The topic of e-cigarettes is controversial. Opponents focus on e-cigarettes’ risks for young people, while supporters emphasize the potential for e-cigarettes to assist smokers in quitting smoking. Most US health organizations, media coverage, and policymakers have focused primarily on risks to youths. Because of their messaging, much of the public—including most smokers—now consider e-cigarette use as dangerous as or more dangerous than smoking. By contrast, the National Academies of Science, Engineering, and Medicine concluded that e-cigarette use is likely far less hazardous than smoking. Policies intended to reduce adolescent vaping may also reduce adult smokers’ use of e-cigarettes in quit attempts.

Because evidence indicates that e-cigarette use can increase the odds of quitting smoking, many scientists, including this essay’s authors, encourage the health community, media, and policymakers to more carefully weigh vaping’s potential to reduce adult smoking-attributable mortality.

We review the health risks of e-cigarette use, the likelihood that vaping increases smoking cessation, concerns about youth vaping, and the need to balance valid concerns about risks to youths with the potential benefits of increasing adult smoking cessation.

The use of nicotine-containing electronic- or e-cigarettes has divided the tobacco control community along a spectrum from fervent opponents to enthusiastic supporters. Opponents emphasize that vaping can cause nicotine addiction among young people and could lead some to become dependent cigarette smokers, possibly “renormalizing” smoking. They cite research indicating that nicotine may harm adolescents’ developing brains. Some consider vaping’s health risks substantial, and some question whether vaping decreases smoking cessation.1 By contrast, proponents present evidence that vaping assists smokers in quitting smoking and believe that vaping poses far less risk to users’ health than does smoking. Smoking among youths, they observe, has declined rapidly during vaping’s ascendancy.2

Many US governmental health agencies36 and nongovernmental medical7,8 and health organizations912 focus primarily on vaping’s risks for young people. These organizations’ pronouncements and their influence on policymakers and the media have had a profound impact on the public’s understanding of vaping. A study of US news articles on e-cigarettes found that, from 2015 to 2018, 70% of articles mentioned vaping’s risks for youths, while only 37.3% noted potential benefits for adult smokers.13 Of respondents to a 2019 national survey, nearly half considered vaping nicotine just as harmful as or more harmful than cigarette smoking. Only 1 in 8 considered vaping less harmful. (The rest responded “I don’t know.”14) By contrast, the US National Academies of Sciences, Engineering, and Medicine15 and the British Royal College of Physicians16 have concluded that vaping is likely far less hazardous than smoking cigarettes.

The public’s inaccurate perception worsened following a 2019 vaping-associated acute pulmonary disease outbreak (named “e-cigarette or vaping use-associated lung injury” [EVALI]) that caused 68 fatalities.17 Media coverage was extensive. Several states and cities promptly banned retail and online sale of flavored e-cigarettes.18 In early 2020, however, research attributed the illness to vitamin E acetate, an adulterant in illicit tetrahydrocannabinol (THC) vaping devices shown to produce pulmonary injury in animals.1921 A small percentage of patients with EVALI reported vaping only nicotine, but they were primarily in states where THC was illegal, and most had no toxicology testing.22 Once the potential harm of vitamin E acetate was publicized and adulterated THC removed from the market, the incidence of new cases fell precipitously.19 Yet, after the outbreak, two thirds of respondents to a poll related the lung disease deaths to use of “e-cigarettes such as JUUL.” Only 28% related the deaths to use of “marijuana or THC e-cigarettes.”23

Scientists differ in their views of the relative risks and benefits of vaping nicotine, and of their implications.1,2,24,25 Many, including this article’s authors, believe that vaping can benefit public health, given substantial evidence supporting the potential of vaping to reduce smoking’s toll. Our objective is to encourage more balanced consideration of vaping within public health and in the media and policy circles.

In the following pages we address:

the health risks of vaping,

the likelihood that vaping increases smoking cessation,

the principal concerns about youth vaping, and

balancing concerns about risks to youths with potential benefits for adult smokers.

According to the National Academies of Sciences, Engineering, and Medicine, “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.”15(p1) The British Royal College of Physicians similarly concluded that “vaping isn’t completely risk-free but is far less harmful than smoking tobacco.”16

High-quality clinical and epidemiological data on vaping’s health effects are relatively sparse. There are no data on long-term health effects, reflecting the relative novelty of vaping and the rapid evolution of vaping products. Determining even short-term health effects in adults is difficult because most adult vapers are former or current smokers.

Some studies find that vaping may worsen asthma, bronchitis, and cough, including among nonsmoking young people.26,27 By contrast, a few studies found that smokers with asthma or chronic obstructive lung disease see symptoms improve after switching to e-cigarettes.28,29 Randomized switching trials (cigarettes to e-cigarettes) document improvements in respiratory symptoms.30,31

Laboratory studies have reported potentially adverse effects of e-cigarette aerosol in cells and animals.26,32 It is difficult, however, to extrapolate from exposure conditions in cells and animals to humans.26 Human experimental studies have focused on acute effects,33 which may not predict future disease. For example, e-cigarettes acutely impair tests of endothelial function, a common feature of cardiovascular disease, but when smokers switch from cigarettes to e-cigarettes, endothelial function normalizes.34,35 A recent study detected no difference in biomarkers of inflammatory and oxidative stress in exclusive e-cigarette users and nonusers of either cigarettes or e-cigarettes.36

There is little evidence that e-cigarettes pose significant cancer risk.15 However, some studies raise concerns that warrant long-term follow-up of vapers.37,38

Many scientists have concluded that vaping is likely substantially less dangerous than smoking because of the following15,16:

The number of chemicals in cigarette smoke, greater than 7000,39 exceeds that of e-cigarette aerosol by 2 orders of magnitude.40,41

Among potentially toxic substances common to both products, cigarette smoke generally contains substantially larger quantities than e-cigarette aerosol.4244 However, e-cigarette aerosol contains some substances not found in cigarette smoke.45

Biomarkers reflecting exposure to toxic substances are present at much higher levels in exclusive cigarette smokers than in exclusive vapers, and studies of smokers who switch to e-cigarettes find decreases in toxicant exposures.31,4650

Tests of lung and vascular function indicate improvement in cigarette smokers who switch to e-cigarettes.28,29,34 Exclusive users of e-cigarettes (most being former smokers) report fewer respiratory symptoms than do cigarette smokers and dual users.51

However, questions remain.52 Ongoing research will lend further insight into the products’ absolute and relative dangers.

A growing body of evidence indicates that vaping can foster smoking cessation, although the evidence is not definitive.53,54

Randomized Trials

In an English smoking cessation randomized controlled trial,55 smokers assigned to e-cigarettes achieved nearly twice the rate of biochemically confirmed smoking cessation at 1 year (18%) than smokers assigned to nicotine replacement therapy (9.9%); all received identical behavioral counseling. While 80% of those who quit with e-cigarettes were still vaping, they were no longer exposed to smoking’s substantially higher risk.

A New Zealand trial found that at 6 months, nicotine patch with nicotine e-cigarettes outperformed patch with nicotine-free e-cigarettes and patch alone. Thus, in addition to aiding quitting when used alone, nicotine e-cigarettes may increase the effectiveness of existing cessation aids.56

Examining 26 randomized controlled trials, a recent Cochrane Review concluded that “There is moderate‐certainty evidence that ECs [electronic cigarettes] with nicotine increase quit rates compared to ECs without nicotine and compared to nicotine replacement therapy.”53 Another meta-analysis drew similar conclusions, albeit with less certainty.57 However, the US Preventive Services Task Force’s smoking cessation practice guideline did not find the evidence convincing.58 As such, and for reasons the Cochrane Review describes, more well-designed clinical trials are needed.

