Background: The prevalence and harms associated with nonmedical prescription opioid use (NMPOU) have risen in Canada, and the prevailing policy response has restricted the supply of prescription opioids (POs) and promoted more responsible patient behaviour. Despite this quick action to address NMPOU, there are key knowledge gaps related to NMPOU initiation, ongoing use, and associated harms among people who use illegal street drugs (PWUD). Objectives: (i) conduct a systematized review of the extant literature related to NMPOU, (ii) identify the prevalence and correlates associated with NMPOU-related initiation trajectories and engaging in recent NMPOU, and (iii) investigate the impact of acquiring POs from physicians for the purposes of NMPOU. Methods: Multiple databases were systematically searched for extant literature on NMPOU. For the empirical studies, data were derived from the Vancouver Drug Users Study, which is an open prospective cohort study of youth and adult PWUD in Vancouver, Canada. Utilizing cross-sectional and longitudinal regression techniques and various sub-samples, I assessed the relationship between various risk factors and the following outcomes: engaging in recent NMPOU, initiating NMPOU before illegal street drugs (vs. after), initiating NMPOU using a physician prescription, and recent non-fatal overdose. Results: The review found some consistent indicators of risk related to NMPOU and gaps in knowledge related to NMPOU among hidden populations. In the empirical analyses, engaging in NMPOU was associated with a higher risk profile regardless of age and sex, and initiating NMPOU before illegal street drugs was also linked with a higher risk profile when compared with those who never engaged in NMPOU. Initiating NMPOU with a physician prescription was not a key indicator of high-intensity substance use or socio-structural vulnerability and acquiring POs using a physician prescription was not associated with recent non-fatal overdose. Conclusions: The results indicate that engaging in NMPOU is associated with a higher risk profile; however, NMPOU-related initiation trajectories and acquisition source do not appear to be a meaningful target for policy solutions or interventions. This dissertation provides some evidence for developing unique strategies to address ongoing NMPOU among younger and older PWUD that includes opioid agonist treatment and income generation opportunities.
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