PROJECT SUMMARY/ABSTRACT. This Mentored Research Scientist Development Award (K01) proposal will develop Dr. Greta Bushnell’s career as an independent investigator, and enable her to advance into a new line of research focused on evaluating misuse and abuse related morbidity of medicines prescribed to young people and the policies and practices that can mitigate these harmful outcomes. This new direction of research requires distinct training in substance abuse policy, misuse and abuse liability of prescription drugs, adolescent development of substance use, analysis of state-level policies, and advanced methods to address confounding control. With a training program supported by an experienced team of investigators, Dr. Bushnell will complete the proposed research, filling key gaps surrounding benzodiazepine (BZD) misuse and abuse related harms in young people and modifiable factors to reduce these harms. This research focus comes at a pertinent time of rising BZD-related morbidity, continued prescribing, lack of safety data in youth at developmental risk for substance use problems, and current opportunities to leverage opioid-related policies to reduce BZD-related harms. Overdose deaths involving BZDs significantly increased in recent years with »11,500 deaths in 2017, partially attributed to the opioid crisis, and in adolescents and young adults there were »39,000 emergency department visits for BZD-related poisonings in 2016. Despite BZDs being frequently prescribed to adolescents (3%) and young adults (6%), there are no estimates on overdose risk following BZD treatment and it is unknown whether and to what extent BZD prescribing to youth inadvertently increases risk of BZD or other substance misuse later in life. Prescription drug monitoring programs (PDMPs) represent a potentially important, but understudied, means to mitigate BZD- related morbidity. PDMPs are state-run surveillance systems collecting patient details on prescriptions for controlled substances with capabilities to detect risky prescribing. Dr. Bushnell will use large, national administrative claims data (2000-2018) covering privately and publicly insured young people (10-29 years) to evaluate whether selected state PDMP features decrease BZD-related harms and risky BZD prescribing in young people (Aim 1). To evaluate individual-level risks, she will quantify overdose risk following BZD treatment in young people compared to alternative treatments and by prescription details (Aim 2) using the national claims datasets with measures from Area Health Resources Files. She will then evaluate whether adolescent BZD treatment increases downstream risks of BZD misuse or harmful substance use in early adulthood (Aim 3) using the nationwide Monitoring the Future sample of high school seniors with panel surveys into early adulthood (»2,450/year, 1976-2016). The proposal will inform an R01 submission on identifying youth-specific risk factors in the progression from treatment with BZDs, or other controlled substances, to abuse and leveraging this knowledge to inform interventions. Addressing these questions and developing this new line of research are only feasible with intensive training, support, and protected time, which the K01 can provide.

PROJECT NARRATIVE. Benzodiazepines are frequently prescribed to adolescents and young adults, yet we lack key data on misuse, abuse, and overdose risk following benzodiazepine treatment and on what policies reduce benzodiazepine- related harms in young people. The proposed research will examine the risk of overdose and harmful substance use following benzodiazepine treatment and will evaluate whether state prescription drug monitoring program features are associated with a reduction in benzodiazepine-related harms and risky benzodiazepine prescribing. As more young people seek treatment for mental illness, it is of urgent public health importance to investigate the misuse and abuse potential of commonly prescribed pharmaceutical treatments and to consider modifiable factors, such as existing prescription drug monitoring programs, that can be leveraged to reduce harms.