Noteworthy is the lack of trials by e-cigarette manufacturers in pursuit of regulatory agency approval to use e-cigarettes for smoking cessation, likely reflecting the profitability of selling e-cigarettes as consumer products, rather than medicinal devices.

Population Studies

Collectively, population studies’ findings are consistent with a near doubling of quit attempt success, found in the randomized controlled trials, and the fact that e-cigarettes are smokers’ most used aid in quit attempts.59 Four studies6063 found significant increases in smoking cessation (10%–15%) that the authors associated with vaping. A Centers for Disease Control and Prevention study reported that, in 2018, 15.1% of smokers had quit smoking for 6 months or longer using e-cigarettes, compared with 3.3% using other noncigarette tobacco products and 6.6% using no tobacco products.64 Another study identified a near doubling of self-reported cessation among users of e-cigarettes or varenicline compared with smokers not using these products.65 Consistent with these population studies, simulation analyses have generally found that vaping increases smoking cessation, avoiding large numbers of premature deaths.6669

Other researchers have found regular and frequent e-cigarette use to be associated with increased smoking cessation, while infrequent use was not.7075 This could reflect self-selection, with frequent vapers possibly liking vaping more and being more motivated to quit smoking. Infrequent vapers might use vaping as a temporary nicotine source where smoking is prohibited.73,76

Other researchers have reported reduced cessation rates among smokers who vape.77,78 However, many failed to distinguish frequency of vaping, introducing the risk of the selection biases just noted. Other studies included only current vapers who also smoke, systematically excluding vapers who had successfully quit smoking.53,78

An often-cited meta-analysis found vapers’ odds of quitting smoking 28% lower than for nonvaping smokers.77 This analysis combined clinical trials, cohort studies, and cross-sectional analyses, an inappropriate practice for meta-analyses.79 Furthermore, the individual studies’ sources of bias could be compounded in a meta-analysis, possibly producing an incorrect result.76

Cigarette Sales

For years, US cigarette sales declined 2% to 3% annually. More recently, as vaping product sales increased, cigarette sales decreased much more rapidly. Conversely, following the EVALI outbreak and e-cigarette sales restrictions, sales of e-cigarettes fell and sales of cigarettes resumed their prevaping pattern.80 Studies finding a positive cross-price elasticity of demand between cigarettes and e-cigarettes support the conclusion that the products are substitutes.81,82

Support for the plausibility of an inverse causal relationship between vaping and smoking comes from countries in which startling decreases in cigarette sales have accompanied rising sales of another novel nicotine product, heated tobacco products (HTPs). Like e-cigarettes, HTPs expose users to lower levels of toxicants than do cigarettes.83 In Japan, HTP adoption from 2015 to 2019 was accompanied by cigarette sales declining by a third.84 In both cases—HTPs in Japan and e-cigarettes in the United States—as sales of reduced-risk products rose, cigarette sales fell.

Unintended Consequences of Policies Restricting Vaping

Studies have found that policies intended to restrict e-cigarette use may have unintentionally increased cigarette smoking. One study associated a Minnesota e-cigarette tax with increased adult smoking and reduced cessation, estimating that taxing e-cigarettes at the same rate as cigarettes nationwide could deter 2.75 million smokers from quitting smoking over a decade.85 Two other studies found state restrictions on minors’ access to e-cigarettes associated with higher adolescent cigarette smoking.86,87


Although not the final word, the totality of the evidence indicates that frequent vaping increases adult smoking cessation. Smokers unable to quit smoking with evidence-based cessation methods88 should be well informed about the relative risks of vaping and smoking and vaping’s potential to help them quit smoking. They should understand that, while the long-term health consequences are unknown, completely substituting vaping for smoking likely reduces health risks, possibly substantially.15 Dual use of cigarettes and e-cigarettes will not have a comparable beneficial effect.88 However, a period of dual use may be necessary for some smokers to transition from smoking. Because vaping itself poses some risk, the best advice is to eventually stop vaping as well.

The principal objections to vaping regard 3 potential effects on youths:

Vaping can cause nicotine addiction among young people who never would have tried smoking.

Vaping by never-smoking youths may cause some to try smoking, risking “renormalizing” smoking among young people.

Nicotine can harm developing brains, and vaping nicotine may have other adverse health effects.

Vaping as a Cause of Nicotine Addiction

Vaping likely addicts some young people to nicotine. However, the evidence does not suggest it is addicting very large numbers.89 Jarvis et al. concluded that “Data . . . do not provide support for claims of a new epidemic of nicotine addiction stemming from use of e-cigarettes.”90 Jackson et al. recently reported that the e-cigarette‒driven increase in nicotine product use among high-school students is not associated with an increase in population-level dependence.89 Among tobacco-naïve youths, in addition to low vaping prevalence (9.1% in the past 30 days in 2020) and frequency (2.3% vaping ≥ 20 days in the past 30 days),91 small percentages exhibited signs of nicotine dependence.90

Frequent use is much more common among current or former smoking youths than among never-smokers.90 Many former smokers were already addicted to nicotine before initiating vaping. With high-school students’ smoking declining at an increasing rate since youths began using e-cigarettes,92,93 some may vape to reduce or quit smoking.

Nonetheless, to the extent that vaping creates nicotine addiction among otherwise tobacco-naïve youths, concerted efforts are needed to reduce youth vaping. The new minimum age of 21 years for purchasing tobacco products should help.94 Governmental agencies3,95 and voluntary organizations12,96 disseminate vaping’s risks to youths through Web sites, social media, and television campaigns. Voluntary organizations lobby Congress and state governments to adopt policies restricting youth access to e-cigarettes.

Recent policy attention has focused on restricting the availability of e-cigarettes with flavors,97 a principal attraction for youths.98101 While flavor bans could reduce youth interest in e-cigarettes, they could also reduce adult smokers’ vaping to quit smoking.102104 Like youths, adults prefer nontobacco flavors,105 both groups favoring fruit and sweet flavors.106,107

Policies regarding flavors reflect the more general issue considered in this article: the need to create a balance between the sometimes-conflicting goals of preventing youth vaping and supporting adults’ smoking cessation attempts, particularly for smokers unable or unwilling to quit otherwise.108

Vaping Causing Smoking Initiation

Prospective studies have found that young people who had vaped but never smoked cigarettes were more likely to have tried cigarettes several months to 2 years later than contemporaries who had neither smoked nor vaped.15,109113 Some commentators thus consider vaping a “gateway” into smoking.114,115

Other observers believe the relationship reflects a “common liability”116: young people who vape are generally more prone to risky behavior117; hence, they might be more likely to try smoking even without vaping.118121 Three recent studies have concluded that vaping likely diverts more young people from smoking than encourages them to smoke.122124 Conversely, some prospective studies have found the vaping‒smoking relationship strongest in youths at low risk of smoking.125127

Obvious plausible correlates are often not considered, however.128 Importantly, few studies include youths’ use of other psychoactive substances, including marijuana and alcohol. In 1 study, inclusion of marijuana and 3 other variables eliminated the otherwise statistically significant link between vaping and subsequent smoking.126,127 Most studies do not even consider previous use of tobacco products other than cigarettes. Adjustment for confounders substantially reduces the relationship between vaping and subsequently trying cigarettes.129

Numbers of cigarettes smoked at follow-up are frequently very low, only 1 or 2 in the past 12 months in one study.130 Furthermore, the prospective studies generally have not examined progression to regular dependent smoking, with 1 recent exception.131 Only a small proportion of youths who experiment with smoking become regular smokers. Kim and Selya found that while e-cigarette use was associated with ever trying smoking, it was not associated with current continued smoking.119 Pierce et al. recently concluded the opposite.131 Shahab et al. reported that less than 1% of US students who initiated nicotine or tobacco use with e-cigarettes were established cigarette smokers.132

If vaping causes some young people to try cigarettes, the aggregate impact must be small. A recent study68 estimated that if vaping increases nonsmoking youths’ odds of trying cigarettes by 3.5 (as reported by Soneji et al.109), smoking initiation among young adults would increase less than 1 percentage point. Furthermore, US survey data demonstrate that smoking among young people has declined at its fastest rate ever during vaping’s ascendancy.92,93,133 If vaping increases smoking initiation, other unknown factors more than compensate.

