In recent years, more than half of all drug overdose deaths in United States involved an opioid. To address this epidemic, antecedents to opioid misuse must be identified and empirically validated. The objective of the current investigation was to examine whether illicit drug use was prospectively associated with nonprescription opioid use among adolescents from a vulnerable population with a greater prevalence of substance abuse. A population based cohort study of 1060 adolescents from 29 alternative high schools in southern California was conducted over a two-year period. A total of 929 adolescents (mean age 17.5 years, 49.9% female, 76.4% Hispanic) who had not experimented with nonprescription opioids at the baseline assessment were included in the analytic sample. The outcome was self-reported use of nonprescription opioids within two years. The predictors tested were illicit drug use, illicit drug use excluding marijuana, and the use of nonmedical marijuana. Covariates included age, sex, ethnicity, socioeconomic status, parental education, weekly income, sensation seeking, stress, anxiety, depression, and the use of alcohol and nicotine products. Multilevel, covariate-adjusted logistic regression models indicated that the odds of experimentation with nonprescription opioids was greater among adolescents who had used illicit drugs or illicit drugs excluding marijuana. Nonmedical marijuana use alone was a statistically significant predictor in unadjusted but not covariate-adjusted models. While prior studies have examined the progression from nicotine, alcohol, and marijuana use to nonprescription opioid use, the present findings emphasize the importance of illicit drug use as a detectable and empirically supported risk factor for future opioid misuse.

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