The gateway hypothesis posits that substance use initiation occurs in a sequential progression through different stages (Kandel, 2003; Kandel et al., 2006), usually beginning with alcohol and tobacco, followed by cannabis, then illegal/illicit substances (Barry et al., 2016; Keyes et al., 2015; Lemyre et al., 2019; Reed et al., 2022). While some research suggests these associations hold even when adjusting for certain individual (e.g., socio-economic status, personality traits) and contextual factors (e.g., family functioning) (Fergusson et al., 2006; Kandel et al., 1986; Lessem et al., 2006), other research indicates the gateway sequence of substance use may no longer hold when accounting for such factors.

One factor potentially impacting order of initiation involves shifts in a country’s product market and use prevalence (Degenhardt et al., 2010). In the US in 2023, lifetime use rates of cigarettes, e-cigarettes, cigars, alcohol, and cannabis among young adults (ages 18-25) were 34.6%, 50.1%, 23.1%, 74.7%, and 50.0% respectively, and past-month rates were 10.6%, 24.1%, 5.3%, 49.6%, and 25.2% (Substance Abuse and Mental Health Services Administration, 2024). Because of the higher use rates for cannabis and e-cigarettes than cigarettes and cigars, the traditional gateway hypothesis may not hold. Furthermore, these associations may be impacted by cohort effects, as cannabis and e-cigarette use has increased in the past decade (Substance Abuse and Mental Health Services Administration, 2024) coinciding with expansion of non-medical cannabis legalization (National Conference of State Legislators, 2024) and e-cigarette popularity since 2010 (Fadus et al., 2019). Notably, cannabis legalization may increase cannabis use but reduce tobacco and alcohol use (Dave et al., 2023; De & Sun, 2025).

Despite these important societal changes, limited research has assessed the gateway effects of cigars or newer substances like e-cigarettes to cannabis. Some studies show effects for e-cigarettes (Morean et al., 2015; Temourian et al., 2024; Temple et al., 2017; Unger et al., 2016) and cigars (Cornacchione Ross et al., 2020), while others show no or minimal effects or associations (e.g., e-cigarettes (Jorgensen & Wells, 2022), cigars (Cohn et al., 2018)). Furthermore, several studies show that some use cannabis before tobacco and/or alcohol or that cannabis use increases the probability of progressing to tobacco/alcohol use (Agrawal et al., 2006; Badiani et al., 2015; Cohn et al., 2018; Kokkevi et al., 2006; Mayet et al., 2016; Patton et al., 2005; Ramo et al., 2012; Reed et al., 2022; Scholes-Balog et al., 2016; Secades-Villa et al., 2015).

Among the explanations for these complex associations is the common liability model of vulnerability (Mayet et al., 2016; Selya, 2024; Vanyukov et al., 2012), which suggests that common genetic and individual factors, like mental health (e.g., depression (Moreno-Mansilla et al., 2021)), behavioral factors (e.g., sensation-seeking, impulse control (Wojciechowski, 2024)), or personality characteristics (Dash et al., 2023; Hokm Abadi et al., 2018; Kotov et al., 2010), increase risk of polysubstance use, regardless of order of initiation (Eaton et al., 2015; Moreno-Mansilla et al., 2021). Relatedly, one study (Melberg et al., 2010) documented the cannabis gateway effect only among youth who initiated substance use at younger ages or showed mental health or behavioral problems.

Given the complexity of previous findings, the range of explanatory models used, and the important implications of such findings for prevention efforts (Jorgensen & Wells, 2022; Melberg et al., 2010; Vanyukov et al., 2012), this topic warrants additional research. In particular, research is needed that considers: 1) the current context with increased e-cigarette and cannabis use in the more recent regulatory and marketing environment; 2) potential age or cohort effects that may manifest due to these shifts; and 3) the anticipated directions of substance use transitions suggested by the gateway theory (i.e., from tobacco/nicotine and alcohol use to cannabis use) and the reverse direction across this range of substances.

