Whether to push or pull? Nicotine reduction and non-combusted alternatives - two strategies for reducing smoking and improving public health

Abstract

Combustible cigarettes remain the most harmful and addictive tobacco product, and reducing the prevalence of smoking continues to be a critical public health goal. While nicotine is the constituent primarily responsible for addiction to cigarettes, most of the harm associated with smoking comes from byproducts of tobacco combustion. Recently, two different approaches for reducing the harms of smoking have emerged, both of which focus on breaking the link between the addiction to nicotine and the harms caused by smoking. First, the addictive potential of cigarettes could be minimized by requiring a large reduction in the nicotine content of cigarettes. Evidence for a nicotine reduction policy thus far shows that the use of very low nicotine content cigarettes results in a reduction in the number of cigarettes people smoke per day and a reduction in cigarette dependence. Second, emerging alternative nicotine delivery systems (ANDS) like electronic cigarettes may provide sufficient nicotine to act as substitutes for cigarettes while delivering much lower levels of toxicants. Evidence suggests that the emergence of ANDS has increased the percentage of smokers who are able to quit. The present paper will briefly review the evidence for each of these approaches, and consider what contemporary reinforcement and addiction theories can tell us about their likely success. We argue that the most effective endgame approach is one that pursues both nicotine reduction and alternative nicotine delivery systems as complementary.

I. Harms associated with burned tobacco

Tobacco use continues to devastate public health, causing an estimated 6 million deaths worldwide annually [1]. The vast majority of the harm from tobacco use is caused by cigarettes and can be traced to the byproducts of combustion and specific constituents in tobacco [2]. Combustion is not necessary for nicotine delivery, although it does facilitate the rapidity with which nicotine is delivered by enabling pulmonary absorption [2]. Nicotine itself, when delivered in cigarette-like doses, is not benign [2], but is far less toxic than other constituents of tobacco smoke and hence would likely be less harmful if it was delivered in a non- combusted vehicle [3]. Indeed, the harms associated with nicotine and tobacco products may be best viewed as a continuum in which abstinence from all tobacco products would be the least harmful, the use of combusted tobacco products would be the most harmful, and non-combusted tobacco products are somewhere in the middle [3–8]. The goal of policies and interventions should be to effectively move the population down that continuum of harm in order to improve public health [5].

Unfortunately, cigarettes are highly addictive, engineered over decades to maximize the development and maintenance of chronic, dependent smoking [2, 9, 10]. In the US, only 7.4% of adult smokers are able to quit smoking each year, despite the fact that 68.0% are interested in quitting and 55.4% make a quit attempt [11]. Since at least 1988 and arguably much longer [10, 12], the addictive properties of cigarettes have been attributed almost exclusively to nicotine. This perspective, that nicotine is the cause of cigarette addiction, has driven smoking cessation medication development and innovation of Alternative Nicotine Delivery Systems (ANDS)—noncombustible nicotine or tobacco products designed to deliver fewer toxicants than cigarettes [13, 14]. ANDS include products like snus, nicotine replacement therapy products, and, in recent years, e- cigarettes. Understanding nicotine as the driving force in cigarette addiction has also provided a rationale for potential tobacco policies such as reducing the nicotine content of combusted tobacco products to render the product less addictive [15].

Of course, smoking is about more than nicotine. Other factors such as the sensory stimuli associated with smoking and the act of smoking itself, become potent drivers of use [16, 17]. Indeed, smoking is interwoven throughout much of smokers’ lives, and smokers have strong expectations and feelings about smoking, both positive and negative [18]. Smoking also remains embedded in culture. Many tobacco control policies have effectively shifted the cultural norms, although implementation and impact of those policies is quite heterogeneous and smoking remains normative in many parts of the world [19]. Traditional tobacco control efforts have and should continue to address these issues, particularly reshaping cultural norms. Nevertheless, managing how people use nicotine - the constituent that is widely considered to be the central determinant of long-term use - has the potential to greatly improve public health. Currently, some 40 million Americans and over one billion smokers worldwide are using a product developed and aggressively marketed over decades, deeply embedded into the environments in which smoker’s live, and integrated into their personal histories, making behavioral change extremely difficult [19, 20].

