy? Are activists and bureaucrats preoccupied with policies for fighting the tobacco and nicotine industry?15 16 Such framing can be harmful for public health: a good idea (making the use of nicotine much less dangerous) does not become a bad idea because tobacco or nicotine companies align their business strategy with supplying the products that make it work. Accepting this concept does not mean embracing the views or interests of the tobacco industry but rather recognising that there is a substantial body of credible, independent public health experts who support tobacco harm reduction on public health grounds.17 18 19

An expert perspective on policy challenges. As the Royal College of Physicians (London) puts it:20

If [a risk-averse and precautionary] approach also makes e-cigarettes less easily accessible, less palatable or acceptable, more expensive, less consumer-friendly or pharmacologically less effective, or inhibits innovation and development of new and improved products, then it causes harm by perpetuating smoking. Getting this balance right is difficult.

For specific policies, policymakers should be aware of the following.

5.2 Prohibitions Prohibitions on novel and emerging products. Prohibitions trigger various responses, including illicit supply, switching to permitted products (cigarettes), and workarounds (making and selling DIY products).21 Similar risks apply to partial prohibitions or high taxation. Australia’s highly restrictive

ENDS regime provides a stark lesson in unintended harmful consequences.22 23 24 The United States has extremely stringent regulation imposed by the Food and Drug Administration, but this has led to unauthorised products meeting more than 90% of the demand and effectively no regulation for most of the market.25 Illicit trade not only reaches young people as users but also involves young people in criminal supply, as the WHO was forced to admit when the ban on tobacco in Bhutan unravelled in 2020.26 27 According to one activist organisation, 46 countries had banned e-cigarettes by May

2025.28 The main argument against such proposals is not merely the harmful, unintended consequences, but also the ethics of denying people at risk of serious disease the lawful right, the information, and the means to switch to much safer, smoke-free products while keeping the most dangerous products widely available on the market.29 30 31 There has been minimal evaluation of these bans, yet a steady stream of press coverage about rising criminality as a response.

5.3 Taxation Taxing ENDS. A substantial body of evidence shows that ENDS and cigarettes behave as economic substitutes and that the demand for nicotine is more resilient than any particular way of consuming it. This means that when ENDS prices increase, the demand for ENDS falls, and the demand for cigarettes rises, all other things being equal,32 including for youth33 and young adults.34 Therefore, it is impossible to analyse the impact of an ENDS tax without also accounting for the effect on alternatives to ENDS, including the impact on cigarette consumption.35 One U.S. estimate suggested a “proposed national e-cigarette tax of $1.65 per millilitre of vaping liquid would raise the proportion

of adults who smoke cigarettes daily by approximately 1 percentage point, translating to 2.5 million extra adult daily smokers.”36

5.4 Banning flavours Banning flavoured ENDS. Tobacco harm reduction works by encouraging consumers of cigarettes to switch their product choice from smoking to much safer, smoke-free products. Smoke-free products must appeal to smokers to compete with cigarettes. One example of this appeal is the wide range of flavoured ENDS.37 While banning flavours might reduce the appeal of ENDS to some users, policymakers cannot just assume that users of flavoured ENDS will become abstinent – they may respond in various ways. A ban on flavours makes alternatives to cigarettes less competitive with cigarettes and, in doing so, protects and aids the cigarette trade. There are virtually no “natural” unflavoured vape products – almost all products contain flavouring ingredients, and even tobacco flavouring is added. Only a small minority of users choose to use tobacco-flavoured vapes – and that applies to adults and youth. In contrast, most smoking products have flavours and aromas created from the combustion of tobacco without the addition of flavouring ingredients (the exception being the addition of menthol to cigarettes).

