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.

Brief procedures for evaluating medication efficacy may reveal which candidate drugs warrant further testing in clinical trials and which do not. We previously carried out a study of smoking abstinence, involving the nicotine patch, and established the sensitivity of our procedure. In this study, we sought to cross-validate our earlier work by comparing short-term smoking abstinence due to varenicline (relative to placebo) in smokers with high intrinsic quit interest (n = 57) and those with low intrinsic quit interest (n = 67). All the subjects were randomly assigned to either abstinence reinforcement ($12/day) or no reinforcement. In a crossover design, all the subjects participated in two 3-week phases: ad libitum smoking (week 1), dose run-up of varenicline (1.0 mg b.i.d.) or placebo (week 2), and quit attempt on medication verified daily by carbon monoxide <5 ppm (week 3). As with the nicotine patch in the previous study, varenicline (relative to placebo) increased abstinence more effectively in those with high intrinsic quit interest than in those with low quit interest but did not affect abstinence due to reinforcement. These data confirm the feasibility of a brief, sensitive test of the efficacy of cessation medications in smokers with high quit interest.

Objective The nine pictorial health warning labels (PWLs) proposed by the US Food and Drug Administration vary in format and feature of visual and textual information. Congruency is the degree to which visual and textual features reflect a common theme. This characteristic can affect attention and recall of label content. This study investigates the effect of congruency in PWLs on smoker’s attention and recall of label content. Methods 120 daily smokers were randomly assigned to view either congruent or incongruent PWLs, while having their eye movements recorded. Participants were asked to recall label content immediately after exposure and 5 days later. Results Overall, the image was viewed more and recalled better than the text. Smokers in the incongruent condition spent more time focusing on the text than smokers in the congruent condition (p=0.03), but dwell time of the image did not differ. Despite lower dwell time on the text, smokers in the congruent condition were more likely to correctly recall it on day 1 (p=0.02) and the risk message of the PWLs on both day 1 (p=0.01) and day 5 (p=0.006) than smokers in the incongruent condition. Conclusions This study identifies an important design feature of PWLs and demonstrates objective differences in how smokers process PWLs. Our results suggest that message congruency between visual and textual information is beneficial to recall of label content. Moreover, images captured and held smokers’ attention better than the text.

Social learning theory considers self-efficacy as a causal factor in behavior change. However, in line with behavioral theory, recent clinical research suggests that self-efficacy ratings may reflect, rather than cause, behavior change. To test these two disparate views, self-efficacy was related to actual smoking abstinence on the next day (i.e. self-efficacy causes change), and abstinence status over one day was tested as a predictor of rated self-efficacy for being quit the next day (i.e. reflects change). All data were from two very similar cross-over studies evaluating the short-term effects of both placebo versus medication, nicotine patch (n=209) or varenicline (n=123), on smoking abstinence during week-long practice quit attempts. Placebo versus active medication periods were separated by an ad lib smoking washout, and analyses controlled for prior day's abstinence or self-efficacy values. Results were very consistent between studies in showing essentially bi-directional associations: daily self-efficacy predicted next day's abstinence, and current day's abstinence status predicted self-efficacy for not smoking the next day. However, secondary factors differentially predicted abstinence and, to a lesser extent, self-efficacy between these two medication studies. These data provide some support for both social learning and behavioral theories of smoking behavior change, although self-efficacy may only briefly predict subsequent short periods of abstinence as assessed in these studies. Nonetheless, because self-efficacy has long been assumed to cause behavior change, including smoking cessation, the notion of self-efficacy as a reflection of recent smoking behavior change in these studies warrants greater attention in clinical research on smoking cessation treatment.

Genes coding for nicotinic acetylcholine receptors may influence response to nicotine replacement therapy for smoking cessation. We examined the association of a 3′ untranslated region polymorphism (rs2072661) in the nicotinic acetylcholine receptor β2 subunit (CHRNB2) gene with quitting success in response to nicotine versus placebo patch during a short-term test of patch effects. In a within-subjects cross-over design, smokers of European descent (n = 156) received 21 mg nicotine and placebo patch in counter-balanced order, during two separate 5-day simulated quit attempts, each preceded by a week of ad libitum smoking. Abstinence was assessed daily by CO < 5 ppm. Smokers with the CHRNB2 GG genotype had more days of abstinence during the nicotine versus placebo patch week compared with those with the AG or AA genotypes (P < 0.01). Moreover, nicotine patch increased the probability of quitting on the target quit day, quitting anytime during the patch week, and avoiding relapse among those with the GG genotype but not the AA/AG genotypes, although the nicotine × genotype interaction was significant only for quitting on the target quit day (P < 0.05). Regardless of patch condition, quitting on the target quit day was more likely in those with the GG genotype versus AA/AG genotypes (P < 0.05). Genetic associations were not observed for craving or withdrawal responses to nicotine versus placebo patch. These findings are consistent with previous evidence of association of this variant with smoking cessation and suggest that polymorphisms in the nicotinic acetylcholine receptor β2 subunit gene may influence therapeutic responsiveness to cessation medications. (Cancer Epidemiol Biomarkers Prev 2009; 18(10):2608-12)