Thus, this study: 1) analyzed 2023 data among US young adults across all 50 states; 2) examined prior initiation of several legal substances – cigarettes, e-cigarettes, cigars, and alcohol – in relation to cannabis initiation, as well as the reverse relationships (i.e., prior cannabis initiation in relation to subsequent initiation of these other substances); 3) qualitatively compared strengths of these associations across substances in directionality and during adolescence vs. young adulthood; and 4) accounted for key contextual factors (i.e., cannabis policy, mental health, personality characteristics).

In this study, prior cigarette, e-cigarette, cigar, and alcohol use had significant effects on subsequent cannabis initiation and vice versa. Furthermore, a larger proportion (79%) of participants followed the gateway sequence (i.e., used some other substance before cannabis) vs. the reverse gateway sequence (21%), consistent with a study documenting that the reverse gateway sequence held among a minority of US adults (28%) and US adults ages 18-29 (33%) (Degenhardt et al., 2010). While this prior study did not report sequences for different specific substances (e.g., cigarettes, e-cigarettes, cigars, alcohol), the current study found that the gateway sequence was particularly applicable to alcohol and cannabis (i.e., over two-thirds used alcohol before cannabis), aligning with prior research (Barry et al., 2016; Keyes et al., 2015; Lemyre et al., 2019; Reed et al., 2022), while the reverse gateway sequence predominantly applied to cannabis, e-cigarette, and cigar use (i.e., >75% used cannabis before e-cigarettes or cigars, respectively). Moreover, effects were generally stronger when initiation occurred during adolescence vs. young adulthood. Collectively, these findings align with both the gateway hypothesis (Kandel, 2003; Kandel et al., 2006) and common liability model of vulnerability (Mayet et al., 2016; Vanyukov et al., 2012), underscoring the importance of prevention efforts addressing underlying mechanisms of various substance use (Kim & Hodgins, 2018), particularly for adolescents.

The more pronounced effects of prior cannabis use on subsequent e-cigarette and cigar use (vs. in the opposite direction) are noteworthy given the mixed findings from the limited research assessing gateway effects of e-cigarettes (Jorgensen & Wells, 2022; Morean et al., 2015; Temple et al., 2017; Unger et al., 2016) and cigars (Cohn et al., 2018; Cornacchione Ross et al., 2020) to cannabis use, and evidence that cannabis use may precede the use and/or increase the probability of subsequently using tobacco and alcohol (Agrawal et al., 2006; Badiani et al., 2015; Cohn et al., 2018; Kokkevi et al., 2006; Mayet et al., 2016; Patton et al., 2005; Ramo et al., 2012; Reed et al., 2022; Scholes-Balog et al., 2016; Secades-Villa et al., 2015). These results should be considered within the context of the cannabis, e-cigarette, and cigar markets in the US, given the expansion of non-medical cannabis legalization since 2014 (National Conference of State Legislators, 2024), the introduction of e-cigarettes in the US around 2010, and the increases in sales of e-cigarettes (Ali et al., 2022), cigars (Wang et al., 2021), and cannabis (Dilley et al., 2023). Since 2010, the use prevalence of both e-cigarettes and cannabis has increased among US young adults (Substance Abuse and Mental Health Services Administration, 2024), and cigar use, particularly small cigar use, has increased among certain populations (Jensen et al., 2025). Furthermore, cannabis is often used via vaping or blunts (Rubenstein et al., 2024; Simpson et al., 2021). Current results may indicate that initiating cannabis also introduces individuals to these other modes of use and promotes tobacco/nicotine use in these forms.

As noted above, the associations between prior use of other substances and initiation of each substance were generally stronger when initiation occurred during adolescence vs. young adulthood. However, this did not hold true for the relationship between prior e-cigarette use and later cannabis initiation. This is difficult to interpret, but it may be because initiating other substances was most commonly reported during the 13-18 age range, while e-cigarette initiation was most commonly reported during the 19-25 age range (45%) – likely due to when many participants were first exposed to e-cigarettes (Ali et al., 2022; Kaplan et al., 2023). Nonetheless, this finding warrants replication and further exploration regarding the mechanisms that might account for this finding.