In December 2023, in a presentation on the Netherlands’ approach to banning flavours, the Dutch public health agency RIVM summarised the plausible negative responses to a flavour ban (see below).38

The slide represents a good summary of the reasons for scepticism about flavour bans. These unintended consequences are far more significant than the intended purposes of a flavour ban. Yet the proponents of flavour bans, including RIVM, have no analysis supporting a flavour ban once these effects are included, and the Dutch government proceeded with a flavour ban, triggering a range of adaptations, including cross-border purchasing and illicit sales, with some returning to smoking.39

Most available evidence comes from the United States, where several flavour bans have been in place at the state and city levels since 2019. One study showed that when vape flavours were banned in San Francisco, cigarette smoking increased among high school students:40

It is essential to examine what happened when flavour bans were implemented in practice. Recent North American studies showed that ENDS flavour bans had the effect of increasing smoking:

In particular, we study the effect of NVP [nicotine vaping product] flavor restrictions enacted in Canada, a country with historically high tobacco regulation, through July of 2023. Using a stacked DID [difference in differences] model, we estimate that flavor restrictions increased cigarette sales by 9.6%. (Davis et al. 2025)41

… state restrictions on flavored ENDS sales were associated with a 3.6−percentage point (ppt) reduction in daily vaping as well as a 2.2 ppt increase in daily smoking relative to trends in states without restrictions.” Friedman et al. (2024)42

We find a trade-off of 12 additional cigarettes for every 1 less 0.7 mL ENDS pod sold due to ENDS flavor restrictions”. Friedman et al. (2023)43

Our findings suggest that statewide comprehensive flavor bans may have generated an unintended consequence by encouraging substitution towards traditional smoking in some populations. Saffer et al. (2025)44

“… we find that the adoption of an ENDS flavor restriction reduces frequent and everyday youth ENDS use by 1.2 to 2.5 percentage points. […]. However, we also detect evidence of an unintended effect of ENDS flavor restrictions that is especially clear among 18-20-year- olds: inducing substitution to combustible cigarette smoking” Cotti et al., 2024)45

A survey of French consumers found that half said they would source flavours illegally, and about one-quarter said they would return to smoking.46 Several academic studies have identified risks with flavour bans: Posner et al. (2021)47 found that one-third of e-cigarette users would be likely to switch to cigarettes. Gravely et al. (2021)48 examined possible responses to flavour restrictions in the United States, Canada, and England, finding that 28.8% would access their preferred flavours via illicit means and 17.1% would stop vaping and smoke instead.

Why flavour bans will not work. Multiple factors drive vaping uptake, not just flavours. In studies reporting the stated motivation of teenage users, harm reduction is an important reason for young people to use ENDS,49 50 51 as well as a wide range of psychosocial factors. A flavour ban stops the lawful supply of flavoured products but does not stop the demand. It follows that many young people will simply find ways around the prohibition or take up smoking. Control of flavours should

focus on descriptors (packaging, branding, and trademarks that describe the flavour), a form of marketing. Not the flavour sensation itself.

5.5 Controls on nicotine Controlling nicotine strength. Proposals to limit nicotine strength are based on a misunderstanding that strength reflects nicotine exposure or ‘addictiveness’. In reality, users control their exposure to nicotine through a widely understood process known as nicotine titration.52 Note, this also applies to alcohol – people drink smaller quantities of whiskey than beer. This titration effect has been well-documented in smokers for several decades.53 54 The user’s puffing pattern and possibly their choice of device will change to achieve a desired nicotine intake, for example, by puffing more deeply or more often – a process known as ‘compensation’. By adjusting their puffing patterns, users consume lower volumes of higher-strength liquid. But a nicotine strength limit also means that users will consume higher volumes of lower-strength liquid using more energy – potentially creating higher exposures to toxicants generated by heating liquids.55 56 57 As with

alcoholic spirits, the strength of nicotine in ENDS is self-limited by consumer acceptability and the excessive harshness of high-strength products. Any limits imposed on nicotine characteristics should focus on pharmacokinetics – the peak nicotine concentration in the brain (Cmax) and how quickly it can be reached (Tmax). As long as these characteristics show lower abuse liability (e.g. Cmax/Tmax) than cigarettes, there is no case for imposing controls.

