Funded Projects

According to SAMHSA’s 2017 National Survey on Drug Use and Health (NSDUH), 11.4 million persons in the U.S. report past-year opioid misuse; out of them, only 2.1 million individuals met criteria for an OUD. Very little is known about efficacious interventions for those who do not meet criteria for moderate/severe OUD (i.e., subthreshold OUD). The prevalence of subthreshold OUD in primary care settings is 5 percent to 10 percent, with higher rates (21 percent to 29 percent) among those receiving prescribed opioids. Although they are at high risk of developing moderate/severe OUD and/or dying from an overdose, little or no empirical evidence exists for pragmatic prevention interventions that can be adopted at integrated general medical settings. To study the efficacy of prevention interventions to arrest the progression from risky opioid use, researchers will test the efficacy of a STOP intervention in primary care settings. STOP adopts an early intervention approach, based on a collaborative care model to prevent progression to moderate/severe OUD, and consists of a practice-embedded nurse care manager who provides patient education and supports the primary care provider (PCP) in engaging, monitoring and guiding patients who have risky opioid use; brief advice delivered to patients by their PCP; and phone counseling of patients by behavioral health providers to motivate and support behavior change. Researchers will determine whether STOP reduces risky opioid use and examine the impact of STOP on progression to moderate/severe OUD, overdose risk behavior and overdose events in adults with risky use of illicit or prescription opioids.

There are no FDA-approved medications for stimulant use disorders, and therapies for opioid use disorders remain suboptimal in ways that are now a focus of national attention. Thus, there is a clear need to identify new targets and explore new approaches for addiction medication development. Several lines of evidence suggest that PTPRD (receptor type protein tyrosine phosphatase D) may be a promising target for development of pharmacotherapeutics to treat not only stimulant use disorders but opioid use disorders as well. This research will focus on improving existing PTPRD ligands, identifying their effects on the dopamine and opioid systems, and moving the best novel, patentable PTPRD ligands toward human studies. If successful, this project will generate novel, well-tolerated, and bioavailable PTPRD ligands that display in vitro potency, selectivity and stability, and in vivo modulation of both cocaine and opioid-mediated reward at doses that present no significant toxicity.

Morbidity and mortality related to prescription opioids are accelerating in the United States. Identifying the factors that lead to new opioid dependence among opioid naïve patients is a critical opportunity to reduce prescription opioid dependence and unintended diversion. In the United States, the majority of individuals who become opioid dependent receive their first opioid prescription following surgical procedures, yet there are no clinical guidelines to inform appropriate postoperative opioid use. We will examine the patient factors that are associated with postoperative pain and opioid consumption among a cohort of patients undergoing common elective abdominal procedures. We will identify the provider characteristics in postoperative opioid prescribing practices, and design and implement a provider-directed intervention to optimize postoperative opioid prescribing. Findings will inform patients and providers regarding the risk of opioid dependence following surgery, and will establish a patient-centered data infrastructure that yields continuous feedback to providers regarding appropriate opioid prescribing practices.

Despite psychopathology robustly increasing the risk for later substance use disorders (SUD), remarkably few studies have examined the impact of treating psychopathology on reducing rates of opioid use disorder (OUD), nicotine, and SUD. The main aims of this study are to implement a pragmatic set of office-based instrumentation using patient related outcome measures linked to electronic health records (EPIC) for intake and follow-up assessments to evaluate psychopathology, OUD, nicotine use disorder, and other SUDs in young people aged 16-30 years old who are receiving psychopathology treatment as part of routine outpatient clinical care. The study will also examine similar age patients with non-opioid SUD in outpatient SUD treatment settings to examine the impact of treatment in mitigating the development of OUD. Data derived from this study will help inform clinical guidelines and public health policy and provide important secondary outcomes for further work on the prevention of OUD, nicotine use disorder, and other SUDs in relation to early-onset psychopathology.

Opioid use disorders (OUD) are a national public health emergency with more than 115 fatal overdoses occurring each day in the U.S. and an economic burden of more than $78 billion a year. Several medications are available for treating OUD, but their access is limited and efficacy is often sub-optimal. It is thus urgent to develop new, affordable strategies for the effective treatment of OUD. Immunopharmacotherapy has emerged as a promising treatment approach against OUD that relies on the induction of drug-specific antibodies to neutralize circulating drug molecules and reduce or cancel their effects. Several groups have attempted to apply this strategy with mixed results, suggesting that novel immunization platforms must be tested to further improve vaccine efficacy against OUD. This project will fabricate novel nanoparticle-based vaccines against OUD that are likely to boost their immunogenicity and lead to a more robust and effective immune response against the target opioid. The broad impact of this project resides in the rational design of nanoparticle-based vaccines that are safe and effective against opioids. This novel nanoparticle-based immunization strategy can be applied to the development of next-generation vaccines against a range of OUD and other substance use disorders.

There is a significant treatment gap between patients diagnosed with OUD and those who seek treatment, and only a small proportion of those seeking treatment receive MOUD. Primary care is the most common point of health care contact in the U.S. and is an important venue to address stigma, improve access to treatment and improve quality of care. Over the past decade, electronic health record (EHR)-linked Web-based point-of-care clinical decision support (CDS) systems designed to improve quality of chronic disease care have become increasingly sophisticated and successful. A Web-based and EHR-integrated OUD CDS system to offer expert guidance to primary care providers (PCPs) on the diagnosis and management of OUD was developed and piloted. This project will implement the OUD clinical decision support system in three large diverse health care systems and randomize a minimum of 30 clinics to receive the OUD-CDS intervention or usual care (UC). The project will evaluate the impact of OUD CDS on practice process measures and patient outcomes. The study will also prepare for scalability and dissemination by evaluating facilitators and barriers to implementation, determining the costs of implementation and maintenance and assessing the short-term cost impacts of the OUD-CDS.

