Funded Projects

Medications for the treatment of opioid use disorders (MOUD) are effective at reducing opioid use, opioid overdose risk, and opioid-related deaths; however, retention and adherence to MOUD treatment, particularly buprenorphine (BUP), are discouragingly low. The objective of the current research is to adapt and extend a cognitive behavioral therapy-based short message system (SMS) intervention (TXT-CBT) to address MOUD treatment retention and adherence using the imFREE (Interactive Messaging for Freedom from Opioid Addiction) platform. imFREE builds upon the efficacious SMS-based TXT-CBT intervention, with content addressing retention and adherence to BUP, including mitigating risk factors for dropout, and features to notify social and provider support contacts in the face of treatment discontinuation and/or other indicators of relapse and overdose risk. By providing support to maximize BUP treatment adherence, coupled with skills to prevent relapse, imFREE may provide a cost-effective, easily deployable strategy for OUD treatment and prevention of overdose deaths.

Effective overdose prevention requires timely, location-specific data to efficiently direct resources and interventions as well as to inform healthcare policy. However, rarely is such information available, resulting in responses that are frequently too late. This project will partner with local government agencies from Los Angeles County, California, to rapidly acquire and analyze information in near real-time from multiple sources to identify overdose hotspots and determine overdose metrics. This information will be used to develop a publicly available Rapid Overdose Surveillance Los Angeles online dashboard with built-in analytics. The dashboard will help determine the scope and specifics of overdose and opioid use in Los Angeles County to help target response and guide mobile addiction treatment and harm reduction services.

Some chemotherapy treatments damage nerves outside the brain and spinal cord. This condition, chemotherapy-induced peripheral neuropathy, involves tingling, burning, weakness, or numbness in hands and/or feet and affects nearly 70% of cancer patients receiving chemotherapy. Common pain medications, including opioids, can relieve pain for short intervals but are not suitable for long-term therapy. This project will develop and test a new type of treatment (reduced size cyclic analogs) for this condition. The research will evaluate the ability of this therapy to reduce inflammation and pain, as well as to repair nerve damage.

Nerve stimulators are devices surgically implanted near a peripheral nerve or on the spinal cord that use electrical signals to reduce the perception of pain. Although these devices can provide effective pain relief to patients, many have high complication rates, resulting from the wire moving, breaking, not working, or the implantable battery pack or permanent wire causing new pain. This project will support the development and animal testing of a peripheral nerve stimulator to treat chronic pain which can be implanted without surgery. Once injected, the device will provide pain relief through electrical stimulation and then be safely degraded and resorbed by the body.

There is an unmet need for an effective parenteral/oral analgesic for acute post- operative pain management without the risks of opioid addiction. Salsalate, a dimer or salicylic acid, is currently available in oral dosage for the treatment of osteoarthritis and rheumatoid arthritis. Salsalate works at multiple levels to target multiple steps along the surgical pain pathway. Salsalate through its active metabolite, salicylic acid (SA), reduces NF-?B activation via IKK-kinase beta inhibition, and has no direct binding to cyclooxygenase 1 (Cox-1); therefore, does not affect function of platelets, resulting in a safer hematological and gastrointestinal safety profile. RH Nano proposes a plan for manufacturing and pre- clinical testing of parenteral M-salsalate in two animal models to assess the efficacy and safety in the treatment of acute postoperative pain management. In this proposal, the team will develop the optimal formulation under strict Chemistry Manufacturing and Control guidelines. In Phase II, the team proposes to conduct the pharmacokinetics and toxicology studies of M-salsalate in two species of animals (rodent and non-rodent). Additionally, the project will use an animal pain model for preclinical efficacy studies, and an in vivo Receptor Occupancy assay in animal brain tissues to assess the opioid sparing properties of M-salsalate. 

Emergency departments (EDs) are key settings for identifying and treating opioid use disorder (OUD), but EDs are underused for this purpose. This project aims to develop a data system that automates and integrates electronic health record and administrative data from EDs into the Clinical Emergency Department Registry, partnering with the American College of Emergency Physicians. The research will assess the digital readiness of ED systems before developing and deploying the enhanced ED OUD data infrastructure. This research aims to guide near-real time hospital quality improvement initiatives, toward development of a web-based, near-real time dashboard that can be used in EDs across the country.

Critical limb ischemia is the most severe form of peripheral artery disease, is very painful, and can lead to amputation and even death. Most patients with this condition live with chronic pain, but comprehensive and effective treatment is lacking. This project will use existing data from three databases to study medical pain management approaches used over time by individuals with critical limb ischemia – toward creating an integrated, patient-centered, and multimodal pain management approach for this condition.

During the COVID-19 public health emergency, the Substance Use and Mental Health Services Administration relaxed regulations for take-home dosing of methadone, offering an opportunity to improve methadone treatment access and address racial and ethnic disparities. This project aims to address regulatory, legal liability, and financial concerns related to clinical practice changes in opioid treatment programs. The project will first review state administrative data and conduct qualitative interviews to inform the intervention approach. The project will then evaluate an opioid treatment program intervention involving take-home methadone and its effect on take-home dosing, retention in care, and health outcomes for Black/African American and Hispanic/Latino individuals who take methadone for opioid use disorder.

Acute and chronic pain vary widely across patients, due in large part to genetic differences between individuals. The same variation occurs in preclinical animal models with diverse genetic backgrounds. The development of automated mouse “pain scales” using high-speed videography, machine learning, and custom software allows pain to be assessed in a quantitative manner in nonverbal animals. This technology will be used to identify genetically different mice with high or low pain sensitivity, which will facilitate the development of new therapeutic strategies to treat pain and reduce reliance on opioids.

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.

The Early Phase Pain Investigation Clinical Network (EPPIC-Net) conducts comprehensive analyses of observable traits (deep phenotyping) and aims to identify molecular and physiological signatures to help characterize specific pain conditions. To achieve these goals, researchers collect complex data using technologies such as magnetic resonance imaging of the brain, actigraphy, and electroencephalography. There is a need to train researchers to be able to extract key information from high-powered computing resources now widely available.  This research will complement the goals of EPPIC-Net by enhancing development of novel statistical methods to analyze complex data generated by EPPIC-Net pain studies.