12C.1 Rationale for reducing the level of nicotine in cigarettes
It is well established that addiction to nicotine maintains most people’s use of tobacco products.1 Once addicted, quitting can be extremely difficult, with many people who smoke repeatedly relapsing following their cessation attempts.2 Young people have a very poor understanding of addiction, often believing that they will be able to stop smoking at will.3 However, once they take up smoking, addiction to tobacco delivered nicotine develops quite rapidly—See Section 6.13—and sustains the behaviour into adulthood, dramatically increasing their risk of tobacco-related harm.4 In 2002, about 90% of people who smoked reported that they regretted ever having started.5
The idea of reducing the nicotine content in tobacco was posed as early as the 1920s6 and regulation of the maximum level of nicotine in tobacco products was first suggested in the mid-1990s as a potential population-level strategy for preventing the transition from experimental smoking to addiction.7,8 Legal proceedings initiated against tobacco companies by US state attorneys general had revealed a great deal of evidence about the centrality of nicotine in industry efforts to maintain customers, despite concerns about the health effects of smoking.9,10 Reducing the nicotine content in cigarettes to a level that they would be non-addictive was proposed as a mechanism to prevent adolescents and people who occasionally smoke from becoming addicted. A gradual reduction could also allow people who smoke to slowly decrease their intake of nicotine, thereby weaning themselves off the product and making quitting substantially easier.11,12
While the idea for nicotine reduction fell out of favour in subsequent years, largely due to concerns about compensatory smoking, since 2010 researchers have taken a renewed interest in this proposal. Unlike ‘low tar and light’ cigarettes promoted by tobacco companies, which did not actually reduce delivery of tar and instead involved design features that allowed people who smoke to easily compensate for the reduced nicotine content by drawing harder (see Section 12.8.2.3), reduced nicotine cigarettes could be manufactured in the same manner as regular cigarettes but—in preference to regular tobacco—using tobacco that has a lower nicotine content. If the nicotine content was low enough, it would be virtually impossible to absorb significant levels of nicotine by using these products.12
12C.2 Development of low nicotine cigarettes
Initial proposals in the mid-1990s suggested a gradual reduction in nicotine in cigarettes to 0.5 mg per cigarette.11 Since then, several studies have established that a >95% reduction in nicotine, from about 10 to 15 mg/nicotine per conventional cigarette to ≤0.4 mg nicotine/g tobacco per ‘very low nicotine content cigarette’, will likely reduce addictiveness13,14 and dependence.15 Others have suggested that that cigarettes with slightly higher nicotine/g tobacco doses (‘reduced nicotine content cigarettes’) can also reduce the reinforcing effects of nicotine,16 with minimal differences between 2.4 and 0.4 mg nicotine doses17,18 or between 1.3 and 0.4 mg/g.19 Nonetheless, most trials have examined responses to the 0.4 mg nicotine dose, leading to greater endorsement of very low nicotine content cigarettes as the product standard.20,21
Production of low-nicotine cigarettes is quite feasible for the tobacco industry. Spectrum cigarettes, created for research purposes, can be made with very low nicotine levels, such as 0.4 mg/g of tobacco. Spectrum cigarettes have been used to demonstrate the feasibility of using low nicotine cigarettes to reduce reduced nicotine exposure, nicotine dependence and the number of cigarettes smoked.15 Experiments using Spectrum cigarettes have also demonstrated reductions in the levels of toxicant biomarkers in users. The lower the nicotine level of the spectrum cigarette, the lower the nicotine in the blood after use.22
One method for producing low-nicotine cigarettes products is to use tobacco plants that produce relatively low amounts of alkaloids, called low-alkaloid plants. These have been discovered in the past, having arisen from natural variation, as well as been produced by genetic modification of tobacco plants.23 An example of naturally-arising tobacco plant variation is the low-alkaloid variant of LA Burley 21, a genetically stable breeding line that was developed in the early 1930s from a Cuban cigar tobacco plant.24 Spectrum cigarettes, on the other hand, are made from genetically modified tobacco plants.
