A pair of studies by Smith et al published in Cancer Epidemiology, Biomarkers & Prevention evaluating whether a mandated reduction in the nicotine content of cigarettes may cause smokers to compensate by engaging in compensatory smoking to obtain more nicotine has found that a reduction in nicotine content is unlikely to result in increased smoke exposure.
In 2018, the U.S. Food & Drug Administration (FDA) issued an advance notice of proposed rulemaking (ANPRM) to obtain information for consideration in developing a tobacco product standard to set the maximum nicotine level for cigarettes. The goal of the ANPRM is to explore a product standard to lower nicotine in cigarettes to minimally or nonaddictive levels to reduce the number of tobacco-related deaths in the United States. According to the Centers for Disease Control and Prevention, cigarette smoking is responsible for more than 480,000 deaths each year in the United States, including more than 41,000 deaths due to exposure to secondhand smoke.
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Study Methodology
In the first study, researchers utilized data from a clinical trial that had randomly assigned smokers (n = 51–70 per group) to receive cigarettes with one of five nicotine contents for 6 weeks. The nicotine levels included a normal nicotine content of 15.8 mg nicotine per 1 g of tobacco or four different low-nicotine content cigarettes ranging from 0.4 mg to 5.2 mg nicotine per 1 g of tobacco. An additional group received a cigarette with the lowest nicotine content but an increased tar yield. The study participants were asked to smoke only the provided cigarettes and to collect and return their used cigarette butts for analysis.
In the second study, researchers evaluated whether smoking low-nicotine cigarettes impacted the number of cigarettes study participants (n = 16) smoked each day. The participants were confined to a hotel for two 4-night hotel stays, during which time they were only able to access the research cigarettes provided in the study. The hotel stays offered normal nicotine cigarettes or very low–nicotine content cigarettes, in an unblinded design, available for “purchase” via a study bank.
Study Results
In the first study, there was no significant increase in smoking intensity for any of the reduced nicotine cigarettes as measured by the compensation index (an estimated 0.4% of the nicotine lost was recovered in the lowest nicotine group; 95% confidence interval = −0.1 to 1.2). There was no significant decrease in smoking intensity for very low–nicotine content cigarettes with an increased tar yield. Reductions in nicotine content did not result in compensatory changes in how intensively participants smoked research cigarettes.
In the second study, the researchers found that there were no significant changes in the number of cigarettes smoked per day when the participants switched to low-nicotine cigarettes. Urine sample analysis found that most of the biomarkers of smoke exposure, which correlated with both the number of cigarettes smoked and smoking intensity, did not increase with low-nicotine cigarettes.
One biomarker—cyanoethyl-MA, a metabolite of acrylonitrile—was significantly increased for the first day of using low-nicotine cigarettes, but not over subsequent days, indicating that any increase in smoking intensity was transient. Among current smokers who exclusively used very low–nicotine content cigarettes for 4 days, there was no significant compensatory smoking behavior.
Impact
“Together, these studies show that when smokers switch to low-nicotine cigarettes, there is no evidence of stable compensatory smoking,” said Tracy T. Smith, PhD, Assistant Professor in the Department of Psychiatry and Behavioral Sciences at the Medical University of South Carolina and Hollings Cancer Center and the lead author of both studies, in a statement. “These data provide critical information about the effects we might observe if the FDA were to implement a policy mandating the reduction of nicotine in cigarettes to a minimally addictive level.”
Dr. Smith is the corresponding author of both studies.
Disclosure: Funding for these studies was provided by the National Institute on Drug Abuse, the National Institutes of Health, the U.S. Food & Drug Administration Center for Tobacco Products, the Centers for Disease Control and Prevention, and the National Cancer Institute. For full disclosures of the study authors, visit cebp.aacrjournals.org.