Nicotine Harming Developing Brains

Animal model studies have found that nicotine can affect maturation of brain parts associated with executive function and decision-making, potentially leading to more impulsive behavior, cognitive deficits, and greater likelihood to self-administer other drugs.134,135 In addition, there is evidence in humans of neurological changes attributed to nicotine in the brains of adolescent smokers, interpreted by some as reflecting similar harmful effects to those in the animal models.136,137

These studies lead some researchers to suspect that adolescent nicotine use in any form may lead to long-term structural and functional brain changes with associated negative implications for cognition or impulse control.138 However, given species differences and questions about the relevance of experimental animal nicotine dosing paradigms to human use patterns, the validity of extrapolation to humans is speculative. Whether impaired brain development with behavioral consequences occurs in young nicotine consumers is difficult to determine because of potential confounding of genetic and socioeconomic factors, the influence of other substance abuse, and the role of preexisting neuropsychiatric problems associated with youth smoking. Research has yet to isolate nicotine use in the adolescent years and then examine later sequelae. Still, concerns about brain function effects of nicotine exposure through vaping deserve serious examination.98

Concerns About Youth Vaping in Context

Several considerations raise the question of whether, for youth as a whole, vaping creates dangerous levels of nicotine exposure that would not have occurred in the absence of vaping.

The large majority of nontobacco product‒using young people do not vape and, thus, have no nicotine exposure.90

Among those who vape, most do so infrequently; many are short-term experimenters.90

Frequent vaping is most common among current or former smokers, individuals already exposed to nicotine.91

The most dangerous form of youth exposure to nicotine, cigarette smoking, has declined at an unprecedented rate during the era of youth vaping.92,93,133 Use of other tobacco products has declined as well.139

Still, concerns emanating from substantial increases in youth vaping in 2018 and 2019 are readily understandable and important to address. A sizable decline in 2020 is encouraging.139 We must continue monitoring youth vaping, learning more about potential harms and identifying effective prevention strategies. However, as public health groups, the media, policymakers, and the general public focus on youth vaping, vaping’s potential to help adults quit smoking too often gets lost. That may come at a significant public health cost. Fourteen percent of US adults smoke; smoking annually causes nearly half a million deaths. Anything that can reduce that toll deserves serious attention.

With the focus on youths creating an environment in which smokers believe that vaping is as dangerous as or more dangerous than smoking,14 many smokers struggling to quit may be unwilling to try vaping as an alternative. This likely translates into less smoking cessation than if smokers correctly understood the relative risks of vaping and smoking.

Research comparing vaping’s risks for youths with potential benefits for adult smokers has found the latter to dominate,66 potentially avoiding the smoking-produced loss of tens of millions of life-years.67,68 Vaping cannot end cigarette smoking. But vaping can complement tried-and-true methods of reducing smoking, including taxes on combustible tobacco products, smoke-free workplace laws, marketing restrictions, plain packaging with graphic warning labels, antismoking media campaigns, tobacco-21 laws,94 and evidence-based smoking cessation treatment.88

We believe the potential lifesaving benefits of e-cigarettes for adult smokers deserve attention equal to the risks to youths.140 Millions of middle-aged and older smokers are at high risk of near-future disease and death. Quitting reduces risk.88 Young people will not experience smoking-related (and conceivably vaping-related) chronic diseases for 3 decades, and likely not at all if they quit within a decade or 2. Social pressures to quit smoking will probably remain strong, and quitting aids may improve. Furthermore, as noted previously, the rate of smoking among young people has declined while vaping has increased.92,93,133 Vaping may addict some youths to nicotine, but many fewer than popularly believed.89,90

Seeking a Sensible Mix of Policies

To date, the singular focus of US policies on decreasing youth vaping may well have reduced vaping’s potential contribution to reducing adult smoking. Those policies include taxing e-cigarettes at rates comparable to cigarette taxes,141 decreasing adult access to flavored e-cigarettes that may facilitate smoking cessation,103 and convincing the public—including smokers—that vaping is as dangerous as smoking.14

The public health objective should be to develop policies and interventions that both reduce youth vaping and increase adult smoking cessation.97,120,140,142 While an in-depth discussion of an optimal policy mix exceeds the scope of this article, we here present illustrative policies that would serve this objective. These are all in addition to conventional evidence-based prevention and cessation measures.

Tax cigarettes and other combustible tobacco products heavily; impose a more modest tax on e-cigarettes. Taxes should be proportionate to risk. A much higher tax on combustibles will encourage adult smokers to quit smoking or to switch to less expensive e-cigarettes. By raising the price of e-cigarettes, a modest tax will discourage their use by price-sensitive youths.141

Because both youth and adult smokers find e-cigarette flavors attractive,98   –107 banning all (or most) flavors risks reducing smokers’ use of e-cigarettes to quit smoking102104 at the same time that it reduces youth vaping.99,101 An alternative would be to limit the retail sale of flavored e-cigarettes to adult-only outlets such as vape shops. An imperfect policy for either goal, this approach could benefit both.

Government agencies and health organizations should develop nuanced, targeted communications that emphasize the realistic concerns about youth vaping and, separately, the potential benefits of e-cigarettes as less-risky (but not risk-free) alternatives for adult smokers otherwise unable or unwilling to quit smoking.

The US Food and Drug Administration (FDA) should strictly regulate e-cigarette advertising and marketing, prohibiting all marketing directed at, or attractive to, youths and young adults, including all “lifestyle” advertising. They should limit advertising to a “switch” theme directed clearly, and exclusively, to adult smokers otherwise unable to quit smoking.

FDA should implement its thoughtful comprehensive 2017 plan,143 mandating reduction of nicotine in cigarettes to levels incapable of sustaining addiction, while ensuring the availability of consumer-acceptable reduced-risk nicotine products. To achieve the latter, the agency should develop product standards for products like e-cigarettes, ensuring minimization of risk associated with the product class while maintaining consumer acceptability.

The Role of Nicotine in Tobacco-Produced Disease

FDA predicated its comprehensive plan on recognition of the continuum of risk in nicotine products.143 Nicotine is the chemical in tobacco that fosters addiction. However, toxic constituents other than nicotine, predominantly in smoked tobacco, produce the disease resulting from chronic tobacco use.143,144 Nicotine-yielding products vary in risk from FDA-approved nicotine replacement therapy products at the lowest end of the risk continuum to combustible cigarettes at the highest.

Unfortunately, the public has a distorted view of the dangers associated with nicotine per se. In a recent survey, 57% of respondents incorrectly agreed that “nicotine in cigarettes is the substance that causes most of the cancer caused by smoking.” Only 18.9% disagreed. (The rest answered “Don’t know.”)14 In a recent survey of physicians, 80% strongly, but incorrectly, agreed that nicotine causes cancer, cardiovascular disease, and chronic obstructive pulmonary disease.145

We share the very legitimate concerns about youth vaping with the entire field of public health. Our goal is to put those concerns in perspective. We agree with former Surgeon General C. Everett Koop who, in 1998, urged that “[A]s we take every action to save our children from the ravages of tobacco, we should demonstrate that our commitment to those who are already addicted . . . will never expire.”146 The latter appears at risk today.

