Smoking remains a leading cause of preventable disease and premature death woridwide. Approximately 1 out of every 5 deaths is associated with cigarette smoking, and roughly half of all daily smokers will die prematurely from tobacco-related illnesses. Nicotine is widely accepted as a necessary constituent in tobacco driving use and dependence. A significant reduction in the nicotine content of cigarettes represents an innovative regulatory strategy with the potential to markedly reduce consumption and lead to greater likelihood of quitting. The Family Smoking Prevention and Tobacco Control Act (FSPTCA) enables the FDA to establish tobacco product standards including placing limits on the allowable nicotine content of cigarettes. For such a policy to be implemented safely and successfully, a number of critical issues and questions must be evaluated. One primary issue is to determine an appropriately low yield of nicotine content per cigarette that is below the addictive 'threshold'of nicotine, while at the same time balances reduced withdrawal effects and maximizes acceptability. Study 1 directly bears on this issue. Study 1 will assess three different low nicotine yields (0.02, 0.06, 0.18 mg) over a 6-week period and the data generated will be used to select an optimal nicotine yield for the remaining study in Project 1 and for Projects 2 and 3. A second major issue is whether simultaneous nicotine replacement therapy (NRT) facilitates the transition to very low nicotine content (VLNC) cigarettes. Recent evidence suggests that NRT may decrease use of VLNC cigarettes, reduce the volume of smoke inhaled per cigarette, and reduce drop-out rate. Study 2 will compare the effects of VLNC cigarettes in participants on 21 mg transdermal nicotine to another group that smokers VLNC cigarettes while wearing a placebo patch. A third group smoking normal nicotine content cigarettes and wearing placebo patches will be included as an additional control.

Public Health Relevance

This project has two goals. Study 1 will determine the optimal yield for very low nicotine cigarettes that leads to reduced smoking, but also minimal discomfort and maximal acceptability. Study 2 will determine if nicotine replacement aids in the transition to very low nicotine cigarettes. Both studies will advance understanding of the feasibility of using very low nicotine cigarettes to reduce the health burden of smoking.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1-EXL-T (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
United States
Zip Code
Smith, Tracy T; Cassidy, Rachel N; Tidey, Jennifer W et al. (2017) Impact of smoking reduced nicotine content cigarettes on sensitivity to cigarette price: further results from a multi-site clinical trial. Addiction 112:349-359
Miller, Mollie E; Tidey, Jennifer W; Rohsenow, Damaris J et al. (2017) Electronic Cigarette Expectancies in Smokers with Psychological Distress. Tob Regul Sci 3:108-114
Rupprecht, Laura E; Koopmeiners, Joseph S; Dermody, Sarah S et al. (2017) Reducing nicotine exposure results in weight gain in smokers randomised to very low nicotine content cigarettes. Tob Control 26:e43-e48
Murphy, Sharon E; Sipe, Christopher J; Choi, Kwangsoo et al. (2017) Low Cotinine Glucuronidation Results in Higher Serum and Saliva Cotinine in African American Compared to White Smokers. Cancer Epidemiol Biomarkers Prev 26:1093-1099
Mercincavage, Melissa; Wileyto, E Paul; Saddleson, Megan L et al. (2017) Attrition during a randomized controlled trial of reduced nicotine content cigarettes as a proxy for understanding acceptability of nicotine product standards. Addiction 112:1095-1103
Benowitz, Neal L; Donny, Eric C; Hatsukami, Dorothy K (2017) Reduced nicotine content cigarettes, e-cigarettes and the cigarette end game. Addiction 112:6-7
Smith, Tracy T; Rupprecht, Laura E; Sved, Alan F et al. (2016) Characterizing the relationship between increases in the cost of nicotine and decreases in nicotine content in adult male rats: implications for tobacco regulation. Psychopharmacology (Berl) 233:3953-3964
Tidey, Jennifer W; Cassidy, Rachel N; Miller, Mollie E et al. (2016) Behavioral Economic Laboratory Research in Tobacco Regulatory Science. Tob Regul Sci 2:440-451
Dermody, Sarah S; Tidey, Jennifer W; Denlinger, Rachel L et al. (2016) The Impact of Smoking Very Low Nicotine Content Cigarettes on Alcohol Use. Alcohol Clin Exp Res 40:606-15
Rupprecht, Laura E; Smith, Tracy T; Donny, Eric C et al. (2016) Self-Administered Nicotine Suppresses Body Weight Gain Independent of Food Intake in Male Rats. Nicotine Tob Res 18:1869-1876

Showing the most recent 10 out of 41 publications