Nicotine e-cigarettes for smoking cessation: a clinical pharmacology perspective

Abstract

Introduction:

Smoking cessation improves quality of life and increases life expectancy by up to a decade. Though two-thirds of people who smoke report a desire to quit, less than a quarter plan to quit within the coming month. The relative risks and benefits of e-cigarettes, proposed as a novel tool to support smoking cessation, are critical to monitor as the evidence evolves.

Areas covered:

This review summarizes the evidence for smoking cessation treatment, characteristics and pharmacology of e-cigarettes, support for e-cigarettes for smoking cessation, and relevant harm reduction principles. Populations at the highest risk for continued cigarette smoking (e.g. individuals with co-occurring substance use and mental health conditions) and those who are vulnerable to initiating nicotine use through access to e-cigarettes (e.g. adolescents), are also discussed.

Expert opinion:

Evidence indicating that e-cigarettes are comparable to nicotine replacement therapy points to their promise as a smoking cessation and harm reduction option for individuals who decline other treatment options. Future work should evaluate the comparative efficacy of e-cigarettes for historically excluded groups and the relative effects of specific products and monitor for any long-term effects. Evidence-based clinical guidelines are also needed to inform clinical practice in this rapidly evolving area.

1. Introduction

1.1. Overview of tobacco use disorder (TUD): a global health problem

Tobacco use disorder continues to be a significant global epidemic. In 2020, the worldwide tobacco smoking prevalence rate was 22.3%, including 36.7% for men and 7.8% for women [1]. The smoking-related consequences are staggering – for those who smoke tobacco, it puts them at high risk for serious medical problems (i.e. myocardial infarctions, lung diseases, stroke, and cancer) and an average of 10 years of potential life lost [2]. Between one-third and one-half of people who smoke over the long term will die of a smoking-related cause [2]. In total, tobacco smoking has killed more than 200 million people over the past 30 years [3] and continues to kill about 8 million people each year [4], with higher rates among certain populations. In the United States (US), for example, rates of smoking are higher for people who are of American Indian or Alaska Native descent (28–40%) and Multiracial individuals (28–36%) compared with White individuals (22%) [5,6]. Individuals with an education level of high school or less have higher smoking rates than people with a college education (6.5%) [7]. People who are socioeconomically disadvantaged have a current smoking prevalence of 25% compared to people who have higher income thresholds (10%) [7]. In the US, 22% of sexual minorities vs. 15% of straight adults currently smoke, whereas 21% of transgender adults vs. 15% of cisgender adults currently smoke [8]. Individuals with mental health and substance use disorders also have much higher rates of current smoking (33%) than people without mental health conditions (18%), with the highest rates among those with bipolar mood (47%) and substance use disorders (41–53%) [9]. The annual economic costs of tobacco smoking due to health expenditures and productivity losses were over U.S. $1.436 billion in 2012, which is equivalent to 1.8% of the world’s annual gross domestic product (GDP) [10].

1.2. Current treatment landscape for TUD

Quitting smoking can increase life expectancy by up to a decade and is associated with improved quality of life [11,12]. More than two-thirds of people who smoke report that they would like to quit smoking, but only a fraction, 20%, report that they want to quit within the next 30 days [13]. However, of the people who attempt to quit, only a small percentage (7.5%) remain abstinent for 1 year [14]. Behavioral (e.g. supportive and cognitive-behavioral counseling) and pharmacotherapy (e.g. nicotine replacement therapy, varenicline, bupropion, combination of nicotine replacement products and/or bupropion) treatments are effective for smoking cessation, particularly when combined [13], but the majority of people who quit smoking never use an evidence-based treatment [15].

