Funded Projects

Overdose fatality review teams review cases of overdose deaths to identify system gaps and innovative prevention and intervention strategies. With the rise in overdose deaths, these multidisciplinary teams require more timely population-level data to inform their recommendations. This project will develop the Overdose Touchpoints Dashboard that uses real-time data and records from multiple sources to help visualize common “overdose touchpoints” for harm reduction services and treatment opportunities. This research will compare use of the dashboard to standard overdose fatality review practices. The project will assess multiple aspects related to use of the dashboard, including process, staff attitudes, implementation successes, and usability.

This project creates the HEAL Data2Action Data Infrastructure Support Center that will conduct research as well as support the HEAL Data2Action Innovation Projects with analytics and support for navigating electronic health records and other “big data” sources, as well as logistical processes related to privacy and ethics. The center will help plan for data collection and assessing outcomes, as well as provide data visualization efforts for various stakeholders. Key support mechanisms include courses, seminars, conferences, trainings, and on-demand technical assistance.

There is an urgent need for non-opioid post-operative pain management solutions.  This research is developing a naturally absorbable polymer film that can release controlled amounts of the non-opioid analgesic bupivacaine – aiming to manage pain for several days following surgery. Project objectives are to optimize the timing of drug release, develop manufacturing standards, determine effective dosage for preserving motor function, and determine safety and efficacy in mouse models of neuropathic pain. Continued development of this film delivery system may lead to a new, non-opioid therapeutic strategy that could be combined with local anesthesia for up to 4 days after surgery to reduce or potentially eliminate opioids use.

There are a lack of clinical tools to effectively identify and monitor opioid use disorder (OUD). This project will develop and test a clinically usable device that uses a range of data inputs and an artificial intelligence (AI) algorithm to help health care providers diagnose and treat OUD. The research aims to help providers choose treatment plans and monitor the timing of release from rehabilitation clinics.

While the mu opioid receptor (MOR) antagonist naloxone has proven invaluable as an opioid overdose antidote, naloxone suffers from a very short duration of action (half-life is approximately 1 hour) and has been found to be less effective against newer, long-acting opioids, including fentanyl (half-life is approximately 7–10 hours). This leads to a highly lethal and increasingly prevalent phenomenon known as “renarcotization,” wherein an overdose patient revived with naloxone can re-enter an overdose state from residual fentanyl in the body. Thus, there is a critical need to develop a long-acting MOR antagonist formulation that can address renarcotization by providing multi-hour protection. The goal of this project is to reformulate naloxone using FDA-approved microencapsulation technology into a long-acting injectable (LAI) that can provide 12–24 hours of sustained antagonist activity in vivo. It will employ a proprietary Computational Drug Delivery™ software, called ADSR™, to perform in silico formulation optimization as well as to predict its in vitro dissolution and in vivo pharmacokinetic behavior.

This project will use a data-to-action framework to guide implementation of opioid use disorder treatment and harm reduction interventions based on rapid data analysis. It will leverage existing data systems such as Emergency Medical Services (EMS) reports, mobile integrated health case management data, and medical examiner data for near real-time data analyses, visualization, and action planning. This research will collect a range of data (opioid treatment, use of acute care services, morbidity, mortality, incarceration, housing support, and cost benefits) from a sub-acute stabilization center for people at high risk for opioid overdose, including those who have recently overdosed and are referred and transported by EMS teams.

About 14% of U.S. adults report experiencing migraine symptoms within any given 3-month period, making it the second most disabling illness in the world. Nonspecific pain medications used in migraine (e.g., acetaminophen, nonsteroidal inflammatory drugs, opioids) are often not effective for severe migraine symptoms or cause significant adverse effects. A research team of migraine care specialists, device and drug developers, and clinical research specialists has created a technology for accurately delivering self-administered migraine medication to the upper nasal cavity. The technology enables development of a self-administered therapy to provide rapid pain relief without harsh and addictive side effects of existing migraine medications. This project will establish efficacy and evaluate commercial design feasibility for this treatment.

This project provides protected time for training and research activities that are required for an independent scientific career in delivering evidence-based treatments for people with opioid use disorder. The increasing presence of fentanyl in the drug supply creates challenges for the use of buprenorphine, because both patients and physicians want to avoid causing withdrawal. This research will interview both patients and physicians to understand their concerns and experiences and work with them to develop a buprenorphine induction toolkit to help balance the advantages of buprenorphine treatment against concerns about the potential presence of unknown fentanyl. 

Neuropathic pain adversely affects quality of life and remains challenging to treat, presenting high unmet medical need. One example of this type of pain, chemotherapy-induced peripheral neuropathy, is a chronic, severely debilitating consequence of cancer therapy for which there are no effective treatment strategies. This research is testing a new cannabidiol (CBD) analogue (KLS-13019) with neuroprotective properties and which has improved drug-like properties compared to CBD. This project will optimize the process to manufacture KLS-13019, develop analytical methods, optimize its formulation, evaluate its safety and toxicity, and test KLS-13019’s efficacy of in a rat model of chemotherapy-induced peripheral neuropathy.

Knee osteoarthritis (OA) is a frequent cause of disability and chronic pain. Treatment often relies on analgesics like opioids to manage OA pain, with all the associated risks; other approaches to treat OA are often invasive and inaccessible to patients. Therefore, novel analgesic strategies are needed to reduce the high burden of knee OA-induced pain. This project aims to study in detail and target the sensory neurons that drive OA pain to assist in the development of more effective pain therapeutics.

With the entwined crises of opioid use and chronic pain, there is a need for alternative, safe therapies to manage opioid use disorder, opioid withdrawal symptoms, chronic pain, and/or associated anxiety and depression. A proof-of-concept preclinical study has already been conducted of a cannabinoid-opioid combination that demonstrated opioid-sparing and synergistic analgesic effects, with the combination providing greater analgesia in a rodent model of chronic pain than a standard dose of the opioid alone. This proposal aims to develop a fixed-dose combination (FDC) of the cannabinoid-opioid that may have improved analgesia with lower opioid doses and thereby lower the risk of dependence, withdrawal, diversion, abuse, and overdose. Preclinical pharmacokinetic and ?in vivo ?safety studies will help determine if co-administration alters the pharmacokinetics and/or respiratory depression related to either compound in rodents.

 Investigating the broader efficacy of sEH inhibition and specifically our IND candidate, EC5026, has indicated that it is efficacious against chemotherapy induced peripheral neuropathy (CIPN). This painful neuropathy develops from chemotherapy treatment, is notoriously difficult to treat, and can lead to discontinuation of life-prolonging cancer treatments. Thus, new therapeutic approaches are urgently needed. The research team will investigate if EC5026 has potential drug-drug interaction with approved chemotherapeutics or alters immune cells function, and assess the effects of sEHI on the lipid metabolome and probe for changes in endoplasmic reticulum stress and axonal outgrowth in neurons. The team proposes to more fully characterize the analgesic potential of our compound and investigate on and off target actions in CIPN models and model systems relevant to cancer therapy.

Side effects from taking the opioid receptor blocker naltrexone make it difficult for patients to adhere to treatment with this medication for opioid use disorder. Cannabidiol (CBD), a bioactive ingredient of cannabis, is not an opioid and is non-psychoactive. Previous research shows that CBD blocks opioid-seeking behaviors, craving, and withdrawal. This project will develop tiny particles containing CBD and low-dose naltrexone. The research will determine if this combined version of CBD and naltrexone helps people stay in treatment and prevents relapse without problematic side effects.