Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial

Dorothy K Hatsukami; Joni A Jensen; Dana Mowls Carroll; Xianghua Luo; Lori G Strayer; Qing Cao; Stephen S Hecht; Sharon E Murphy; Steven G Carmella; Rachel L Denlinger-Apte; Suzanne Colby; Andrew A Strasser; F Joseph McClernon; Jennifer Tidey; Neal L Benowitz; Eric C Donny

doi:10.1016/j.lana.2024.100796

Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial

Lancet Reg Health Am. 2024 Jun 3:35:100796. doi: 10.1016/j.lana.2024.100796. eCollection 2024 Jul.

Authors

Dorothy K Hatsukami^{1

2}, Joni A Jensen², Dana Mowls Carroll³, Xianghua Luo^{2

4}, Lori G Strayer², Qing Cao², Stephen S Hecht^{2

5}, Sharon E Murphy^{2

6}, Steven G Carmella², Rachel L Denlinger-Apte⁷, Suzanne Colby⁸, Andrew A Strasser⁹, F Joseph McClernon¹⁰, Jennifer Tidey⁸, Neal L Benowitz¹¹, Eric C Donny¹²

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Medical School, University of Minnesota, Minneapolis, MN, USA.
² Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
³ Division of Environmental Health Sciences, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
⁴ Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
⁵ Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN, USA.
⁶ Biochemistry, Molecular Biology and Biophysics, Medical School, University of Minnesota, Minneapolis, MN, USA.
⁷ Department of Social Sciences and Health Policy, School of Medicine, Wake Forest University, Winston Salem, NC, USA.
⁸ Center for Alcohol and Addiction Studies, School of Public Health, Brown University, Providence, RI, USA.
⁹ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁰ Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA.
¹¹ Department of Medicine, School of Medicine, University of California, San Francisco, CA, USA.
¹² Department of Physiology and Pharmacology, School of Medicine, Wake Forest University, Winston Salem, NC, USA.

Abstract

Background: Reducing cigarette addictiveness has the potential to avert millions of yearly tobacco-related deaths worldwide. Substantially reducing nicotine in cigarettes decreases cigarette consumption, but no large clinical trial has determined the effects of reduced-nicotine cigarettes when other nicotine-containing products are available. The aim of this study was to examine the effects of reduced-nicotine cigarettes in the context of the availability of alternative nicotine delivery systems.

Methods: In a U.S. six-site, open-label, parallel-arm study, smokers were randomized for twelve weeks to an experimental marketplace containing cigarettes with either 0.4 mg or 15.8 mg nicotine per gram of tobacco; all had access to non-combusted alternative nicotine delivery systems (e.g., e-cigarettes; medicinal nicotine). Group differences in the primary outcomes (cigarettes per day, number of smoke-free days) were examined using linear and negative binomial regression, respectively (Trial Registration: NCT03272685).

Findings: Among 438 randomized participants (mean [standard deviation (SD), range] age, 44.5 [11.9, 20-73] years, 225 [51.4%] women, 282 [64.4%] White and 339 [77.4%] trial completers), those in the 0.4 mg vs. 15.8 mg nicotine cigarette condition experienced significantly lower cigarettes per day at the end of intervention (mean [SD], 7.05 [7.88] vs. 12.95 [9.07], adjusted mean difference, -6.21 [95% CI, -7.66 to -4.75], P < 0.0001) and greater smoke-free days during intervention (mean [SD], 18.59 [27.97] vs. 5.06 [13.77], adjusted rate ratio, 4.25 [95% CI, 2.58-6.98], P < 0.0001).

Interpretation: A reduced-nicotine cigarette standard in the context of access to other non-combusted nicotine products has the potential to benefit public health.

Funding: U.S. NIH/FDA U54DA03165.

Keywords: Cigarettes; Electronic cigarettes; Nicotine; Nicotine delivery systems; Reduced nicotine cigarettes; Smoking cessation; Tobacco; Tobacco control; Tobacco policy; Tobacco product regulations.

Associated data

ClinicalTrials.gov/NCT03272685