Very Low Nicotine Content (VLNC) cigarettes VLNC cigarettes, also known as reduced nicotine cigarettes or denicotinized cigarettes, contain tobacco with

primary cause of the detrimental health effects of tobacco, it is the primary addictive agent (U.S. Department of Health and Human Services, 2014). Thus, the reduction of nicotine in tobacco may help reduce smoking prevalence and smoking-related health outcomes in three ways: 1) reducing nicotine reinforcement and therefore dependence in current smokers and thus providing them with a greater opportunity to reduce or quit smoking, 2) reducing reinforcement in new users making them less likely to develop dependence and habitual smoking behaviour, and 3) ex-smokers who lapse are less likely to experience the positively reinforcing effects of nicotine and become regular smokers again (Donny et al., 2014). These mechanisms are primarily supported through reducing the chemical addictive potential, giving a greater possibility of behaviour change.

One concern about the introduction of VLNC cigarettes to the market is that smokers would smoke more frequently or more intensively in order to attain optimal nicotine

reinforcement levels. When considering this, it is important to distinguish VLNC cigarettes from ‘low yield’ or ‘light’ cigarettes which generate lower yield of nicotine in machine testing due to features such as faster burn time or filter ventilation. Low yield cigarettes are prone to high rates of compensatory behaviours such as blocking ventilation holes, taking bigger or more frequent puffs, or smoking more cigarettes per day. Engaging in these behaviours can lead to increased toxicant exposure and smoking-related health risks

(Kozlowski & O'Connor, 2002; National Cancer Institute, 2001). On the other hand, VLNC cigarettes contain substantially less nicotine in the tobacco itself (<0.05mg) yet similar satiating amounts of tar, chemical irritants and taste. This makes it extremely difficult or impossible for smokers to engage in compensatory smoking in order to obtain larger doses of nicotine (Benowitz & Henningfield, 2013; Donny et al., 2014). Studies comparing VLNC and regular cigarettes show that VLNC cigarettes are associated with low levels or complete absence of compensatory smoking based on behavioural smoking changes (e.g. cigarettes

smoked, number of puffs, puff volume), changes in biomarker exposure and cardiovascular effects (Benowitz et al., 2012; Benowitz et al., 2007; Benowitz, Jacob, & Herrera, 2006; Donny et al., 2015; Donny, Houtsmuller, & Stitzer, 2007; Donny & Jones, 2009; Hatsukami et al., 2010; Strasser, Lerman, Sanborn, Pickworth, & Feldman, 2007). As such the majority of studies support the idea that when smokers use VLNC cigarettes they do not engage in significant compensatory smoking behaviour in order to attain their usual level of nicotine.

Several studies have examined the efficacy of VLNC cigarettes for smoking cessation in clinical trials. However, the results are mixed and studies are difficult to compare due to differing methodologies, timeframes and intended use of VLNC cigarettes. Intended uses across studies include immediate switching to VLNC cigarettes from regular cigarettes, gradual nicotine reduction or “tapering”, combination with NRT, and as a pre-cessation treatment. Clinical trials have shown that immediately switching to VLNC cigarettes leads to reduced nicotine exposure, dependence and cigarettes smoked per day relative to continuing to smoke regular cigarettes after 11 days (Donny et al., 2007) and six weeks (Donny et al., 2015). Another series of studies has shown that gradual nicotine reduction or “tapering” using cigarettes with progressively lower nicotine contents (12, 8, 4, 2 and 1mg) leads to greater reductions in cigarette consumption during the study and up to 6 months follow-up compared to controls smoking their regular cigarettes (Benowitz et al., 2012; Benowitz et al., 2007; Benowitz et al., 2015). Cessation studies have shown that switching immediately to VLNC cigarettes leads to similar levels of cessation as switching to NRT (Becker, Rose, & Albino, 2008; Hatsukami et al., 2010). There is also some evidence that a combination approach of VLNC cigarettes plus NRT produces greater cessation rates and reductions in cigarette consumption than either VLNC cigarettes or NRT alone (Hatsukami, Hertsgaard, et al., 2013; Walker et al., 2012).

These studies support the view that VLNC cigarettes can reduce smoking behaviour by reducing the reinforcement properties of cigarettes and thus smoking dependence (Donny et al., 2014). However, it has been suggested that reductions in smoking could be attributed to the novel or aversive nature of the research cigarettes rather than the nicotine content per se (Donny et al., 2007). As such it is unclear whether smokers would make the decision to use VLNC cigarettes if they were not required to as part of a clinical trial. Thus it is important to also consider consumer response to VLNC cigarettes. The self-reported subjective effects (taste and satisfaction, psychological reward, and craving reduction) may provide information as to whether smokers would actually use VLNC cigarettes. This data could also be

complemented by demand data from hypothetical purchase tasks and cross price tasks to inform whether individuals would purchase and use alternative products.