1.3. The pressing need for innovative treatment approaches

With approximately 30% of people who smoke reporting no interest in quitting, and up to 80% intending to continue smoking for at least the next month, the need for innovation is clear. In addition to efforts to expand access to evidence-based smoking cessation [16], a harm reduction approach is proposed for the substantial number of individuals who are unwilling or unable to quit smoking. Harm reduction, a strategy focused on minimizing the negative consequences of substance use, has been successfully used for multiple substance use disorders but remains controversial for tobacco use disorder. The Institute of Medicine defines tobacco harm reduction as ‘minimizing harms and decreasing total mortality and morbidity, without completely eliminating tobacco and nicotine use’ [17]. E-cigarettes are noncombustible tobacco products that deliver nicotine with fewer harmful effects than tobacco cigarettes [18]. These products are unique in that they address the physical, psychological, cultural, identity, and social-related features of tobacco use [19], making them a potentially acceptable and effective way to help people quit smoking. Here, we provide an overview of the evolving pharmacology of e-cigarettes and the state of the evidence for their role in supporting smoking cessation and reducing the harms of nicotine use. We conclude with our expert opinion, given the current evidence, in addition to the key remaining questions in this area.

2. E-cigarettes: an overview

2.1. E-cigarette characteristics and diversity

Electronic cigarettes (e-cigarettes), also known as electronic nicotine delivery systems (ENDS), vaporizers, or e-cigs, are a diverse group of battery-powered devices that are designed to deliver nicotine in aerosol without burning tobacco. E-cigarettes heat a liquid (e-liquid), typically containing variable concentrations of propylene glycol (PG), and glycerin (GLY)), nicotine, water, and flavorings to create vapor. The main components of e-cigarettes typically include a battery, a cartridge holding the e-liquid, and a vaporizing chamber with a heating element. Since their introduction in the early 2000s, e-cigarettes have undergone rapid evolution. First-generation e-cigarettes, resembling conventional cigarettes, were called ‘cig-a-likes’ and had limited ability to deliver nicotine. Second-generation e-cigarette ‘vape pens’ offered a more powerful battery and refillable cartridges for larger e-liquid volumes and greater user customization of nicotine concentration and flavors. Third-generation e-cigarettes ‘box mod’ allowed even more customization options, allowing users to choose heating coils, batteries, wicking materials, e-liquids, and batteries. Fourth-generation e-cigarettes, or ‘pods,’ were introduced in 2015 and gained popularity, especially among youth, due to their discrete look, which appears like USB devices rather than an e-cigarette. These e-cigarettes are typically pre-filled and made to be disposable. Unlike earlier e-cigarette devices that use freebase nicotine, pod devices typically use e-liquids with nicotine salt that offers a less harsh throat hit.

2.2. Pharmacology (PK and PD) of nicotine delivery by e-cigarettes

Nicotine, the primary addictive substance in tobacco, is highly lipid soluble. This allows nicotine to rapidly cross the blood-brain barrier following cigarette smoking and affects multiple brain functions, including reward, mood, and cognition. Nicotine’s absorption is influenced by its pH; it exists in either ionized (charged) or non-ionized (freebase) forms. In alkaline (high-pH) environments, nicotine primarily exists in its freebase form, readily penetrating lipid membranes like the buccal mucosa [20]. Conversely, cigarette smoke has an acidic pH (5.5 to 6), and as a result, nicotine from cigarettes is not well-absorbed from the mouth. For this reason, transdermal and oral nicotine products are formulated at high pH levels to improve their absorption from the skin and buccal mucosa, respectively. E-liquids typically contain freebase nicotine concentrations ranging from 3 to 36 mg/mL. However, high concentrations of freebase nicotine can be irritating to inhale, limiting nicotine concentration in e-liquids with freebase nicotine. However, the fourth-generation ‘pods’ pioneered using e-liquids that contain ionized nicotine (nicotine salt) by reducing the pH by adding benzoate or lactate. The aerosol generated from nicotine salt is described as less harsh to inhale. This reduced irritation and increased nicotine bioavailability contributed to the popularity of nicotine salt e-cigarettes. E-liquids containing nicotine salt can be as high as 100 mg/mL, with popular pod-type brands often exceeding 50 mg/mL. To reduce the addictive potential of e-cigarettes, some countries, including Canada, the United Kingdom, and most of the European Union countries, limited the upper limit of nicotine in e-liquids to 20 ng/ml [21].