Nicotine is produced in the roots of tobacco plants and transported through the stems into the leaves, where it serves as a natural defence against pests. The protein products of numerous genes are involved in the biosynthesis of nicotine in tobacco plants and the regulation of this complex biological process.25 Genes called NIC1 and NIC2 are influential regulators of nicotine production. Disruption of the NIC1 gene (by naturally occurring DNA variations or those made by genetic modification) leads to tobacco plants that produce very low amounts of nicotine.25-27 Similar techniques have been used to generate low-alkaloid tobacco plants by disrupting all six BBL genes.28 Tobacco plants with BBL disruptions combined with disruptions in other genes in the nicotine synthesis pathway have been shown to produce nicotine at lower than 0.4 mg/g.29,30 Importantly, other potentially addictive alkaloids such as anatabine, nornicotine and anabasine remained at low levels in these plants.28
Manufacturing techniques can also be used to reduce nicotine after harvesting of the plants. Over 90% of the nicotine content of plants can be removed by treatment with chemicals such as ammonia. However, this treatment also removes some of the flavours from the tobacco and can leave residual chemicals that may be toxic.23 Using a filter that removes much of the nicotine from cigarette smoke is another option for creating low-nicotine cigarettes.31
A number of low nicotine cigarettes have been sold in the past, such as the Quest brand, however these have not been commercially successful. Consumers have rated them as less satisfactory and less palatable.23 It is possible that alkaloids contribute somewhat to the taste of the tobacco, so reducing them leads to flavour changes that are unavoidable.23 The US FDA has authorised the sale of a number of variants of reduced nicotine content cigarettes from 22nd Century Group. According to the company’s website, its products are created through genetic engineering, gene-editing, and modern plant breeding.32
12C.3 Effects of reduced nicotine content cigarettes on smoking and health
Studies modelling the public health impacts of lowering the nicotine content of cigarettes to minimally addictive levels have concluded that it would lead to substantial reductions in tobacco-related morbidity and mortality, both through decreasing uptake and increasing cessation.33,34 One such study estimated that a reduced nicotine cigarette content standard implemented in the US in 1965—decades after patents and internal company documents from the 1920s and ‘30s first described methods to extract nicotine from tobacco—could have averted 21 million smoking attributable deaths (54% reduction) and 272 million life years lost (64% reduction) from 1965 to 2064.35 The subsequently repealed Smokefree Aotearoa/New Zealand 2025 legislation included denicotinised tobacco products, and a modelling study concluded that it is plausible that the policy could help achieve the Government’s goal of 5% smoking prevalence by 2025, particularly if it formed part of a comprehensive tobacco control program and targeted Maori people who smoke.36 A major report by the US FDA concluded that a potential nicotine product standard would lead to an immediate and substantial reduction in smoking prevalence, resulting in an estimated 20 million additional people quitting smoking within five years and almost 48 million fewer people taking up smoking by 2100. These reductions would lead to over 4 million fewer tobacco-attributable deaths and almost 77 million additional years of life. Additional benefits include reductions in deaths from secondhand smoke exposure, smoking-related perinatal conditions, and smoking-related fires.37 Another recent modelling study highlighted the potential for implementation of a nicotine reduction policy to reduce disparities in the US, with life-years saved potentially nearing the millions for American Indian, Alaska Native or Asian people, and nearing or surpassing tens of millions among Black, Hispanic, and rural-residing people.38
Research with adolescents and young adults has found that reduced nicotine cigarettes can decrease the positive subjective effects of smoking, and therefore may reduce abuse liability.39-41 One study with adolescents who smoke found that reduced nicotine content cigarettes were less satisfying, and reduced withdrawal symptoms, negative affect, and craving,40 and another found reduced consumption among adolescents who smoke who were assigned very low nicotine cigarettes.42 Young people have also reported that they would reduce or quit smoking if a reduced nicotine policy was implemented.43 A major review found that one of the main benefits to public health of reducing nicotine would be decreasing uptake of regular smoking. Research to date suggests that reduced nicotine cigarettes may achieve this by reducing positive expectancies about smoking, and by reducing the likelihood of transitioning to regular smoking through making cigarettes inherently less reinforcing.44,45 Concerns that reduced nicotine content cigarettes might be more appealing to young people and/or might lead to compensatory smoking in youth have not been borne out by research.46
