Impact of reduced nicotine content on behavioral economic measures of cigarette reinforcement in adolescents who smoke cigarettes

Despite decades of progress reducing smoking initiation, and promoting cessation, combustible cigarette smoking remains the leading cause of preventable morbidity and mortality in the U.S. (Creamer et al., 2019). Nicotine is the highly addictive tobacco constituent that contributes to cigarettes’ high abuse liability (Benowitz, 2010), and persistent use upon initiation (Carter and Griffiths, 2009). The Food and Drug Administration (FDA) has the authority to regulate tobacco products (United States Congress, 2009), and one potential policy is to mandate a nicotine product standard that would reduce nicotine in combustible cigarettes to levels below which developing or maintaining addiction is unlikely (<0.5 mg/g nicotine) (Benowitz and Henningfield, 2018; U.S. Food and Drug Administration, 2017). Given that most tobacco use is initiated in youth and young adulthood (U.S. Department of Health and Human Services, 2012), investigating the extent to which a reduced nicotine product standard may reduce the abuse liability of cigarettes among these populations is critical.

An important aspect of evaluating the abuse liability, or addictive potential, of cigarettes is describing the relative reinforcement individuals who smoke receive from smoking a cigarette (Bickel et al., 2014, Johnson and Bickel, 2006, MacKillop et al., 2008). A common method for assessing the relative reinforcement efficacy (RRE) of tobacco products is by using a hypothetical cigarette purchase task (CPT). The CPT asks study participants to indicate how many cigarettes they would purchase at different prices as prices steadily increase. The CPT yields information about five different dimensions (indices) of demand, which are highly correlated with real world purchasing and use behaviors (Carter et al., 2009, Carter and Griffiths, 2009, MacKillop et al., 2008). In the context of tobacco regulatory science, product purchase tasks are an expeditious method of investigating the potential effects of tobacco product standards on tobacco use in priority populations (Tidey et al., 2016). Understanding the effects of reduced nicotine content in cigarettes on both the RRE of cigarettes and measured smoking behavior is critical to inform policymakers about the likely public health impact of a reduced nicotine policy.

A growing body of evidence from clinical trials has offered insight into the effects of switching individuals who smoke to very low nicotine content cigarettes (VLNC, 0.4 mg/g nicotine), though most such studies have enrolled adult participants. Among adult participants drawn from the general population, 6-week assignment to reduced nicotine cigarettes significantly reduced self-reported smoking behavior (Donny et al., 2015, Hatsukami et al., 2013) and demand for cigarettes (assessed via CPT) (Smith et al., 2017). Similar effects of VLNC assignment on reductions in smoking behaviors and demand were also observed in both acute and extended exposure studies among high-risk populations of adults who smoke (affective disorders, adults who use opioids, and socioeconomically disadvantaged women) (Higgins et al., 2017a, Higgins et al., 2017b; Higgins et al., 2020). Among studies investigating age as a moderator of responses to VLNC cigarettes, investigators found that younger adults (ages 18–24) found VLNC study cigarettes less satisfying and reinforcing compared to participants ages 25 and older (Cassidy et al., 2021; Cassidy et al., 2019; Davis et al., 2019). Furthermore, one study found no evidence of a dose-dependent relationship between the nicotine content of study cigarettes and their reinforcing effects among adolescents under acute exposure (Cassidy et al., 2019), unlike the dose-dependent relationships that have been observed in acute exposure studies in older adults (Higgins et al., 2017b). Despite mounting evidence that a nicotine reduction policy may safely and effectively reduce smoking among a diverse range of adult study participants, there is a significant gap in knowledge regarding the potential impact of nicotine reduction on cigarette demand among adolescents.

The current study is a secondary analysis of data from adolescent participants enrolled in a randomized clinical trial (Cassidy et al., 2022). This study extends the current literature by comparing the RRE of NNC and VLNC study cigarettes among adolescents over an extended (three week) period of use in the natural environment. Study goals were to 1) characterize variation in indices of demand for study cigarettes by nicotine dose and across time, 2) investigate the effects of nicotine dose assignment on changes in demand for study cigarettes at Week 3, and 3) investigate whether baseline demand for study cigarettes is a significant predictor of study cigarette and total (study plus supplemental, non-study cigarette) consumption reported at Week 3. A priori hypotheses were that adolescent participants would find VLNC cigarettes less reinforcing than NNC cigarettes, and that baseline indices of demand would significantly predict later consumption patterns.

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