E-cigarettes, like tobacco cigarettes, deliver nicotine. However, the amount of nicotine delivered varies significantly among e-cigarette devices due to factors such as e-liquid nicotine concentration, PG/GLY ratio, device power, and use characteristics (e.g. puff frequency, volume, duration, and length) [22]. Following tobacco cigarette smoking, nicotine is rapidly absorbed through the lungs, reaching the brain within 5–10 seconds after inhalation [23,24], while peak venous plasma nicotine concentrations (10 to 50 ng/ml) are reached within 5–8 minutes. With e-cigarettes, nicotine delivery varies more widely depending on e-liquid ingredients, battery voltage, coil resistance, and the number of heating coils. Individual vaping habits influence nicotine intake, including experience level, inhalation depth, puff duration, and inter-puff interval. Nicotine from e-cigarette use is absorbed primarily from the oral mucosa, but it can also reach upper airways or lungs, especially with e-cigarettes with refillable tanks and more powerful batteries [25,26]. The time to peak plasma levels is similar for tobacco cigarettes or e-cigarettes. However, the peak plasma nicotine levels from e-cigarettes can be more variable; they may reach levels comparable to tobacco cigarettes (up to 30 ng/mL vs. 10–50 ng/mL for combustibles). Only about 10% (1–1.5 mg) of the amount of nicotine found in a cigarette (10–16 mg) is delivered to the user, with the remainder delivered to the air as secondhand smoke. In contrast, with e-cigarettes, more than 90% of the nicotine inhaled nicotine is retained by the user. E-cigarettes can alleviate urges to smoke and withdrawal symptoms and produce enjoyment and satisfaction, but these effects are less pronounced than those produced by cigarette smoking.

2.3. Beyond nicotine: other constituents of e-cigarette aerosol

E-cigarette vapor typically contains propylene glycol (PG), glycerin (GLY), nicotine, water, and flavorings. Based on their safety profile for ingestion, many of the chemicals used in liquids have been recognized as safe (GRAS). However, their safety for inhalation is not established. Further, there is an unknown risk from exposure to multiple chemicals used for flavorings and new products formed during vaping [27].

2.3.1. Flavorings

Evidence suggests that flavors increase the appeal of e-cigarettes and may contribute to the initiation and maintenance of e-cigarette use, especially among youth and young adults [28]. While there are over 7,000 different e-liquid flavors [29], surveys of e-cigarette users found that the majority of e-liquid flavors used by consumers can be categorized as either tobacco (23.7%), fruit (20.3%), dessert/sweets (20.7%), or menthol/mint (14.8%) varieties [30,31]. Flavors may facilitate e-cigarette initiation or maintenance by reducing nicotine’s aversive effects (e.g. menthol) or through their inherent appeal (e.g. ‘coolness’ or ‘sweetness’). Studies have shown that e-liquids with higher perceived sweetness and cooling are more appealing, while those with higher harshness and bitterness are less so [32].

While flavors play a significant role in the appeal of e-cigarettes, their effectiveness in helping individuals quit smoking remains uncertain. In a clinical trial, those who were assigned to menthol-flavored e-cigarettes had a greater reduction in tobacco cigarette consumption than those who were assigned to chocolate or fruit-flavored e-cigarettes [33]. Another epidemiological study also reported that individuals who use flavored e-cigarettes were more likely to quit smoking than those who did not use e-cigarettes, a difference that did not emerge for those who used tobacco-flavored e-cigarettes [34]. Another study reported that non-tobacco flavors were not related to success in quitting smoking [35]. Together, these findings suggest that flavors influence the appeal of e-cigarettes, but their effects in reducing tobacco cigarette use remain to be determined.

