Nicotine Reduction in Cigarettes: Literature Review and Gap Analysis

Abstract

Background The US Food and Drug Administration (FDA) is considering reducing nicotine levels in cigarettes to “minimally or non-addictive levels.” However, important research gaps remain, and the FDA must determine when the available research is sufficient to support moving forward. Methods The authors conducted a systematic review of research articles in PubMed relating to nicotine reduction. Building on a review of risk assessment best practices, the authors also developed a risk assessment framework for tobacco regulation and used it to guide a gap analysis of nicotine reduction research. Results The final sample consisted of 78 articles. The majority examined either nicotine dependence on very low nicotine cigarettes (VLNCs) or markers of potential health effects of using VLNCs. One-third of the identified articles reported results from four large randomized controlled trials (RCTs). While these studies report promising results and suggest that a nicotine reduction rule would be a powerful tool to reduce cigarette smoking, our gap analysis suggests that there is a need for studies that better reflect the use and availability of a wide range of tobacco/nicotine products and the potential for dual- or multi-product use. Conclusion The current body of research on nicotine reduction is weighted towards RCTs, which is appropriate for a policy that has not yet been implemented anywhere in the world. The FDA must consider a wide range of factors that may impact a product standard’s public health impact, including those difficult to assess in RCTs, such as a nicotine reduction rule’s impact on smoking initiation and relapse. Implications This systematic review presents a gap analysis based on a risk assessment framework to help identify remaining research priorities to inform FDA’s potential product standard to reduce nicotine levels in cigarettes. Quickly addressing those gaps would support the FDA’s effort to develop a nicotine reduction product standard that will be effective and withstand legal challenges.

Acute effects of a very low nicotine content cigarette on laboratory smoking lapse: Impacts of nicotine metabolism and nicotine dependence

“…Our results are consistent with those of other human laboratory findings, where VLNCs reduce craving and withdrawal and delay the onset of subsequent preferred tobacco self‐administration 8,9,20 . Our findings also support evidence from clinical trials, where switching to VLNCs is associated with reduced craving/withdrawal, increased cessation success and reduced relapse 5,46 …”

“…Reducing cigarette nicotine content to nonreinforcing levels may reduce addiction severity and facilitate smoking cessation 3,4 . In clinical trials, very low nicotine content cigarettes (VLNCs; ≤0.4 mg/g of nicotine) can reduce exposure to nicotine, smoking quantity and dependence severity and increase cessation attempts and success, 5,6 with minimal evidence of harm, such as compensatory smoking (i.e., increasing smoking to maintain desired nicotine levels) 7 . In laboratory research, VLNCs alleviate abstinence‐induced craving and withdrawal and delay the onset of subsequent smoking 8,9 .…”

Nicotine Standards in the United States

“…It has also been made clear that in order to mitigate any negative consequences, the availability of regulated alternative nicotine products is important and protective measures to reduce the use of illegal cigarettes need to be implemented. Although several gaps in research have been identified, some of these gaps are currently being addressed and, as stated by Berman and Glasser, 26 “given the overwhelming amount of harm caused by combusted tobacco products and the substantial and rapidly growing body of literature on nicotine reduction, the remaining research gaps should not prevent the FDA from moving forward with the rulemaking process.”…”

“…Finally, Berman and Glasser’s 26 literature review summarized the state of the science and identified gaps, which include the need for more studies that better reflect the availability and use of a wide variety of tobacco and nicotine products (including cigarettes from illegal markets) and the potential for dual or multiproduct use, that model the impact of a nicotine standard in the context of other control measures, and that determine the impact of product standards on cessation, initiation and relapse.…”

Communication challenges of a tobacco addictiveness reduction policy

“…Initial ideas for a nicotine reduction strategy involved gradually reducing the allowable level of nicotine in cigarettes to non-addicting levels, both as a way to prevent youth from becoming addicted and to help existing smokers to quit 3 . A growing body of small experimental studies suggests that removing nicotine from cigarettes may assist smokers to successfully quit, but no large-scale interventions, under real-world conditions, have yet been conducted 4 . Nonetheless, there is some interest in exploring possible policy solutions to reducing the addictiveness of tobacco products, especially given the current proliferation of novel and alternative nicotine and tobacco products.…”