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

Abstract

Background The U.S. FDA has the authority to reduce cigarette nicotine content if found to benefit public health. Reduced nicotine content (RNC) cigarette use does not appear to increase harm exposure, but studies have not rigorously assessed smoking behavior or utilized a comprehensive panel of biomarkers. This study examined the effects of progressively decreasing RNC cigarettes on smoking behaviors, biomarkers of exposure, and subjective ratings. Methods 158 daily, non-treatment-seeking smokers participated in a 35-day randomized, unblinded, parallel study. After a 5-day baseline period, participants were randomly assigned to an experimental group (n = 80) that smoked progressively decreasing RNC cigarettes during three 10-day periods, or control group (n =78) that smoked their own brand throughout the study. Results Daily cigarette consumption significantly increased for the intermediate RNCs (P’s < 0.001) but approached baseline rate for the lowest RNC (P = 0.686); in contrast, puffing behavior significantly decreased at intermediate levels and increased for the lowest RNC (P’s < 0.001). Cotinine and NNAL significantly decreased by RNC period (P’s ≤ 0.001–0.02), while CO boost initially increased (P’s = 0.001–0.005). 1-HOP did not change by period (P = 0.109). Conclusions Smoking behaviors changed by RNC period via CPD and puffing behavior. Biomarkers of exposure generally decreased with nicotine content. Impact Findings suggest that RNC use does not ubiquitously reduce smoking behaviors or biomarkers, yet the lowest RNC level tested may reduce harm exposure. This emphasizes the importance of utilizing multiple behavioral and biological measures to address the impact of RNC cigarette smoking.

Nicotine Replacement, Topography, and Smoking Phenotypes of E-cigarettes

“…The study used a similar study design as used by Eissenberg et al 15 for assessing e-cigarettes, and by Goniewicz et al 21 and others to examine smoking behavior differences across tobacco products. 22,23 The study was conducted in 3 sessions: Day 1 (usual brand cigarette smoking) and Days 5 and 10 (single brand of e-cigarette use). Following Day 1, participants were required to refrain from using regular cigarettes and were asked to use the provided brand of e-cigarette; an assessment of breath carbon monoxide (CO) was conducted to verify refraining from cigarette use (≤10 ppm on Day 5 and Day 10), using a cut-off for cigarette smoking abstinence often used in clinical trials.…”

Reducing the nicotine content of combusted tobacco products sold in New Zealand

“…Although smokers may attempt to compensate when they first try VLNC cigarettes, numerous studies have shown that most smokers do not compensate after the first few cigarettes5 34 35 and that biomarkers of smoke exposure do not increase when participants are switched to VLNC cigarettes 4 5 8 9 16 17. One limitation of clinical trials suggesting little or no compensation is that smokers could easily purchase normal nicotine cigarettes, although an inpatient study in which participants could only use VLNC cigarettes also demonstrated a reduction in smoke exposure 8.…”

A two-site, two-arm, 34-week, double-blind, parallel-group, randomized controlled trial of reduced nicotine cigarettes in smokers with mood and/or anxiety disorders: trial design and protocol

“…Further, there was differential drop out for those with more severe nicotine dependence as evidenced by higher baseline Fagerström Test for Nicotine Dependence (FTND) scores. In more recent studies [10, 22], participants were excluded for having a serious medical or psychiatric disorder, other than depression.…”