3. E-cigarettes as a treatment for TUD

3.1. Efficacy of e-cigarettes as a smoking cessation aid

A critical resource for evaluating the potential efficacy of e-cigarettes for smoking cessation is the living Cochrane review by the Cochrane Tobacco Group, most recently updated in 2024 [36]. Focusing on studies with outcome data after a minimum of six months or safety data markers for both randomized trials and uncontrolled intervention studies, this ‘living’ review was first published in 2014 [37] and has been updated every 1–2 years as additional randomized controlled trial (RCT) data becomes available [36,38–41]. The main comparators for the efficacy of nicotine e-cigarettes for smoking cessation are nicotine replacement therapy (NRT), non-nicotine e-cigarettes, and (starting in 2020) behavioral support only/no support. Before 2020, the authors rated the evidence for e-cigarettes with nicotine relative to non-nicotine e-cigarettes and NRT as ‘low certainty/quality’ due to the small number of trials [37,38]. In 2020, enough evidence had accumulated for the authors to conclude with moderate certainty that e-cigarettes with nicotine increase quit rates compared to both non-nicotine e-cigarettes and NRT [39]. In 2022, the evidence for e-cigarettes with nicotine compared to NRT was upgraded to ‘high certainty,’ with the comparison to non-nicotine e-cigarettes remaining at ‘moderate certainty’ due to imprecise estimates resulting from the small number of RCTs [41]. The most recent findings, published in 2024, indicate that in a sample of 100 people treated, 10 in the e-cigarette group will demonstrate smoking cessation at 6–12 months [36]. The relative benefit of nicotine e-cigarettes compared to NRT, non-nicotine e-cigarettes, and behavioral or no support for this most recent update are summarized in Table 1, along with evidence grading and statistical information for each comparison.

Table 1.

Summary of Cochrane review [36] findings on relative quit rate for nicotine e-cigarettes compared to nicotine replacement therapy (NRT), non-nicotine e-cigarettes, and behavioral/no support for smoking cessation.

Comparator	Relative quit rate for nicotine e-cigarettesa	Risk Ratio (95% CI)	Evidence Grading
Nicotine replacement therapy (NRT)	+4 per 100	1.59 (1.29–1.93)	High certainty
Non-nicotine e-cigarettes	+3 per 100	1.03 (0.91–1.17)	Moderate certainty
Behavioral Support only/no support	+4 per 100	1.20 (0.90–1.60)	Low certainty

^aRelative quit rates at 6–12 month study endpoints (n.b. estimated quit rate for nicotine e-cigarettes is 10 per 100).

The Cochrane series has also aimed to synthesize the evidence for the relative harms of e-cigarette use compared to standard smoking cessation treatments. Adverse events overall are largely comparable to NRT and non-nicotine e-cigarettes, with relatively higher rates compared to behavioral/no support. Rates of serious adverse events (SAEs) also appear comparable, with ‘very low certainty’ of evidence due to low rates of SAEs overall. While these findings are promising, the Cochrane team has emphasized the need for continued monitoring, as all comparison estimates for AEs are limited by imprecise estimates due to low rates overall [36]. Researchers are also exploring the potential for e-cigarettes among people who currently use cigarettes who do not intend to quit and may otherwise be subject to the harms of cigarette use. For example, one multi-wave survey study across four countries indicated that initiation of daily e-cigarette use (‘vaping’) increased the odds of smoking cessation, specifically for people who initially reported no plans to quit within the coming six months, with no apparent effects among those who did report intention to quit [42]. In this way, e-cigarettes may be a resource for reducing harm among people who are smoking and do not intend to quit.

3.2. E-cigarettes as harm reduction

Broadly defined, harm reduction approaches focus on reducing one or more harms related to a behavior, typically substance use, rather than focusing on the use behavior itself [43]. Many harm reduction approaches focus on reducing the harm of opioid and other IV drug use, largely due to the range and severity of harms associated with these types of substance use [44,45]. In this context, some of the most common examples include needle exchange services to reduce the risk of HIV and other blood-borne pathogens and the distribution of overdose reversal medication and testing strips to reduce the risk of overdose and death related to opioid use [43,46]. Many harm reduction advocates in this area emphasize a non-judgmental stance to providing care and the societal- and community-level benefits of harm reduction, including reduced disease transmission and overdose incidents [47].

