Funded Projects

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.

Adolescents face increased HIV risk, infrequent testing, inconsistent linkage to care, and a lack of prevention-related knowledge. We propose to complete and evaluate the Mobile Augmented Screening (MAS) tool to privately and discretely offer routine HIV testing and counseling, including prevention education, to high-need, diverse adolescent and young adult populations at a low cost. The MAS will consist of a tablet-based intervention including a brief video designed to increase adolescent HIV testing, automated text messages to facilitate linkage to care for those who test positive, and text-based education for those who test negative or decline testing. Phase I was conducted with young emergency department (ED) patients. Preliminary evaluations indicate the video led to significant knowledge increases and encouraged testing. In phase II, we seek to complete intervention development and evaluate through a randomized controlled trial with ED patients, with qualitative interviews for a subset of young patients and ED staff.

Medication-assisted treatment (MAT) for opioid use disorder (OUD) is highly efficacious, but only a fraction of people with OUD access MAT, and treatment non-adherence is common and associated with poor outcomes. This project aims to increase rates of Suboxone (buprenorphine/naloxone) treatment initiation and adherence among OUD patients recruited from emergency and inpatient acute care by enhancing the Opioid Addiction Recovery Support (OARS)—an existing Q2i company technology—with a new evidence-based reward, contingency management (CM) function that allows for the automatic calculation, delivery, and redemption of rewards contingent on objective evidence of Suboxone initiation and adherence.

In this study, 600 to 700 hemodialysis patients receiving chronic opioids will be randomized across the Hemodialysis Opioid Prescription Effort (HOPE) Consortium to enhanced treatment as usual, buprenorphine therapy, or buprenorphine plus mindfulness-based cognitive therapy intervention delivered by telephone and adapted for pain (MBCT-TP). The following specific aims will be assessed: Aim 1—to assess the effectiveness of buprenorphine in reducing chronic opioid use and prescriptions in hemodialysis patients on opioids at baseline, compared with an enhanced treatment as usual intervention and to assess the effectiveness of buprenorphine in improving pain intensity, quality of life measures, and hospitalizations; Aim 2—to assess the incremental effectiveness of MBCT-TP added to buprenorphine compared with buprenorphine alone on pain interference with physical, social, and mental functioning, opioid use, pain intensity, other quality of life measures, hospitalizations, and mortality.

Repetitive drug use forms powerful memories associating drug-evoked experiences with its proximal environmental cues. Memories are major obstacles for successfully treating addiction, since even after a prolonged period of abstinence, reexposure to such cues often triggers craving that promotes relapse. A polysynaptic pathway from the paraventricular nucleus of the thalamus (PVT) to the lateral hypothalamus (LH) has been shown to play a role in the maintenance of the opioid-associated memories. Hypocretin (Hcrt) neurons in the LH strongly innervate the PVT, required for maintaining wakefulness and involved in drug seeking. These factors may link sleep disorders in opioid addicts with their long-lasting drug-associated memories. This study will (1) determine whether Hcrt neurons in the LH are the major target; (2) examine whether manipulating the LH (Hcrt)-PVT pathway can effectively prevent relapse; and (3) test whether sleep intervention could be an effective strategy to prevent relapse.

This project will examine the association between end plate pathology and chronic low back pain (cLBP) and improve patient selection by developing and translating new imaging tools, technologies, and/or methods (iTTM) that provide accurate, noninvasive measures of end plate pathologies. A search for clinically relevant biomarkers of end plate pathology will focus on novel imaging measures of end plate bone marrow lesion (BML) severity with IDEAL MRI and cartilage endplate (CEP) fibrosis/damage with UTE MRI, assess interactions with paraspinal muscles, and identify metrics that associate with pain, disability, and degeneration. The research will refine imaging and post-processing methodologies by leveraging and expanding existing cross-sectional cohorts and then deploy and validate the new end plate iTTM to other BACPAC sites to test the most promising metrics’ clinical utility. These studies will provide validated iTTM that are useful for addressing the end plates pathology’s role in cLBP, identifying sub-phenotypes, discovering pain mechanisms, uncovering treatment targets, and selecting patients.