5.6 Banning disposable vapes Banning disposables. Use of disposable, single-use ENDS products has risen rapidly among adults and adolescents in several jurisdictions. However, they are still overwhelmingly used by adults: in 2023, compared to youth (11-17), around nine times as many adults (18+) use disposable vapes in Britain.58 They have been essential in reaching poorer smokers because they are low-cost, have no

upfront cost, are easy to use, and deliver an immediately satisfactory alternative to cigarettes. They offer the easiest exit route from smoking and work well for people experiencing various forms of disadvantage. In June 2025, the U.K. banned these products. A post-ban survey by Haypp Group, an online retailer, found 62.5% of vapers continued to use disposable products (82% for those aged 25- 34) via illicit sources and that 6% had reverted to smoking,59 and many may be using technically compliant reusable vapes as disposables, a workaround.60 Because the harms of smoking are so much greater than vaping, the effect of any anti-vaping measure will be dominated by its impact on smoking. Based on this survey, the U.K. disposable ban has likely had largely adverse effects, without achieving its environmental or youth protection goals.

5.7 Controls on marketing and branding Banning the advertising and promotion of novel and emerging products. Advertising has multiple functions, including introducing new designs and products, gaining market share, building premium brands, and raising consumer awareness. Almost all ENDS advertising functions as “anti-smoking advertising” because it is trying to draw users towards an alternative to smoking. Banning advertising favours incumbents (the cigarette trade) and penalises entrants and innovators (ENDS) who must build their competitive position against cigarettes. There is some evidence that suggests

that bans on advertising ENDS reduce the number of smokers who quit,61 and increase demand for cigarettes.62

Plain packaging for ENDS. Some activists have proposed using standardised or plain packaging to reduce the appeal of e-cigarettes to youth,63 drawing on evidence that such packaging does not

affect the appeal to adults.64 65 Yet, this is weak evidence drawing on stated, not revealed, preferences in the contrived circumstances of an experimental study. The study did not investigate the likely behavioural response to reduced appeal to youth – it could lead to more smoking or other risky behaviours. There is also conflicting evidence that standardised packaging for ENDS can adversely change risk perceptions.66 There is, therefore, a danger that some adults would be deterred from switching and some youth would revert to smoking. Given that smoking is far more dangerous than vaping, only a slight uptick in smoking (among adults or youth) compared to a counterfactual without standardised packaging would overwhelm any benefits from reduced youth vaping. Finally, a recent assessment of standardised cigarette packaging found no public health benefit.67 Without a valid proof of concept and with the additional risk of unintended consequences, there is no credible case for standardised packaging for ENDS.

5.8 Controls on nicotine pouches Oral nicotine pouches. Oral nicotine pouches represent the safest, low-risk nicotine product, as they do not produce inhalable aerosol or undergo chemical decomposition from heating. The risk profile for products made by reputable manufacturers is similar to that of nicotine replacement therapy.68 However, pouches may be more effective in delivering nicotine with pharmacokinetics satisfactory to smokers and, therefore, a better approach to displacing cigarettes. Pouches follow the same harm-reduction model as snus,69 which shows how low-risk products have driven out

high-risk products in Sweden and other Nordic countries.70 71 As with vapes, pouch users have ways to control their nicotine exposure, for example, by where the pouch is placed, how long it is used for, and how many pouches are placed in the mouth. There is no simple relationship between the nicotine content of a pouch and its nicotine delivery,72 73 74 and there is a wide range of nicotine

exposures among users of the same pouch.75 Users can control their exposure by how the pouch is placed and moved in the mouth, how long it is kept there, the choice of pouch (moist or dry, nicotine content), and, ultimately, the number of pouches used simultaneously. It will not be possible to control nicotine exposure by setting (realistic) limits on nicotine content. It may be worthwhile setting a nicotine content limit (e.g. 20mg/pouch) for safety reasons, but this should be set at a high level initially and only reduced subsequently if any unintended consequences are shown to be manageable and acceptable.

