The impact of exclusive use of very low nicotine cigarettes on compensatory smoking: An inpatient crossover clinical trial

Tracy T. Smith, Joseph S. Koopmeiners, Cassidy M. White, Rachel L. Denlinger-Apte, Lauren R. Pacek, Víctor R. De Jesus, Lanqing Wang, Clifford Watson, Benjamin C. Blount, Dorothy K. Hatsukami, Neal L. Benowitz, Eric C. Donny, Matthew J. Carpenter

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: The FDA is considering a mandated reduction in the nicotine content of cigarettes. Clinical trials have been limited by non-study cigarette use (noncompliance), which could mask compensation. The goal of this study was to assess whether compensation occurs when smokers provided with very low nicotine cigarettes cannot access normal nicotine cigarettes. Methods: In a within-subjects, crossover design, current smokers (n = 16) were confined to a hotel for two 4-night hotel stays during which they were only able to access the research cigarettes provided. The hotel stays offered normal nicotine cigarettes or very low nicotine content (VLNC) cigarettes, in an unblinded design, available for "purchase" via a study bank. Results: In the context of complete compliance with the study cigarettes (n = 16), there was not a significant increase during the VLNC condition for cigarettes smoked per day, expired carbon monoxide, or N-acetyl-S-(cyanoethyl)-L-cysteine (cyanoethyl-MA, metabolite of acrylonitrile). There was a significant nicotine × time interaction on urine N-acetyl-S-(3-hydroxypropyl)-L-cysteine (hydroxypropyl-MA, metabolite of acrolein), driven by an increase in the VLNC condition during the first 24 hours. By the end of the VLNCcondition, there was no evidence of compensation across any measure of smoking or smoke exposure. Conclusions: Among current smokers who exclusively used VLNC cigarettes for 4 days, there was no significant compensatory smoking behavior. Impact: These data, combined with the larger body of work, suggest that a mandated reduction in nicotine content is unlikely to result in an increase in smoking behavior to obtain more nicotine.

Original languageEnglish (US)
Pages (from-to)880-886
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Issue number4
StatePublished - Apr 2020

Bibliographical note

Funding Information:
The research reported in this article was supported by the National Institute on Drug Abuse and the FDA Center for Tobacco Products (R03DA045197 to T.T. Smith). Salary support during the preparation of the article was provided by the National Institute on Drug Abuse (K01DA047433 to T.T. Smith and K01DA043413 to L.R. Pacek). The authors would like to thank the following individuals for their work in data collection: Lisa Coles, Noelle Natale, Amy Boatright, David Braak, Nathan Silvestri, and Mason Deinema. Thank you to Dr. Kevin Gray for serving as the licensed medical provider.

Publisher Copyright:
© 2020 American Association for Cancer Research.

Copyright 2020 Elsevier B.V., All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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