Among people who smoke, switching to reduced nicotine cigarettes can lead to a reduction in dependence,47,48 consumption (i.e., the number of cigarettes smoked per day),44,49,50 and toxicant exposure, with minimal symptoms of nicotine withdrawal.15,51-56 It may also increase the number and success of quit attempts.44,57,58 A common concern regarding low nicotine cigarettes is that people would engage in compensatory smoking—whereby people who smoke take more and deeper puffs from each cigarette, and smoke more of it, in order to obtain the same level of nicotine—resulting in minimal reductions in toxin exposure despite a reduction in cigarette consumption. However, studies have consistently shown that a reduction in nicotine content is unlikely to result in an increase in compensatory smoking.59-66 Compared to gradual reduction, immediate nicotine reduction appears to result in greater reductions in smoking behaviour and biomarkers of exposure67-70 and in product satisfaction and cigarette reward value.71 After trialling the products, people who smoke have reported generally positive outcomes such as feeling less dependent72 and support for nicotine reduction policies.73-75 Studies have also shown that switching to very low nicotine content cigarettes leads to reduced demand for the person’s usual-brand cigarettes76 and may also break the link between affect and smoking,77 indicating reductions in the reinforcing efficacy of cigarettes.78 These reductions in reinforcement value and consumption appear to occur even in the context of widespread availability of alternative nicotine products, indicating that obtaining nicotine from another source does not undermine the intended effects of reduced nicotine content cigarettes.79,80 Nonetheless, despite significant reductions in consumption and biomarkers of exposure with reduced nicotine content cigarettes, their use still carries significant health risks, highlighting their primary role as a step toward quitting.81
Research also suggests that reduced nicotine cigarettes could equally benefit heterogeneous population groups, including vulnerable or disadvantaged groups who are at greater risk of tobacco-related harm. Studies in people with mental illness and/or socioeconomic disadvantage who smoke have found that switching to reduced nicotine content cigarettes may improve respiratory health,82 reduce cigarette reinforcement,83 reduce consumption and dependence,17,84 and increase smoking cessation.85 In one study, low nicotine cigarettes elicited similar responses (in measures of consumption, dependence, and toxin exposure) across people who smoke regardless of indicators of disadvantage.86 Randomised controlled trials have generally found no differences in responses to very low nicotine cigarettes among young compared with older people who smoke,87,88 and regardless of the education level, race,67 or gender,67,89 though one recent trial suggested slightly attenuated benefits for older people who smoke and those with lower education levels.90 Findings of additional studies suggest that such a policy may also benefit people who identify as sexual- and/or gender-minoritised91 and those with chronic health conditions,92 and does not result in compensatory drinking among people who drink alcohol93,94 or increase substance use among at-risk individuals.95 One trial found slightly attenuated benefits for co-users of cannabis in terms of overall toxicant and carcinogen exposure, but similar benefits as cigarette-only users for reductions in consumption and tobacco-specific exposure.96 For pregnant women who smoke, some studies have found positive effects of switching to reduced nicotine cigarettes,97 though one that included women with high levels of dependence who smoked heavily did not find evidence of benefits (however there was also no evidence of harms).98 Very low nicotine cigarettes also appear to be effective across individual differences in nicotine metabolism and dependence,99 with one study finding that the most pronounced nicotine dependency reductions were observed in fast and medium compared with slow metabolisers who switched to very low nicotine content cigarettes.100 Overall, reviews have concluded that this policy could benefit those with psychiatric comorbidities, those who use other substances, those with low socioeconomic status, young people, people who smoke infrequently and people who prefer menthol cigarettes.44,101
12C.4 Public health considerations in implementing a nicotine reduction policy
