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.

Neonatal Opioid Withdrawal Syndrome (NOWS) affects a growing number of neonates each year due to the ongoing opioid epidemic ravaging the United States. Complex neurobehavioral observation of newborns is the primary modality used. It is subjective and time-consuming by nature, requires significant expertise, and can lead to delays in treatment. The goal of this project is to develop an innovative, low-cost, non-invasive, and easy-to-use brain monitor to objectively assess the severity of withdrawal symptoms in newborns exposed to opioids and provide evidence-based decision support to care providers to improve both short- and long-term developmental outcomes. This device, referred to as NeoGUARD, is based on the continuous, automated, and real-time monitoring of brain function to detect EEG abnormalities shown to be related to NOWS and determine severity to guide pharmacological intervention. This study will focus on the initial prototyping and refinement of the hardware and software, as well as initial evaluations of its use.

Use of both opioids and stimulants is increasing, but little is known about how polysubstance use evolves over time and how it influences overdose risk. This project will use data from two groups at high risk for overdose: i) participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study who inject drugs and ii)  participants in the new Stimulant Opioid Non-Injection Cohort (SONIC) study. This research will identify drug use patterns and their association with treatment and overdose over time – toward informing overdose prevention efforts and interventions to improve the U.S. opioid crisis.

Older adults make up more than half of all surgical patients in the United States, putting them at risk for a range of harmful outcomes including misusing opioids, developing opioid use disorder (OUD), opioid overdose, and surgical complications. This project seeks to understand whether pre-surgery interventions can prevent harmful opioid-related outcomes. The research will combine data from a registry of electronic health records and from Medicare claims data to learn about the relationship between these interventions and opioid-related outcomes including persistent opioid use, OUD, and other harmful outcomes.

Noninvasive brain stimulation (NIBS) may be effective in treating some forms of addiction, but the most common NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), have not been found to be effective in treating opioid use disorder (OUD). This project seeks to test the efficacy in OUD patients of Electrosonic Stimulation (ESStim™), an improved NIBS modality that combines independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue.

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.

Opioids affect the body by attaching to certain types of receptors that attach to G-proteins (particularly, a subtype called G-alpha). Opioids vary in their ability to provide pain relief as well as in their ability to require more drug to provide a response, known as tolerance. This project will explore the potential of various G-alpha subunits to increase or decrease opioid receptor signaling. The research findings will lay the groundwork for tailoring G-alpha related opioid effects to provide more pain relief while being less addictive.

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. 

In 2018, new opiate prescribing limits (SB 273) were implemented across West Virginia to combat the opiate misuse epidemic. This study will utilize quantitative and qualitative measures to determine the effect of the recent opiate prescription laws in West Virginia, how a change in policy affects the opiate misuse epidemic, and how communities may apply this knowledge more broadly. The research team will: 1) collaborate with the West Virginia Board of Pharmacy to ascertain changes in opiate prescribing habits before and after the start of SB 273 using an interrupted time series methodology, and 2) achieve broad and deep understanding of how SB 273 has affected prescribing practices and experiences amongst primary care physicians, specialists (pan physicians, surgeons, emergency room physicians, etc.), and patients who currently or previously utilized opiate medications.

Chronic pain is a significant public health problem associated with tremendous personal and economic burden. First-line treatment consists of opioid medications, but despite only moderate efficacy and unpleasant side effects, rates of opioid prescriptions have quadrupled over the past 15 years, and this has contributed to high rates of misuse, overdose, and mortality. Clearly, alternative, or non-opioid strategies for treating pain are needed. In this context, “opioid-sparing” medications refer to compounds that can be combined with and enhance the analgesic effects of lower-dose opioids without increasing the rewarding properties of either drug. There is preclinical evidence suggesting that cannabidiol (CBD) may have the potential to function as “opioid-sparing” medications, but its ability to alter opioid-mediated analgesia in humans has yet to be determined. This proposal will fill this gap by conducting a double-blind, placebo-controlled, within-subject randomized crossover study of the effects of CBD and morphine co-administration on pain sensitivity and subjective reinforcement on 28 healthy males and females. This is the first known study to investigate the ability of CBD to alter morphine’s analgesic effects in humans. If successful, the model will have a lasting impact on our ability to develop and test medications that reduce our reliance on chronic use of opioid medications for pain relief.

Hospital inpatient stays due to opioid-related health problems are a reachable moment for increasing access to treatment with medications for opioid use disorder (MOUD). Hospitalized patients with opioid use disorder (OUD) are at particularly high risk for morbidity, mortality, and high medical costs in the U.S. This study will substantially inform the care management of OUD in hospitalized patients. The project includes a comparative effectiveness research trial and an implementation research trial, which will lead to models of broad dissemination for treatment approaches to this largely unaddressed population. They will examine whether (1) in hospitals with addiction medicine consultation services, hospital-initiated extended-release buprenorphine (XR-BUP), compared with other OUD medications, results in increased engagement in treatment with MOUD following hospital discharge and (2) training hospitals without such consultation services on best practices for initiating MOUD using consultation service hubs improves medication uptake in hospitals and increased MOUD treatment engagement following discharge.

There has been a substantial increase in overdose deaths among Black and Hispanic/Latino people who use drugs. This project will test and evaluate delivery of harm reduction services from a mobile van. A community-based care coordinator will assess the specific needs of each participant (such as housing, food assistance, and mental health treatment) toward the goal of linking each person to appropriate services.