An Ethnographic Exploration of Opioid Agonist Treatment Barriers and Facilitators Among Opioid Users in Rural Nebraska

Led by Dr. Roberto AbadieUniversity of Nebraska-Lincoln

Study Overview:

This project aims to collect ethnographic data on opioid users living in two rural communities in Nebraska to document behavioral and structural factors affecting barriers and facilitators to Opioid Agonist Treatment enrollment.

Specific Aims:

(Aim 1): To document opioid users’ experiences of the barriers they face to enroll in and adhere to Opioid Agonist Treatment as well as the resources they can draw upon to help them remain in the program.

(Aim 2): To apply an integrated knowledge-exchange approach with our target audiences (policy makers, public health, Opioid Agonist Treatment providers, and harm reduction practice communities in Nebraska), providing them with the knowledge and tools to implement evidence based strategies to improve recruitment and adherence of Opioid Agonist Treatment in rural populations.

Study Sample Population:

N=600 (the entire Rural Health Cohort Study sample; all individuals that have been selected in the cohort study who are 19 years old or older and who report using opioids at least once in the past 30 days will be eligible for inclusion, up to the enrollment tallies for each treatment state; since this study does not keep personal information linked to data regarding opioid use and Opioid Agonist Treatment access, we won’t know which participants in this large study will meet our eligibility criteria).

Unique Study Procedures:


Long-Term Goals:

Understanding the individual and structural obstacles to Opioid Agonist Treatment participation in rural settings will contribute to evidence-based policies to improve Opioid Agonist Treatment access in relatively poorly served areas in the United States. By exploring the social determinants of Opioid Agonist Treatment access, this project fulfills the requirements of RFA-CE-19-002 Research Grants to Identify Effective Strategies for Opioid Overdose Prevention and is responsive to the NIH-wide mandate of improving minority health and reducing health disparities in the United States.

Photo of Roberto Abadie title=
Roberto Abadie

Dr. Roberto AbadiePROJECT Director

As a trained medical anthropologist, Dr. Abadie's research focuses on how different forms of social stratification, in particular, class, race, and ethnicity, contribute to produce and reproduce health inequalities in marginalized populations. He has conducted extensive fieldwork on the ethics of clinical trials, HIV risk, People Who Inject Drugs (PWID), and health disparities among Latino populations in a variety of settings in Latin America, the Caribbean and the US.

Full Roberto Abadie bio

Interpersonal Conflict and Drug Use in the Great Plains

Led by Dr. Robin GauthierUniversity of Nebraska-Lincoln

Study Overview:

This project aims to create a dynamic multi-level network model that utilizes relationship characteristics and contextual factors to better understand the interpersonal context of rural drug use.

Specific Aims:

(Aim 1): Determine the associations between interpersonal conflict and frequency of drug use. Analyzing existing ego network data from a longitudinal cohort study of PWUD adults in the Great Plans, this project will a: Determine whether or not interpersonal conflict is more strongly related to frequent drug use when it is embedded in a particular type of relationship. b: Determine whether or not interpersonal conflict is more strongly related to frequent drug use when it is embedded in a particular relational context (i.e. drug use or friendship).

(Aim 2): Determine how social conflict (i.e. interpersonal conflict among drug-use partners and confidants) affects participants’ frequency of drug use. Aim 2 will expand the goals of Aim 1 to include data on the relationships between respondents’ drug-use partners and confidants. This extension will allow for assessing of conflict in the larger social context.

(Aim 3): Use cross-lagged panel analysis to examine the reciprocal relationships between conflict and drug use and their relationship with relational types, behavioral context and network context.

Unique Study Procedures:


Long-Term Goals:

Understanding relational dynamics is crucial for the development of successful community intervention strategies targeting drug use behaviors in a social setting. These pilot results are expected to have tremendous translational impact by determining the factors most critical to target through prevention and intervention efforts.

Photo of Robin Gauthier title=
Robin Gauthier

Dr. Robin GauthierPROJECT Director

Dr. Gauthier's work shows how crucial relational processes are for answering pressing questions about health in a dynamic and changing world. Network theories share the fundamental premise that individual behaviors and outcomes cannot be fully understood without reference to the social context that facilitates and constrains access to risk, resources and support. She has applied this insight to several substantive problems including domestic violence support, epidemic potential, and intervention evaluation.

Full Robin Gauthier bio

Predictors of Sex-Linked Marijuana and Alcohol Use in Sexual Minority and Heterosexual Women

Led by Dr. Tierney LorenzUniversity of Nebraska-Lincoln

Study Overview:

This project aims to research how individual differences in sexual response may contribute to sexual minority women’s risk for substance use and misuse.

Specific Aims:

(Aim 1): Develop a novel behavioral measure of sexual reward value.

(Aim 2): Test if sexual response predicts differences in sex-linked substance use in exclusively heterosexual vs. mostly heterosexual women.

Study Sample Population:

N=105 (young adult women grouped by sexual orientation, N=35 exclusively heterosexual/mostly heterosexual/bisexual).

Unique Study Procedures:

This project will use several psychophysiological measures of women’s arousal and reward processing, including vaginal photoplethysmography and heart rate variability.

Long-Term Goals:

This project will have significant impacts on the field. First, it will create a new tool for researchers to assess individual differences in sexual reward value, using behavioral testing. Second, it will create an open access database on substance use risk factors among sexual minority women. Lastly, results from these aims will provide critical pilot data that will support future studies of sex-specific etiology and mechanisms of substance abuse among MHW women.

