InDepth 12C: Reducing the nicotine content of cigarettes

Last updated:  January 2022

Suggested citation: Greenhalgh, EM, Winnall, WR & Scollo, MM. InDepth 12C: Reducing the nicotine content of cigarettes. In Greenhalgh, EM, Scollo, MM and Winstanley, MH [editors]. Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2023. Available https://www.tobaccoinaustralia.org.au/chapter-12-tobacco-products/indepth-12c-reducing-the-nicotine-content-of-cigarettes

 

12C.1 Rationale for reducing the level of nicotine in cigarettes
12C.2 Development of low nicotine cigarettes
12C.3 Effects of reduced nicotine content cigarettes on smoking and health
12C.4 Public health considerations in implementing a nicotine reduction policy

12C.1 Rationale for reducing the level of nicotine in cigarettes

It is well established that addiction to nicotine maintains most smokers’ use of tobacco products.1 Once addicted, quitting can be extremely difficult, with many smokers 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—sustains the behaviour into adulthood, dramatically increasing their risk of tobacco-related harm.4

The regulation of the maximum level of nicotine in tobacco products was first suggested in the mid-1990s as a potential strategy for avoiding the transition from experimental smoking to addiction.5, 6 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.7, 8  Reducing the nicotine content in cigarettes so that they are non-addictive was proposed as a mechanism to prevent adolescents and occasional smokers from becoming addicted. A gradual reduction could also allow smokers to slowly decrease their intake of nicotine, thereby weaning themselves off the product and making quitting substantially easier.9, 10

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 smokers 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.10

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.9 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 addictiveness11, 12 and dependence.13 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,14 with minimal differences between 2.4 and 0.4 mg nicotine doses15, 16 or between 1.3 and 0.4 mg/g.17 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.18, 19

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.13 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.20

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.21 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.22 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.23 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.23-25 Similar techniques have been used to generate low-alkaloid tobacco plants by disrupting the BBL gene.26 Importantly, other potentially addictive alkaloids such as anatabine, nornicotine and anabasine remained at low levels in these plants.26

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.21 Using a filter that removes much of the nicotine from cigarette smoke is another option for creating low-nicotine cigarettes.27

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.21 It is possible that alkaloids contribute somewhat to the taste of the tobacco, so reducing them leads to flavour changes that are unavoidable.21 The US FDA recently 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.28

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.29, 30 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 2064.31 Following a recent announcement in New Zealand of a nicotine reduction strategy,32 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 smokers. However, the authors note that there is a high level of uncertainty with the findings.33

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.34-36 A study with adolescent smokers found that reduced nicotine content cigarettes were less satisfying, and reduced withdrawal symptoms, negative affect, and craving.35 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.37 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.38

Among smokers, switching to reduced nicotine cigarettes can lead to a reduction in dependence,39, 40 consumption (i.e., the number of cigarettes smoked per day),37, 41, 42 and toxicant exposure, with minimal symptoms of nicotine withdrawal.13, 43-48 It may also increase the number and success of quit attempts.37, 49, 50 A common concern regarding low nicotine cigarettes is that smokers would engage in compensatory smoking—whereby smokers 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.51-55 Compared to gradual reduction, immediate nicotine reduction appears to result in greater reductions in smoking behaviour and biomarkers of exposure56, 57 and in product satisfaction and cigarette reward value.58 After trialling the products, smokers have reported generally positive outcomes such as feeling less dependent59 and support for nicotine reduction policies.60-62 Studies have also shown that switching to very low nicotine content cigarettes leads to reduced demand for smokers’ usual-brand cigarettes63 and may also break the link between affect and smoking,64 indicating reductions in the reinforcing efficacy of cigarettes. 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.65 

Research also suggests that reduced nicotine cigarettes could equally benefit heterogeneous groups of smokers, including vulnerable or disadvantaged groups who are at greater risk of tobacco-related harm. Studies in smokers with mental illness and socioeconomic disadvantage have found that switching to reduced nicotine content cigarettes may improve respiratory health66 and reduce consumption and dependence.15, 67 In one study, low nicotine cigarettes elicited similar responses (in measures of consumption, dependence, and toxin exposure) across smokers regardless of indicators of disadvantage.68 Several randomised controlled trials found no differences in responses to very low nicotine cigarettes among young compared with older smokers,69, 70 and regardless of the education level, race,56 or gender.56, 71 Findings of additional studies suggest that such a policy may also benefit pregnant women who smoke72 as well as people with chronic health conditions,73 and may also help to reduce alcohol use and binge drinking among smokers.74 Responses to nicotine reduction appear to be largely similar regardless of individual differences in nicotine metabolism and dependence.75 A review published in 2021 similarly 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.37

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).76 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.18 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.77

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.11 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.18

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 smokers erroneously believe that nicotine is one of the main causes of smoking-related disease.78-81 Research has shown that descriptions and marketing of reduced nicotine cigarettes can affect consumers’ perceptions,82, 83 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.84 One study found that smokers 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.85 Evidence from focus groups in the US suggests that messaging should include that low nicotine content cigarettes are still harmful, but also that such products can make it easier for smokers to quit.86 Another US study found that when communicating a nicotine reduction standard to smokers, framing the information as cigarettes no longer being able to relieve cravings was the most effective for potentially promoting quitting.87

Along with harm misperceptions, researchers have also noted other potential unintended consequences, such as product manipulation37 and an illicit market.37, 50, 88 In order to minimise illicit trade, researchers have recommended tracking and tracing products and greater surveillance and enforcement,89 and in the context of enforcement, targeting manufacturing, distribution, and commercial sales, rather than individuals.37 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.90 It may also be important to consider extending the product standard to other combusted tobacco products,19, 91, 92 and to increase availability and access to cessation aids, support and education.37 Some smokers may benefit from concurrent use of nicotine replacement therapy to support quit attempts using very low nicotine cigarettes.93-95

Further, some researchers highlight that factors other than nicotine/addiction can also influence and reinforce smoking behaviours,96-98 and given that smoking reduced nicotine content cigarettes65 and low-level smoking (see Section 3.36) carry substantial health risks, regulatory efforts should be cognisant of these non-nicotine factors.96 For example, the relative prices of high nicotine versus low nicotine products may influence users’ choices.99, 100 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.101

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,102 and issued another in 2018 requesting industry feedback regarding the feasibility and costs associated with procuring a supply of very low nicotine cigarettes.103 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,104 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.105 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.106 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.”107 As at late 2021, the FDA was reportedly still considering requiring tobacco companies to reduce the amount of nicotine in cigarettes to nonaddictive levels.108

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.76 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.109-111 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.112

In December 2021, the 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 is 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.”  The Government has stated that in 2022 it will introduce an amendment Bill to allow only very low nicotine levels in smoked tobacco products for manufacture, importation, distribution, and sale in New Zealand, and that it will introduce product assurance systems to support compliance with these requirements.32 All Imperial Brands cigarette products sold in Australia are currently manufactured in New Zealand.113

 

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