Electronic nicotine delivery system (ENDS) use (“vaping”) resembles cigarette smoking in terms of product appearance, inhalation and exhalation behaviors, and hand to mouth movements. Similarities between ENDS and combustible cigarettes in terms of form and function (i.e., appearance, inhalation and exhalation behaviors, similar nicotine content) (Jackler and Ramamurthi, 2019), have led to investigations on cross-cue reactivity for these methods of nicotine delivery. Among individuals who smoke, exposure to ENDS use not only increases vaping desire but also elicits smoking urge and behavior (Miloslavich et al., Vena et al., 2020, Vena et al., 2020, King et al., 2021, Brett et al., 2021). Nearly one-third of U.S. adults who smoke cigarettes also vape/use ENDS (Owusu et al., 2019), and dual use of these products may increase nicotine dependence and toxicant exposure from use of both products versus either product alone (Goniewicz et al., 2014, Hiler et al., 2023). Those who use both ENDS and cigarettes also show heightened cigarette craving following exposure to ENDS cues relative to people who smoke but do not use ENDS (Brett et al., 2023), likely due to Pavlovian, i.e., classical conditioning, generalizing ENDS cues to the desired effects of combustible cigarettes.

In the U.S., most states allow the sale of cannabis for medical or recreational use, which has contributed to an increase in cannabis vaping via ENDS-like, aerosol-based devices (Holt et al., 2023, Liu et al., 2024, Masson et al., 2022). High rates of cannabis co-use among people who smoke cigarettes (Hindocha and McClure, 2021, Goodwin et al., 2018) has been well documented, along with impacts related to smoking cessation. Importantly, inhaled cannabis use is associated with lower success with smoking cessation (Danzo et al., 2025) and cannabis vaping in particular has been associated with a decrease in daily smoking cessation efforts (Danzo et al., 2025). As cannabis vaping closely resembles ENDS use and is often used comorbidly, it may be that classical conditioning underlying ENDS cues triggers cravings for both nicotine and cannabis in adults who both smoke and vape cannabis. To our knowledge, no prior published studies have reported on reactivity to ENDS cues among individuals who smoke and vape cannabis. Further, with few exceptions (Venegas and Ray, 2023, Shiffman et al., 2015), the majority of cross-substance cue reactivity research has been conducted within in-laboratory studies with strong experimental controls but with limited external validity (Vena et al., 2020, Vena et al., 2020, Brett et al., 2021) Thus, in this secondary data analysis, we compared people who smoke cigarettes and vape cannabis (co-use group) to those who smoke but do not vape cannabis (non-co-use group) on reactivity to ENDS cues, as expressed by ratings of desire for cigarettes, ENDS, and cannabis. Given similarities in appearance and function between ENDS and cannabis vaping, we predicted increased reactivity to ENDS cues across outcomes in the co-use group versus the non-co-use group.