2.3.3.1.1. Subjective effects. Both clinical and laboratory studies show that smokers tend to rate VLNC cigarettes as lower quality and less satisfying than their usual brand cigarettes (Becker et al., 2008; Benowitz et al., 2006; Donny et al., 2007; Gross, Lee, & Stitzer, 1997; Strasser et al., 2007). However in some cases these effects are minimal and it has been suggested that ratings may be affected by switching from a familiar brand to a novel research cigarette and unrelated to nicotine content (Shahan et al., 1999). For example, Donny et al. (2007) found that switching from usual brand cigarettes to 0.3mg and 0.05mg cigarettes produced an immediate decrease in positive and increase in negative self-reported effects, regardless of nicotine content. On the other hand, smokers report that VLNC

cigarettes reduce craving and withdrawal symptoms similarly to regular cigarettes (Donny et al., 2015; Donny et al., 2007; Gross et al., 1997), and similarly or better than some NRT products such as nicotine lozenges and patches (Donny & Jones, 2009; Hatsukami,

Cummings, 2007). This suggests that despite lower favourability and minimal nicotine delivery, VLNC cigarettes may be helpful in reducing symptoms of nicotine withdrawal.

Some studies have found that the subjective effects of VLNC cigarettes are different for men and women. Barrett (2010) found that smoking a VLNC cigarette after 12 hour abstinence reduced craving in women but not men, and Vogel et al. (2014) found that women reported greater satisfaction for VLNC cigarettes in a clinical trial, while men reported greater satisfaction and suppression of withdrawal symptoms when VLNC cigarettes were combined with nicotine replacement therapy (NRT). This is supported by previous research that has found that NRT leads to greater suppression of withdrawal symptoms (Hatsukami, Skoog, Allen, & Bliss, 1995; Wetter, Fiore, Young, McClure, & de Moor, 1999) and craving (Killen, Fortmann, Newman, & Varady, 1990; Perkins et al., 2006), and higher abstinence rates (Becker et al., 2008; Perkins & Scott, 2008) in males verses females. These findings are consistent with a review which concluded that females have reduced sensitivity to nicotine reinforcement than males with less differential self-administration of nicotine versus placebo nasal spray, reduced self-reported effects of nicotine, and less response to pre-treatment with nicotine, especially at lower doses (Perkins, 2009). Studies have shown that females appear more sensitive to visual, olfactory and taste cues than males (Evans, Blank, Sams, Weaver, & Eissenberg, 2006; Perkins, Epstein, Grobe, & Fonte, 1994; Perkins et al., 2001; Perkins, Jacobs, Sanders, & Caggiula, 2002), greater behavioural dependence (Bohadana, Nilsson, Rasmussen, & Martinet, 2003), and greater importance placed on concurrently presented cues in nicotine self-administration in animal studies (Chaudhri et al., 2005; Donny et al., 2000). This potential physiological difference may account for sex differences reported in the aforementioned studies.

2.3.3.1.2. Demand. Only two studies have investigated demand for VLNC cigarettes. These studies used self-administration procedures with behavioural responses (plunger pulls)

as an analogue for price (Johnson, Bickel, & Kirshenbaum, 2004; Shahan et al., 1999). Shahan et al. (1999) examined the elasticity of conventional and VLNC cigarettes using a progressive ratio schedule of reinforcement where each were available independently, before comparing preference when available concurrently. They found that when available

independently, VLNC cigarettes and conventional cigarettes were similarly sensitive to price and had similar breakpoints and peak responding rates. However, when the two cigarette types were available concurrently, there was a strong preference for conventional cigarettes. This supports the theory that smoking-related stimuli can be conditioned reinforcers in the absence of the primary reinforcing properties of nicotine, but without nicotine they function as a less potent reinforcer. However, participants rated taste and smoothness lower for VLNC cigarettes, thus it is unclear to what extent preference and favourability of conventional cigarettes is due to the nicotine level or other taste and sensory differences. Johnson et al. (2004) examined the substitutability of nicotine gum and VLNC cigarettes for conventional cigarettes. By making each alternative product available at a constant unit price concurrently with conventional cigarettes at increasing unit prices, they calculated CPE for both products. They found that increasing unit price of conventional cigarettes caused an increase in

consumption of nicotine gum and VLNC cigarettes in separate trials, indicating that both products act as behavioural economic substitutes for conventional cigarettes. The CPE estimates were similar for VLNC cigarettes and nicotine gum (0.20 and 0.19 respectively). However, VLNC cigarettes caused a significant reduction in conventional cigarette

consumption, while nicotine gum did not. Furthermore, when both alternative products were available concurrently while conventional cigarettes increased in price, consumption of VLNC cigarettes was significantly higher than consumption of nicotine gum.

