Funded Projects

Tens of thousands of people die each year from opioid overdose. Many of these people began taking opioids for pain. A critical treatment goal is to reduce the development of opioid dependence either by enhancing opioid analgesia so lower doses can be used or by blocking withdrawal symptoms. Current pharmacological treatments in these two categories, although effective, present serious limitations. The recent finding that reducing the signaling through mu-delta opioid heterodimers appears to enhance opioid antinociception and reduce dependence suggests that a blocker of mixed mu-delta receptors (MDOR antagonist) could be effective in reducing dependence by limiting opioid tolerance and preventing opioid withdrawal. This research group has developed a compound with that characteristic, called D24M, which preliminary studies have shown could reduce opioid dependence by enhancing opioid antinociception, reducing opioid tolerance, or directly inhibiting opioid withdrawal. They propose to extend this research by investigating whether it can reduce chronic pain in an animal model that mimics the clinical situation of pain patients who transition to dependence. If these studies are successful, they could lead to the development of an optimized drug ready for Investigational New Drug (IND) application and enable translational and clinical testing.

Many opioid harm reduction services are designed and implemented to serve urban populations in traditional centers of opioid use and leave rural patients underserved. The proposed project seeks to demonstrate improved MAT participation, naloxone distribution, and syringe support services (SSPs) among justice-involved persons with opioid use disorders, and thus improve health and criminal justice outcomes across diverse urban and rural settings in Illinois. Reducing Opioid Mortality in Illinois (ROMI) is a multi-site trial that will be carried out using a hub-and-spoke model, with centralized long-standing social services infrastructure at the Community Outreach Intervention Projects (COIP) hosted at the University of Illinois at Chicago. COIP provides case management/transition of care services to justice-involved opioid users, extending resources and technical assistance to less-populated rural areas hardest hit by the opioid epidemic.

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.

Opioid use disorder (OUD) and opioid overdose (OD) are major health issues. Breathing can be restored after OD by naloxone, but its short half-life can require multiple administrations to reverse OD, and OD symptoms may return after initial reversal if illicit opioids are still present after the effects of naloxone have worn off. Additionally, while the standard treatment of OUD with buprenorphine and methadone reduces relapse and mortality, access and adoption are limited by dosage forms, metabolic liabilities, and potential for misuse and diversion. This study seeks to develop chemically novel, potent mu-opioid receptor (MOR) antagonists and low- and mid-efficacy partial agonists. Current lead counts can outcompete opioid overdoses in preclinical models with a longer half-life, a key naloxone liability for treating OD. The potent, low-efficacy partial agonists add a low opioid tone, diminishing the aversive effects of pure antagonists. These, and the mid-efficacy partial agonists, are leads to maintenance therapeutics for OUD.

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.

Structural and functional neuroimaging measures are prone to errors induced by subject motion. Many comorbid features of opioid exposure are likely to increase children’s in-scanner motion. In total, this raises substantial concern that existing neuroimaging methods are not sufficiently motion-robust to be used in studies of children ages 3–5. Researchers will address these concerns with a feasibility study, comparing the existing methods developed for the Adolescent Brain Cognitive Development (ABCD) study with novel methods we will develop and optimize for young children. They will evaluate research methods in a sample of 100 children and test whether novel technologies improve the quality of the raw imaging data and reduce motion biases in the derived measures. Researchers will determine predictors of successful imaging to inform sampling strategies in future studies. The primary outcomes will be novel, validated structural and functional neuroimaging imaging methods for young children and feasibility data to inform the design of future studies addressing developmental questions, particularly those related to opioid exposure.

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.

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.

Online peer-led support interventions may increase medication-assisted therapy (MAT) initiation and sustainment among participants with opioid use disorder (OUD) because they can leverage peers to widely and rapidly scale changes in social norms (e.g., interest in using MAT) throughout people’s natural, real-world, virtual environments. Harnessing Online Peer Education (HOPE), an online peer support community intervention designed to reduce stigma and increase health behavior change, has effectively changed health behaviors among stigmatized populations, such as for HIV. This study will determine how to adapt the HOPE online support intervention to increase MAT initiation and sustainment among participants with OUD, assess the intervention’s effectiveness at increasing MAT use among OUD participants recruited online who are not using MAT, and use an implementation science approach to determine the relationship between social network dynamics (e.g., network size), topics discussed on the online community, and behavior change.

Millions of Americans undergo surgery each year, with fewer than half of patients reporting adequate postoperative pain relief and approximately 75 percent reporting moderate to severe postoperative pain. Gaps in postoperative pain management that lead to the unnecessary introduction and over-prescription of opioids continue to exacerbate the opioid crisis, but virtual reality (VR) has been demonstrated to be an effective strategy for pain management. This project will enhance and improve the functionality of a VR-based technology, AppliedVR, to provide acute perioperative pain management through a new software-based VR medical device, RelieVRx™. As a non-opioid alternative intended to reduce postoperative pain, RelieVRx can potentially reduce the need for and utilization of opioids in the postoperative setting.

Very little research has been conducted on better understanding of phenotypic characterization of individuals with OUD (beyond DSM-5 diagnoses) and how these features predict illness severity, treatment retention or outcomes. The primary objective of the deep phenotyping study is to provide a comprehensive phenotypic characterization (e.g., domains of negative affect, reward salience, cognitive control, mental health) of a heterogeneous sample of individuals (n = 1,000) who currently meet one or more DSM-5 diagnostic criteria for OUD and are in treatment for OUD. In a subset of this sample (n = 100), the investigators conduct digital phenotyping to examine the utility of ecological momentary assessment (EMA), digital sensing and social media to predict retention, medication adherence and opioid use outcomes in patients receiving buprenorphine for OUD. It is anticipated that this foundational study will inform the feasibility and utility of such assessments that can be successfully embedded into imminent and future CTN and other OUD clinical trials.