Funded Projects

This study will (1) test pharmacologic and behavioral strategies to improve OUD pharmacotherapy treatment retention and to improve outcomes among patients who have been successfully stabilized on OUD medications and want to stop medication and (2) identify predictors of successful outcome and develop a stage model of relapse risk.

According to SAMHSA’s 2017 National Survey on Drug Use and Health (NSDUH), 11.4 million persons in the U.S. report past-year opioid misuse; out of them, only 2.1 million individuals met criteria for an OUD. Very little is known about efficacious interventions for those who do not meet criteria for moderate/severe OUD (i.e., subthreshold OUD). The prevalence of subthreshold OUD in primary care settings is 5 percent to 10 percent, with higher rates (21 percent to 29 percent) among those receiving prescribed opioids. Although they are at high risk of developing moderate/severe OUD and/or dying from an overdose, little or no empirical evidence exists for pragmatic prevention interventions that can be adopted at integrated general medical settings. To study the efficacy of prevention interventions to arrest the progression from risky opioid use, researchers will test the efficacy of a STOP intervention in primary care settings. STOP adopts an early intervention approach, based on a collaborative care model to prevent progression to moderate/severe OUD, and consists of a practice-embedded nurse care manager who provides patient education and supports the primary care provider (PCP) in engaging, monitoring and guiding patients who have risky opioid use; brief advice delivered to patients by their PCP; and phone counseling of patients by behavioral health providers to motivate and support behavior change. Researchers will determine whether STOP reduces risky opioid use and examine the impact of STOP on progression to moderate/severe OUD, overdose risk behavior and overdose events in adults with risky use of illicit or prescription opioids.

Novel treatments for opioid use disorder are urgently needed. Previous research has shown that angiotensin-converting enzyme (ACE) can control levels and activity of natural, “endogenous,” opioids in a way that might reduce the rewarding effects of opioids like fentanyl. ACE inhibitors have been used to treat hypertension for decades, with no evidence of addiction or dependence. This research will evaluate ACE effects on endogenous opioids toward generating new, domain-specific ACE inhibitors with optimized properties for treating opioid use disorder. The research will also test the behavioral impact of these compounds in preclinical models of opioid use disorder. 

Though prenatal exposure to opioids and other substances have adverse effects on neurodevelopment, advances in neuroimaging and developmentally sensitive phenotypic measurement now enable characterization of typical and atypical brain-behavior pathways on an unprecedented scale. The Brains Begin Before Birth (B4) Midwest Consortium, a partnership of neuroscience, substance use, perinatal mental health, and child welfare scientists at Washington University School of Medicine (WUSM) and neuroscience, bioethics, pediatric population health, maternal-fetal, and addiction scientists at Northwestern University (NU). This regional consortium will leverage the contrasting approaches of Illinois (punitive) and Missouri (non-punitive) to prenatal opioid use, providing a platform for examining the impact of jurisdictional variations on science and practice. The consortium provide a framework for addressing three major areas of challenge: (1) legal/ethical, (2) recruitment/retention, and (3) imaging/assessment methods.

Pain is one of the most common and debilitating symptoms of a wide range of injuries and diseases. Safe and effective alternatives for treating pain that reduce dependence on opioids are, therefore, a primary goal of the NIH. This project proposes a non-invasive, non-pharmacological alternative to treat pain by combining an innovative electroencephalography (EEG)-based Neurofeedback (NF) solution in an immersive virtual reality (VR) environment. NF and VR have been shown to independently produce ameliorative effects on pain, and it is hypothesized that an NF training in VR would have synergistic effects, as VR would distract from pain perception to improve patient compliance in more engaging NF protocols that improve their ability to control pain perception. In the scope of this project, we will initially focus our work on chronic low back pain (cLBP), as this is a growing segment of chronic pain sufferers with a 39 percent worldwide lifetime prevalence, and whose sufferers have historically been heavy users of opiates; later stages of this project will expand this application to address other forms of pain.

We propose to estimate the impact of expanded access to medication-assisted treatment (MAT) in prisons and jails on post-release rates of overdose. Our approach will use agent-based modeling, data collected through the parent study, existing surveillance data, and recently published data from similar settings to understand how different MAT interventions in the prison and jail setting impact overdose death post-release. We will examine the impact of standard of care/no intervention, providing access to depot-naltrexone alone, providing access to all three MATs to only those who were prescribed it prior to incarceration, and comprehensive provision of all three MATs on post-release rates of overdose. These models will incorporate advanced methodological techniques that will allow for the investigation of engaged treatment, program attrition, and other complex events on a population level. This study’s findings may be used by health agencies, policymakers, and correctional systems to inform their efforts to expand MAT access.