5.9 Controls on environmental exposures Banning ENDS use in enclosed spaces. The primary policy question regarding bans on smoking or vaping in enclosed spaces turns on who decides the policy. Should it be up to lawmakers, enacted through generally applicable legislation, or should it be a matter for the property owner or manager to determine the policy? Typically, the case for regulatory intervention is strengthened when there is a material risk to workers or bystanders, when people have little choice but to be present, and when children are likely to be present. There is little evidence that exhaled aerosol poses a material risk. As Public Health England put it:76

The evidence of harm from secondhand smoke is conclusive and provides the basis for U.K. smokefree laws. In contrast, international peer-reviewed evidence indicates that the risk to the health of bystanders from secondhand e-cigarette vapour is extremely low and insufficient to justify prohibiting e-cigarettes. This evidence should inform risk assessments.

That finding does not confer a right to ENDS use in any indoor space. Instead, it suggests that the property’s owner or manager should determine the policy, taking sound policy guidance into account.77

5.10 Protecting youth Protecting youth. The aim of preventing youth uptake drives much ENDS policy. This aim must be placed in perspective with competing aims, including reducing adult smoking (which also has significant benefits to youth), preventing youth uptake of cigarettes, and allowing young people to switch later if they make an initial decision to smoke. Youth-oriented ENDS policies should focus on five main elements:78

1. Keeping the market mainly legal: regulators should aim to meet much larger legitimate adult demand without imposing excessive restrictions that trigger uncontrolled illicit trade. A large illicit market is the worst outcome for young people: it will supply any illicit product to anyone, regardless of age, and engage young people in criminal supply, introducing them to criminal networks. The focus of regulation should be on consumer protection (safety standards, product quality, accurate labelling, risk communication), which increases users’ confidence in switching from smoking to ENDS. Policymakers should be cautious about regulations that aim to force behaviour change (e.g., prohibitions, product limitations, limits on access via prescription or pharmacy, taxes). This type of regulation generates a range of unintended consequences as people exercise their autonomy and respond in ways that undermine the policy goal

2. Candid risk communication: Most of the control over youth risk behaviours will be self- imposed by young people acting in their own interests. Good information from trusted sources will help young people and adults make good decisions, if they want to. Being honest and respectful about the consequences of ENDS use, but without exaggeration or hyperbole, which are likely to be ineffective and degrade trust. Adults and young people must receive the same basic messaging. A good example from the U.K. National Health Service is included below.

3. Age-secure retailing: It should be difficult for young people to access any tobacco or nicotine products, though it is inevitable that some will. This means using age restrictions (up to 21), age- verification technology (that does not create an impediment to purchase and use by adults), proportionate fines and licensing, and the threat of suspension or closure. It is essential to recognise the limitations in this context, where informal economies, street traders, and limited enforcement capabilities coexist – but the alternative is illicit supply.

4. Control of youth-themed marketing: The ENDS marketing proposition should not be youth- oriented (i.e. cartoons, frivolous branding, bright colours, provocative or ironic language), and a range of principles should govern advertising, promotion, and sponsorship, as well as be extended to product branding and packaging. As far as possible, this should be enforced through an industry code of marketing practice, supported by retailers, backed up by law and enforced by Trading Standards.

5. Control of flavour descriptors: flavour descriptors are a particular case of marketing and branding. ENDS flavours can be conceptualised in three ways: (i) a chemical recipe, (ii) a sensory characteristic (“apple”, “mint”) or (iii) a descriptor and branding, including cartoons or images. Control over chemical recipes should only focus on product safety. There is no basis to allow some flavour characteristics but not others, or to permit only the flavours that users do not want. However, there is a good argument for controls over flavour descriptors and branding, as with other forms of marketing.