As suggested by the common liability model of vulnerability (Mayet et al., 2016; Vanyukov et al., 2012), lifetime mental health diagnoses and personality characteristics were related to initiation in several of the models (Dash et al., 2023; Hokm Abadi et al., 2018; Kotov et al., 2010; Moreno-Mansilla et al., 2021). Specifically, cannabis initiation was predicted by lifetime depression diagnosis in the models assessing effects of previously using each other substance, and by lifetime anxiety diagnosis in the model accounting for prior cigarette use. Meanwhile, lifetime anxiety disorder or ADD diagnosis predicted e-cigarette initiation only, after accounting for prior cannabis use. Furthermore, certain personality characteristics were protective against substance initiation, including agreeableness and conscientiousness for each substance, openness to new experiences for cigarettes and cigars, and emotional stability for cannabis, cigarettes, and cigars. Meanwhile, extraversion was associated with increased hazards of initiating cannabis and e-cigarettes. These findings largely align with prior research highlighting certain personality risk profileds (Dash et al., 2023; Hokm Abadi et al., 2018; Kotov et al., 2010) that might help target those in need of intervention.

Notably, state non-medical cannabis laws were not associated with cannabis, e-cigarette, or alcohol initiation, but were with lower hazards of initiating cigarettes and cigars, which may underscore the general availability and appeal of cannabis, e-cigarettes, and alcohol (relative to cigarettes and cigars), regardless of regulatory context (Berg et al., 2015). Findings regarding sociodemographics also warrant consideration. Besides being younger, other groups at higher risk for substance use initiation in certain models included those identifying as non-Hispanic White (vs. Hispanic, Black, and Asian), in rural areas, and with parents <bachelor’s degree educated. Additionally, males were more likely to initiate e-cigarettes and cigars, whereas females were more likely to initiate cannabis and alcohol. Finally, sexual minorities were less likely to initiate cigars but more likely alcohol and cannabis. These findings may reflect different substance use contexts across different populations (Pokhrel et al., 2015) and the need to better understand mechanisms contributing to disparities in substance use.

This study has limitations. First, generalizability is limited due to participant recruitment via social media and purposive sampling (~50% reporting past-month cannabis use). Second, self-reported measures and retrospective reports (e.g., age of initiation) introduce potential bias. Third, measures included lifetime mental health diagnoses but not when diagnoses occurred, precluding the ability to account for sequencing of mental health diagnosis and substance use. Similarly, state non-medical cannabis legalization at the time of W1 assessment (but not prior periods or residences) was assessed; thus, we could not account for when individuals were exposed to legal non-medical cannabis. Along these lines, cohort effects may have impacted findings (e.g., some participants may not have been exposed to e-cigarettes during adolescence, some may not have been exposed to cannabis retail (Fadus et al., 2019)). Finally, the strength of the gateway effect vs. reverse gateway effect was not compared statistically.

Findings have implications for research and practice. Results generally supported gateway effects in both directions (tobacco/alcohol to cannabis, vice versa) as well as common liability theory, suggesting the need for preventive efforts targeting initiation of multiple substances in various sequences and that address common mechanisms, such as psychological (e.g., mental health, neuroticism, disagreeableness) (Moreno-Mansilla et al., 2021; Zuckerman, 2007) and socio-environmental factors (e.g., social norms) (Windle et al., 2017), especially early in life (e.g., in adolescence) (Melberg et al., 2010). Certain tobacco/nicotine products, particularly those used with cannabis or via similar modes as cannabis (e.g., e-cigarettes, cigars/blunts), may be especially mixed in use sequence (Kim & Hodgins, 2018). Future research should consider replicating these findings and apply this analytic approach to assessing other substance use patterns (e.g., derived cannabis products, hallucinogens) given the ongoing substance-related regulatory and market changes (Wojciechowski, 2024).