The Role of Nicotine and Flavor in the Abuse Potential and Appeal of Electronic Cigarettes for Adult Current and Former Cigarette and Electronic Cigarette Users: A Systematic Review

Abstract

Introduction Many adult cigarette smokers use electronic cigarettes (e-cigarettes) to cut down on or quit smoking cigarettes. E-cigarettes with higher abuse potential and appeal might facilitate complete switching. E-liquid nicotine concentration and flavor are two of the characteristics that may affect the abuse potential and appeal of e-cigarettes. The objective of this systematic review was to compile results from survey, animal, human laboratory, and clinical studies to understand the possible effects of nicotine concentration and flavor on abuse potential and appeal of e-cigarettes in adult current and former cigarette and e-cigarette users. Methods A comprehensive literature search was conducted in Ovid Medline and PsycINFO followed by citation tracking in Web of Science Core Collection. Peer-reviewed studies published in English between 2007 and August 2020 were selected that analyzed differences between e-liquid nicotine concentration and/or flavors, had outcome measures related to abuse potential and/or appeal, and included adult humans (18+) or animals. 1624 studies were identified and screened. A qualitative synthesis of results was performed. Results Results from 104 studies included in this review suggest that higher nicotine concentration and access to a variety of flavors are likely to be associated with higher abuse potential and appeal of e-cigarettes for adult current and former cigarette and e-cigarette users. Conclusions Higher nicotine concentrations and the availability of a variety of flavors in e-cigarettes might facilitate complete substitution for cigarettes. Future e-cigarette regulations should take into account their impact on smokers, for whom e-cigarettes may be a cessation tool or reduced-harm alternative. Implications E-cigarettes may provide a reduced-harm alternative to cigarettes for smokers unwilling/unable to quit or serve as a path for quitting all nicotine products. Higher nicotine concentrations and flavor variety are associated with higher abuse potential and appeal of e-cigarettes. Higher abuse potential and appeal products may help facilitate complete switching from cigarettes to e-cigarettes. Regulation of nicotine concentration and flavors aimed at decreasing naïve uptake may inadvertently decrease uptake and complete switching among smokers, reducing the harm reduction potential of e-cigarettes. Evidence-based effects of regulating nicotine concentration and flavors must be considered for the population as a whole, including smokers.

Randomized trials assessing the impact of flavors on pharmacokinetic, pharmacodynamic, and subjective parameters in dry and moist nicotine pouch products

“…However, great variability was observed for the parameters 'product-liking' and 'intent to use again'; no product variety appealed to everyone, but each variety appealed to someone. This concept is in line with a recent systematic literature review indicating that su cient nicotine delivery and variety of avors can facilitate consumer switching [20].…”

“…While numerous NP products are currently commercially available, the nicotine pharmacokinetics (PK) and pharmacodynamics (PD) have been investigated in only a limited number of these products [15-18, 12, 19]. Previous studies have also highlighted the importance of avors in order to help transition smokers to less risky nicotine products [20]. On the other hand, it has been hypothesized that avor may have an impact on the abuse potential of a nicotine product both by enhancing nicotine uptake as well by increasing their appeal [21].…”

Combinations of electronic nicotine delivery system device and liquid characteristics among U.S. adults

“…The amount of nicotine and non-nicotine toxicants that an ENDS device/liquid combination can deliver has implications for how effective it can be to help people stop using cigarettes, for dependence (abuse liability), and for potential health effects. (Gades et al, 2022;Hoetger et al, 2021 Oct 14) A device's power characteristics (wattage: a function of battery voltage and heating coil resistance), nicotine concentration of the liquid, and nicotine form (salt or free-base) all influence the amount of nicotine delivered to the user. (Shihadeh and Eissenberg, 2015 Feb;El Hourani et al, 2022;Wagener et al, 2017 Mar;Leventhal et al, 2021 Jan 4;Talih et al, 2021;Talih et al, 2020 Oct 1;Hiler et al, 2020 Oct) Which products are being used and by whom has implications for understanding how ENDS use benefits or harms individual and public health.…”

An exploration of flavours in studies of e‐cigarettes for smoking cessation: secondary analyses of a systematic review with meta‐analyses

“…A systematic review, including any type of study that analysed differences between EC flavours published between 2007 and August 2020, found evidence that people who smoked combustible cigarettes and used non-tobacco flavoured e-liquids were more likely to have reduced or quit smoking than those using tobacco or unflavoured e-liquids. (5) Simply having a choice of flavour options to switch between could also make EC a more desirable quitting aid, able to meet a person's changing preferences throughout their quit attempt. The previously mentioned systematic review found that EC users valued the ability to switch between flavours and it was one of the main reasons given for EC use; following health and smoking cessation.…”

“…Experimentation was less common in those who chose a tobacco-flavoured e-liquid at baseline. Finally, the aforementioned systematic review of any study that investigated differences in EC flavours published up to August 2020 found evidence that flavour preferences had changed over time [5], with a preference for the more traditional cigarette flavours of tobacco and menthol shifting towards sweet flavours. This appeared to be true even in people using In addition, due to the limited and aggregated data included in this review, we were unable to examine variables that may be mediating or confounding the relationship between flavour use and smoking cessation in more depth; for example, nicotine concentration, device power, amount of e-liquid used, number of puffs taken.…”