Funded Projects

This project will refine an experimental non-invasive light therapy to create an effective, safe, convenient, and affordable method for treating opioid use disorder. This research will test whether a short treatment of near infra-red light administered through the skull can reduce drug use, relapse, and craving, and improve overall function in people with opioid use disorder. If effective, the findings could support a path toward commercialization of this new treatment.

New and safe therapeutic targets for treating opioid use disorder are needed. One promising approach is to test drugs currently approved by the U.S. Food and Drug Administration that work independently of the body’s opioid system. The medication memantine targets N-methyl-D-aspartate (NMDA) receptors in the brain, which have been implicated in the development and maintenance of addiction. This project will study a miniature version of multiple memantine molecules bound together that attaches only to NMDA receptors that are not within nerve connections. The research will evaluate the safety, misuse potential, and effectiveness of this molecular assembly in preclinical models. 

This project will develop and refine a wearable device (forearm bracelet) designed to rapidly sense and report the presence of opioids in the wearer. This research will optimize this device to provide ultra-high sensitivity, enhanced drug specificity, long-term durability, low power consumption, and cost-effective production. The findings could support a path toward commercialization of this new device.

We discovered a class of non-opioid modulators of the T-type Cav3.2 channel that could treat neuropathic pain. In vivo pharmacokinetic and pharmacodynamic studies and preliminary toxicological studies identified AFA-279 and other candidates, which did not produce observable side-effects and showed greater analgesic effects than other neuropathic pain medications in rodent models. The goal of this proposed project is to submit the IND application on our Cav3.2 modulator to the Food and Drug Administration (FDA). We will produce AFA-279 under Good Manufacturing Practice (GMP)–like conditions using chemical manufacturing controls for Good Laboratory Practice (GLP) nonclinical toxicity studies and GMP clinical batch future Phase 1 clinical trials, complete toxicological and safety studies to establish the safety profile of AFA-279, prepare and submit the IND application, and then initiate early clinical trials. Our ultimate goal is to deliver a safer, more effective, non-opioid Cav3.2 channel modulator to patients suffering from neuropathic pain.

The emergency department (ED) is an ideal venue to reach and intervene with adolescents and young adults at risk for opioid misuse, particularly as young adults may disconnect from primary care when transitioning out of pediatric medicine. This study will evaluate the efficacy of interventions of varying type/intensity to prevent/reduce opioid misuse or opioid use disorder (OUD). The research leverages technology that is appealing to youth to facilitate intervention delivery by health coaches. In this study, adolescents and young adults in the ED screening positive for opioid use or misuse will be randomly assigned to one of four intervention conditions with outcomes measured at 4, 8, and 12 months. Technology-driven, scalable interventions delivered via health coach allow for real-time tailoring to the rapidly changing opioid epidemic, with the potential for a sustainable impact on preventing escalation of opioid misuse among adolescents and young adults. While we know that Black/African American youth are at increased risk for opioid and other substance use, they often do not participate in research studies. As a result, we do not know how well prevention interventions work with Black/African American individuals. This supplement will focus on increasing participant diversity and inclusion by recruiting additional Black/African American participants for this ongoing randomized controlled trial to study technology-driven prevention interventions.

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 ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study – also called the ACT NOW Longitudinal Study – is a longitudinal cohort study to prospectively examine longitudinal outcomes from birth to 2 years of age among infants who were exposed to opioids in utero as compared to matched controls. The objectives of this study are to i) determine the impact of pre-birth opioid exposure on brain structure and connectivity over the first 2 years of life, ii) define medical, developmental, and behavioral outcomes over the first 2 years of life in infants exposed to opioids, and iii) Explore whether and how the home environment, maternal mental health, and parenting affect brain connectivity and neurodevelopment trajectories over the first 2 years of life. This research will use an innovative approach to engage a more diverse study population and thereby improve the generalizability of the research findings.

There is a great deal of research aimed at better understanding transitions in alcohol and other drug (AOD) use patterns from early to late adolescence and from late adolescence to emerging adulthood. However, no studies to date have (a) assessments of AOD use from ages 10 to 24 across all developmental periods (middle school, high school, and emerging adulthood); (b) a large sample with substantial racial and ethnic diversity, particularly among Hispanic and Asian youth; (c) in-depth coverage of 10 areas of functioning across three key domains; (d) subjective and objective neighborhood data; or (e) the capacity to examine developmental trajectories for more than one substance. The current proposal is a continuation of previous projects that assessed AOD use across nine waves of data from age 10 to age 19. The proposed study capitalizes on the longitudinal data on protective and risk factors we have collected since age 10 in an ethnically diverse cohort by continuing to annually assess these youth in order to capture important transitions to emerging adulthood (through age 24). By advancing the epidemiology of alcohol use during adolescence and emerging adulthood, our findings can affect prevention and intervention programming for young people and address critical issues of public health policy.

Over 30% of adults aged 65 years and older in the United States suffer from osteoarthritis (OA). Opioid analgesics are often used for patients with moderate to severe symptomatic OA. When non-pharmacologic and pharmacologic treatments are not effective, patients with severe OA may undergo total joint replacement (TJR). Our primary objectives are to evaluate patterns of opioid use before and after TJR and to assess the effect of opioid use patterns on clinical outcomes and safety events in a large U.S. population–based cohort of OA patients. The specific aims are to: 1) identify predictors of persistent opioid use and opioid dose escalation in patients after TJR for hip or knee OA and 2) evaluate effects of opioid use patterns on short- and long-term clinical outcomes and safety following TJR. The results of this study will provide guidance on surgical risk stratification and pain management of patients before and after TJR.