5.11 Risk proportionate regulation The right overall approach: risk-proportionate regulation. The aim of tobacco and nicotine policy should be to realise the vast benefits of displacing cigarettes with far less risky products. Advocates of tobacco harm reduction are not opposed to the regulation of safer alternatives to nicotine. The table below provides an overview of a risk-proportionate regulatory system.

An outline of a risk-proportionate regulatory system for tobacco and nicotine

Measure Cigarettes, hand-rolling tobacco, and other combustibles

Vaping, heated and smokeless tobacco and oral nicotine

Overall aim Reduce appeal and deter use Consumer protection

Taxation Relatively high taxes Low or zero tax (sales tax only)

Advertising Prohibit other than within trade Control themes and placement

Warnings Graphic warnings depicting disease Messages encouraging switching

Public places Legally mandated controls Up to the discretion of the owner

Plain packaging Yes No. Controls on imagery and branding

Risk communication Major risks to health A far safer alternative to smoking

Age restrictions No sales to under-21s No sales to under-18s

Flavours Ban characterising flavours Control flavour descriptors

Product standards Control risks and reduce appeal Control safety risks to the user

The policy aim should be to take the toughest, most restrictive measures to address the risks of smoking to the user and bystanders. The regulation of safer nicotine products should focus on consumer protection (chemical, electrical, and thermal safety, and reliable information) and on limiting youth uptake through measures to ensure responsible supply, retailing, and marketing.

5.12 References

1 Evidence Briefing: ENDS use is far safer than smoking, Clive Bates, Counterfactual, January 2025 [link]

2 Evidence Briefing: ENDS use reduces smoking, Clive Bates, Counterfactual, January 2025. [link]

3 Evidence Briefing: ENDS use and youth, Clive Bates, Counterfactual, January 2025. [link]

4 Evidence Briefing: Nicotine for Policymakers, Clive Bates, Counterfactual, May 2025. [link]

5 FCTC Article 3: Objective “protect present and future generations from the devastating health, social, environmental and economic consequences of tobacco consumption and exposure to tobacco smoke”. [link]

6 Sustainable Development Goal Target 3.4. “Reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being” [link]

7 Europe’s Beating Cancer Plan [link] and Healthier Together action on non-communicable disease [link], Accessed 8 November 2023.

8 Department of Health and Social Care. (2022, August 25). Making smoking obsolete: Summary. GOV.UK. [link]

9 World Health Organisation, Dr Harsh Vardhan conferred WHO award for leadership in tobacco control, 2 June 2021 [link] “Dr Harsh Vardhan received the award for spearheading the Government of India’s legislation to ban e-cigarettes and heated tobacco products in 2019.”

10 For example, UK government policymaking guidance includes: Managing Public Money [link], HM Treasury The Green Book (policy appraisal) [link] and the Better Regulation Framework [link]

11 Li, D., et al. (2022). Impact of the FDA flavour enforcement policy on flavoured electronic cigarette use behavior changes. Tob Control, 31(Suppl 3): s176-s183 [link].

12 Friedman, A. S. (2015). How does electronic cigarette access affect adolescent smoking? J Health Econ, 44, 300- 308. [link]

13 Wong, L. P., et al. (2017). E-Cigarette Users’ Attitudes on the Banning of Sales of Nicotine E-Liquid, Its Implication on E-Cigarette Use Behaviours and Alternative Sources of Nicotine E-Liquid. J Community Health, 42(6), 1225-1232. [link]

14 Kerber, P. J., et al. (2023). Effects of E-Cigarette Flavor Enhancing Capsules on Inhalable Aerosols. Chem Res Toxicol, 36(1), 8-13. [link]

15 Global Alliance for Tobacco Control (GATC). (2025, November 11). GATC – COP11 Brief: Tobacco Harm Reduction. [link]

16 Tobacco Free Initiative. (2025). WHO position on Tobacco Control and Harm Reduction [Position statement]. World Health Organisation. 12 November 2025 [link]

