A Randomized Clinical Trial of Snus Examining the Effect of Complete Versus Partial Cigarette Substitution on Smoking-Related Behaviors, and Biomarkers of Exposure

Ellen Meier, Bruce R. Lindgren, Amanda Anderson, Sarah A. Reisinger, Kaila J. Norton, Joni Jensen, Lori Strayer, Laura Dick, Mei Kuen Tang, Menglan Chen, Steven G. Carmella, Stephen S. Hecht, Sharon E. Murphy, Jing Yang, Irina Stepanov, Richard J. O'Connor, Peter G. Shields, Dorothy K. Hatsukami

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


INTRODUCTION: This 8-week multisite, randomized controlled trial of snus examined the differential effects of instructions on (1) snus use, (2) smoking and smoking-related measures, and (3) exposure to tobacco-related constituents.

METHOD: US adult daily cigarette smokers (n = 150; 43.3% female; Medianage = 43.5) were recruited from Minneapolis, Minnesota; Columbus and Coshocton, Ohio; and Buffalo, New York. Following a 1-week sampling phase of snus, participants who used at least 7 pouches were randomized to either (1) partial substitution (PS; "use snus as you like with your cigarettes"), (2) complete substitution (CS; "avoid cigarettes"), or (3) usual brand cigarettes (UB). Analyses included between-group analyses (eg, PS vs. CS) using Wilcoxon rank sum test of cigarettes per day and snus pouches per day, and a linear mixed model (biomarkers).

RESULTS: Compared to the PS and UB groups, smokers assigned to CS reported greater reductions in cigarettes per day (ps < .001), using more snus pouches per day (p = .02), and more smoke-free days (CS median = 14.5, PS and UB medians = 0, p < .001). In addition, results demonstrated reductions in carbon monoxide (p < .001), total nicotine equivalents (p = .02), and four out of five measured volatile organic compounds (ps < .01) over time among the CS group. Exposure to N'-nitrosonornicotine increased by trial end only among the PS group (p < .04). Phenanthrene tetraol increased among all groups by trial end (p = .02) with no difference between groups.

CONCLUSIONS: Instructions to completely switch from cigarettes to snus resulted in the greatest reduction in cigarettes and exposure to harmful constituents.

IMPLICATIONS: Directly instructing smokers to switch completely to snus, rather than using ad libitum (with no instructions to avoid cigarettes), is necessary for reductions in smoking and subsequent exposure to harmful constituents.

Original languageEnglish (US)
Pages (from-to)473-481
Number of pages9
JournalNicotine and Tobacco Research
Issue number4
StatePublished - Apr 1 2021

Bibliographical note

Funding Information:
Research reported in this publication was supported by grants from National Cancer Institute (U19CA157345 to DKH/PGS), National Center for Advancing Translational Science of the National Institutes of Health (UL1 TR000062), National Cancer Institute (R01 CA180880 to IS), and National Institute of Drug Abuse (T32 DA007097 to EM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Publisher Copyright:
© 2019 The Author(s). Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.


  • Adolescent
  • Adult
  • Biomarkers/metabolism
  • Carbon Monoxide/analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Minnesota/epidemiology
  • New York/epidemiology
  • Nitrosamines/administration & dosage
  • Smoking/epidemiology
  • Smoking Cessation/methods
  • Tobacco Use Disorder/diagnosis
  • Tobacco, Smokeless/statistics & numerical data
  • Young Adult

PubMed: MeSH publication types

  • Randomized Controlled Trial
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Comparative Study


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