The impact of exclusive use of very low nicotine cigarettes on compensatory smoking: An inpatient crossover clinical trial

Background: The FDA is considering a mandated reduction in the nicotine content of cigarettes. Clinical trials have been limited by non-study cigarette use (noncompliance), which could mask compensation. The goal of this study was to assess whether compensation occurs when smokers provided with very low nicotine cigarettes cannot access normal nicotine cigarettes. Methods: In a within-subjects, crossover design, current smokers (n = 16) were confined to a hotel for two 4-night hotel stays during which they were only able to access the research cigarettes provided. The hotel stays offered normal nicotine cigarettes or very low nicotine content (VLNC) cigarettes, in an unblinded design, available for "purchase" via a study bank. Results: In the context of complete compliance with the study cigarettes (n = 16), there was not a significant increase during the VLNC condition for cigarettes smoked per day, expired carbon monoxide, or N-acetyl-S-(cyanoethyl)-L-cysteine (cyanoethyl-MA, metabolite of acrylonitrile). There was a significant nicotine × time interaction on urine N-acetyl-S-(3-hydroxypropyl)-L-cysteine (hydroxypropyl-MA, metabolite of acrolein), driven by an increase in the VLNC condition during the first 24 hours. By the end of the VLNCcondition, there was no evidence of compensation across any measure of smoking or smoke exposure. Conclusions: Among current smokers who exclusively used VLNC cigarettes for 4 days, there was no significant compensatory smoking behavior. Impact: These data, combined with the larger body of work, suggest that a mandated reduction in nicotine content is unlikely to result in an increase in smoking behavior to obtain more nicotine.