Funded Projects

The ongoing epidemic of opioid use disorder (OUD), overdose, and death is unprecedented. Available pharmacologic therapies for OUD have failed to stem the tide, plagued by poor adherence and retention, the principal factors associated with relapse and treatment failure. More than 80 percent of individuals with OUD are untreated. More treatment options are needed. This proposal seeks to develop a better antagonist-based OUD pharmacotherapy for populations highly motivated to achieve abstinence, such as military personnel, criminal justice clients, and the currently employed. A series of novel and proprietary small molecules will be designed and synthesized to address the adherence problem by inducing effective opioid antagonism with a single injection lasting at least 2 months, and up to 4 months or more. The goal of this project is to advance to Phase 3 clinical trials toward FDA approval of our lead compound. If successful, this project could lead to a novel therapeutic with superior adherence and retention, resulting in a significant public health impact by reducing rates of relapse, overdose, and death.

As prescription opioid drug abuse and overdose-related deaths continue to skyrocket in the United States, the need for new and more effective non-addictive pain drugs to treat chronic pain remains critical. This research is conducting studies in animal models of a small molecule that has high potential to treat chronic pain conditions associated with neuropathy and/or inflammation. The goal of this project is to conduct dosing and other studies leading up to an animal model study of the potential drug in a toxicology study for 28 days. Results may lead to Investigative New Drug regulatory clearance to begin clinical studies to validate the potential drug’s efficacy and safety.

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.

Drug checking services provide individuals who use drugs with information about the true contents of their purchases, and thus may help prevent overdoses. However, current technologies are either costly, technically complex, and non-portable or subject to false signals and restricted in their detection capabilities. This project will continue development of a new, simple-to-use, point-of-care analytical technology (DoseCheck) that can rapidly detect established drug threats in a sample and recognize newly emerging drugs. The project will also attempt to adapt DoseCheck to provide rapid results in emergency overdose situations and improve the analytical capabilities of medical examiners in under-resourced jurisdictions.

Data from 2015 show that American Indian/Alaska Natives (AI/AN) have the highest rates of diagnosis for opioid use disorders (OUD) and deaths from drug overdose; yet, there are no prevention programs addressing opioid misuse among urban AI/AN young adults that integrate culturally-appropriate strategies with evidence-based treatment. This project proposes to address that gap and help prevent OUD in Older Adolescents and Young Adults (ages 16-30) by developing and implementing a culturally-centered intervention to address opioid misuse among urban AI/AN emerging adults in California. The study will examine outcomes at 3-, 6-, and 12- months, and explore potential mechanisms of change for decreases in opioid and alcohol and other drug use outcomes through mediation analyses, including changes in social networks and cultural connectedness. Results from this study could significantly advance scientific knowledge and clinical practice for AI/AN emerging adults.

Since 2002, persons with opioid use disorders who desire medication-assisted treatment can be treated with buprenorphine, which has been shown to be efficacious. Buprenorphine treatment can occur in any medical office-based setting, is prescribed by any physician who seeks to become waivered, and is taken by patients at home unsupervised. However, without visual confirmation of medication ingestion, providers remain unsure if patients divert part or all of their buprenorphine medication. This project will develop the technical and logistical workflow needed to implement a video-­based application, miDOT, for office-­based buprenorphine monitoring during the initial months of care, which will allow health care providers to monitor whether patients ingest the drug and adhere to treatment. The project will configure a video-based DOT platform, evaluate its effectiveness in securing medication ingestion and care retention for illicit opiate users, and solidify routes of sustainable commercial viability with commercial partners.

The Family School Partnership (FSP) and classroom-centered (CC) interventions targeted aggressive-coercive behavior and poor academic achievement as antecedents of the distal outcomes of antisocial behavior, substance abuse/dependence, psychiatric symptoms/disorders, high-risk sexual behavior and successful adaptation to the relevant developmental demands of the educational, work, romantic relationships and family (both family of procreation and origin/orientation) social fields/contexts. The participants of the FSP and CC original prevention trial were a population (n = 798) of urban, predominately African-American young adults, who began first grade in the fall of 1993 in nine elementary schools in predominantly low- to lower-middle-income Baltimore areas. The central purpose of the proposed study is to extend through ages 31-35 an examination of normal and pathogenic development and the impact of these two universal first-grade preventive interventions on the distal targets mentioned above. We will continue to study the role of phenotypic and genetic factors (and their interactions) as well as the impact of the interventions on the development and course of substance use/abuse/dependence, psychiatric symptoms/disorders, antisocial behavior/disorder and high-risk sexual behavior through young adulthood. The knowledge accrued over the course of the proposed assessments should serve to inform the nature, targets and timing of our future preventive intervention efforts.

Many people in jail have both opioid use disorder (OUD) and posttraumatic stress disorder (PTSD). Among people with OUD released from jail, only few engage in treatment and medication therapy once they are back in the community, and opioid overdose is a leading cause of death in this population. This project will test whether identifying and initiating treatment of PTSD in people receiving OUD treatment in jail can increase these individuals’ likelihood of starting and staying in medication treatment after release and thus reduce overdose risk.

Addressing the current opioid overdose crisis requires tracking risky opioid use in a timely manner so that public health agencies can plan accordingly and supply life-saving resources. American Indian Tribes often lack such tools, even though American Indians and Alaska Natives have the highest rates of opioid overdose fatalities. This project will adapt commercialized monitoring technologies for use in Tribal communities, in consultation with affected Tribes. Through a partnership with a Tribal Fire Department and a software company providing data analytics for public safety agencies, this research will build a near real-time opioid overdose dashboard for use within Tribal boundaries. The findings may also improve data collection and outbreak monitoring for other substances, including methamphetamine and cocaine.

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.

Given the severity of the current opioid crisis, there is a pressing need to maximize the effectiveness of our interventions and increase retention in medication for opioid use disorder (MOUD) treatment. Measurement-based care (MBC), in which patient progress is regularly and systematically assessed to aid in treatment decisions, is a promising approach. Assessment tools are needed that can be administered quickly and that yield information that can be used to suggest improvements in treatment. In this study, the Investigator will conduct a series of analyses with data from the Brief Addiction Monitor (BAM), which has been selected for a national MBC initiative within the Veterans Administration. The goal of the work will be to derive and validate two new scales from the BAM. One scale is intended for use in opioid use disorder (OUD) specialty care programs. The second version is intended for use in primary care–based MOUD.

Profound sleep disturbances during abstinence have long been suspected of perpetuating vulnerability to relapse of people who misuse or are addicted to opioids. An animal model has shown that long-term sleep deficiency results in a persistent state of physiological dysregulation that is expected to modify the biology of abstinence and increase relapse potential. This study seeks to discover how persistent sleep restriction during withdrawal from opioid use increases vulnerability to relapse in the animal model by testing whether persistent sleep restriction during abstinence from opioid use is sufficient to increase opioid drug seeking. The functional outcome measure will be the degree of mitigation of opioid seeking. These studies will provide a basis for novel translational approaches to target mechanisms that are demonstrated to cause increased vulnerability to relapse.