17 The Counterfactual, Expert Wall (2025) Statements on tobacco harm reduction. November 2025. https://clivebates.com/papers-and-letters/cop11experts/

18 Beaglehole, R., Bates, C., Youdan, B., & Bonita, R. (2019). Nicotine without smoke: fighting the tobacco epidemic with harm reduction. The Lancet, 394(10200), 718–720. [link]

19 100 independent experts in tobacco and nicotine science, policy, and practice. Letter to Heads of Delegation Parties to the FCTC Ninth Conference of the Parties. October 2021 English, Français, Español, Deutsch

20 Tobacco Working Group. Royal College of Physicians (London) Nicotine without smoke: tobacco harm reduction 28 April 2016 [link]

21 International Network of Nicotine Consumer Organizations (INNCO), 10 reasons why blanket bans of e-cigarettes and HTPs in low- and middle-income countries (LMICs) are not fit for purpose [link] Press release, 16 March 2021 [link]

22 Hall, W. D. (2024). Will Australia’s tightened prescription system reduce nicotine vaping among young people?

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25 Satel, S., Bates, C. D., Kenkel, D., & Rodu, B. (2025). Regulating the Tobacco and Nicotine Market in the American Public Interest: A Reform Agenda for the FDA. American Enterprise Institute. [link]

26 World Health Organization. Country Office for Bhutan. (2020). The big ban: Bhutan’s journey towards a tobacco- free society. World Health Organization. Country Office for Bhutan. [link]

27 Clive Bates, The Evil Twins (Prohibition and Illicit trade), Tobacco Reporter, 1 February 2022 [link]

28 Global Center for Good Governance in Tobacco Control, E-Cigarette Ban & Regulation: Global Status as of May 2025 [link]

29 Knowledge Action Change, The right to health and the right to tobacco harm reduction — Global State of Tobacco Harm Reduction, June 2022. [link]

30 Kozlowski, L. T. (2002). Harm reduction, public health, and human rights: Smokers have a right to be informed of significant harm reduction options. Nicotine & Tobacco Research, 4(Suppl_2), S55–S60. [link]

31 Hall, W., Gartner, C., & Forlini, C. (2015). Ethical issues raised by a ban on the sale of electronic nicotine devices. Addiction, 110(7), 1061–1067. https://doi.org/10.1111/add.12898

32 Selya, A., et al (2023). Meta-analysis of e-cigarette price elasticity. F1000Research 2023 12:121, 12, 121. [link]

33 Abouk, R. et al. (2023). Intended and unintended effects of e-cigarette taxes on youth tobacco use. Journal of Health Economics, 87, 102720. [link]

34 Friedman, A. S., & Pesko, M. F. (2022). Young Adult Responses to Taxes on Cigarettes and Electronic Nicotine Delivery Systems. Addiction. [link]

35 Cotti, C., Courtemanche, C., Maclean, J. C., Nesson, E., Pesko, M. F., & Tefft, N. W. (2022). The effects of e- cigarette taxes on e-cigarette prices and tobacco product sales: Evidence from retail panel data. Journal of Health Economics, 86, 102676. https://doi.org/10.1016/j.jhealeco.2022.102676

36 Pesko, M. F., Courtemanche, C. J., & Maclean, J. C. (2020). The effects of traditional cigarette and e-cigarette tax rates on adult tobacco product use. Journal of Risk and Uncertainty, 60(3), 229–258. [link]

37 Farsalinos, et al. (2023). Patterns of flavored e-cigarette use among adult vapers in the USA: an online cross- sectional survey of 69,233 participants. Harm Reduction Journal 2023 20:1, 20(1), 1–14. [link]

38 Reinskje Talhout, Flavours and flavourings in e-cigarettes, National Institute for Public Health and the Environment (RIVM), Ministry of Health, Welfare and Sport, The Netherlands. Presentation [presentation PDF] to French National Cancer Institute Conference, International Scientific Conference on E-cigarette, Paris, 5-6 December 2022.