Although there are effective prevention and treatment programs and services to address opioid misuse, opioid use disorder (OUD), and overdose, gaps remain between those needing and those receiving prevention and treatment, in part because of a need to better understand how to make these programs and services most effective at a local level. The National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) launched the HEALing Communities Study to generate evidence about how tools for preventing and treating opioid misuse and OUD are most effective at the local level. This multisite implementation research study will test the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings. The goal of the study is to reduce opioid-related overdose deaths by 40 percent over three years. The Ohio State University is partnering with academic institutions in three other states to study the impact of these efforts in 67 highly affected communities. The study will also look at the effectiveness of coordinated systems of care designed to increase the number of individuals receiving medication to treat OUD, increase the distribution of naloxone, and reduce high-risk opioid prescribing.

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.

Researchers will develop multi-organ, microphysiological systems (MPSs) based on human induced pluripotent stem cell-derived midbrain-fated dopamine (DA)/gamma-aminobutyric acid neurons on a three-dimensional platform that incorporates microglia, blood–brain barrier (BBB), and liver metabolism. RNA sequencing and metabolomics analyses will complement the primary DA release measure to identify novel mechanisms contributing to chronic opioid-induced plasticity in DA responsiveness. The chronic pain-relevant aspect of the model will be realized by examination of aversive kappa-mediated opioid effects on DA transmission in addition to commonly abused mu opioid receptor agonists, and by incorporation of inflammatory-mediating microglia. Incorporation of BBB and liver metabolism modules into the microphysiologic system platform will permit screening of drugs. Throughput will be increased by integration of online sensors for online detection of DA and other analytes. Researchers will use a curated set of 100 chemical genomics probes.

This project will develop a human cell-based model of the afferent pain pathway in the dorsal horn of the spinal cord. The research team’s approach utilizes novel human pluripotent stem cell (hPSC)-derived phenotypes in a model that combines 3D organoid culture with microfabricated systems on an integrated, three-dimensional (3D) microelectrode array. Researchers will establish the feasibility of a physiologically relevant, human 3D model of the afferent pain pathway that will be useful for evaluation of candidate analgesic drugs. They will then improve the physiological relevance of the system by promoting neural network maturation before demonstrating the system’s utility in modeling adverse effects of opioids and screening compounds to validate the model. Completion of the study objective will establish novel protocols for deriving dorsal horn neurons from hPSCs and create the first human microphysiological model of the spinal cord dorsal horn afferent sensory pathway.

As the opioid crisis claims more and more lives, there is a need to develop new, safer analgesics. Biased agonists could activate beneficial signaling pathways while avoiding those that cause adverse effects. This project aims to speed the discovery of non-addictive analgesics by providing drug discovery teams with simpler, more robust, more quantitative assays for agonist bias. The goal is to optimize and test new assays for agonist bias at NOP, D3 dopamine, CB1 cannabinoid, and OPRM1 opioid receptors, which couple to both the Gi and ?-arrestin signaling pathway, and create new tools to improve the analysis of structure/activity relationships that can be used in drug discovery and distribute to researchers who are developing new drugs for OUD.

Many states across the country have experienced an increase in children involved in the foster care system because of young parental opioid and methamphetamine use disorders (OUD; MUD). The Families Actively Improving Relationships (FAIR) program is a recently developed, rigorously evaluated, intensive outpatient treatment program for parents involved in the child welfare system for parental OUD and/or MUD. The FAIR effectiveness trial showed the potential for FAIR to be adapted as a prevention program, and to be implemented in counties with low service availability and access. This project will adapt and implement FAIR for prevention in collaboration with Oregon State Department of Human Services (DHS). Across two counties, parents referred by DHS for OUD or MUD with risk for escalation will be recruited and randomized to receive the adapted FAIR as prevention, or standard case management and referral. Outcomes will inform further FAIR refinement and potential broader scale-up.

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.