Association of Nonmedical Prescription Opioid Use With Subsequent Heroin Use Initiation in Adolescents

Importance: There is concern that nonmedical prescription opioid use is associated with an increased risk of later heroin use initiation in adolescents, but to our knowledge, longitudinal data addressing this topic are lacking.

Objective: To determine whether nonmedical prescription opioid use is associated with subsequent initiation of heroin use in adolescents.

Design, Setting, And Participants: This prospective longitudinal cohort study conducted in 10 high schools in Los Angeles, California, administered 8 semiannual surveys from 9th through 12th grade that assessed nonmedical prescription opioid use, heroin use, and other factors from October 2013 to July 2017. Students were baseline never users of heroin recruited through convenience sampling. Cox regression models tested nonmedical prescription opioid use statuses at survey waves 1 through 7 as a time-varying and time-lagged regressor and subsequent heroin use initiation across waves 2 to 8 as the outcome.

Exposures: Self-reported nonmedical prescription opioid use (past 30-day [current] use vs past 6-month [prior] use without past 30-day use vs no past 6-month use) at each wave from 1 to 7.

Main Outcomes And Measures: Self-reported heroin use initiation (yes/no) during waves 2 to 8.

Results: Of 3298 participants, 1775 (53.9%) were adolescent girls, 1563 (48.3%) were Hispanic, 548 (17.0%) were Asian, 155 (4.8%) were African American, 529 (16.4%) were non-Hispanic white, and 220 (6.8%) were multiracial. Among baseline never users of heroin in ninth grade with valid data (3298 [97% of cohort enrollees]; mean [SD] age, 14.6 [0.4] years), the number of individuals with outcome data available at each follow-up ranged from 2987 (90.6%) to 3200 (97.0%). The mean per-wave prevalence of prior and current nonmedical prescription opioid use from waves 1 to 7 was 1.9% and 2.7%, respectively. Seventy students (2.1%) initiated heroin use during waves 2 to 8. Prior vs no (hazard ratio, 3.59; 95% CI, 2.14-6.01; P < .001) and current vs no (hazard ratio, 4.37; 95% CI, 2.80-6.81; P < .001) nonmedical prescription opioid use were positively associated with subsequent heroin use initiation. For no, prior, and current nonmedical prescription opioid use statuses at waves 1 to 7, the estimated cumulative probabilities of subsequent heroin use initiation by wave 8 (42-month follow-up) were 1.7%, 10.7%, and 13.1%, respectively. In covariate-adjusted models, associations were attenuated but remained statistically significant and current nonmedical prescription opioid use risk estimates were stronger than corresponding associations of nonopioid substance use with subsequent heroin use initiation.

Conclusions And Relevance: Nonmedical prescription opioid use was prospectively associated with subsequent heroin use initiation during 4 years of adolescence among Los Angeles youth. Further research is needed to understand whether this association is causal.