39 Hans Molenaar. (2024). Survey among Dutch vapers on the consequences of the online sales and flavor ban. ACVODA (consumer organisation). [link] “80% of consumers are circumventing the flavor ban: 50% are going abroad, and 30% of respondents are still ordering online and through social media, thanks to the lack of controls. Only 2% of users switched to the tobacco flavor required in the Netherlands. Nearly 10% of e-cigarette users returned to smoking.”

40 Friedman, A. S. (2021). A Difference-in-Differences Analysis of Youth Smoking and a Ban on Sales of Flavored Tobacco Products in San Francisco, California. JAMA Pediatrics, 175(8), 863–865. https://doi.org/10.1001/jamapediatrics.2021.0922

41 Davis, B. A., Friedman, A. S., & Pesko, M. F. (2025). Restricting Sales of Flavored Nicotine Vaping Products: Effects on Nicotine Vaping Product and Cigarette Sales in Canada. Working Papers, Article 2515. https://ideas.repec.org//p/umc/wpaper/2515.html

42 Friedman, A. S., Pesko, M. F., & Whitacre, T. R. (2024). Flavored E-Cigarette Sales Restrictions and Young Adult Tobacco Use. JAMA Health Forum, 5(12), e244594. https://doi.org/10.1001/jamahealthforum.2024.4594

43 Friedman, A., Liber, A. C., Crippen, A., & Pesko, M. (2024). E-cigarette Flavor Restrictions’ Effects on Tobacco Product Sales (SSRN Scholarly Paper No. 4586701). Social Science Research Network. https://doi.org/10.2139/ssrn.4586701

44 Saffer, H., Ozdogan, S., Grossman, M., Dench, D., & Dave, D. (2025). Comprehensive E-Cigarette Flavor Bans and

Tobacco Use Among Youth and Adults. Health Economics. https://doi.org/10.1002/hec.70030

45 Cotti, C., Courtemanche, C., Liang, Y., Maclean, J. C., Nesson, E., & Sabia, J. J. (2025). The effect of e-cigarette flavor bans on tobacco use. Journal of Health Economics, 102, 103013. https://doi.org/10.1016/j.jhealeco.2025.103013

46 AIDUCE, SOVAPE, La Vape du Coeur and FIVAPE, Communiqué : Première synthèse de l’enquête MERCI LA VAPE – 40000 réponses + 1 alerte sanitaire, 3 November 2023 [link] Full report (French) [PDF link]

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48 Gravely S, Smith DM, Liber AC, Cummings KM, East KA, Hammond D, et al. Responses to potential nicotine vaping product flavor restrictions among regular vapers using non-tobacco flavors: Findings from the 2020 ITC Smoking and Vaping Survey in Canada, England, and the United States. Addict Behav. 2021 https://bit.ly/3oRuSo3

49 Shiffman S. Sembower MA. PATH Data: Harm Reduction is Teens' Top Reason for Using e-cigarettes, Poster SRNT, Florence March 2017 [link]

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51 Nicksic NE et al. Reasons to use e-cigarettes among adults and youth in the Population Assessment of Tobacco and Health (PATH) study. Addict Behav 2019;93:93–99. [link]

52 Dawkins LE, Kimber CF, Doig M, Feyerabend C, Corcoran O. Self-titration by experienced e-cigarette users: blood nicotine delivery and subjective effects. Psychopharmacology (Berl) 2016;233(15–16):2933–2941. [link]

53 Benowitz NL, Hall SM, Herning RI, Jacob P, Jones RT, Osman AL. Smokers of Low-Yield Cigarettes Do Not Consume Less Nicotine. N Engl J Med. 1983 Jul 21;309(3):139–42. [link]