While evidence suggests that vaping is currently increasing smoking cessation, the impact could be much larger if the public health community paid serious attention to vaping’s potential to help adult smokers, smokers received accurate information about the relative risks of vaping and smoking, and policies were designed with the potential effects on smokers in mind. That is not happening.

The need to pay attention to adult smokers is particularly important from a social justice perspective. African Americans suffer disproportionately from smoking-related deaths, a disparity that, a new clinical trial shows, vaping could reduce.31 Today’s smokers come disproportionately from lower education and income groups, the LGBTQ (lesbian, gay, bisexual, transgender, and queer or questioning) community,147 and populations suffering from mental health conditions148 and from other drug addictions.149 Smoking accounts for a significant proportion of the large life expectancy difference between affluent and poorer Americans.150,151 For smokers with serious psychological distress, two thirds of their 15-year loss of life expectancy compared with nonsmokers without serious psychological distress may be attributable to their smoking.152 Vaping might assist more of these smokers to quit.148,153

To the more privileged members of society, today’s smokers may be nearly invisible. Indeed, many affluent, educated US persons may believe the problem of smoking has been largely “solved.” They do not smoke. Their friends and colleagues do not smoke. There is no smoking in their workplaces, nor in the restaurants and bars they frequent. Yet 1 of every 7 US adults remains a smoker today.

Smoking will claim the lives of 480 000 of our fellow citizens this year alone.

See also Samet and Barrington-Trimis, p. 1572.


The paper was presented by K. E. Warner at the E-Cigarette Summit: Science, Regulation & Public Health, USA Virtual Summit, May 25, 2021.

The authors are former presidents of the Society for Research on Nicotine and Tobacco (SRNT), the world’s leading professional organization dedicated to the subject. They are listed in alphabetical order. All 26 of the then‒past presidents were invited to participate as co-authors of this article. (A 27th past president was the active president at the time of preparation of the article.) We were unable to reach one of them. Three were not included because of institutional commitments that they felt might be interpreted as conflicts of interest. The remaining 7 declined to co-author.

Note. The opinions expressed in this article are solely those of the authors. They do not represent those of SRNT, which has taken no organizational position on the issues discussed in this article and had no involvement in the preparation of this article.


N. L. Benowitz is a consultant to Pfizer and Achieve Life Sciences, companies that market or are developing smoking cessation medications, and has been an expert witness in litigation against tobacco companies. S. J. Leischow is conducting a clinical trial supported by Achieve Life Sciences, which is developing a nonnicotine medication for smoking cessation, and has consulted with them. He also consulted more than 1 year ago for GSK, which is working to bring a new nicotine-replacement product to market, and he receives medication for a National Institutes of Health– funded smoking-cessation study from Pfizer. N. A. Rigotti receives royalties from UpToDate Inc for writing about smoking cessation and e-cigarettes and is a consultant for Achieve Life Sciences for an investigational smoking-cessation medication. R. West has undertaken research and consultancy for Pfizer and GSK, companies that manufacture smoking-cessation medications.


There were no human participants involved.