The role of e-cigarettes as a harm reduction tool has been a topic of ongoing international debate, with advocates for the potential value of reduced chemical exposure of e-cigarettes [48,49] contrasted with opponents’ concerns regarding the profit-driven incentives of the tobacco industry and the risk of industry-funded research on researchers’ ability to clearly evaluate the evidence [50]. This high level of skepticism for tobacco harm reduction is impacted by the tobacco manufacturers’ history of deceptively marketing new products as reduced-harm products. From a clinical perspective, the US Food and Drug Administration (FDA) does cite lower levels of toxicants in e-cigarettes relative to cigarettes while emphasizing the importance of people who use cigarettes transitioning entirely to e-cigarettes in order to benefit [51]. In doing so, the FDA identifies a key challenge in the potential impact of e-cigarettes for people who smoke – since no level of cigarette use is considered ‘safe’ for most health effects of smoking, co-use of combustible cigarettes and e-cigarettes is not the goal. Unfortunately, of the 3.4% of Americans who report using two or more tobacco products (18.1% of those reporting current tobacco use), 31.4% report co-use of combustible cigarettes and e-cigarettes, making it the most common combination [52]. Approximately 16% [53] of e-cigarette users report using e-cigarettes specifically for smoking cessation, and the reduced health risks of e-cigarettes are commonly cited as a motive for use [54]. Thus, like other forms of harm reduction, many people who use cigarettes are already pursuing e-cigarettes for their potential use, citing the reduced harms relative to cigarette smoking.

3.3. Special populations and e-cigarette use

Individuals with mental health and substance use disorders demonstrate much higher rates of smoking than individuals without mental health conditions (33% vs. 18%), with the highest rates among those with bipolar mood and substance use disorders [9]. Although people with mental health and substance use disorders are often motivated to quit smoking [55], smoking cessation support may not be offered or available in mental health and addiction treatment settings [56]. These groups also experience unique barriers to smoking cessation. For instance, people with mental health disorders often report strong peer pressure from social norms related to smoking [57]. People with mental health conditions also have more severe nicotine dependence levels and report fear of mental health deterioration due to increased anxiety during efforts to quit smoking. Therefore, new approaches to helping people with mental health conditions to quit smoking are critically needed. Individuals with mental health disorders are more likely to have tried e-cigarettes (15%) and be current users of e-cigarettes (3%) compared to those without mental health disorders (7% and 1%, respectively [58]), demonstrating interest in e-cigarettes in mental health populations. Current evidence shows a positive association between e-cigarette use and depression [59], but the causal association between e-cigarette use and depression remains unclear. Longitudinal studies are needed to understand the relationship between depressive symptoms and e-cigarette use still needs more investigation [59].