For many individuals in recovery from a substance use disorder, certain cues—including stress and drug-related cues—can trigger a physiological state in which they are more likely to relapse. In this SBIR project, the investigators intend to deploy a system—consisting of a wearable sensor, a smartphone app, and a clinical portal—to provide individuals in recovery and their treatment providers with an opportunity to identify moments of high risk for relapse and to access real-time intervention opportunities. The sensors will identify signals of stress or drug use, interface with a smartphone app, and provide options for annotations, stress-reduction techniques, or contact with an individual’s support system and treatment providers, as well as log and encourage healthy behaviors. This study will deploy and optimize the system, as well as test its effects on addiction-related outcomes, such as rate of relapse.

An increasing number of Americans use multiple drugs at the same time, and overdose deaths from stimulants have increased. However, there are no available treatments for stimulant use disorder. This project aims to develop new treatment (SBS-518) for cocaine use disorder. Previous research using animal models showed that SBS-518 decreases stimulant self-administration without being rewarding itself. The research will continue the development of SBS-518 toward testing in human research participants.

The opioid epidemic continues unabated in the United States, and despite the rapid expansion of this crisis, the nature of the risk factors that contribute to opioid misuse remain poorly understood compared with other substances of abuse. The goal of this project is to examine cannabis use and cannabis identification measures as risk factors for opioid misuse while also developing and evaluating novel implicit measures of opioid associations as risk factors for opioid misuse among an at-risk sample of adolescents. Findings from the proposed research are intended to improve the prediction of opioid misuse among adolescents and to potentially identify novel targets for prevention and intervention strategies that aim to combat the opioid epidemic.

Fatal opioid overdose rates are higher among American Indian/Alaska Native populations than among Hispanics, African Americans, and Asian Americans, and are just below non-Hispanic Whites. AI/AN opioid overdose rates vary significantly by state and county; however, tribe-level differences are difficult to ascertain due to decentralized data systems that divide state health data and Indian Health Service data. This study will conduct a two-phase research project that leverages Center for Disease Control funding awarded to the Albuquerque Area Southwest Tribal Epidemiology Center for improving data quality in opioid overdose surveillance in New Mexico. In the first phase, geocoding and data linkages will be studied to address the need in New Mexico for tribe-specific data and analyses on opioid use disorder and opioid overdose. After disseminating analyses to tribal communities and Indian Health Service, Tribal and Urban Indian health facilities, the second phase of the study will establish a collaboration with interested tribes and facilities in a community-based participatory intervention research project to develop and test a culturally centered implementation program for providing medication for opioid use disorders to American Indian people.

Opioid use disorder interventions need to address the complex needs of patients, which include substantial mental health comorbidity and high rates of chronic pain. This study takes advantage of recent federal and state opioid use disorder treatment initiatives as a platform for testing a promising mind-body intervention, Mindful Awareness in Body-oriented Therapy (MABT) as an adjunct to Medication Assisted Treatment (MAT) with buprenorphine in clinical settings funded through the Washington Opioid State Targeted Response (STR) program. Using a randomized, repeated measures design, the study team will compare those who receive MABT+ MAT to MAT only. The overarching goal of this application is to test MABT to improve MAT outcomes among patients receiving buprenorphine to treat OUD. Results of this study will inform the evidence base for behavioral treatment adjuncts to MAT with buprenorphine and directly impact the future direction of opioid use disorder treatment in Washington state.

The United States has seen dramatic increases in fatal overdoses due to heroin, counterfeit prescription drugs, and cocaine adulterated with fentanyl or fentanyl-like analogs. Current medications may not be sufficient to address the opioid overdose epidemic. As a complementary strategy, the researchers plan to develop vaccines against fentanyl and fentanyl-like compounds to reduce their abuse liability and the growing incidence of fatal overdoses. This research team has already developed vaccines against heroin and oxycodone that stimulate the production of antibodies effective in reducing opioid distribution to the brain, opioid-induced behaviors, and opioid-induced respiratory depression and have identified a promising fentanyl vaccine candidate cued up for optimization. Successful completion of an anti-fentanyl vaccine development project could offer a long-lasting, safe, and cost-effective intervention complementary to medication-assisted treatment (MAT) and may reduce overdoses in opioid users as well as protect people in professions (e.g., law enforcement, airport security, postal workers) at risk of accidental exposure to fentanyl and fentanyl analogs.