II. Two approaches to breaking the link between nicotine and harm

Two approaches to reducing combusted product use have recently received considerable attention. One approach is to encourage smokers to switch to ANDS rather than continue to smoke cigarettes [21, 22], and thus to reduce the harms of nicotine delivery among those who are unable or unwilling to quit using nicotine. The other approach focuses on reducing the nicotine content of combusted tobacco products to render them less addictive [23–26]. The intent is to reduce the harms associated with smoking, not by altering the toxicity of the product, but by reducing the likelihood that someone will start smoking or continue to smoke. Both represent approaches directed at breaking the link between nicotine consumption and the harms associated with inhalation of smoke from combusted tobacco. At the core, both are harm reduction approaches in that neither is particularly concerned with nicotine use per se, but instead focus on reducing exposure to smoke as a delivery vehicle for nicotine. Indeed, when the Food and Drug Administration (FDA) recently announced a new strategy for regulating tobacco products, these two approaches were considered essential and complementary components of a comprehensive FDA strategy [7].

Despite the shared focus on reducing use of combusted products and the two-pronged approach announced by FDA, some have argued that these two approaches are fundamentally and philosophically opposed. ANDS have been conceptualized as a bottom-up or pull approach, emphasizing that market-driven, consumer-driven approaches will persuade smokers to switch products while still protecting individual rights. ANDS, and policies that favor use of ANDS over cigarettes (e.g., light-touch regulation, differential taxation), might be conceptualized as a “nudging” approach to public health or what Loewenstein has called “asymmetric paternalism” [27]. Conversely, nicotine reduction has been described as a top-down or push technique, emphasizing the forced nature of product standards that some smokers may not want [28]. Kozlowski and Bates have described nicotine reduction as cigarette prohibition [28, 29] - more of a shove than a nudge. It is true that reducing nicotine would likely result in a reduction in cigarette sales, but it is important not to confound a reduction in the appeal and addictiveness of cigarettes with the prohibition of nicotine itself. Regardless, nicotine reduction is undeniably a more invasive tobacco control policy, and thus it is important to justify its necessity [30].

III. Promises, pitfalls, and prognosis of alternative nicotine delivery systems (ANDS)

Proponents of ANDS point to the number of smokers who have quit or reduced their smoking using ANDS [31]. Evidence of the potential utility for reducing smoking is most clearly observed in surveys focusing on the number of ANDS users who were smokers and have subsequently switched partly or entirely to e- cigarettes. For example, Farsalinos and colleagues estimated that as of 2014, 6.1 and 9.2 million European Union citizens have quit or reduced their smoking with the help of ANDS, respectively [31]. The evidence seems clear that for some smokers, ANDS may provide a path towards cessation [32]. Smokers who use e- cigarettes frequently, particularly those using systems that more effectively deliver nicotine, may be more likely to quit smoking [33–38]. Furthermore, some data have shown that in 2014 and 2015, when the prevalence of ANDS use rose drastically among adolescents, use of cigarettes in the same population decreased [39], which might suggest that the availability of ANDS reduces the use combustible cigarettes in youth. In Japan, a class of ANDS known as heat-not-burn products are increasing in prevalence. These products may provide a superior sensory experience to e-cigarettes because they involve heated tobacco rather than nicotine isolated from tobacco and reduced harm in comparison to cigarettes because the tobacco is not combusted [40, 41]. As these products have taken off in Japan, cigarette sales have declined, again suggesting that their availability reduces cigarette use [42]. Proponents of ANDS argue that these encouraging findings are only the tip of the iceberg because the nicotine delivery and positive subjective effects associated with ANDS products should continue to improve if innovation in this area is encouraged [28].