Special considerations should also be given to the use of e-cigarettes by adolescents and young adults [60]. The 2023 National Youth survey indicated that about 10% of U.S. secondary school students vape nicotine, and that the use of e-cigarettes exceeds all other tobacco product use combined [61,62]. Some researchers and public health advocates indicate that given that combustible cigarette use reduced for youth while e-cigarette use increased, e-cigarette use may have displaced combustible cigarette use [63]. As a result, it has been suggested that e-cigarette use will result in future declines in adolescent combustible cigarette use [63]. Others are concerned about any level of nicotine product use in youth due to this critical developmental period and potential long-term health effects of use [61]. There are concerns that e-cigarettes can independently lead to the initiation of tobacco smoking among adolescents and young adults, serving as a ‘gateway’ to the use of combustible cigarettes [64]. Indeed, a meta-analysis of several longitudinal studies shows that for youth who have never used combustible cigarettes, e-cigarette use was significantly associated with the onset of combustible cigarette use [65]. In addition, studies show that for youth who have a history of using combustible cigarettes, e-cigarette use is positively associated with the progression of tobacco smoking, demonstrating that rather than inhibiting combustible cigarette use, e-cigarettes appear to contribute to further establishment of regular combustible cigarette use [66], although in a systematic review and meta-analysis, Chan and colleagues indicated that the evidence for a causal association between e-cigarette use and the initiation of combustible cigarette use may be limited by publication bias, high sample attrition and inadequate adjustment for potential confounders [67]. There are also concerns of nicotine exposure to adolescents and young adults as a result of vaping, which affects brain development, and could lead to impairments in attention and increases in impulsivity over the long-term [61,64,68]. In addition, nicotine exposure interferes with affect regulation, and there are concerns that nicotine exposure will lead to increased mental health problems and suicidal thoughts [61,62]. A systematic review determined that e-cigarette use by youth is associated with greater mental health problems compared with nonuse [69]. A scoping review demonstrated positive associations between e-cigarette use, depression, and suicidality [70]. Since many of the studies are cross-sectional, the direction of the effect between e-cigarette use and mental health symptoms is unclear [69]. Longitudinal studies are needed to better understand the long-term mental health consequences of e-cigarette use in youth.

3.4. Health consequences

The long-term health consequences of e-cigarette use are important to consider, particularly in comparison to combustible cigarette smoking [71]. Epidemiological studies have shown that the odds of cardiovascular disease, stroke, and metabolic disease are similar between current e-cigarette use and current combustible cigarette use [71]. The odds of oral disease, asthma, and chronic obstructive pulmonary disease among people who use e-cigarettes are lower than for those who smoke combustible cigarettes but are still associated with increased odds compared to those who do not use e-cigarettes or combustible cigarettes. The long-term risk of cancer from e-cigarette use is unknown [72]. However, research indicates that e-cigarettes are likely less of a health hazard than combustible cigarettes [73]. A recent meta-analysis found that the level of tobacco-specific nitrosamines (TSNA), which included the main carcinogens in tobacco smoke, reduced significantly in smokers who switched to vaping over an observation period of up to 12 months [74]. However, there are particular concerns about these long-term health consequences for youth who have never used any nicotine product in the past and people who have already quit smoking combustible cigarettes who initiate e-cigarette use [71].

4. Expert opinion and future directions

In summary, evidence from numerous studies as well as systematic reviews sponsored by the United States and the United Kingdom governments indicate that e-cigarettes are generally less harmful than tobacco cigarettes [18,75]. Further, e-cigarettes may help people to quit smoking. However, unlike FDA-approved smoking cessation medications like NRT, varenicline, or bupropion, the long-term effects of e-cigarettes are not well studied, and more work is needed to ‘decouple’ the long-term effects of nicotine use from that of tobacco use [76]. The potential use of e-cigarettes for harm reduction for those who are unable or unwilling to quit smoking also remains controversial. This ongoing controversy and lack of clear guidelines have created challenges for healthcare providers seeking to help individuals quit smoking or reduce harm from smoking. Some of these issues will be discussed in more detail below.

1. Role of e-cigarettes for smoking cessation: There is a need for more effective treatments for smoking cessation. Unfortunately, there have not been any new medications marketed for smoking cessation since 2006. In this landscape, e-cigarettes were suggested to be potential smoking cessation aids. The most recent update to the living Cochrane review, summarized earlier, concluded that e-cigarettes with nicotine were more effective than NRT, a finding first categorized as ‘high certainty’ in 2022 and continued in the most recent update in 2024 [36,41]. The review also found no evidence of serious harm over up to 2 years of follow-up. The primary caveat of these findings is that the evidence for nicotine e-cigarettes versus non-nicotine e-cigarettes, as well as adverse event prevalence for all comparisons, are limited by imprecision due to limited RCT data [36]. The US Preventative Services Task Force (USPSTF) concluded that there was insufficient evidence to recommend their use for smoking cessation, primarily due to a limited number of clinical trials [77]. These conclusions are consistent with the 2020 Surgeon General Report [78]. In contrast, in the United Kingdom, the use of e-cigarettes for smoking cessation is encouraged, though critical areas of recommended study are also noted [76,79].