1. Glantz SA, Bareham DW. E-cigarettes: use, effects on smoking, risks, and policy implications. Annu Rev Public Health. 2018;39(1):215235. Crossref, MedlineGoogle Scholar
2. Abrams DB, Glasser AM, Pearson JL, Villanti AC, Collins LK, Niaura RS. Harm minimization and tobacco control: reframing societal views of nicotine use to rapidly save lives. Annu Rev Public Health. 2018;39(1):193213. Crossref, MedlineGoogle Scholar
3. Centers for Disease Control and Prevention. Quick facts on the risks of e-cigarettes for kids, teens, and young adults. Available at: Accessed December 9, 2020. Google Scholar
4. California Department of Public Health. Vaping devices, electronic cigarettes (e-cigarettes): pod-based devices. Available at: Accessed December 26, 2020. Google Scholar
5. New York State Department of Health. Get the facts—electronic cigarettes (e-cigarettes) and similar vapor products. Available at: Accessed December 26, 2020. Google Scholar
6. New York City Health Department. E-cigarettes. Available at: Accessed December 26, 2020. Google Scholar
7. American Medical Association. E-cigarettes and vaping: a public health epidemic. September 18, 2019. Available at: Accessed December 9, 2020. Google Scholar
8. Jenssen BP, Walley SC; Section on Tobacco Control. E-cigarettes and similar devices. Pediatrics. 2019;143(2):e20183652. Crossref, MedlineGoogle Scholar
9. American Cancer Society. American Cancer Society position statement on electronic cigarettes. Available at: Accessed December 26, 2020. Google Scholar
10. American Heart Association. The ugly truth about vaping. Available at: Accessed December 26, 2020. Google Scholar
11. American Lung Association. E-cigarettes. Available at: Accessed December 26, 2020. Google Scholar
12. Campaign for Tobacco-Free Kids. Electronic cigarettes and youth. September 16, 2020. Available at: Accessed December 9, 2020. Google Scholar
13. Wackowski OA, Sontag JM, Singh B, et al. From the Deeming Rule to JUUL—US news coverage of electronic cigarettes, 2015‒2018. Nicotine Tob Res. 2020;22(10):18161822. Crossref, MedlineGoogle Scholar
14. National Cancer Institute. Health Information National Trends Survey. HINTS 5 cycle 3, 2019. Available at: Accessed December 13, 2020. Google Scholar
15. National Academies of Sciences, Engineering, and Medicine. Public Health Consequences of E-Cigarettes. The National Academies Press. 2018. Available at: Accessed December 9, 2020. Google Scholar
16. Royal College of Physicians. RCP advice on vaping following reported cases of deaths and lung disease in the US. Available at: Accessed December 9, 2020. Google Scholar
17. Centers for Disease Control and Prevention. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. Available at: Accessed December 26, 2020. Google Scholar
18. Campaign for Tobacco Free Kids. States & localities that have restricted the sale of flavored tobacco products. October 23, 2020. Available at Accessed December 15, 2020. Google Scholar
19. Krishnasamy VP, Hallowell BD, Ko JY, et al. Update: characteristics of a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury—United States, August 2019‒January 2020. MMWR Morb Mortal Wkly Rep. 2020;24;69(3):9094. Crossref, MedlineGoogle Scholar
20. Blount BC, Karwowski MP, Shields PG, et al. Vitamin E acetate in bronchoalveolar-lavage fluid associated with EVALI. N Engl J Med. 2020;382(8):697705. Crossref, MedlineGoogle Scholar
21. Muthumalage T, Lucas JH, Wang Q, Lamb T, McGraw MD, Rahman I. Pulmonary toxicity and inflammatory response of e-cigarette vape cartridges containing medium-chain triglycerides oil and vitamin E acetate: implications in the pathogenesis of EVALI. Toxics. 2020;8(3):46. CrossrefGoogle Scholar
22. Ghinai I, Navon L, Gunn JKL, et al. Characteristics of persons who report using only nicotine-containing products among interviewed patients with e-cigarette, or vaping, product use-associated lung injury—Illinois, August‒December 2019. MMWR Morb Mortal Wkly Rep. 2020;69 (3):8489. Crossref, MedlineGoogle Scholar
23. Wilson S. E-cigarettes increasingly blamed for lung illnesses, as evidence points elsewhere. Morning Consult. February 5, 2020. Available at: Accessed December 9, 2020. Google Scholar
24. Fairchild AL, Bayer R, Lee JS. The e-cigarette debate: what counts as evidence? Am J Public Health. 2019;109(7):10001006. LinkGoogle Scholar
25. Carroll DM, Denlinger-Apte RL, Dermody SS, et al. Polarization within the field of tobacco and nicotine science and its potential impact on trainees. Nicotine Tob Res. 2021;23(1):3639. Crossref, MedlineGoogle Scholar
26. Polosa R, O’Leary R, Tashkin D, Emma R, Caruso M. The effect of e-cigarette aerosol emissions on respiratory health: a narrative review. Expert Rev Respir Med. 2019;13(9):899915. Crossref, MedlineGoogle Scholar
27. Wills TA, Soneji SS, Choi K, Jaspers I, Tam EK. E-cigarette use and respiratory disorders: an integrative review of converging evidence from epidemiological and laboratory studies. Eur Respir J. 2021;57(1):1901815. Crossref, MedlineGoogle Scholar
28. Polosa R, Morjaria J, Caponnetto P, et al. Effect of smoking abstinence and reduction in asthmatic smokers switching to electronic cigarettes: evidence for harm reversal. Int J Environ Res Public Health. 2014;11(5):49654977. Crossref, MedlineGoogle Scholar
29. Polosa R, Morjaria JB, Prosperini U, et al. COPD smokers who switched to e-cigarettes: health outcomes at 5-year follow up. Ther Adv Chronic Dis. 2020;11:2040622320961617. CrossrefGoogle Scholar
30. Campagna D, Cibella F, Caponnetto P, et al. Changes in breathomics from a 1-year randomized smoking cessation trial of electronic cigarettes. Eur J Clin Invest. 2016;46(8):698706. Crossref, MedlineGoogle Scholar
31. Pulvers K, Nollen NL, Rice M, et al. Effect of pod e-cigarettes vs cigarettes on carcinogen exposure among African American and Latinx smokers: a randomized clinical trial. JAMA Netw Open. 2020;3(11):e2026324. Crossref, MedlineGoogle Scholar
32. Gotts JE, Jordt SE, McConnell R, Tarran R. What are the respiratory effects of e-cigarettes [erratum in BMJ. 2019;367:l5980]? BMJ. 2019;366:l5275. Crossref, MedlineGoogle Scholar
33. Fetterman JL, Keith RJ, Palmisano JN, et al. Alterations in vascular function associated with the use of combustible and electronic cigarettes. J Am Heart Assoc. 2020;9(9):e014570. Crossref, MedlineGoogle Scholar
34. George J, Hussain M, Vadiveloo T, et al. Cardiovascular effects of switching from tobacco cigarettes to electronic cigarettes. J Am Coll Cardiol. 2019;74(25):31123120. Crossref, MedlineGoogle Scholar
35. MacDonald A, Middlekauff HR. Electronic cigarettes and cardiovascular health: what do we know so far? Vasc Health Risk Manag. 2019;15:159174. Crossref, MedlineGoogle Scholar
36. Stokes AC, Xie W, Wilson AE, et al. Association of cigarette and electronic cigarette use patterns with levels of inflammatory and oxidative stress biomarkers among US adults: Population Assessment of Tobacco and Health Study. Circulation. 2021;143(8):869871. Crossref, MedlineGoogle Scholar
37. Canistro D, Vivarelli F, Cirillo S, et al. E-cigarettes induce toxicological effects that can raise the cancer risk. Sci Rep. 2017;7(1):2028. Crossref, MedlineGoogle Scholar
38. Tommasi S, Caliri AW, Caceres A, et al. Deregulation of biologically significant genes and associated molecular pathways in the oral epithelium of electronic cigarette users. Int J Mol Sci. 2019;20(3):738. CrossrefGoogle Scholar
39. Rodgman A, Perfetti TA. The Chemical Components of Tobacco and Tobacco Smoke. 2nd ed. Boca Raton, FL: CRC Press; 2013. CrossrefGoogle Scholar
40. US Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2010. Available at: Accessed December 9, 2020. Google Scholar
41. Sleiman M, Logue JM, Montesinos VN, et al. Emissions from electronic cigarettes: key parameters affecting the release of harmful chemicals. Environ Sci Technol. 2016;50(17):96449651. Crossref, MedlineGoogle Scholar
42. Goniewicz ML, Knysak J, Gawron M, et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014;23 (2):133139. Crossref, MedlineGoogle Scholar
43. Belushkin M, Tafin Djoko D, Esposito M, et al. Selected harmful and potentially harmful constituents levels in commercial e-cigarettes. Chem Res Toxicol. 2020;33(2):657668. Crossref, MedlineGoogle Scholar
44. Margham J, McAdam K, Forster M, et al. Chemical composition of aerosol from an e-cigarette: a quantitative comparison with cigarette smoke. Chem Res Toxicol. 2016;29(10):16621678. Crossref, MedlineGoogle Scholar
45. Wei B, O’Connor RJ, Goniewicz ML, Hyland A. Emerging chemicals of health concern in electronic nicotine delivery systems. Chem Res Toxicol. 2020;33(10):26372646. Crossref, MedlineGoogle Scholar
46. Cravo AS, Bush J, Sharma G, et al. A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks. Regul Toxicol Pharmacol. 2016;81(suppl 1):S1S14. Crossref, MedlineGoogle Scholar
47. D’Ruiz CD, Graff DW, Robinson E. Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes. BMC Public Health. 2016;16(1):543. Crossref, MedlineGoogle Scholar
48. Goniewicz ML, Gawron M, Smith DM, Peng M, Jacob P3rd, Benowitz NL. Exposure to nicotine and selected toxicants in cigarette smokers who switched to electronic cigarettes: a longitudinal within-subjects observational study. Nicotine Tob Res. 2017;19(2):160167. Crossref, MedlineGoogle Scholar
49. Shahab L, Goniewicz ML, Blount BC, et al. Nicotine, carcinogen, and toxin exposure in long-term e-cigarette and nicotine replacement therapy users: a cross-sectional study. Ann Intern Med. 2017;166(6):390400. Crossref, MedlineGoogle Scholar
50. St Helen G, Liakoni E, Nardone N, Addo N, Jacob P3rd, Benowitz NL. Comparison of systemic exposure to toxic and/or carcinogenic volatile organic compounds (VOC) during vaping, smoking, and abstention. Cancer Prev Res (Phila). 2020;13(2):153162. Crossref, MedlineGoogle Scholar
51. Cassidy RN, Tidey JW, Colby SM. Exclusive e-cigarette users report lower levels of respiratory symptoms relative to dual e-cigarette and cigarette users. Nicotine Tob Res. 2020;22(suppl 1):S54S60. Crossref, MedlineGoogle Scholar
52. Eissenberg T, Bhatnagar A, Chapman S, Jordt S-E, Shihadeh A, Soule EK. Invalidity of an oft-cited estimate of the relative harms of electronic cigarettes. Am J Public Health. 2020;110(2):161162. LinkGoogle Scholar
