Funded Projects

Evidence suggests that homeless youth have the highest rates of opioid use among youth subgroups in the country (Brands et al., 2005). Resolution of youth homelessness through housing and prevention services, often referred to as “Housing First”, has great potential to reduce the likelihood for the development of an opioid use disorder as well as other problem behaviors associated with living on the streets. However, only 20 percent to 30 percent of homeless youth samples report ever having stayed at a crisis shelter, 9 percent report having ever accessed mental health services, and 15 percent report ever having received treatment for substance use disorder (Ray, 2006), indicating a need to reach and engage youth in services that are feasible and acceptable. The results of this study will provide essential information for researchers and providers on the efficacy of housing plus opioid and related risk prevention services in a randomized controlled trial on opioid use, how moderators affect the response, and mechanisms underlying change.

Opioid use disorder (OUD) is a key driver of the current opioid epidemic in the United States, but nearly 80% of individuals with OUD do not receive treatment. Buprenorphine medication-assisted treatment (MAT) is an effective form of care for OUD. This project will develop a state-of-the-art, digital therapeutic tool that effectively promotes buprenorphine adherence by providing contingency management rewards and educational content and enables home induction using a new self-monitoring support tool. This tool, named reSET-O+, will be integrated with Pear Therapeutics’ reSET-O, an FDA market-authorized mobile application delivering validated behavioral therapy and intended for use in conjunction with buprenorphine and standard outpatient treatment for OUD.

The increase in prevalence of cancer coupled with an increase in the cancer survival rates due to chemotherapy regimens is transforming cancer pain into a large, unmet medical problem. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially dose-limiting side effect of many cancer drug treatment regimens and is caused in part by alterations in ion channels; blocking or depleting Cav3.2 channels in dorsal root ganglion (DRG) neurons should thus mediate analgesic effects. This proposal aims to develop and test potent, orally available, and selective Cav3.2 channel antagonists, building on the structure of a medicinal plant product—betulinic acid (BA)—that has been identified to be Cav3.2-selective and antinociceptive in CIPN. Such compounds could reduce the reliance on opioids in cancer patients.

As of 2012, an infant with neonatal abstinence syndrome (NAS) was born every 25 minutes in the United States, accounting for more than $1.5 billion in national health care expenditures. These infants frequently require hospital stay in a neonatal intensive care unit (NICU), with an average hospital stay of 25 days at an average treatment cost of $66,000. Treatment of NAS usually follows a multimodal regime based on drug therapy with an oral morphine solution, mostly in combination with a sedative, but there is a need for nonpharmacological approaches. This project will test a transcutaneous auricular neurostimulation device to help NAS babies recover from opioid withdrawal without harmful side effects. The non-invasive, auricular neurostimulation device will be placed around the ear (similar to a hearing aid), and stimulation will be delivered transcutaneously.

Over 30% of adults aged 65 years and older in the United States suffer from osteoarthritis (OA). Opioid analgesics are often used for patients with moderate to severe symptomatic OA. When non-pharmacologic and pharmacologic treatments are not effective, patients with severe OA may undergo total joint replacement (TJR). Our primary objectives are to evaluate patterns of opioid use before and after TJR and to assess the effect of opioid use patterns on clinical outcomes and safety events in a large U.S. population–based cohort of OA patients. The specific aims are to: 1) identify predictors of persistent opioid use and opioid dose escalation in patients after TJR for hip or knee OA and 2) evaluate effects of opioid use patterns on short- and long-term clinical outcomes and safety following TJR. The results of this study will provide guidance on surgical risk stratification and pain management of patients before and after TJR.

Methadone is useful in the treatment of opioid dependence; however, methadone misuse and methadone-related fatalities have increased. Ensysce has created two complementary, novel technologies that can be applied to methadone. Their Trypsin Activated Abuse Protection (TAAP™) prodrugs are “enzyme-activated” to release clinically effective opioid drugs only when taken orally and exposed to the correct physiologic conditions, such as exposure to trypsin in the small bowel. Their multi-pill abuse resistance (MPAR™) feature involves in situ bioregulation of opioid delivery from the TAAP™ systems, enabling control over oral multi-dose pharmacokinetic profiles. It is envisaged that an R-methadone-TAAP™ prodrug would demonstrate similar reduced addiction liability as with other opioid-TAAP products. The objective of this proposal is to develop an R-methadone-TAAP™/MPAR™ drug through Phase 1 clinical studies and to translate R-methadone-TAAP™/MPAR™ results into humans, to ultimately reduce the misuse and oral overdose potential of methadone.