However, several observations warrant caution with regard to the impact of ANDS on current smokers. First, the vast majority of smokers either have not tried e-cigarettes, have tried them but abandoned them after a short trial period, or continue to use both products (i.e., dual use). In the EU, only an estimated 31.1% of current smokers have ever tried e-cigarettes, with just 4.2% reporting current use [31]. In the UK, an estimated 45% of e-cigarette users continue to smoke cigarettes, suggesting a sizeable portion of users do not switch completely in the timeframe assessed [43]. Likewise, although population data in England and the U.S. have concluded that e-cigarettes are increasing the rate of smoking cessation [45, 46], most smokers have not benefitted. For example, in England, an estimated 16,000–28,000 additional long-term quitters were generated by e-cigarettes in 2014 [44], an important contribution, but a relatively small fraction of England’s 8.46 million adult smokers. Furthermore, 891,000 smokers tried to quit and used an e-cigarettes over the same time period [44]. Thus, it appears that while e-cigarettes are a popular product for current smokers to try, a minority of smokers are able to switch completely from cigarettes to ANDS. Second, many smokers report that e- cigarettes are an unacceptable alternative to smoking. The most common reason for stopping use of e- cigarettes among current smokers in the UK is that they did not feel enough like smoking a cigarette, and the second most common reason is that they did not help deal with cravings to smoke cigarettes [43]. Third, many smokers appear to harbor misperceptions about the harm of e-cigarettes relative to cigarettes, and these misperceptions are growing. In 2017, an estimated 22% of smokers in the UK reported that they believed e- cigarettes were as or more harmful than cigarettes, up from 9% in 2013 [43]. These beliefs were strongest among smokers who have never tried e-cigarettes, which may mean that these beliefs are a barrier to even trying e-cigarettes [43]. Combined, these limitations may mean that while ANDS are likely to offer a good alternative to smoking for those who find them appealing or are less dependent on traditional cigarettes, they may not be a satisfactory alternative to cigarettes for the masses of smokers who try to stop smoking each year. For ANDS to truly displace smoking, an intervention that can reduce the addictiveness of conventional cigarettes may be required.

In addition, several other concerns have been raised about the ultimate impact of ANDS on public health. First, while the health implications of nicotine replacement therapy [47] and products like snus are well understood [48, 49], we still know relatively little about the health risks of more novel ANDS like e-cigarettes [50]. It seems clear that ANDS deliver substantially lower levels of many of the toxicants present in cigarette smoke [51–54] and thus, they likely represent reduced health risks for smokers who switch completely [50]. However, nicotine is not harmless [55], and ANDS such as e-cigarettes and heat-not-burn products may present health risks that are not yet fully understood [51, 55, 56]. These risks are important given that the prevalence of smoking has been decreasing for a long time in much of the developed world, and the rise in use of these products may mean maintaining some health risks for tobacco use that may have dissipated on its own given enough time and increased use of established tobacco control policies. Second, recent evidence suggests that youth who use e-cigarettes are more likely to go on to initiate cigarette use [50, 57–64]. Proponents of ANDS argue that these data are limited because e-cigarette use among nonsmokers is rare [65] and e-cigarette and cigarette use may both be a product of a shared vulnerability for tobacco use, rather than evidence of a causal gateway effect. Indeed, national surveys show a rapid decline in adolescent smoking since the emergence of e-cigarettes [39, 66]. Nonetheless, the possibility is difficult to dismiss. Finally, a rise in the prevalence of ANDS use could slow the decline in combustible product use by renormalizing tobacco products [67]. Any of these concerns has the potential to limit the beneficial impact of ANDS on public health.