53. Hartmann-Boyce J, McRobbie H, Lindson N, et al. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2020;10(10):CD010216. MedlineGoogle Scholar
54. McNeill A, Brose LS, Calder R, Simonavicius E, Robson D. Vaping in England: An Evidence Update Including Vaping for Smoking Cessation, February 2021. A Report Commissioned by Public Health England. Public Health England. 2021. Available at: Accessed March 6, 2021. Google Scholar
55. Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019;380(7):629637. Crossref, MedlineGoogle Scholar
56. Walker N, Parag V, Verbiest M, Laking G, Laugesen M, Bullen C. Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial. Lancet Respir Med. 2020;8(1):5464. Crossref, MedlineGoogle Scholar
57. Grabovac I, Oberndorfer M, Fischer J, Wiesinger W, Haider S, Dorner TE. Effectiveness of electronic cigarettes in smoking cessation: a systematic review and meta-analysis. Nicotine Tob Res. 2021;23(4):625634. Crossref, MedlineGoogle Scholar
58. US Preventive Services Task Force, Krist AH, Davidson KW, et al. Interventions for tobacco smoking cessation in adults, including pregnant persons: US Preventive Services Task Force recommendation statement. JAMA. 2021;325(3):265279. Crossref, MedlineGoogle Scholar
59. Caraballo RS, Shafer PR, Patel D, Davis KC, McAfee TA. Quit methods used by US adult cigarette smokers, 2014–2016. Prev Chronic Dis. 2017;14:E32. Crossref, MedlineGoogle Scholar
60. West R, Shahab L, Brown J. Estimating the population impact of e-cigarettes on smoking cessation in England. Addiction. 2016;111(6):11181119. Crossref, MedlineGoogle Scholar
61. Beard E, West R, Michie S, Brown J. Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: time series analysis of population trends. BMJ. 2016;354:i4645. Crossref, MedlineGoogle Scholar
62. Beard E, West R, Michie S, Brown J. Association of prevalence of electronic cigarette use with smoking cessation and cigarette consumption in England: a time–series analysis between 2006 and 2017. Addiction. 2020;115(5):961974. Crossref, MedlineGoogle Scholar
63. Zhu SH, Zhuang YL, Wong S, Cummins SE, Tedeschi GJ. E-cigarette use and associated changes in population smoking cessation: evidence from US current population surveys. BMJ. 2017;358:j3262. Crossref, MedlineGoogle Scholar
64. Walton K, Wang TW, Prutzman Y, Jamal A, Babb SD. Characteristics and correlates of recent successful cessation among adult cigarette smokers, United States, 2018. Prev Chronic Dis. 2020;17:E154. Crossref, MedlineGoogle Scholar
65. Jackson SE, Kotz D, West R, Brown J. Moderators of real-world effectiveness of smoking cessation aids: a population study. Addiction. 2019;114(9):16271638. Crossref, MedlineGoogle Scholar
66. Lee PN, Abrams D, Bachand A, et al. Estimating the population health impact of recently introduced modified risk tobacco products: a comparison of different approaches. Nicotine Tob Res. 2021;23(3):426437. Crossref, MedlineGoogle Scholar
67. Levy DT, Borland R, Lindblom EN, et al. Potential deaths averted in USA by replacing cigarettes with e-cigarettes. Tob Control. 2018;27(1):1825. Crossref, MedlineGoogle Scholar
68. Mendez D, Warner KE. A magic bullet? The potential impact of e-cigarettes on the toll of cigarette smoking. Nicotine Tob Res. 2021;23(4):654661. Crossref, MedlineGoogle Scholar
69. Levy DT, Sanchez-Romero LM, Li Y, et al. England SimSmoke: the impact of nicotine vaping on smoking prevalence and smoking-attributable deaths in England. Addiction. 2021;116(5):11961211. Crossref, MedlineGoogle Scholar
70. Levy DT, Yuan Z, Luo Y, Abrams DB. The relationship of e-cigarette use to cigarette quit attempts and cessation: insights from a large, nationally representative US survey. Nicotine Tob Res. 2018;20(8):931939. Crossref, MedlineGoogle Scholar
71. Giovenco DP, Delnevo CD. Prevalence of population smoking cessation by electronic cigarette use status in a national sample of recent smokers. Addict Behav. 2018;76:129134. Crossref, MedlineGoogle Scholar
72. Berry KM, Reynolds LM, Collins JM, et al. E-cigarette initiation and associated changes in smoking cessation and reduction: the Population Assessment of Tobacco and Health Study, 2013–2015. Tob Control. 2019;28(1):4249. MedlineGoogle Scholar
73. Kalkhoran S, Chang Y, Rigotti NA. Electronic cigarette use and cigarette abstinence over 2 years among US smokers in the Population Assessment of Tobacco and Health study. Nicotine Tob Res. 2020;22(5):728733. Crossref, MedlineGoogle Scholar
74. Glasser AM, Vojjala M, Cantrell J, et al. Patterns of e-cigarette use and subsequent cigarette smoking cessation over two years (2013/2014 to 2015/2016) in the Population Assessment of Tobacco and Health (PATH) Study. Nicotine Tob Res. 2021;23(4):669677. Crossref, MedlineGoogle Scholar
75. Wang RJ, Bhadriraju S, Glantz SA. E-cigarette use and adult cigarette smoking cessation: a meta-analysis. Am J Public Health. 2021;111(2):230246. LinkGoogle Scholar
76. Villanti AC, Feirman SP, Niaura RS, et al. How do we determine the impact of e-cigarettes on cigarette smoking cessation or reduction? Review and recommendations for answering the research question with scientific rigor. Addiction. 2018;113(3):391404. Crossref, MedlineGoogle Scholar
77. Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med. 2016;4(2):116128. Crossref, MedlineGoogle Scholar
78. WHO Study Group on Tobacco Product Regulation. Report on the Scientific Basis of Tobacco Product Regulation: Seventh Report of a WHO Study Group. WHO Technical Report Series, No. 1015. World Health Organization. 2019. Available at: Accessed December 10, 2020. Google Scholar
79. Higgins JPT, Thomas J, Chandler J, et al., eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 6.1. Cochrane. 2020. Available at: Accessed December 10, 2020. Google Scholar
80. Jain G, Sangha M, Mittal P. Global tobacco. US nicotine industry model 2020. Figures 1 and 2. London, England: Barclays Bank; 2020. Google Scholar
81. Pesko MF, Courtemanche CJ, Maclean JC. The effects of traditional cigarette and e-cigarette tax rates on adult tobacco product use. J Risk Uncertain. 2020;60(3):229258. Crossref, MedlineGoogle Scholar
82. Cotti CD, Courtemanche CJ, Maclean JC, Nesson ET, Pesko MF, Tefft N. The effects of e-cigarette taxes on e-cigarette prices and tobacco product sales: evidence from retail panel data. NBER Working Paper 26724. Cambridge, MA: National Bureau of Economic Research; August 2020. Google Scholar
83. Simonavicius E, McNeill A, Shahab L, et al. Heat-not-burn tobacco products: a systematic literature review. Tob Control. 2019;28(5):582594. Crossref, MedlineGoogle Scholar
84. Cummings KM, Nahhas GJ, Sweanor DT. What is accounting for the rapid decline in cigarette sales in Japan? Int J Environ Res Public Health. 2020;17 (10):3570. CrossrefGoogle Scholar
85. Saffer H, Dench DL, Grossman M, Dave DM. E-cigarettes and adult smoking: evidence from Minnesota. NBER Working Paper No. 26589. National Bureau of Economic Research. December 2019. Available at: Accessed December 9, 2020. Google Scholar
86. Friedman AS. How does electronic cigarette access affect adolescent smoking? J Health Econ. 2015;44:300308. Crossref, MedlineGoogle Scholar
87. Pesko MF, Hughes JM, Faisal FS. The influence of electronic cigarette age purchasing restrictions on adolescent tobacco and marijuana use. Prev Med. 2016;87:207212. Crossref, MedlineGoogle Scholar
88. US Department of Health and Human Services. Smoking Cessation: A Report of the Surgeon General. Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2020. Available at: Accessed December 10, 2020. Google Scholar
89. Jackson SE, Brown J, Jarvis MJ. Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use. Addiction. 2021;116(7):18591870. Crossref, MedlineGoogle Scholar
90. Jarvis M, Jackson S, West R, Brown J. Epidemic of youth nicotine addiction? What does the National Youth Tobacco Survey 2017‒2019 reveal about high school e-cigarette use in the USA? Preprint. Posted online September 2, 2020. Qeios. Google Scholar
91. Centers for Disease Control and Prevention. National Youth Tobacco Survey, 2020. Available at: Accessed December 27, 2020. Google Scholar
92. Levy DT, Warner KE, Cummings KM, et al. Examining the relationship of vaping to smoking initiation among US youth and young adults: a reality check. Tob Control. 2019;28(6):629635. Crossref, MedlineGoogle Scholar
93. Meza R, Jimenez-Mendoza E, Levy DT. Trends in tobacco use among adolescents by grade, sex, and race, 1991‒2019. JAMA Netw Open. 2020;3(12):e2027465. Crossref, MedlineGoogle Scholar
94. Liber AC, Xue Z, Cahn Z, Drope J, Stoklosa M. Tobacco 21 adoption decreased sales of cigarette brands purchased by young people: a translation of population health survey data to gain insight into market data for policy analysis. Tob Control. 2020; epub ahead of print December 3, 2020. CrossrefGoogle Scholar
95. US Food and Drug Administration. The Real Cost Campaign. Available at: Accessed December 10, 2020. Google Scholar
96. truth initiative. Emerging tobacco products. Available at: Accessed December 10, 2020. Google Scholar
97. Sindelar JL. Regulating vaping—policies, possibilities, and perils. N Engl J Med. 2020;382(20):e54. Crossref, MedlineGoogle Scholar
98. US Department of Health and Human Services. E-Cigarette Use Among Youth and Young Adults. A Report of the Surgeon General. Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2016. Available at: Accessed December 9, 2020. Google Scholar
99. Leventhal AM, Goldenson NI, Cho J, et al. Flavored e-cigarette use and progression of vaping in adolescents. Pediatrics. 2019;144(5):e20190789. Crossref, MedlineGoogle Scholar
100. Schneller LM, Bansal-Travers M, Goniewicz ML, McIntosh S, Ossip D, O’Connor RJ. Use of flavored e-cigarettes and the type of e-cigarette devices used among adults and youth in the US—results from wave 3 of the Population Assessment of Tobacco and Health Study (2015–2016). Int J Environ Res Public Health. 2019;16(16):2991. CrossrefGoogle Scholar
101. King BA. Flavors are a major driver of the youth e-cigarette epidemic. Am J Public Health. 2020;110(6):773774. LinkGoogle Scholar
102. Russell C, McKeganey N, Dickson T, Nides M. Changing patterns of first e-cigarette flavor used and current flavors used by 20,836 adult frequent e-cigarette users in the USA. Harm Reduct J. 2018;15(1):33. Crossref, MedlineGoogle Scholar
