1. Phase II / III – 840 Subjects

Randomized Trial of Reduced-Nicotine Standards for Cigarettes
University of Pittsburgh

Donny et al. – October 2015, New England Journal of Medicine. 373:1340-1349

  • Participants who were assigned VLN cigarettes smoked fewer cigarettes per day (14.9) than those assigned to their usual brand (22.2)
  • Smokers of VLN cigarettes doubled their quit attempts versus smokers of conventional cigarettes
  • Funded by the National Institute on Drug Abuse (NIDA) and the U.S. Food and Drug Administration (FDA)

2. Phase II – 165 Subjects

Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation.
University of Minnesota Masonic Cancer Center

Hatsukami et al. – February 2010, Addiction. 105:343-355

  • VLN cigarettes produced significantly better results than the FDA-approved nicotine lozenge; even the smokers who ultimately did not quit ended up reducing their cigarette consumption by 37%
  • The 0.05 mg nicotine yield cigarettes may be a tobacco product that can facilitate cessation
  • This study was funded by the National Institutes of Health (NIH), (grant id: P50 DA013333)

3. Phase III – 1,410 Subjects

The combined effect of very low nicotine content cigarettes, used as an adjunct to usual Quitline care (nicotine replacement therapy and behavioural support), on smoking cessation: a randomized controlled trial.
Clinical Trials Research Unit, University of Auckland

Walker et al. – October 2012, Addiction. 107:1857–1867

  • VLN cigarettes plus NRT (nicotine patch, gum and/or lozenge) significantly increased quit rates at all measured time points (3 & 6 weeks and 3 & 6 months) over use of NRT only
  • Addition of very low nicotine content cigarettes to standard Quitline smoking cessation support may help some smokers to become abstinent
  • Funded by the Health Research Council of New Zealand

4. Phase II – 219 Subjects

Reduced Nicotine Content Cigarettes and Nicotine Patch – Follow-up Study
University of Minnesota Masonic Cancer Center

Hatsukami et al. – June 2013, Cancer Epidemiology, Biomarkers & Prevention. 22:1015-1024

  • VLN cigarettes produced significantly better results than FDA-approved nicotine lozenges; even those smokers who ultimately didn’t quit ended up reducing their cigarette consumption from 19 cigarettes per day to 12 cigarettes per day
  • Very Low Nicotine cigarettes were associated with greater relief of withdrawal than the nicotine lozenge
  • Funded by the National Institutes of Health (NIH), (grant id: R01 DA025598 and U54DA031659)

5. Phase II – 112 Subjects

Greater reductions in nicotine exposure while smoking very low nicotine content cigarettes predict smoking cessation
Department of Psychology, University of Pittsburgh

Dermody et al. – September 2014, Tobacco Control. DOI: 10.1136/tobaccocontrol-2014-051797

  • Reducing the nicotine content of cigarettes is a potential regulatory strategy that may enable cessation
  • When smoking Very Low Nicotine cigarettes, lower levels of nicotine exposure prior to a quit attempt enables cessation
  • Funded by the National Institutes of Health (NIH), (grant id: R01 DA025598 and U54DA031659)

6. Phase II – 346 Subjects

A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation.
Department of Psychiatry & Behavioral Sciences, Duke University Medical Center

Becker et al. – July 2008, Nicotine & Tobacco Research. 10:1139-1148

  • The use of reduced nicotine cigarettes for 6 weeks, including VLN cigarettes for 2 weeks, before the use of the nicotine patch significantly increased quit rates over use of the nicotine patch alone
  • VLN cigarettes plus nicotine replacement therapy offers promise as a new smoking cessation treatment.
  • Funded by Vector Tobacco Inc.

7. Phase II – 200 Subjects

Complementing the Standard Multicomponent Treatment for Smokers With Denicotinized Cigarettes: A Randomized Trial.
Queen Mary University, London

McRobbie et al. – May 2016, Nicotine & Tobacco Research. 18:1134-1141

  • The group that used VLN cigarettes had a 70% quit rate one week after stopping VLN cigarette use compared to a 53% quit rate of the group not using VLN cigarettes
  • Adding VLN cigarettes to standard treatments has the potential to assist smokers early in their quit attempt, but research is needed to determine how best to utilize VLNs.
  • Funded by Pfizer, Inc.

8. Phase II – 168 Subjects

A Randomized Controlled Trial of Progressively Reduced Nicotine Content Cigarettes on Smoking Behaviors, Biomarkers of Exposure, and Subjective Ratings
Department of Psychiatry, University of Pennsylvania

Mercincavage et al. – July 2016, Cancer Epidemiology, Biomarkers & Prevention. DOI: 10.1158/1055-9965.EPI-15-1088

  • The lowest reduced nicotine level cigarette tested (0.05 mg nicotine yield) may reduce harm exposure
  • Use of VLN cigarettes decreased daily consumption, as well as nicotine and toxicant exposure, relative to use of moderate nicotine content cigarettes
  • Funded by the National Institutes of Health

9. Phase II – 98 Subjects

Treating smokers before the quit date: Can nicotine patches and denicotinized cigarettes reduce cravings?
Roswell Park Cancer Institute

Rezaishiraz et al. – November 2007, Nicotine & Tobacco Research. 9:1139-1146

  • Use of VLN cigarettes before use of nicotine patches increased quit rates over similar use of reduced nicotine cigarettes (containing 10 times more nicotine than the VLN) before nicotine patches
  • The use of a VLN cigarettes combined with the nicotine patch appears to lessen cravings to smoke in the immediate post cessation period
  • Funded by institutional resources from Roswell Park Cancer Institute

