Funded Projects

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 HEALthy Brain and Child Development National Consortium (HBCD-NC) will establish a normative model of developmental trajectories over the first 10 years of life. All sites in the HBCD-NC will carry out a common research protocol and will assemble and distribute a comprehensive research dataset to the scientific community. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. Most participants will be recruited in the second trimester of pregnancy, with a smaller subset recruited at birth, and followed for the first 10 years of life. The University of Florida study site will recruit a diverse group of mother-infant pairs from urban and rural communities in North Central Florida.

The widespread availability of fentanyl and other potent synthetic opioids has dramatically increased opioid-related fatal overdoses. This project will develop and manufacture immune molecules (monoclonal antibodies) to reverse and treat overdose from fentanyl by keeping it out of the brain. This research will advance promising results in animal studies (preventing and reversing fentanyl- and carfentanil-induced breathing problems and irregular heartbeat) to clinical testing in people with opioid use disorder and others at high risk of opioid overdose from accidental or deliberate exposure to fentanyl and fentanyl-like drugs.

Deaths from opioid overdose continue to rise; from 2015 to 2016, there was a 28 percent increase in the number of fatal overdoses. Currently available pharmacotherapies include MOR agonists (e.g., buprenorphine) and antagonists (e.g., naloxone), all of which suffer from specific and clear limitations. To address the main deficits in these treatments, the researchers will develop and optimize medications with longer duration of action that prevent and reverse the effects of opioids in a manner that is not surmounted by increasing doses of agonist. Their pilot studies in monkeys show that the pseudo irreversible MOR selective antagonist methocinnamox (MCAM) decreases heroin but not cocaine self-administration, decreases choice for remifentanil in a food/drug choice procedure, and reverses—as well as protects against—respiratory depression by heroin, with a single injection being effective for a week or longer. Bringing a medication like this to marketable fruition could significantly improve the treatment of OUD and save lives by providing insurmountable extended protection after rescue from overdose, including from ultra-potent fentanyl analogs.

As the opioid crisis claims more and more lives, there is a need to develop new, safer analgesics. Biased agonists could activate beneficial signaling pathways while avoiding those that cause adverse effects. This project aims to speed the discovery of non-addictive analgesics by providing drug discovery teams with simpler, more robust, more quantitative assays for agonist bias. The goal is to optimize and test new assays for agonist bias at NOP, D3 dopamine, CB1 cannabinoid, and OPRM1 opioid receptors, which couple to both the Gi and ?-arrestin signaling pathway, and create new tools to improve the analysis of structure/activity relationships that can be used in drug discovery and distribute to researchers who are developing new drugs for OUD.

Significant racial, ethnic, socioeconomic, and geographic disparities affect access to opioid use disorder (OUD) treatment and have thus contributed to the opioid overdose crisis. Patient navigator interventions after hospitalization can improve access to treatment, but challenges prevent full adoption of these strategies. These include lack of coordination across institutions, inadequate data sharing, workforce shortages, and lack of awareness, especially in resource-limited communities. This project aims to develop a hospital system-wide patient navigation protocol that can be scaled up to address OUD treatment linkage and continuity after hospitalization.

While effective treatments exist for substance use disorders, adhering to treatment and retaining patients in treatment can be a challenge. The objectives of this project are to facilitate the implementation of loyalty/reward-based programs to increase adherence to medical treatment among patients with substance use disorders through innovative solutions to common challenges. Building on experience developing software to promote patient appointment attendance, the project will build a new tool to test on a sample of 10 providers and 10 patients who are prescribed but not fully adherent to substance use disorder treatment. Patients will receive tailored text messages (in English or Spanish) encouraging adherence, self-report their treatment adherence (which will be verified through smart pill caps and biological testing), earn points for adherence that can be exchanged for rewards customized for them based on a baseline survey, and report their satisfaction with the program and process at the end of the 4-week study. This pilot will assess the feasibility and perceived usefulness of the product in support of eventual larger-scale testing in a clinical trial.

Although there are effective prevention and treatment programs and services to address opioid misuse, opioid use disorder (OUD), and overdose, gaps remain between those needing and those receiving prevention and treatment, in part because of a need to better understand how to make these programs and services most effective at a local level. The National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) launched the HEALing Communities Study to generate evidence about how tools for preventing and treating opioid misuse and OUD are most effective at the local level. This multisite implementation research study will test the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings. The goal of the study is to reduce opioid-related overdose deaths by 40 percent over three years. The University of Kentucky is partnering with academic institutions in three other states to study the impact of these efforts in 67 highly affected communities. The study will also look at the effectiveness of coordinated systems of care designed to increase the number of individuals receiving medication to treat OUD, increase the distribution of naloxone, and reduce high-risk opioid prescribing.

One of the most widely used treatments for chronic pain is opioid analgesics. Importantly, there is evidence of a pathological interaction between opioids and the immune system that can contribute to both opioid tolerance and elevated levels of pain. Chronic pain conditions for which opioids are most often prescribed have been shown to involve dysregulation of the immune system, which may contribute to pathological effects of opioid use in these patients. To address this unmet need, this study aims to develop a reliable, cost-effective, and non-invasive in vitro diagnostic assay for chronic pain with an underlying inflammatory pathology, as a blood test available in primary care settings, with the hope that doctors can use the test to identify which patients might benefit less from opioids and be more likely to become addicted.

There is a need for longer-acting prophylactic pharmacologic options for opioid use disorder (OUD) patients during maintenance therapy. This study tests a titanium implant loaded with a formulation of naltrexone and a naturally occurring carboxylic acid. The device is implanted subcutaneously with local anesthetic during an in-office procedure. The technology is based on a unique formulation that keeps the pH within the reservoir low and promotes passive diffusion of naltrexone. The benefits of the product include complete medication adherence for one year after administration, fewer relapses, smooth profile ensuring complete prophylaxis without sub-therapeutic plasma troughs, full reversibility, and similar efficacy with less drug exposure. This technology has been validated clinically with another drug and tested preclinically with naltrexone. This project will finalize the chemistry manufacturing and controls, produce IND supplies, conduct an IND-enabling safety study, and submit the IND.

Although there are effective prevention and treatment programs and services to address opioid misuse, opioid use disorder (OUD), and overdose, gaps remain between those needing and those receiving prevention and treatment, in part because of a need to better understand how to make these programs and services most effective at a local level. The National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) launched the HEALing Communities Study to generate evidence about how tools for preventing and treating opioid misuse and OUD are most effective at the local level. This multisite implementation research study will test the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings. The goal of the study is to reduce opioid-related overdose deaths by 40 percent over three years. As the Data Coordinating Center, RTI will provide coordination and facilitate communications to unite the HEALing Communities Study research centers into a cohesive research cooperative.

Many individuals with opioid use disorder pass through the criminal justice system over the course of their life. Improved access to high-quality, evidence-based addiction treatment in justice settings is critical to addressing the opioid crisis. The Justice Community Opioid Innovation Network (JCOIN) is studying approaches to increase high-quality care for people with opioid misuse and opioid use disorder in justice populations. This research supports a scientist from a group underrepresented in biomedicine to expand capacity of the Mason Coordination and Translation Center that is managing logistics, stakeholder engagement, and dissemination of findings and products from the JCOIN network.