Funded Projects

Exposure to opioid analgesics during medical care is a key driver of the opioid epidemic. Such exposures are widespread. Yet opioids remain essential first-line agents in treating pain, and it remains vital that pain be appropriately managed. Non-opioid pain treatments help to resolve the opioid/pain conflict. This project will examine the opioid-sparing and pain-relieving potential of a novel, non-pharmacological treatment for pain, using the effects of green light exposure to reduce pain and thereby reduce the quantity of opioids needed for pain relief.

Given the magnitude of the opioid death epidemic, we need multiple approaches to increase use of medication treatment for opioid use disorder (MOUD) for people from diverse geographical locations. Pharmacists as dispensers of and gatekeepers to opioid medications, including those used for OUD treatment, are natural partners of health care providers. Community pharmacists are widely available even in rural areas. This 2-year study will use a mixed-method design that includes qualitative and quantitative approaches to study pharmacists’ knowledge of, attitudes about, and intention to provide patient care and services for screening, brief intervention, and referral to treatment for substance use disorders and MOUD. Study aims are to conduct stakeholder interviews, develop a survey instrument to assess such barriers and facilitators, pilot test the survey instrument, and conduct the survey among licensed pharmacists.

This study will evaluate the implementation of the Zero Suicide framework across six health systems serving over nine million people in collaboration with the Mental Health Research Network. The project will incorporate the voice of the patient and provider stakeholders as part of the implementation of the Zero Suicide framework in three health settings from the NIMH-funded parent award as well as the Southcentral Foundation which is an Alaska Native-owned, nonprofit health care organization serving nearly 65,000 American Indian/Alaskan Native people living in and around Anchorage, Alaska. The team will first systematically engage patients, providers, national consumer advocacy groups, and MHRN scientists in formulating research questions to address the prevention of opioid-related overdoses in people with Opioid Use Disorders (OUD) or people without diagnosed OUD who are using opioids for pain management. Next, the team will utilize semi-structured interviews to determine how people with OUD or people without diagnosed OUD who are using opioids for pain management are experiencing the implementation of the Zero Suicide framework in four diverse health systems. Experiences will be recorded using 80 semi-structured phone interviews in a diverse sample of patients who have survived an opioid-related overdose (50% intentional; 50% unintentional), as well as 20 Addiction Medicine, Primary Care, and/or Specialty Pain Medicine providers.

This supplement supports the goals of the current award, “An Evaluation of the National Zero Suicide Model Across Learning Healthcare Systems” (U01MH114087). Safety planning is a highly recommended practice within the Zero Suicide framework, but little is known about the effectiveness of the individual elements that can make up a safety plan, such as lethal means assessment, identification of supportive contacts, coping skills, warning signs, and sources of distraction. All of the documentation lives in text-based clinical narratives. This supplement will support development of new metrics using natural language processing to determine baseline rates, from which we can quantify the change in safety planning and lethal means assessment practice longitudinally after implementation of new safety planning templates using our Zero Suicide main award.

Currently available treatments for opioid use disorder (OUD) are insufficient for many patients. Novel compounds that can promote alterations in brain connections (i.e., neural plasticity) possess enormous potential for improving substance use disorder (SUD) treatments. Psychedelic compounds induce neural plasticity and can elicit long-lasting, beneficial impacts on a wide variety of SUDs. However, these compounds have significant side effects, including hallucinations and cardiotoxicity. Researchers have developed a novel, synthetic derivative of the psychedelic ibogaine, called tabernanthalog, that does not have these side effects. This compound has demonstrated both short- and long-term therapeutic effects in a preclinical model of OUD. This research study will determine the molecular and neural mechanisms through which tabernanthalog affects opioid seeking. It will also evaluate whether the effects are specific to opioids and do not alter response to natural rewards and will examine the efficacy of tabernanthalog in a preclinical model of comorbid opioid and alcohol use disorder.

Safe and effective options are urgently needed to prevent and treat opioid use disorder and polysubstance use disorders. Previous research in humans and animals suggests that activating the calcium-activated potassium channel KCa2.2 is a promising therapeutic approach for treating substance use disorders and associated health conditions. This project will perform a virtual high-throughput screen using novel machine learning approaches to discover new molecules that interact with the KCa2.2 channel. The newly discovered molecules help develop novel drugs for the treatment of opioid use disorder and associated health conditions.

This project is focused on identifying the clinical, genetic, and neural characteristics that convey risk for prescription opioid addiction. We will leverage the central biorepository and electronic health record (EHR) database of the Geisinger Health System to conduct large-scale genomics research and phenotype development. Through a collaboration with Regeneron Pharmaceuticals, the Geisinger biobank currently contains DNA samples on about 110,000 participants and includes both Illumina OmniExpressExome genotyping and whole exome sequence data, including common and rare variants, from over 60,000 of these subjects. This discovery cohort contains thousands of chronic musculoskeletal pain patients who have been taking greater than 120 mg equivalents of morphine for more than three months. Using EHR and self-report tools to develop a case definition and quantitative scoring, we will derive a clinical/genetic profile of prescription opioid addiction. This profile will be enhanced via integration of neuroimaging data.

Most people with opioid use disorder are either not in treatment or receive inconsistent treatment. Peer support is proven to be effective at engaging patients who are unwilling or unable to seek traditional treatment, but commonly available group support models are often separate from other clinical care or are otherwise hard for patients to access. This research will test a novel, machine learning enabled, digital peer support program added to an anonymous text-based social network that can provide 24/7 support for patients at all stages of recovery. The project will examine the ability of this digital service to engage and retain patients with opioid use disorder and will also develop novel techniques to automatically analyze patient messages for clinical and social determinants of health-related needs.

This training and dissemination project will develop an office-based buprenorphine treatment module for primary care, including the algorithm for buprenorphine treatment and integration of OUD measures; assess the acceptability of the OUD module; evaluate the impact of the OUD module on screening and identification rates of problem opioid use and successful initiation and maintenance rates of buprenorphine in primary care; assess barriers to implementation of buprenorphine treatment and methods for overcoming these barriers in the network partner clinics; and develop a strategy to refine and more broadly implement opioid problem use and OUD treatment.

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.

Maternal use and addiction to opioids or other drugs has resulted in an unprecedented rise in drug withdrawal complications in newborns known as neonatal abstinence syndrome (NAS). While there is no accepted standard for treating NAS, non-pharmacological bundles are recommended as an initial course of treatment. Unfortunately, non-pharmacological care (swaddling, rocking, frequent feedings, and skin contact) require significant use of human resources. This project studies the technical feasibility of a stochastic vibrotactile stimulation (SVS) technology incorporated into the hospital bassinet pad, which provides gentle vibrating sensory stimulation to soothe infants with NAS. Building on preliminary evidence that this type of stimulation calms NAS infants without altering their sleep, this study aims to develop a commercially viable bassinet pad that could be used in a hospital setting.

The lack of timely data about drug use and overdose deaths has hindered the ability of communities and state agencies to allocate resources to regions where they are most needed. This project will develop a secure data pool that combines individual and community-level real-time data from multiple sources, including urine drug testing. These data will then be used to model the contribution of opioid, cocaine, and stimulant use to overdoses, overdose deaths, and cases of substance use disorder. This research will also use urine drug testing results and demographic/contextual data to identify populations and subpopulations at highest risk of drug use and overdose. This information will be displayed through a data platform tailored to the needs of end users (e.g., communities or agencies) and with user-friendly tools that help users make informed decisions on where resources are most urgently needed.

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.