Developing low-nicotine cigarettes has been a prominent approach in considerations of tobacco endgame strategies; it is endorsed by the American Medical Association, the British Medical Association, the US Food and Drug Administration (FDA) and the US Surgeon-General, and is also supported within the WHO Framework Convention on Tobacco Control (FCTC; see Chapter 19).102 A product standard for nicotine could be implemented through Articles 9 and 10 of the FCTC, which relate to the disclosure, testing, and regulation of the contents and emissions of tobacco products.20 The approach more broadly calls for research, government regulation, gradual reduction, consumer education, and increased availability of lower-risk options, in order to combat addiction and eliminate gateway risks.103
In its 2015 advisory note on a global nicotine reduction strategy, the WHO Study Group on Tobacco Product Regulation recommended that implementation of a nicotine-reduction policy should be supported by a comprehensive tobacco control program.13 That is, rather than being seen as a ‘silver bullet’, very low nicotine cigarettes should be implemented alongside investment in public education, accessible and affordable smoking cessation interventions, community engagement, and monitoring of tobacco and nicotine product use.90,104 In 2018, a joint meeting was held by the World Health Organization (WHO) and the Convention Secretariat of the FCTC to examine the potential effects of a regulatory policy to reduce nicotine in cigarettes to minimally addictive levels. It concluded that while some countries lack the capacity to implement such a policy, for those that can, it could substantially reduce the burden of tobacco use.20
An important consideration in the adoption of a nicotine reduction policy is ensuring that reduced nicotine content cigarettes are not perceived as less harmful, as some people who smoke erroneously believe that nicotine is one of the main causes of smoking-related disease.105-110 Many people also have misunderstandings regarding the role of nicotine in addiction.111 Research has shown that descriptions and marketing of reduced nicotine cigarettes can affect consumers’ perceptions,112,113 with a systematic review finding that commercial features (i.e., advertising, packaging and descriptors from manufacturers) were generally related to favourable responses to the products, while public health features (such as warning labels) often offset these positive responses, though findings were more mixed.114 One study found that people who smoke perceived a cigarette described as containing very low nicotine content as having lower risks of health issues and various cancers compared with a cigarette with “average” nicotine.115 Evidence from several studies suggests that messaging might educate people about the rationale for the policy,116 as well as include that low nicotine content cigarettes are as harmful as regular cigarettes and that they produce equally harmful secondhand smoke, but also that such products cannot relieve cravings and are less addictive and can make it easier to quit smoking.117-122 It may also be important to ensure that messages about potential benefits of the products (e.g. quitting efficacy) do not make the products appealing for people who do not smoke.123
Along with harm misperceptions, researchers have also noted other potential unintended consequences, such as product manipulation44—for example, tobacco industry manipulations of low nicotine cigarettes to make them more appealing and to maximise nicotine delivery124,125—and the development of an illicit market in tobacco products with higher nicotine levels.44,58,124,126 In order to minimise illicit trade, researchers have recommended tracking and tracing products and greater surveillance and enforcement,127 and in the context of enforcement, targeting manufacturing, distribution, and commercial sales, rather than individuals.44 Some have also argued that the risks of an illicit market are minimal, and do not outweigh the potential public health gains or justify a delay in implementing a reduced nicotine standard.128 Findings from one clinical trial in the US suggested that most people who smoke would be unlikely to seek out illicit cigarettes in response to a reduced nicotine policy.129 It may also be important to consider extending the product standard to other combusted tobacco products,21,130,131 and to increase availability and access to cessation aids, support and education.44 Some people who smoke may benefit from concurrent use of nicotine replacement therapy to support quit attempts using very low nicotine cigarettes.132-135 It has also been claimed that the effects of very low nicotine cigarettes on smoking may also be enhanced by use of e-cigarettes, though this would need to be balanced against the effects of policies to minimise youth access and uptake.136,137 There has been limited discussion about the potential of a nicotine reduction policy to increase illicit sales in a market where supply of vapes is restricted to therapeutic contexts and where illicit tobacco is not well controlled.