103. Friedman AS, Xu S. Associations of flavored e-cigarette uptake with subsequent smoking initiation and cessation. JAMA Netw Open. 2020;3(6):e203826. Crossref, MedlineGoogle Scholar
104. Li L, Borland R, Cummings KM, et al. How does the use of flavored nicotine vaping products relate to progression towards quitting smoking? Findings from the 2016 and 2018 ITC 4CV Surveys. Nicotine Tob Res. 2021;ntab033; e-pub ahead of print February 25, 2021. Google Scholar
105. Meernik C, Baker HM, Kowitt SD, et al. Impact of non-menthol flavours in e-cigarettes on perceptions and use: an updated systematic review. BMJ Open. 2019;9(10):e031598. Crossref, MedlineGoogle Scholar
106. Du P, Bascom R, Fan T, et al. Changes in flavor preference in a cohort of long-term electronic cigarette users. Ann Am Thorac Soc. 2020;17(5):573581. Crossref, MedlineGoogle Scholar
107. Wang TW, Neff LJ, Park-Lee E, Ren C, Cullen KA, King BA. E-cigarette use among middle and high school students—United States, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(37):13101312. Crossref, MedlineGoogle Scholar
108. Warner KE. How to think—not feel—about tobacco harm reduction. Nicotine Tob Res. 2019;21(10):12991309. Crossref, MedlineGoogle Scholar
109. Soneji S, Barrington-Trimis JL, Wills TA, et al. Association between initial use of e-cigarettes and subsequent cigarette smoking among adolescents and young adults: a systematic review and meta-analysis. JAMA Pediatr. 2017;171(8):788797. Crossref, MedlineGoogle Scholar
110. Glasser A, Abudayyeh H, Cantrell J, Niaura R. Patterns of e-cigarette use among youth and young adults: review of the impact of e-cigarettes on cigarette smoking. Nicotine Tob Res. 2019;21(10):13201330. Crossref, MedlineGoogle Scholar
111. Chan GCK, Stjepanović D, Lim C, et al. Gateway or common liability? A systematic review and meta‐analysis of studies of adolescent e‐cigarette use and future smoking initiation. Addiction. 2021;116(4):743756. Crossref, MedlineGoogle Scholar
112. Khouja JN, Suddell SF, Peters SE, Taylor AE, Munafo MR. Is e-cigarette use in non-smoking young adults associated with later smoking? A systematic review and meta-analysis. Tob Control. 2021;30(1):815. CrossrefGoogle Scholar
113. Keller-Hamilton B, Lu B, Roberts ME, Berman ML, Root ED, Ferketich AK. Electronic cigarette use and risk of cigarette and smokeless tobacco initiation among adolescent boys: a propensity score matched analysis. Addict Behav. 2021;114:106770. Crossref, MedlineGoogle Scholar
114. Bell K, Keane H. All gates lead to smoking: The “gateway theory,” e-cigarettes and the remaking of nicotine. Soc Sci Med. 2014;119:4552. Crossref, MedlineGoogle Scholar
115. Chapman S, Bareham D, Maziak W. The gateway effect of e-cigarettes: reflections on main criticisms. Nicotine Tob Res. 2019;21(5):695698. Crossref, MedlineGoogle Scholar
116. Vanyukov MM, Tarter RE, Kirillova GP, et al. Common liability to addiction and “gateway hypothesis”: theoretical, empirical and evolutionary perspective. Drug Alcohol Depend. 2012;123(suppl 1):S3S17. Crossref, MedlineGoogle Scholar
117. Gilbert PA, Kava CM, Afifi R. High-school students rarely use e-cigarettes alone: a sociodemographic analysis of polysubstance use among adolescents in the United States. Nicotine Tob Res. 2021;23(3):505510. Crossref, MedlineGoogle Scholar
118. Etter J-F. Gateway effects and electronic cigarettes. Addiction. 2018;113(10):17761783. Crossref, MedlineGoogle Scholar
119. Kim S, Selya AS. The relationship between electronic cigarette use and conventional cigarette smoking is largely attributable to shared risk factors. Nicotine Tob Res. 2020;22(7):11231130. Crossref, MedlineGoogle Scholar
120. Mendelsohn CP, Hall W. Does the gateway theory justify a ban on nicotine vaping in Australia? Int J Drug Policy. 2020;78:102712. Crossref, MedlineGoogle Scholar
121. Khouja JN, Wootton RE, Taylor AE, Smith GD, Munafò MR. Association of genetic liability to smoking initiation with e-cigarette use in young adults: a cohort study. PLoS Med. 2021;18(3):e1003555. Crossref, MedlineGoogle Scholar
122. Foxon F, Selya AS. Electronic cigarettes, nicotine use trends and use initiation ages among US adolescents from 1999 to 2018. Addiction. 2020;115(12):23692378. Crossref, MedlineGoogle Scholar
123. Selya AS, Foxon F. Trends in electronic cigarette use and conventional smoking: quantifying a possible “diversion” effect among US adolescents. Addiction. 2021;116(7):18481858. Crossref, MedlineGoogle Scholar
124. Sokol NA, Feldman JM. 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. 2021:ntab102; e-pub ahead of print May 15, 2021. Crossref, MedlineGoogle Scholar
125. Barrington-Trimis JL, Urman R, Berhane K, et al. E-cigarettes and future cigarette use. Pediatrics. 2016;138(1):e20160379. Crossref, MedlineGoogle Scholar
126. Wills TA, Gibbons FX, Sargent JD, Schweitzer RJ. How is the effect of adolescent e-cigarette use on smoking onset mediated: a longitudinal analysis. Psychol Addict Behav. 2016;30(8):876886. Crossref, MedlineGoogle Scholar
127. Wills TA, Knight R, Sargent JD, Gibbons FX, Pagano I, Williams RJ. Longitudinal study of e-cigarette use and onset of cigarette smoking among high school students in Hawaii. Tob Control. 2017;26(1):3439. Crossref, MedlineGoogle Scholar
128. Kozlowski LT, Warner KE. Adolescents and e-cigarettes: objects of concern may appear larger than they are. Drug Alcohol Depend. 2017;174:209214. Crossref, MedlineGoogle Scholar
129. Lee P, Fry J. Investigating gateway effects using the PATH study. F1000Res. 2019;8:264. Crossref, MedlineGoogle Scholar
130. Miech R, Patrick ME, O’Malley PM, Johnston LD. E-cigarette use as a predictor of cigarette smoking: results from a 1-year follow-up of a national sample of 12th grade students. Tob Control. 2017;26(e2):e106e111. Crossref, MedlineGoogle Scholar
131. Pierce JP, Chen R, Leas EC, et al. Use of e-cigarettes and other tobacco products and progression to daily cigarette smoking. Pediatrics. 2021;147(2):e2020025122. Crossref, MedlineGoogle Scholar
132. Shahab L, Beard E, Brown J. Association of initial e-cigarette and other tobacco product use with subsequent cigarette smoking in adolescents: a cross-sectional, matched control study. Tob Control. 2021;30(2):212220. Crossref, MedlineGoogle Scholar
133. Monitoring the Future. National adolescent drug trends press release: text and tables. Table 3. Trends in 30-day prevalence of use of various drugs in grades 8, 10, and 12. Available at: Accessed December 9, 2020. Google Scholar
134. England LJ, Aagaard K, Bloch M, et al. Developmental toxicity of nicotine: a transdisciplinary synthesis and implications for emerging tobacco products. Neurosci Biobehav Rev. 2017;72:176189. Crossref, MedlineGoogle Scholar
135. Thorpe HHA, Hamidullah S, Jenkins BW, Khokhar JY. Adolescent neurodevelopment and substance use: receptor expression and behavioral consequences. Pharmacol Ther. 2020;206:107431. Crossref, MedlineGoogle Scholar
136. Yuan M, Cross SJ, Loughlin SE, Leslie FM. Nicotine and the adolescent brain. J Physiol. 2015;593(16):33973412. Crossref, MedlineGoogle Scholar
137. Ren M, Lotfipour S. Nicotine gateway effects on adolescent substance use. West J Emerg Med. 2019;20(5):696709. Crossref, MedlineGoogle Scholar
138. Leslie FM. Unique, long-term effects of nicotine on adolescent brain. Pharmacol Biochem Behav. 2020;197:173010. Crossref, MedlineGoogle Scholar
139. Gentzke AS, Wang TW, Jamal A, et al. Tobacco product use among middle and high school students—United States, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(50):18811888. Crossref, MedlineGoogle Scholar
140. Miller TJ. The harm-reduction quandary of reducing adult smoking while dissuading youth initiation. Am J Public Health. 2020;110(6):788789. LinkGoogle Scholar
141. Chaloupka FJ, Sweanor D, Warner KE. Differential taxes for differential risks—toward reduced harm from nicotine-yielding products. N Engl J Med. 2015;373(7):594597. Crossref, MedlineGoogle Scholar
142. Ashley DL, Spears CA, Weaver SR, Huang J, Eriksen MP. E-cigarettes: how can they help smokers quit without addicting a new generation? Prev Med. 2020;140:106145. Crossref, MedlineGoogle Scholar
143. Gottlieb S, Zeller M. A nicotine-focused framework for public health. N Engl J Med. 2017;377 (12):11111114. Crossref, MedlineGoogle Scholar
144. US Department of Health and Human Services. The Health Consequences of Smoking: 50 Years of Progress. A Report of the Surgeon General. Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2014. Available at: Accessed December 13, 2020. Google Scholar
145. Steinberg MB, Bover Manderski MT, Wackowski OA, Singh B, Strasser AA, Delnevo CD. Nicotine risk misperception among US physicians. J Gen Intern Med. 2020; epub ahead of print September 1, 2020. CrossrefGoogle Scholar
146. Koop CE. Don’t forget the smokers. Washington Post. March 8, 1998. Available at: Accessed December 9, 2020. Google Scholar
147. Caputi TL, Smith LR, Strathdee SA, Ayers JW. Substance use among lesbian, gay, bisexual, and questioning adolescents in the United States, 2015. Am J Public Health. 2018;108(8):10311034. LinkGoogle Scholar
148. Caponnetto P, DiPiazza J, Kim J, Maglia M, Polosa R. A single-arm, open-label, pilot, and feasibility study of a high nicotine strength e-cigarette intervention for smoking cessation or reduction for people with schizophrenia spectrum disorders who smoke cigarettes. Nicotine Tob Res. 2021;23(7):11131122. Crossref, MedlineGoogle Scholar
149. Centers for Disease Control and Prevention. Burden of cigarette use in the US: current cigarette smoking among US adults aged 18 years and older. Available at: Accessed December 13, 2020. Google Scholar
150. National Research Council. Explaining Divergent Levels of Longevity in High-Income Countries. Washington, DC: The National Academies Press; 2011. Google Scholar
151. Chetty R, Stepner M, Abraham S, et al. The association between income and life expectancy in the United States, 2001‒2014 [erratum in JAMA. 2017;317(1):90]. JAMA. 2016;315(16):17501766. Crossref, MedlineGoogle Scholar
152. Tam J, Warner KE, Meza R. Smoking and the reduced life expectancy of individuals with serious mental illness. Am J Prev Med. 2016;51 (6):958966. Crossref, MedlineGoogle Scholar
153. Giovenco DP. Different smokes for different folks? E-cigarettes and tobacco disparities. Am J Public Health. 2019;109(9):11621163. LinkGoogle Scholar




