BACKGROUND AND AIMS: Most extant evidence has addressed between-person differences, short-term, or cross-sectional associations of electronic nicotine delivery systems (ENDS) use with other substance use, the majority focusing on current use rather than escalated use. The present study aimed to examine within-person changes in escalated ENDS use and their associations with individual and combined substance use over a 6-year period.

DESIGN: Longitudinal analysis. A generalized linear mixed model approach was employed to fit a series of weighted logistic regression models. In the United States, data were drawn from Wave 1-5 of the Population Assessment of Tobacco and Health (PATH) Study. Of the 9,110 young adults at baseline, ages 18-24, a total of 5,042 individuals had matched data across all five waves of assessments.

MEASUREMENTS: Escalated ENDS use was computed by subtracting the number of days of ENDS use within the past 30 days at wave w- 1 from that at wave w and coded as 1=escalated, if the value was greater than zero (otherwise, coded as 0=not escalated).

FINDINGS: Escalated ENDS use gradually decreased over time, with the lowest prevalence at Wave 4 (4.0%) but sharply increasing at Wave 5 (8.4%). Escalated ENDS use was associated with increased odds of using each substance (binge drinking, marijuana use, marijuana vaping, prescription and illicit drugs) and different combinations of polysubstance use between cigarette smoking, binge drinking, and marijuana use (ps<0.05). In addition, sweet/fruit flavor use (vs. menthol/mint) was associated with increased likelihood of reporting co-use of cigarettes and marijuana.

CONCLUSIONS: In the United States, the prevalence of young adults using electronic nicotine delivery systems (ENDS) appears to have increased steadily between 2013-2019, although the rate of increase may have started to accelerate in recent years. Escalated ENDS use and time-lagged established ENDS use appear to be prospectively associated with individual and combined substance use, particularly between cigarettes, alcohol, and marijuana. Among established ENDS users, sweet/fruit flavor appears to be associated with increased risk of co-using cigarettes and marijuana.