10. Phase II / III – 839 Subjects

The Impact of Smoking Very Low Nicotine Content Cigarettes on Alcohol Use.
Department of Psychology, University of Pittsburgh

Dermody et al. – March 2016, Alcoholism, Clinical & Experimental Research. 40:606-615

  • A reduced nicotine product standard could positively impact related health risk behaviors like drinking
  • Compensatory drinking is unlikely to occur in response to switching to VLN cigarettes and reducing the nicotine content of cigarettes may reduce alcohol consumption
  • Funded by the National Institute on Drug Abuse and FDA Center for Tobacco Products (CTP) (grant id: U54 DA031659) and
  • National Institute on Alcohol Abuse and Alcoholism (grant id: F31AA022291)

11. Phase II / III – 717 Subjects

Evaluation of a reduced nicotine product standard: Moderating effects of and impact on cannabis use.
Duke University

Pacek et al. – August 2016, Drug & Alcohol Dependence. DOI: 10.1016/j.drugalcdep.2016.08.620

  • Nicotine reduction in cigarettes could have beneficial effects on cigarette smoking regardless of cannabis use
  • Among cannabis users and non-users, smokers randomized to VLNC cigarettes reported lower nicotine dependence, cigarettes per day, biomarkers of nicotine exposure, and craving compared to smokers randomized to normal nicotine content cigarettes
  • Funded by the National Institute on Drug Abuse and FDA Center for Tobacco Products (grant id: U54 DA031659)

12. Phase II – 136 Subjects

Reduced Nicotine Content Cigarettes and Use of Alternative Nicotine Products: Exploratory Trial.
University of Minnesota Masonic Cancer Center

Hatsukami et al. – September 2016, Addiction. DOI: 10.1111/add.13603

  • There were higher rates of abstinence when smoking VLNC cigarettes compared with the normal nicotine condition
  • The offer of, and instructions to use, reduced nicotine content cigarettes over an 8 week period led to greater reductions in smoking rates
  • Funded by National Cancer Institute, and U.S. Food and Drug Administration (grant id: U19CA157345)

13. Phase II / III – 717 Subjects

Effects of 6-Week Use of Reduced-Nicotine Content Cigarettes in Smokers With and Without Elevated Depressive Symptoms.
Center for Alcohol and Addiction Studies, Brown University

Tidey et al. – August 2016, Nicotine & Tobacco Research. DOI: 10.1093/ntr/ntw199

  • Relative to normal nicotine level cigarettes, VLN cigarettes reduced smoking rates, nicotine dependence and cigarette craving.
  • These findings provide initial evidence that a reduced-nicotine standard for cigarettes may reduce smoking, without worsening depressive symptoms, among smokers with elevated depressive symptoms.
  • Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products (grant id: U54DA031659)

14. Phase I – 50 Subjects

Smoking Topography Characteristics of Very Low Nicotine Content Cigarettes, With and Without Nicotine Replacement, in Smokers With Schizophrenia and Controls
Center for Alcohol and Addiction Studies, Brown University

Tidey et al. – March 2016, Nicotine & Tobacco Research. DOI: 10.1093/ntr/ntw089

  • Acute use of VLN cigarettes does not increase intensity of smoking in schizophrenics and this supports the feasibility of a nicotine reduction policy
  • During VLN cigarette sessions, puff duration increased and time between puffs decreased, but participants smoked fewer puffs, resulting in a net decrease in cigarette and total session volume
  • Funded by the National Institute on Drug Abuse (NIDA)

15. Phase II / III – 242 Subjects

Estimations and predictors of non-compliance in switchers to reduced nicotine content cigarettes
Department of Medicine, University of California, San Francisco

Nardone et al. – August 2016, Addiction. DOI: 10.1111/add.13519

  • Despite high levels of non-compliance, smokers reduced their intake of nicotine by an average of 60% after smoking only VLN cigarettes for six weeks
  • After six weeks of smoking VLN cigarettes, self-reported dependence and daily nicotine intake were lower at the end of the trial compared to the control condition
  •  Funded by the National Institute on Drug Abuse (NIDA) and FDA Center for Tobacco Products (CTP) (grant id: U54 DA031659) and the National Cancer Institute (NLB) (grant id: R01 CA78603)

16. Phase I – 26 Subjects

Response to varying the nicotine content of cigarettes in vulnerable populations:  an initial experimental examination of acute effects
University of Vermont Center on Tobacco Regulatory Science

Higgins et al. – October 2016, Psychopharmacology. DOI: 10.1007/s00213-016-4438-z

  • There was no evidence of compensatory smoking with VLN cigarettes in these vulnerable populations and there were significant reductions in nicotine withdrawal and cravings with VLN cigarettes
  • These initial results in more vulnerable populations of smokers are encouraging regarding the feasibility of a national policy to reduce the nicotine content of cigarettes to very low levels without substantial adverse effects
  • Funded by a Tobacco Centers of Regulatory Science (TCORS) award (P50DA036114) from the National Institute on Drug Abuse and Food and Drug Administration

17. Phase II / III – 839 Subjects

Reducing nicotine exposure results in weight gain in smokers randomized to very low nicotine content cigarettes.
Department of Psychology, University of Pittsburgh

Rupprecht et al. – November 2016, Tobacco Control. DOI: 10.1136/tobaccocontrol-2016-053301

  • Weight gain at week 6 was negatively correlated with nicotine exposure in the 2 lowest nicotine content cigarette conditions
  • The study indicates that weight gain is a likely consequence of reduced exposure to nicotine
  • Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products (grant id:  U54DA031659)