David J. K. Balfour, DSc , Neal L. Benowitz, MD , Suzanne M. Colby, PhD , Dorothy K. Hatsukami, PhD , Harry A. Lando, PhD , Scott J. Leischow, PhD , Caryn Lerman, PhD , Robin J. Mermelstein, PhD , Raymond Niaura, PhD , Kenneth A. Perkins, PhD , Ovide F. Pomerleau, PhD , Nancy A. Rigotti, MD , Gary E. Swan, PhD , Kenneth E. Warner, PhD , and Robert West, PhD David J. K. Balfour is professor emeritus with the Division of Systems Medicine, School of Medicine, University of Dundee, Dundee, UK. Neal L. Benowitz is with the Department of Medicine, School of Medicine, University of California San Francisco. Suzanne M. Colby is with the Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, RI. Dorothy K. Hatsukami is with the Department of Psychiatry and Behavioral Sciences, Medical School, University of Minnesota, Minneapolis. Harry A. Lando is with the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota. Scott J. Leischow is with the College of Health Solutions, Arizona State University, Phoenix. Caryn Lerman is with the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles. Robin J. Mermelstein is with the Department of Psychology, University of Illinois‒Chicago. Raymond Niaura is with the Department of Epidemiology, School of Global Public Health, New York University, New York, NY. Kenneth A. Perkins is with the Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA. Ovide F. Pomerleau is professor emeritus with the Department of Psychiatry, Medical School, University of Michigan, Ann Arbor. Nancy A. Rigotti is with the Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston. Gary E. Swan is with the Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA. Kenneth E. Warner is with the Department of Health Management and Policy, School of Public Health, University of Michigan. Robert West is with the Department of Behavioural Science and Health, University College London, London, UK. “Balancing Consideration of the Risks and Benefits of E-Cigarettes”, American Journal of Public Health 111, no. 9 (September 1, 2021): pp. 1661-1672.

PMID: 34410826