Funded Projects

This project aims to develop a novel abuse deterrent formulation (ADF) that will be uniquely designed to prevent abuse of the prescription pill. The study will focus on the development of the ADF with design aspects specifically focused on abuse through insufflation, smoking, injection, and taking multiple pills. The study will also validate the design by putting the pill through a rigorous test following the procedures outlined by the FDA Abuse-Deterrent-Opioids-Evaluation and Labeling guidelines. The study could result in the development of a novel ADF that will be resistant to a wide range of tampering, resulting in a safer formulation and pill design.

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.

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.

The University of Pittsburgh Low Back Pain: Biological, Biomechanical, and Behavioral Phenotypes (LB3P) Mechanistic Research Center (MRC) will to perform in-depth phenotyping of patients with chronic low back pain (cLBP), using a multimodal approach to characterize patients and provide insight into the phenotypes associated with experience of cLBP to direct targeted and improved treatments. The LB3P MRC will be formed of three Research Cores, three support cores, and one research project. This approach will leverage and integrate distinctive resources at the University of Pittsburgh laboratories to deliver quantified biomechanical, biological, and behavioral characteristics; functional assessments; and patient-reported outcomes, coupled with advanced data analytics using a novel Network Phenotyping Strategy (NPS). By eliminating isolated and disconnected approaches to treatment and focusing on personalized patient-centric approaches, this approach will yield improved outcomes and patient satisfaction.

Four out of five youth in the juvenile justice (JJ) system show evidence of being under the influence during their offenses, and more than half test positive for substances at the time of their arrest. Preventive intervention approaches that can be easily implemented within JJ settings may offer greater access to substance use care as well as increase families’ motivation to comply with court referrals to seek further services. It is especially important to evaluate interventions for court-involved, non-incarcerated (CINI) juveniles, as these youth account for two-thirds of those arrested; however, the bulk of extant research has been conducted with detained or incarcerated youth. In this application for supplemental funding, we capitalize on our parent grant (Brief Individual and Parent Interventions for Marijuana Misuse in Truant Adolescents) by proposing to develop an adjunctive, targeted preventive intervention for marijuana-using, JJ youth who are at elevated risk for illicit opioid use. The goal will be to develop a protocol for a single-session, parent-adolescent preventive intervention to decrease the likelihood of illicit opioid use in CINI adolescents. This formative work will culminate in a draft intervention manual.

The U.S. is in the midst of an opioid crisis, and efforts to tackle the complex and dynamic nature of this public health challenge must comprehensively consider a multitude of contributing factors. In response, states have implemented a wide range of policies and initiatives. However, the dynamic nature of the crisis and the speed with which different policy approaches are being implemented pose numerous challenges for researchers evaluating the effects of such efforts. These challenges stem in part from limited information regarding policy implementation; insufficient information about policy characteristics that may influence effectiveness; little consideration of how the chosen analytic method may influence findings, given simultaneous or concurrent implementation of multiple policies; and limited training on how to best communicate findings to policymakers. To address these challenges, the proposed Center for Opioid Policy Research (COPR) will serve as a national resource, fostering innovative and high-quality research in the opioid policy arena and developing and disseminating methods, tools and information to the research community, policymakers and the public.

The opioid overdose epidemic is increasingly affecting urban, poor and predominantly minority populations in the U.S., including Washington, D.C., as indicated by rapidly increasing overdoses clustered in medically underserved, economically disadvantaged, largely African American areas of the District and many of the nation’s other largest cities. This study seeks to (1) develop, implement and conduct a preliminary evaluation of an integrated, community-based collaborative care model, employing peer recovery coaches and telepsychiatry services, to improve utilization and effectiveness of MOUD in Federally Qualified Health Centers (FQHCs) and (2) use a community-based participatory research approach to develop, implement and conduct a preliminary evaluation of outreach, engagement and recovery support interventions in nontraditional community settings (e.g., grassroots community groups, churches or religious organizations, soup kitchens, black barber shops or nail or hair salons).

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.

More than 100 million adults in the U.S. suffer from intermittent or constant chronic pain, and chronic pain affects at least 10 percent of the world’s population. The primary pharmaceuticals for treatment of chronic pain have been natural or synthetic opioids, and the use of opioids for pain treatment has resulted in what has been called an “epidemic” of opioid abuse, addiction, and lethal overdoses. Through a process of rational drug design, the research team has generated a new chemical entity (NCE) and have given it the name Kindolor, a non-opiate, non-addicting molecule that was shown to reduce or eliminate chronic pain in five animal models at doses compatible with use of Kindolor in humans. This project intends to complete the pre-clinical studies required for an IND application, which, if approved, would allow for proceeding onto the Phase 1 and 2 studies to assess safety and efficacy of the compound against osteoarthritic pain.

Many individuals with opioid use disorder (OUD) pass through the criminal justice system over the course of their life. Improved access to high-quality, evidence-based addiction treatment in justice settings will be critical to addressing the opioid crisis. Through the Justice Community Opioid Innovation Network (JCOIN), the National Institutes of Health will study approaches to increase high-quality care for people with opioid misuse and OUD in justice populations. The Mason Coordination and Translation Center (MCTC) will manage logistics, stakeholder engagement, and dissemination of findings and products from the JCOIN network. This will include establishing infrastructure to support research education and rapid response and pilot research.

Most of the 200k Americans who undergo thoracotomy each year receive opiates to reduce postoperative pain because clinicians have few non-addictive, cost-effective choices to control the severe pain patients often experience in the first two weeks after surgery. Managing pain post-thoracotomy is critical to enable patients to take deep breaths and remove (via coughing) lung secretions that otherwise significantly increase risk of pneumonia and collapsed lung, hospital re-admission and morbidity. The most severe pain associated with thoracotomy is transmitted along the intercostal nerves, but no long-term analgesic or nerve block device exists that can provide safe and effective long-term reduction of pain. A reversible, patient-controlled, non- addictive, intercostal nerve block device would reduce suffering due to thoracotomy, broken ribs and herpes zoster. In this Phase I project, the team will develop a minimally invasive thermal nerve block device that can control nerve conduction by gently warming and cooling a short nerve segment between room temperature and warm water temperature. This novel approach is based on the discovery that warm and cool temperature mechanisms of nerve block are different and additive, enabling moderate-temperature nerve block by cycling neural tissues slightly above and below body temperature. Reversible thermal nerve blocks represent a completely new approach to managing pain.  

Structural and functional neuroimaging measures are prone to errors induced by subject motion. Many comorbid features of opioid exposure are likely to increase children’s in-scanner motion. In total, this raises substantial concern that existing neuroimaging methods are not sufficiently motion-robust to be used in studies of children ages 3–5. Researchers will address these concerns with a feasibility study, comparing the existing methods developed for the Adolescent Brain Cognitive Development (ABCD) study with novel methods we will develop and optimize for young children. They will evaluate research methods in a sample of 100 children and test whether novel technologies improve the quality of the raw imaging data and reduce motion biases in the derived measures. Researchers will determine predictors of successful imaging to inform sampling strategies in future studies. The primary outcomes will be novel, validated structural and functional neuroimaging imaging methods for young children and feasibility data to inform the design of future studies addressing developmental questions, particularly those related to opioid exposure.