Some researchers highlight that factors other than nicotine/addiction can also influence and reinforce smoking behaviours.138-140 In addition to concerns about product manipulation and illicit markets, and given that smoking reduced nicotine content cigarettes81 and low-level smoking (see Section 3.36) carry substantial health risks, regulatory efforts should also, they argue, be cognisant of these non-nicotine factors.138 For example, the relative prices of high nicotine versus low nicotine products may influence users’ choices.124,141,142 Very low nicotine cigarettes containing menthol appear to be more appealing than non-menthol variants among young people and people who regularly smoke menthol cigarettes may be less likely to adhere to very low nicotine cigarettes, suggesting that menthol bans should occur alongside and extend to low nicotine cigarettes to maximise the effectiveness of the policy.143,144 Others have argued that the complexities of communicating a reduced tobacco product addictiveness policy to the public, combined with the potential for the tobacco industry to co-opt the messaging and for many other unintended consequences, may make such product standards ultimately ineffective. Instead, they suggest that it may be more beneficial for public health to focus on proposals to phase out retail sales of tobacco products entirely.145
12C.5 International approaches to reducing nicotine in cigarettes
Although a nicotine reduction standard for cigarettes has not been implemented anywhere in the world, several countries have taken some initial steps. Health Canada issued a tender in 2016 calling for research into the possibility of forcing tobacco companies to make their cigarettes less addictive,146 and issued another in 2018 requesting industry feedback regarding the feasibility and costs associated with procuring a supply of very low nicotine cigarettes.147 To date, it appears there has been no further progress on this strategy in Canada.
The US FDA included in its 2009 tobacco law the authority to reduce nicotine,148 and in 2018, issued an advance notice of proposed rulemaking to obtain information for consideration in developing a tobacco product standard to set the maximum nicotine level for cigarettes.149 In 2019, the FDA authorised the marketing of two variants of reduced nicotine content cigarettes manufactured by 22nd Century Group Inc., Moonlight and Moonlight Menthol.150 In 2021, the FDA further authorised 22nd Century Group to market two of its products – VLN King and VLN Menthol King – with certain reduced exposure claims regarding nicotine, including: “95% less nicotine”; “Helps reduce your nicotine consumption” and “...Greatly reduces your nicotine consumption.”151 Observations of the first retail test market found the products were being advertised and displayed prominently in stores, and using similar marketing strategies to high nicotine cigarettes.152 Plans for a proposed rule were again announced in 2022,153 and at the beginning of 2025, the FDA issued a proposed rule that would make cigarettes and certain other combusted tobacco products minimally or nonaddictive by limiting the level of nicotine in those products. The proposal included a request for public feedback and comments which would be open through September 2025 and would inform the next steps and further action.154 Surveys in the US show that a reduced nicotine policy receives greater support from people who have never smoked or who have quit than those who currently smoke, highlighting the importance of public education that corrects misperceptions and increases support among those targeted by the policy.155
Critics of the US proposal have argued that it may not be practicable within the confines of FDA law. Or, if it is, it may take many years to implement, and would require mandatory low nicotine content to succeed. They contend that resources would be better allocated to more pleasurable and likely less harmful forms of nicotine use, such as vaping and snus.102 Alternatively, others have suggested a combination of these strategies; that is, reducing the nicotine content of smoked tobacco products while allowing non-combustible recreational nicotine products to be sold.156-158 A review of legal arguments that the tobacco industry is likely to advance in response to the FDA implementing non-addictive nicotine levels concluded that the FDA stands on solid legal ground, and that there are strong arguments that it has the authority to implement such policy.159
In December 2021, the Aotearoa/New Zealand Government released its Smokefree Aotearoa 2025 Action Plan, outlining its proposals for the next four years to meet its goal of a daily smoking prevalence of less than five percent for all population groups by 2025. One of the focus areas of the report was to reduce the addictiveness and appeal of smoked tobacco products, as “Reducing nicotine in smoked tobacco products to minimally addictive levels will help people to either quit or swap to a less harmful alternative.”160 The Smokefree Aotearoa legislation—which included a dramatic reduction in nicotine content in smoked tobacco products to non-addictive levels alongside a tobacco-free generation and a significant reduction in the number of tobacco retail outlets—was passed in late 2022 but subsequently repealed in early 2024.
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References
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