Science

Scientific Evidence

There’s a large body of scientific evidence for the efficacy of Very Low Nicotine (VLN) Cigarettes for smoking reduction and smoking cessation. Scientific research resulting in peer-reviewed publications spans well a decade, funded by over $100M in by various federal funding agencies including the FDA.

This scientific evidence was one crucial component in the MRTP Application for VLN Cigarettes resulting in the FDA Authorization for VLN Kings and VLN Menthol Kings on December 23, 2021, the first and only one for combustible cigarettes.

Here we present a curated list of selected publications that may be highly relevant in the practical context of smokers trying to smoke less or to quit smoking.

It is not informative simply to list all publications related to VLN, especially since there are currently a few dozen clinical trials involving low nicotine cigarettes in various stages of completion that would result in many more publications as time passes.

The researcher is encouraged to search PubMed for key phrases such as: “low nicotine”, “smoking cessation”, “compensatory smoking”, “spectrum cigarettes” (these were the name of variable nicotine cigarettes used for research based on the same technology as VLN cigarettes), and similar keyphrases for related publications and newer publications.

Selected Publications

Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure

Hatsukami et al, JAMA. 2018 Sep 4; 320(9): 880–891.
DOI: 10.1001/jama.2018.11473

Conclusions and Relevance: Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control.


Randomized Trial of Reduced-Nicotine Standards for Cigarettes

Donny et al, NEJM. 2015 Oct 1; 373:1340-1349
DOI: 10.1056/NEJMsa1502

Conclusions: In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875.)


Effects of 6-Week Use of Reduced-Nicotine Content Cigarettes in Smokers With and Without Elevated Depressive Symptoms

Tidey et al, Nicotine Tob Res. 2017 Jan;19(1):59-67.
DOI: 10.1093/ntr/ntw199

Conclusions: 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.

Implications: This secondary analysis of a recent clinical trial examined whether depressive symptom severity moderated the effects of reduced-nicotine cigarettes on smoking and depressive symptoms. Results indicate that, regardless of baseline depressive symptoms, participants randomized to reduced-nicotine cigarettes had lower smoking rates, nicotine intake, nicotine dependence, and craving at week 6 post-randomization than those assigned to normal-nicotine cigarettes. In participants with higher baseline depressive symptoms, those assigned to reduced-nicotine cigarettes had lower week 6 depressive symptoms than those assigned to normal-nicotine cigarettes. These results suggest that a nicotine reduction policy could have beneficial effects for smokers, regardless of depressive symptom severity.


Estimations and predictors of non-compliance in switchers to reduced nicotine content cigarettes

Nardone et al, Addiction. 2016 Dec;111(12):2208-2216.
doi: 10.1111/add.13519

Conclusions: Among smokers volunteering to smoke only very low nicotine cigarettes for 6 weeks, non-compliance was common and biochemical assessments detected more cases of non-compliance than self-report. Despite high levels of non-compliance, smokers reduced their intake of nicotine by an average of 60%.


The Impact of Smoking Very Low Nicotine Content Cigarettes on Alcohol Use

Dermody et al, Alcohol Clin Exp Res. 2016 Mar; 40(3):606-15.
DOI: 10.1111/acer.12980

Conclusions: The findings suggest that compensatory drinking is unlikely to occur in response to switching to VLNC cigarettes. In contrast, reducing the nicotine content of cigarettes may reduce alcohol use (clinicalTrials.gov number, NCT01681875).