Growing evidence suggests that income inequality is associated with adolescent substance use behaviors, prompting the presumption that it may also be associated with poly-substance use. This study examined the association between income inequality and poly-substance use and tested whether anxiety indirectly affects this relationship. We used cross-sectional survey data from the 2018–2019 Cannabis, Obesity, Mental health, Physical activity, Alcohol, Smoking, and Sedentary behavior (COMPASS) project. The analytical sample comprised 71,396 students from 136 secondary schools and 43 census divisions across four Canadian provinces. Using multilevel path analyses, we examined the direct and indirect association between income inequality and poly-substance use. Students in neighborhoods with moderate income inequality relative to those in low-income inequality neighborhoods had higher odds of poly-substance use, with similar odds observed for both females (ORmod = 1.34; 95% confidence interval [CI] = [1.02, 1.66]) and males (ORmod = 1.38; 95% CI = [1.05, 1.72]). In relation to the indirect association through anxiety, gender-stratified results showed that attending schools in neighborhoods with moderate- and high-income inequality was associated with slightly higher odds of poly-substance use among females (ORmod = 1.09; 95% CI = [1.01, 1.18] and ORhigh = 1.10; 95% CI = [1.00, 1.21]). Income inequality is associated with poly-substance use, and this relationship is also indirectly influenced by anxiety among females. Reducing neighborhood income inequality may contribute to lowering poly-substance use among adolescents. In addition, anxiety management in schools located in highly unequal neighborhoods may be an effective intervention approach in reducing poly-substance use among female adolescents.
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