Results of these studies suggest that not only can VLNC cigarettes function as a substitute for conventional cigarettes, but that they may function as a more effective

behavioural economic substitute than nicotine gum. Although nicotine is the primary tobacco constituent that maintains dependence, VLNC cigarettes share a number of common non- nicotine features including: non-nicotine pharmacological agents; sensory features of the appearance, size and shape of the cigarette and the sight, smell and taste of smoke in the air, mouth and throat; and behaviours associated with smoking including preparatory behaviours and hand-to-mouth motor action. Over time, these features have been repeatedly paired with the self-administration of nicotine for smokers and thus may have become conditioned reinforcers and may elicit some of the reinforcing properties usually elicited from nicotine intake when administered in the absence of nicotine. This is consistent with the evidence suggesting that VLNC cigarettes tend to be rated as lower quality and less satisfying than regular cigarettes (whether due to the novel nature of research cigarettes or due to the absence of nicotine itself), but can reduce symptoms of nicotine withdrawal including craving

cigarettes.

2.3.3.1.3. Summary and application to New Zealand. VLNC cigarettes may reduce smoking behaviour by reducing nicotine intake and thus dependence in smokers who choose to use them. VLNC cigarettes deliver minimal quantities of nicotine and thus provide reduced levels of the positively or negatively reinforcing effects of nicotine, which is likely to lead to reductions in smoking behaviour. Though they appear to reduce withdrawal symptoms at a similar rate to regular cigarettes, VLNC cigarettes are subjectively rated as less satisfying and enjoyable, suggesting their abuse liability may be lower than that of regular cigarettes.

Behavioural economic studies suggest that VLNC cigarettes are partially substitutable for regular cigarettes, and it is unclear whether the properties that these products share constitute enough of a positive consumer response to encourage smokers to progress from trial or experimental use to prolonged use or actual substitution for regular cigarettes, if the two were concurrently available. Due to smokers’ preferences and the partial substitutability of VLNC

cigarettes for regular cigarettes, price differentials between the two products would likely need to be maintained in order for smokers to choose to purchase VLNC cigarettes over regular cigarettes.

Another option for the use of VLNC cigarettes in tobacco control policy is a

mandated nicotine reduction policy; requiring that all cigarettes must contain very low levels of nicotine. This type of population-level policy is likely to have the greatest impact on smoking behaviour by preventing concurrent use of VLNC cigarettes and regular cigarettes, which would lead to intermittent nicotine reinforcement and continuation of cigarette

smoking behaviour. If VLNC cigarettes were the only combustible tobacco product available to smokers, smoking prevalence would be likely to decline more rapidly. However, there is limited behavioural economic research using VLNC cigarettes and as such little is known about demand for these products using monetary prices. Using hypothetical purchase tasks to compare demand for, and substitutability of VLNC cigarettes and regular cigarettes could inform how VLNC cigarettes may best contribute to tobacco control policy.

In New Zealand, the concept of a nicotine reduction policy is supported by the general public, researchers and public health professionals (Donny et al., 2016; Laugesen et al., 2010; Li, Bullen, Newcombe, Walker, & Walton, 2013). A population-based survey of New

Zealanders found that 81% of the sample indicated that they agreed with the statement “the nicotine content of cigarettes should be reduced to very low levels so that they are less addictive”, including 63% of smokers, 73% of Māori and 87% of Pacific Island respondents (Li et al., 2013). This provides some preliminary evidence that policies using VLNC

cigarettes may be accepted in New Zealand. Donny et al. (2016) highlighted the advantages of implementing and evaluating a nicotine reduction policy, potentially using VLNC

cigarettes in New Zealand including: the comprehensive tobacco control programmes and support for quitting; the aspirational Smokefree 2025 goal; advertising bans to control health

messaging around VLNC cigarettes; and the support of tobacco control advocates, smoker and non-smokers, including priority population groups such as Māori and Pacific Island peoples. Furthermore, proposals to legalise the sale and supply of nicotine-containing e- cigarettes and e-liquid as consumer products (Ministry of Health, 2017) may provide a novel opportunity for the development of a more comprehensive and integrated nicotine policy (Donny et al., 2016).

2.3.3.2. Electronic cigarettes. E-cigarettes may have a role in tobacco control by

In document Behavioural economic studies of tobacco control : excise tax, alternative products, and application to priority populations in New Zealand (Page 42-50)