Despite extensive public health efforts, over 30 million US adults currently smoke cigarettes (Cornelius et al., 2022), and cigarette smoking remains the leading cause of preventable morbidity and mortality in the United States (US Department of Health and Human Services, 2014). Electronic nicotine delivery systems (ENDS) are intended as alternative and less harmful sources of nicotine for adults who smoke and would not otherwise quit in the near term, to facilitate transitions away from combustible cigarettes (Balfour et al., 2021).

The public health implications of menthol-flavored ENDS are debated. Evidence demonstrates that people who smoke menthol (vs. nonmenthol) cigarettes prefer menthol-flavored ENDS (Bold et al., 2022, Goldenson et al., 2022b, Rostron et al., 2020), and recent observational data suggests use of menthol-flavored (vs. tobacco-flavored) ENDS is associated with increased rates of switching away from cigarettes (Goldenson et al., 2023, Mok et al., 2022). However, regulators have expressed concern that menthol-flavored ENDS may demonstrate increased appeal and risk of use to underage individuals (Food and Drug Administration, 2022).

Established clinical laboratory methodologies can assess the abuse liability (i.e., likelihood of producing pharmacological reinforcement that could lead to persistent use and dependence) of menthol-flavored ENDS (Carter et al., 2009, Food and Drug Administration Center for Drug Evaluation and Research, 2017, Henningfield et al., 2011, Vansickel et al., 2022). In such assessments, cigarettes, which are known to have high abuse liability, are a key comparator (Carter et al., 2009, Fearon, 2023, Vansickel et al., 2022). Importantly, indices of subjective reinforcing effects (e.g., measures of product liking, satisfaction, and intent-to-use-again) relevant to the abuse liability of ENDS also inform the potential ability of ENDS to serve as effective alternatives or substitutes for cigarettes (Abrams et al., 2018, Fearon, 2023). Positive initial responses to use of ENDS (i.e., reinforcement) are prospectively associated with continued use of ENDS (Gades et al., 2020, Pearson et al., 2020) and switching away from cigarettes (Goldenson et al., 2021).

Previous controlled laboratory studies have assessed the abuse liability of ENDS relative to cigarettes, consistently finding that ENDS have lower abuse liability than cigarettes (Breland et al., 2020, Maloney et al., 2019, National Academies of Sciences, Engineering, and Medicine, 2018). However, these studies primarily evaluated earlier-generation ENDS products, which deliver lower levels of nicotine than more recent pod-based ENDS (Jacobson et al., 2021).

The primary aim of the current behavioral pharmacology study was to evaluate the abuse liability and switching potential of several widely-used menthol-flavored pod-based ENDS products relative to cigarettes among US adults who smoke cigarettes, via assessment of subjective responses. Given concerns regarding the appeal of menthol-flavored ENDS to underage individuals, the study oversampled young adults who smoke (between the ages of 22 and 29), as data on young adults may be particularly relevant to underage individuals. Further, adults who smoked mentholated cigarettes were also oversampled, as menthol-flavored ENDS are preferred in this population. Secondary analyses assessed if differences in subjective responses between study products differed by age group, concurrent ENDS use (dual use) or menthol cigarette smoking.