54 Russell MAH, Jarvis M, Iyer R, Feyerabend C. Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers. Br Med J. 1980 Apr 5;280(6219):972–6. [link]

55 Kośmider L, Kimber CF, Kurek J, Corcoran O, Dawkins LE. Compensatory Puffing With Lower Nicotine Concentration E-liquids Increases Carbonyl Exposure in E-cigarette Aerosols. Nicotine Tob Res 2018 [link]

56 Kosmider L, Cox S, Zaciera M, et al. Daily exposure to formaldehyde and acetaldehyde and potential health risk associated with use of high and low nicotine e-liquid concentrations. Sci Rep [Internet] 2020;10(1):6546. [link]

57 Dawkins L, Cox S, Goniewicz M, et al. ‘Real-world’ compensatory behaviour with low nicotine concentration e- liquid: subjective effects and nicotine, acrolein and formaldehyde exposure. Addiction 2018;113(10):1874–1882. [link]

58 Jackson, S. E., et al. (2024). Who would be affected by a ban on disposable vapes? A population study in Great Britain. Public Health. [link] The study shows that 2.6 million adults use disposable vapes in 2023 in Britain. ASH/YouGov data [link] shows a vaping prevalence of 7.6% in 11-17-year-olds in Britain, of which 69% were most commonly using disposables. The estimated population of British 11–17-year-olds in 2023 is 5.5 million [ONS], suggesting around 288,000 were using disposables. The adult use is nine times greater.

59 Haypp Group. (2025). New Survey Reveals Scale of Disposable Vape Black Market. Haypp UK. 7 November 2025. https://www.haypp.com/uk/nicopedia/news/disposable-vape-black-market

60 GB News. (2025). Loophole in Labour’s disposable vape ban exposed as ‘raison d’être’ of new rules branded ‘meaningless’. [link] - includes a letter to ministers from Imperial Brands.

61 Dave, D. et al. (2019). Does e-cigarette advertising encourage adult smokers to quit? Journal of Health Economics, 68, 102227. [link]

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63 Mark Greaves, UCL media office. (2025). Plain packaging may help tackle teen vaping. 22 September 2025. [link]

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66 Simonavičius, E., et al. (2024). Impact of E-liquid Packaging on Vaping Product Perceptions Among Youth in

England, Canada, and the United States: A Randomized Online Experiment. Nicotine & Tobacco Research, 26(3), 370–379. [link]

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69 Patwardhan, S., & Fagerström, K. (2022). The New Nicotine Pouch Category: A Tobacco Harm Reduction Tool? Nicotine and Tobacco Research, 24(4), 623–625. [link]

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78 New Nicotine Alliance, NNA writes to Labour Health Secretary, 11 July 2024 [link]

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Teie 07.08.2026 Meie 14.08.2026 nr 2-6/26-5824-2

Vastus teabenõudele Lugupeetud Henri Elias Edastame Teile soovitud kirjad. Teavitame, et kirjadest on kinni kaetud füüsiliste isikute eraelulised andmed, kuna nimetatud teave on tunnistatud asutusesiseseks kasutamiseks mõeldud teabeks avaliku teabe seaduse § 35 lõike 1 punkti 12 alusel. Lugupidamisega (allkirjastatud digitaalselt) Silja Tammeorg nõunik Lisa: 1. 8-1/5425-3 Soov kohtuda nikotiinitoodete eelnõu teemal

2. 8-1/5425-6 Nikotiinitoodete piirangu eelnõu 3. 8-1/5425-10 Feedback on the Draft Amending the Tobacco Act 4. 8-1/5425-12 Nicotine policy evidence briefings 5. 8-1/5425-12 Comment on Estonia proposals 2026 - Bates - EE 6. 8-1/5425-12 Comment on Estonia proposals 2026 - Bates – EN 7. 8-1/5425-12 Comment on proposed new nicotine product restrictions

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