Juvenile justice (JJ)-involved youth represent a particularly vulnerable population for substance use and substance use disorders (SUDs), because they often experience mental health disorders, dysfunctional family/social relationships, and complex trauma. This study will adapt and test an intervention for preventing initiation and/or escalation of opioid misuse among older JJ-involved youth aging out of JJ (16-18 years), who are transitioning to their communities after a period of detainment in a secure treatment or correctional facility. Trust-Based Relational Intervention® (TBRI®, a relational, attachment-based intervention that promotes emotional regulation through interaction with responsive adults) will be adapted as a prevention intervention targeting youth at risk for substance use, especially non-medical use of opioids. Safe adults (e.g., parent/guardian) will be trained in behavior management techniques for empowering youth to appropriately express their needs, connecting them with others in pro-social ways, and correcting or reshaping undesirable behavior.

There are alarming rates of substance abuse and diversion in hospitals, with multiple studies finding that roughly 10% of our nation’s nurses, anesthesiologists, and pharmacists are currently diverting drugs in their workplaces. Diversion continues even though most hospitals already lock addictive drugs in Automated Dispensing Machines (ADMs) and run monthly “anomalous usage” computer reports to try to detect diversion. This SBIR project will research mechanisms to detect when health care workers (HCWs) in hospitals steal or “divert” legal drugs, either to abuse themselves or to illegally sell to others, by building a computer system with (a) automated data feeds from multiple existing hospital computer systems and (b) advanced analytics to flag potential diversion for investigation. This research has the potential to reduce injuries to HCWs who are becoming addicted, destroying their careers, jeopardizing their patients’ safety, and increasingly dying from drug diversion overdoses.

Low back pain (LBP) is one of the most common reasons for all physician visits in the U.S. The financial costs associated with the care of LBP are staggering. The treatments for chronic low back pain (cLBP) are far from satisfactory, and opioids are often prescribed with varying degrees of success. This study builds on prior work suggesting that auricular transcutaneous vagus nerve stimulation (tVNS), a non-invasive therapeutic, can significantly reduce symptoms of chronic pain and common comorbidities of chronic pain, such as depression and anxiety. This proposal aims to investigate the treatment effect and underlying mechanism of tVNS on chronic low back pain. Patients with chronic low back pain will be randomized to either real or sham tVNS treatment for 1 month, with a 3-month follow-up. This study, if successful, could provide new treatment options for chronic low back pain and reduce the use of opioid analgesics in chronic pain management.

Rapid technological advances are leading to field-deployable mobile sensing devices that can quantify complex dynamics of key physical, biological, behavioral, social, and environmental factors, enabling us to understand causation in complex disorders. Significant new investment is needed to develop and disseminate data analytics tools. The Center of Excellence for Mobile Sensor Data-to-Knowledge (MD2K) will generate generalizable theory, methods, tools, and software to address major barriers to processing complex mobile sensor data and its use in biomedical knowledge discovery and just-in-time care delivery. We will develop and implement a standards-based, interoperable, extensible, and open-source big data software platform for efficient implementation of MD2K data analytics. MD2K will demonstrate the feasibility, utility, and generalizability of this approach by implementing the entire MD2K data analytics system in the context of two biomedical applications: reducing relapse among abstinent daily smokers and reducing readmission among congestive heart failure patients

Chronic pain affects an estimated 100 million Americans, or one third of the U.S. population, and it is the primary reason Americans are on disability. Although many treatments are available for pain, the most potent class of analgesics relies on opioid analogs, whose limitations and well-known adverse effects have contributed to the present opioid crisis. New pharmacotherapies for pain management are sorely needed. MTX1604, a synthetic endomorphin analog, has emerged as a highly effective analgesic that exhibits reduced reward potential and respiratory suppression, and a robust duration of efficacy in a variety of validated animal models of acute, neuropathic, inflammatory, post-operative, and visceral pain. This project will generate additional preclinical characterization data of MTX1604 and advance clinical development toward FDA approval. If successful, this medication development project could offer patients a novel non-addictive, potent, and safe analgesic and thus have a direct impact on the opioid crisis.

The orbitofrontal cortex (OFC) plays an important role in regulation of addiction, and OFC impairment from cocaine and opioids use leads to repetitive drug use. Brief optogenetic activation of the OFC reduces self-administration of drugs in neurobiology studies. However, the OFC is less accessible for noninvasive stimulation using direct transcutaneous current stimulation or transcranial magnetic stimulation. The small business EvON Medics LLC and Howard University have created a home-based olfactory pulsing prototype, called computerized chemosensory-based orbitofrontal cortex training (CBOT), using a high-fidelity chemosensory and computerized olfactory training approach to enable home-based neuromodulation of the OFC for treatment of opioid use disorder (OUD). A pilot feasibility study in OUD samples suggests that CBOT can minimize withdrawal symptoms, reduce drug cravings, enhance positive affect, and reduce rate of positive urine drug tests. The project seeks to establish CBOT stimulation parameters needed to maximally improve outcome inference and emotion regulation in OUD.