IV. Promises, pitfalls, and prognosis for nicotine reduction

The Tobacco Control Act in the U.S. and World Health Organization Framework Convention on Tobacco Control provide a regulatory framework for product standards and have reignited debate as to whether nicotine reduction would improve public health. The policy approach envisioned by most would involve large reductions in the nicotine content of combusted tobacco, including roll-your-own, cigarillos, little cigars, and potentially large cigars, but not non-combusted products, which are assumed to be less harmful. Hence, it is, by definition, an approach aimed at reducing the harm associated with nicotine use. Clinical trials investigating the impact of nicotine reduction have had promising results. Sizeable reductions in nicotine content [68, 69] reduce the rate of smoking, decrease nicotine dependence, and increase quit attempts [68, 70–73]. Reducing nicotine in cigarettes is technologically feasible. In fact, several very low nicotine content (VLNC) cigarettes have been manufactured and sold in the past (e.g., Next, Quest), suggesting that large scale production is feasible. The magnitude of nicotine reduction is important. A reduction from about 15.8 mg nicotine / g tobacco to at least 2.4 mg/g appears to be required to observe any reduction in smoking rate, and a reduction to 0.4 mg/g was required to observe significant changes in nicotine dependence across multiple measures [68].

A primary concern of critics has been the potential for compensatory smoking. Some have even boldly stated that VLNC cigarettes are a “more toxic product” because nicotine reduction would increase the ratio of toxicants to nicotine within a cigarette [28]. The assumption is that in an attempt to maintain nicotine exposure, people will smoke more and will therefore be exposed to higher toxicant levels. This assumption, which is based on a loose analogy to “light” and “mild” cigarettes, runs counter to the data [25]. Light cigarettes have similar levels of nicotine to conventional cigarettes, but a reduced nicotine yield (i.e., when a machine smokes the product) because the design of the cigarette dilutes the smoke with ambient air and/or alters cigarette papers to accelerate burn times [74–77]. Smokers can easily adjust how they smoke light cigarettes to maintain a similar level of nicotine [74, 78]. Similarly, when smokers switch to cigarettes with small to moderate reductions in nicotine content, there is some evidence that they may compensate by increasing the number of cigarettes they smoke per day [70, 79] (but see [80]). However, when nicotine is reduced to very low levels (0.4 mg/g), changes in smoking behavior cannot maintain nicotine exposure [68, 70]. Indeed, studies have consistently shown that smokers who are switched to VLNC cigarettes for at least 6 weeks do not engage in compensatory smoking [80]. In this case, smokers are more likely to compensate for the reduction of nicotine in cigarettes by titrating their nicotine intake through a much more effective means - use of alternative products.

Some concerns center around how the public might respond to a mandated reduction in the appeal of such a popular product. Interestingly, surveys suggest that the majority of both non-smokers and smokers support reducing nicotine as a means to reducing addictiveness of cigarettes [81–84]. Even in studies in which participants have experience with VLNC cigarettes, the majority of participants report they are supportive of such a policy [85]. However, there is strong evidence that smokers find these cigarettes unappealing. Although VLNC cigarettes have been available commercially before, they were commercial failures, suggesting that given the choice, smokers will continue to use the normal nicotine content cigarettes to which they are addicted rather than choose a novel brand with very low nicotine content [86]. When participants try VLNC cigarettes, they rate them as less satisfying than research cigarettes with a normal nicotine content [24]. Furthermore, in clinical trials where participants are asked to smoke only the VLNC cigarettes provided to them, most participants smoke non-study normal nicotine content cigarettes anyway [68], even though the VLNC cigarettes are provided for free. We also know that attrition is higher in clinical trials when smokers are asked to switch directly from their usual brand to a VLNC cigarette rather than transitioning to an intermediate nicotine content before ultimately switching to VLNC cigarettes, suggesting that smokers find VLNC cigarettes especially unappealing when contrasted directly with their usual brand [87]. Collectively, these data suggest that if a nicotine reduction policy were implemented, many would likely find VLNC cigarettes to be unsatisfying and may seek out alternative sources of nicotine.

