E-cigarettes were introduced into the U.S. market in 2007, and their popularity has continued to grow since then. Since 2014, they have become the most widely used tobacco product among youth and young adults in the U.S. (U.S. Department of Health and Human Services, 2014). Promoted as a safer alternative to traditional combustible cigarettes, e-cigarettes have been adopted by some as substitutes for other harmful tobacco products and by others as a means to quit the use of combustible cigarettes (Mayer et al., 2020). The shift towards e-cigarette use among varying demographics highlights the possibly increasing reduced harm perception of e-cigarettes over traditional cigarettes (Jackson et al., 2024).

However, the safety of e-cigarettes remains debatable, as the varying levels of nicotine content in e-cigarettes may predispose individuals to addiction and the use of other tobacco products (U.S. Department of Health and Human Services, 2016, Ren and Lotfipour, 2019). Additionally, the constituents in e-cigarette liquids, which include toxic metals and differ across devices, may cause harm to individuals who use them (Rom et al., 2015, Jackler and Ramamurthi, 2019, Obisesan et al., 2019). Despite these uncertainties, e-cigarette use remains high, with approximately 2 million middle and high school students and around 15 million adults reporting use in 2023 (Erhabor et al., 2023, Birdsey et al., 2023).

It is well established that both psychological distress and substance use are associated with tobacco use. Psychological distress is broadly defined as a state of emotional pain marked by signs of anxiety, suicidal ideation, symptoms of depression such as loss of interest and unhappiness (Pengpid and Peltzer, 2020). Substance use encompasses the consumption of illegal drugs, prescription medications, and over-the-counter drugs, either outside their intended use or in excessive amounts. Several studies have examined the association between e-cigarette use, substance use, and mental health outcomes in both adolescents and adults (Obisesan et al., 2019, Javed et al., 2022, Lee and Lee, 2019, Han et al., 2024, Becker et al., 2021, Grant et al., 2019, Chadi et al., 2019). For example, a systematic review of 40 articles found that e-cigarette use among youth is associated with mental health across several domains of mental health problems, particularly in adolescents (Becker et al., 2021). Similarly, in 2019, a study among college students found that e-cigarette use was associated with higher odds of substance use, including the use of opiates and alcohol use, as well as attention-deficit hyperactivity disorder, posttraumatic stress disorder, gambling disorder, and anxiety (Grant et al., 2019). A more recent study found associations between e-cigarette use and depression, suicidal ideation, and suicidal attempts (Javed et al., 2022).

While several studies have explored the association between e-cigarette use, psychological distress, and substance use, many rely on convenience sampling and focus on a limited range of variables. To confirm findings and improve our understanding of these associations, it is important to build on existing studies using larger and more diverse samples. The All of Us dataset addresses these limitations by providing a broad and diverse sample, improving the generalizability and reliability of findings.

This study builds on prior research by providing additional evidence on the associations between e-cigarette use, mental health, and substance use. We examined these associations among U.S. adults aged 18 and older. We hypothesize that e-cigarette use will be associated with higher levels of psychological distress and substance use compared to non-use.