2. Role of e-cigarettes for tobacco harm reduction. For those who are unable or unwilling to quit smoking, less harmful alternatives, such as e-cigarettes, can play a crucial role in reducing tobacco-related harms. For those who decline the opportunity to engage in pharmacotherapy or behavioral treatment options for tobacco cessation, e-cigarettes represent an additional tool to reduce harm while respecting individual autonomy, a key tenet of harm reduction approaches [43]. This may be particularly impactful for groups who carry a disproportionate burden of tobacco-related harms, including those with low socio-economic status (SES), mental illnesses, or other substance use disorders. Notably, the primary priority should continue to be ensuring access to evidence-based tobacco cessation treatments, including efforts to enhance motivation and access to the full range of options (including low-barrier behavioral options such as quit lines and/or text messaging programs) in the context of addiction and mental health treatment settings. Those who decline these evidence-based tobacco cessation options may benefit from innovative strategies, including e-cigarettes, to reduce tobacco-related harms from smoking, and increase their motivation and engagement with gold standard evidence-based smoking cessation treatments [57,80]

3. Long-term effects of e-cigarettes: Another important consideration is the potential long-term effects of e-cigarette use and the risk of relapse to tobacco cigarettes. For individuals who currently smoke cigarettes and switch to e-cigarettes, there may be a need to provide guidance on a gradual transition from e-cigarette use for those who wish to quit completely. This should also include strategies to prevent a return to cigarette smoking. Given the limited research in this area, organizations such as the National Health Service in England recommend quitting e-cigarette use once an individual feels ready. However, they provide basic guidance for avoiding returning to cigarette use in this process [81].

4. Prevention of e-cigarette use among youth: The increasing prevalence of e-cigarette use among young people over the past decade, particularly following the rapid rise in popularity of pod-style e-cigarettes, remains a significant public health concern. The FDA recognizes the delicate balance between controlling youth access to e-cigarettes to prevent them from becoming a gateway to traditional cigarettes and ensuring that adults who wish to quit smoking or switch to a less harmful alternative have access to these products. In 2019, the American Academy of Pediatrics released a policy statement indicating that there is an important need for e-cigarette regulation and counter-promotion to protect youth from transitioning from e-cigarettes to combustible cigarettes and to reduce harm to youth from the use of e-cigarettes [82]. As a result, many counties, states, and provinces have instituted policies and regulations to prevent access to these products among youth, including taxation/price increases, warning labels, age restrictions, and flavor bans [62].

5. Future Research Directions: First, rigorous clinical trials are needed to test the comparative efficacy of e-cigarettes against the currently available smoking cessation aids. Such studies should prioritize individuals with low SES, mental illnesses, substance use disorders, and other groups who are not well represented in smoking cessation trials. Second, government-sponsored agencies, like USPSPT, should develop evidence-based clinical guidelines for the use of e-cigarettes in both smoking cessation and harm reduction approaches. Third, given the wide variety of e-cigarette types and flavors, it is important to identify specific products that are most effective for smoking cessation. This requires careful evaluation and guidance to help individuals make informed choices. Finally, while addressing the concerns of youth e-cigarette use is critical, equally important is to ensure that individuals seeking to quit smoking have access to e-cigarettes. Balancing these competing priorities requires a nuanced approach that prioritizes reducing tobacco-related harm.

Article highlights.

• E-cigarettes may help with smoking cessation and reduce harm among people who smoke cigarettes but do not currently want to quit.

• Outcomes at 6- to 12-months post-quit attempt are promising, but critical unknowns include long-term outcomes and risks, including best practices for cessation of e-cigarette use.

• Novel treatment options are particularly critical for groups such as those who are unable or unwilling to quit using existing treatments.