In an environment where smokers can no longer purchase their normal nicotine content cigarettes, consumers may respond by hoarding normal-nicotine content cigarettes, product tampering, and/or turning to an illicit market. Hoarding of normal nicotine content cigarettes would seem to be a minor concern since the effective delay in nicotine reduction through hoarding is likely small. Smokers could try to add nicotine to their cigarettes, possibly by adding e-liquids or other nicotine-containing fluids. The effectiveness of this practice and the extent of its use (relative to just using ANDS, for which the fluids are designed) are difficult to predict, but would need to be monitored. Finally, regulation would almost certainly contribute to an increased demand for illicit cigarettes. Like other unintended consequences, the critical question is not whether this would occur, but rather how much harm would likely result and whether regulators could effectively mitigate both the supply of and demand for illicit cigarettes. The size of an illicit market is likely to depend on factors such as the speed at which nicotine in cigarettes is reduced (immediate vs. a stepped or gradual approach), effective enforcement of manufacturers and retailers, and the availability of alternative products [88]. If consumers can easily access a satisfying and legal alternative to VLNC cigarettes such as ANDS, hoarding, tampering, and participation in an illicit market may be much less appealing.

Some of the impact of nicotine reduction will depend on choices that regulatory agencies make when designing the policy. We do not know the exact nicotine target that would be required for reduction, but lower nicotine contents produce greater benefits [68, 89]. A gradual reduction in nicotine content has the potential to produce compensatory smoking at intermediate levels [79], but may be tolerated better by consumers than an immediate reduction [87]. Any policy will need to be accompanied by well-researched public health messages because smokers harbor misperceptions about the harms associated with nicotine and perceive VLNC cigarettes to be safer than conventional cigarettes [90]. Thus, it is important that agencies clearly communicate the relative risks of available products.

V. A theoretical perspective on approaches to reducing combusted product use

The central premise of both strategies is that the harm caused by tobacco products will be reduced because current and potential smokers will be less likely to smoke and more likely to opt for a less harmful product or abstinence. In this section, we review what contemporary theories on reinforcement, choice behavior, and addiction tell us about the likely impact of each approach. This review is not meant to be exhaustive, but instead to provide a starting framework for understanding both the challenges and opportunities related to the choice to use cigarettes, use ANDS, or be abstinent. We set aside issues related to the health consequence of use, except to the degree to which it may impact choice.

Reinforcement and choice.

We have known for decades that the primary reinforcer for using tobacco is nicotine [10, 12]. We also know that non-nicotine stimuli (such as the taste, smell, and sights associated with smoking) become conditioned reinforcers through their pairing with nicotine [16, 17], and contribute to the reinforcement value of smoking. Ultimately, the choices people make about which tobacco products to use, if any, will depend on the overall reinforcement value of cigarettes relative to ANDS.

Contemporary learning theory emphasizes that behavior is allocated in a manner that is proportional to the reward value of one behavior relative to other possible behaviors (i.e., matching, [91–94]) and that some behaviors may be even more likely to occur than predicted because of bias (i.e., because of a preference for one environment or mode of responding [95]). In the case of cigarettes and ANDS, use behavior might be shifted from smoking to alternative ways to use nicotine by decreasing the reward derived from smoking or by increasing the reward derived from alternative ways to use nicotine. Relying on ANDS as an endgame strategy alone requires the belief that emerging products will ultimately provide enough reinforcement through improved sensorimotor cues and nicotine delivery to compete with combustible products [96], and that smokers would give up a product they are already using, that is ubiquitous in their environment, and maintains an extremely high value both related to its rapid nicotine delivery and conditioned reinforcement value. Alternatively, relying on a nicotine reduction strategy alone as an endgame strategy requires the belief that the reinforcement value of cigarettes following nicotine reduction will be low enough that smokers will choose to abstain, that the motivation to smoke doesn’t drive harmful alternative smoking behaviors such as product tampering or use of illicit cigarettes, and that the bias to persist in smoking even VLNC cigarettes doesn’t maintain use.