Despite increased efforts to understand the neurodevelopmental sequelae of in utero opioid and other substance exposure on long-term behavioral, cognitive, and societal outcomes, important questions remain, specifically, 1) How is brain growth disrupted by fetal substance and related pre- and post-natal exposures? and 2) How are these disrupted growth patterns causally related to later cognitive and behavioral outcomes? This project seeks to formulate an approach to addressing these key questions and decipher the individual and cumulative effect of these intertwined pre- and post-natal exposures on child neurodevelopment. First, researchers will address the legal, ethical, and mother-child care and support concerns implicit in this study. Next, they will integrate across our areas of neuroimaging expertise to develop, implement, and harmonize a multi-modal MRI and EEG protocol to assess maturing brain structure, function, and connectivity. Finally, researchers will develop and test advanced statistical approaches to model and analyze this multidimensional and longitudinal data.

The opioid crisis continues its highly negative impact, with more than 49,000 opioid-related overdose deaths in 2017. In 2016, the Centers for Disease Control and Prevention (CDC) issued guidelines for opioid prescribing that included opioid dosing and risk mitigation strategies, and health systems implemented similar initiatives even earlier. This has resulted in a quickly changing and more conservative prescribing environment. National data indicate the number of prescriptions has fallen between 2013 and 2016. Registries and electronic health record (EHR) data are increasingly cited as valuable resources to address critical research questions on opioid use with high efficiency. To our knowledge, no investigators have established an EHR-based prescription opioid registry across several diverse health systems with common data algorithms with the flexibility to address multiple questions. The goal of the proposed research is to develop a prescription opioid registry across 10 diverse health systems with harmonized EHR data from years 2012-2018 and leverage it to answer several key “next-step” research questions in response to the opioid crisis. The registry will include medications prescribed for treatment of OUD, including buprenorphine products.

The Planning for the HEALthy Early Development Study will contribute to the design and recommended protocol for a future large-scale, multi-site research study to prospectively examine human brain, cognitive, behavioral, social, and emotional development of children beginning prenatally through ages 9–10 and to determine the impact of maternal pre- and postnatal substance use on short- and long-term development of children. The planning study will link investigators across 6 research sites who have complementary experience and expertise in the areas that are essential to designing the study. Planning activities will be accomplished using a coordinated set of 10 working groups. By the end of the planning phase, the 6 consortium sites will have produced and tested a recommended protocol for the future multi-site study and will have established feasibility of carrying out the study protocol at each of the 6 linked sites.

People who use opioids in rural areas suffer worse health and less insurance coverage. The opioid problem in rural areas is of particular concern, as rural areas have higher overdose rates despite equivalent rates of OUD. This is because rural areas have a scant number of clinics and clinicians who provide medication treatment for OUD. Thus, people living in rural areas must travel long distances to access clinics that may or may not have expertise in providing treatment to patients with OUD. Telemedicine (TM) could efficiently increase capacity for delivery of buprenorphine in rural areas and may increase the number of patients receiving medication treatment and improve treatment retention and outcomes. While the development of medication treatments for opioid use disorder (MOUD) capacity in primary care settings with optimal/comprehensive services is desirable, the current opioid crisis with escalating overdose death rates in rural areas suggests a need to implement an efficient, cost-effective system of MOUD services that can be scaled up quickly. The use of a centralized and Medicare-covered TM vendor utilizing a developed methodology and established organizational infrastructure offers the great potential for a rapid rollout to increase access to MOUD and improve treatment retention in rural areas. This cluster randomized clinical trial with two phases will test expanded treatment access to improve retention on MOUD in highly affected rural areas. Phase I will include implementing telemedicine in a limited number of rural sites with varying levels of office-based opioid treatment (OBOT) to inform implementation strategies for the main trial, and Phase II will include evaluate comparative effectiveness between OBOT alone and OBOT + TM at 30 sites.

Most opioid misuse begins during adolescence and young adulthood. Adolescence is the best time for prevention interventions in settings like school-based health centers (HCs), yet few programs focus on preventing initiation of opioid misuse. This study harnesses the power of video game interventions and incorporates components of effective substance use prevention programs to develop an evidence-informed intervention to prevent the initiation of opioid misuse in adolescents. In partnership with the national School-Based Health Alliance (SBHA), researchers will develop and test a new video game intervention, PlaySmart. It will build on our previous video game intervention that has demonstrated efficacy in improving attitudes and knowledge related to risk behaviors. The study will evaluate the game in a randomized controlled trial (RCT) in 10 school-based HCs and examine strategies for implementing PlaySmart in school-based HCs nationally. This research has considerable potential for wide implementation, reach, and impact on high-risk adolescents through school-based HCs.

A large number of probationers/parolees with opioid use disorder have limited access to effective treatment. This study is the first random clinical trial in the United States that will assess the effectiveness of buprenorphine treatment using MedicaSafe, a system composed of secure pre-packaged buprenorphine/naloxone cartridges, designed to be dispensed by a SmartKey device that enables clinicians to track patient adherence. The study will initiate treatment at a community corrections office compared to referral to a community program. The public health impact of the proposed study would be widespread, as this model of care could be implemented throughout many areas of the United States with high rates of opioid use disorder in their probation/parolee populations that lack access to methadone treatment.