The belief that most people will choose to switch to ANDS instead of continuing to smoke conventional cigarettes assumes that people will make a rationale choice to use ANDS because of their reduced negative health consequences. However, people often do not make rationale choices about their individual health [97]. First, when people are choosing between two or more options, there is a bias for the default option [97], regardless of which option is the most beneficial. For example, when choosing home, car, or health insurance, one can shift the most popular insurance plans just by changing the default plan [98]. Applied to the choice of ANDS and cigarettes, this bias suggests that while people might choose ANDS if they had never used either product and they were presented with an array of tobacco products and their health consequences at the same time, current smokers will have a bias for the option they are currently using. Second, when people are choosing between two or more options, they discount the value of reinforcers that are delayed in time [99, 100], like any perceived health benefits of switching from cigarettes to e-cigarettes. Thus, in order for people to choose ANDS, the discounted value of long-term health has to be larger than the value of the immediate reward of their preferred product.

Addiction Theory.

Rational choice between ANDS and cigarettes is even more complicated because a sizeable portion of daily smokers are addicted [101–103]. Addiction processes may make this choice different from the choices that people make between products in other categories. This addiction is not just to nicotine, but to cigarettes [104, 105]. Adult smokers typically have used cigarettes for decades, taking tens of thousands of puffs associating the taste, smell, and feel of their cigarette with nicotine delivery. The product is deeply embedded in their daily lives. When a smoker runs out of cigarettes, they do not substitute smokeless tobacco - they seek out, sometimes with great effort, their preferred product and often their preferred brand.

Some theories of addiction focus on the importance of smoking cues and smoking-associated contexts, which are relevant for understanding why smokers may be unable or unwilling to switch to ANDS. The incentive salience theory posits that, as a consequence of the pharmacological actions of nicotine and other drugs of abuse, the neural systems mediating the relationship between stimuli and behavior become hypersensitive, rendering drug-associated cues “attractive” to smokers and robust triggers for drug use [106]. The importance of smoking cues in nicotine addiction is one reason that some ANDS products, like e- cigarettes and heat-not-burn products, are likely to be better substitutes for cigarettes than NRT—because the sensory cues associated with using these products are more similar to smoking. However, because the cues associated with using ANDS are not the same as cigarettes, smokers are likely to continue to be attracted to and biased by the cues associated with smoking. One advantage of nicotine reduction is that the power of smoking cues will be reduced through extinction over time as they are no longer paired with a reinforcing dose of nicotine. However, cigarette use can also become automated (i.e., habitual) in the presence of stimuli and contexts where cigarette use has occurred before, and changes in reinforcement value (such as those associated with reducing nicotine in cigarettes) sometimes do not alter these habit-driven tendencies [107– 109]. These automated memory sequences, called drug use action schemas, make it difficult for a smoker to refrain from smoking; in the presence of stimuli that trigger automatic smoking behaviors, abstaining requires that smokers exert a great deal of cognitive effort to deviate from this otherwise automated process. Any mental state that reduces cognitive processing availability, such as stress or nicotine withdrawal, will make it more difficult for smokers to successfully stop smoking or switch to another product [110]. Nonetheless, automated processes are not immutable; their influence is impacted by one’s goals and underlying motivation [111]. For smoking, the availability of ANDS that act as highly satisfying alternatives to smoking may activate goal-driven systems allowing smokers to abstain from using reduced nicotine cigarettes.

Another important concept in addiction theory is related to the perceived probability of and expected effects of use. First, the perceived availability of tobacco products is a potent contextual determinant of dependence (craving, mood, use behavior) [112, 113]. Indeed, smokers who view visual smoking cues have greater activation of brain areas involved in reward value if they are expecting to smoke in the near future [114, 115], suggesting that cigarettes may actually hold greater incentive value when smokers perceive them to be available. In smokers who are currently trying to switch to ANDS, the wide availability of normal nicotine cigarettes may maintain craving for cigarettes, whereas if normal-nicotine cigarettes were unavailable, cigarette craving may be less intense. Second, the expectancies that users have about each class of tobacco products impacts their reinforcement value. Real or imagined, smokers generally believe that cigarettes are more likely to reduce stress, reduce negative affect, control weight, and provide more stimulation than e- cigarettes [116]. ANDS may have other advantages such as reduced belief they will be addictive, cause craving, and negatively impact health [116, 117]. However, the latter expectancies about ANDS are related to outcomes that are more delayed than immediate and could consequently have less impact on choice.

VI. Complementary approaches to ending combusted tobacco

The concurrent emergence of the nicotine reduction strategy and ANDS has triggered a contentious debate within the public health community. At times, this debate seems to have fueled a division between those who support vs. oppose nicotine reduction. Some advocates for ANDS have argued that nicotine reduction is unnecessary or a costly distraction with the advent of ANDS. We want to be clear - we consider ANDS an important technological advance that could help reduce the prevalence of smoking and reduce the harms associated with nicotine use. However, as discussed above, there is reason to be skeptical about whether ANDS can function as an endgame for smoking on their own. Likewise, nicotine reduction clearly holds promise in its ability to reduce reinforcement and dependence from cigarettes. However, in nicotine reduction clinical trials, most participants continue to smoke at some level [68, 70] and to supplement their study cigarettes with non-study normal nicotine cigarettes, highlighting a persistent demand for nicotine. The endgame should be to end combustible cigarette use. Tobacco regulators and public health experts should set clear goals for reaching this objective, and then ask whether either approach is likely to reach these goals on its own. If not, they should consider how much more likely we are to shift product use away from combusted products in favor of alternatives if we consider the two approaches as complementary. Indeed, these two approaches may ultimately need each other to have the greatest public health impact [7, 13].

Some have emphasized that much larger and potentially very long trials would need to be conducted or that evidence from a single country or locality is needed before any other country should entertain mandated reductions in the nicotine content of combusted products [29, 118]. The empirical basis for policy is never complete and clinical trials cannot fully predict real-world experience [119]; nevertheless, past and current studies [26, 68, 70, 72, 73, 120] are likely to provide a strong foundation well within the likely timeframe for regulatory change. A nicotine reduction policy will take years to enact. Given that most smokers intend/want to quit smoking, it is likely that these pending changes will increase quit attempts and/or use of alternative products. Indeed, when new cigarette taxes are announced, there is a spike in online searches for non-cigarette tobacco products, including ANDS [121]. Consequently, any locality considering reducing nicotine should have a strong infrastructure for providing smoking cessation services and be prepared for a potential increase in the use of alternative products.

Some critics of nicotine reduction are worried about the heavy-handed role of government in a potential nicotine reduction policy. One has likened nicotine reduction to a stick and ANDS to a carrot [122]. Critics have asked If nicotine is reduced, what’s next? What precedent does it set? Regulators and society broadly have to struggle with where to draw lines that infringe on personal freedom for the public good. The issue is not new nor is it unique to tobacco [30]. However, we must not lose sight of the unique nature of cigarettes in society. They are the only legal product that kills a third to half its users and maintains its use through addiction. Most users want to stop [123]. For smokers, continuing to use cigarettes as they are currently designed in a marketplace dominated by these products is not a free choice [13]. One might reasonably ask… What precedent does it set when agencies with the regulatory authority to limit the addiction to and devastation from cigarettes fail to act? Indeed, when the stakes are high enough, a stick may be needed when a carrot will not do [30, 124]. Addiction is not rationale. We may have to loosen its grip to enable change.

Highlights:

• Cigarettes are the most harmful and addictive tobacco product available

• The nicotine content of cigarettes could be lowered to reduce their addictiveness

• New alternative nicotine delivery systems may be less harmful than cigarettes

• Both nicotine reduction and alternative products could reduce cigarette use

• The most effective strategy is to pursue both approaches simultaneously