Photo of Tierney Lorenz title=
Tierney Lorenz

Dr. Tierney LorenzPROJECT Director

Dr. Lorenz is an Assistant Professor in the Psychology Department and Center for Brain, Biology and Behavior at the University of Nebraska-Lincoln. Her lab, the Women, Immunity and Sexual Health (WISH) lab, examines the interaction between women's mental, physical and sexual health, including the ways that sexual behavior impacts women's immune and endocrine function, as well as ways to help women with mental and/or physical health conditions have happy, healthy sexual lives.

Full Tierney Lorenz bio

Cocaine-Mediated Microglial Activation Involves Epigenetic Dysregulation of DNMT1/INCRNA XIST/PPARG Signaling Axis

Led by Dr. Palsamy PeriyasamyUniversity of Nebraska-Lincoln

Study Overview:

This project aims to research whether cocaine activates the microglia via lncRNA Xist-DNMT1-mediated epigenetic promoter DNA hypermethylation of PPARG, thereby resulting in elevated secretion of proinflammatory cytokines.

Specific Aims:

(Aim 1): To determine the epigenetic mechanism(s) underlying cocaine-mediated microglial activation in vitro.

(Aim 2): To validate the epigenetic mechanism(s) underlying cocaine-mediated microglial activation in vivo.

Study Sample Population:

N=20 (pregnant C57BI/6 wild-type mouse dams - and their newborn pups); N=48 (C57BL/6 wild-type mouse, 8-weeks-old).

Unique Study Procedures:


Long-Term Goals:

Findings from this proposal will provide evidence that noncoding RNAs and epigenetic mechanisms play critical roles in the cocaine abuse-mediated neuroinflammation. Also, the proposal outcome will provide robust preliminary data for the successful submission of an R01 grant in early 2022. Understanding the mechanisms responsible for microglial activation induced by cocaine will set the stage for the future development of novel therapeutic targets aimed at dampening the neuroinflammatory responses caused by drug addiction.

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Palsamy Periyasamy

Dr. Palsamy PeriyasamyPROJECT Director

Dr. Palsamy Periyasamy is an Assistant Professor in the Department of Pharmacology and Experimental Neuroscience, UNMC. His long-term goal is to investigate the epigenetic changes that occurred during HIV-1 infection and drug abuse leading to glial cell activation and to identify potential therapeutic strategies for HIV-associated neurocognitive disorder (HAND) treatment.

Full Palsamy Periyasamy bio

Sex specific brain derived extracellular vesicle markers associated with chronic methamphetamine use

Led by Dr. Sowmya YelamanchiliUniversity of Nebraska Medical Center

Study Overview:

Though often perceived to be a problem of the inner city, substance abuse has long been prevalent in rural areas. Rural adults have higher rates of alcohol abuse, tobacco use, and methamphetamine use, while prescription drug abuse and heroin use has grown in towns of every size. Factors contributing to substance abuse in rural America include- low education attainment, poverty, unemployment, high risk behaviors and isolation. The current proposal focuses on the potent psychostimulant methamphetamine (MA) that continues to pose a significant threat globally but importantly here in rural Nebraska.

Specific Aims:

(Aim 1): Identification of BDEV protein cargo signatures as potential sex specific markers for MA relapse using quantitative mass spectrometry-based proteomics.

(Aim 2): Detection of validated BDEV protein signatures in blood plasma from preclinical and clinical samples using an immunoaffinity approach

Study Sample Population:

In addition to our preclinical rat samples (which have already been collected), we will also isolate EVs from archived blood plasma from human subjects with a chronic history of meth dependency which are available from the Biobank at UNMC. The biobank employs rigorous criteria per the International Classification of Diseases, Tenth Revision, ICD-10) in identifying and classifying such samples. We currently have the availability of 17 plasma samples: 9 males, 8 females cataloged according to their race (12 caucasian, 2 black, 1 hispanic and 2 unknown race) and age (<30years =3; 30-40 years =8 and 40-60 years= 6) with a history of meth use. These samples were selected per the ICD10 criteria F15.1 and F15.2 that includes amphetamine related disorders and excludes cocaine related disorders. [Note: Since these are archived samples, they are exempt from human subjects’ studies]. Control subjects are balanced for both genders, race, age and carefully screened to exclude for any cancers and/or severe liver and kidney diseases.

Unique Study Procedures:

1. BDEV isolation and characterization

2. Plasma EV isolation and characterization

3. Immunocapturing validated BDE markers in blood plasma

Long-Term Goals:

Rural communities make up 97% of America’s land area, yet less than 20% of the population lives in these smaller communities. Many don’t suspect these seemingly idyllic rural areas are impacted by substance abuse — a disease that wreaks havoc on both individuals and their families. From the early 2000s, the number of substance use-related deaths in rural communities has risen, especially in comparison to deaths in urban areas. The proposed research aims to address a very important question on decoding sex differences associated with MA abuse given the widespread use of MA in rural Nebraska. On completion of these studies, we anticipate filling a significant gap in knowledge on how impaired BDEV dynamics affects neuronal function between the sexes during meth reinstatement including identification of key BDEV proteins as potential biomarkers. The wealth of information arising will break new ground and importantly provide novel proof of concept studies which will further as a prelude to future basic research on developing EVs as sex-specific medication development for treating meth addiction. Importantly, the proposed research encompassing preclinical and clinical samples fit aptly to the mission of RDAR – “advancing understanding of causes, impacts, and interventions related to rural drug addiction using both preclinical studies to field-based behavioral, neural, social, clinical, and translational research”.

Photo of Sowmya Yelamanchili title=
Sowmya Yelamanchili

Dr. Sowmya YelamanchiliPROJECT Director

The long term goals of my independent research program are to understand the role of regulatory molecules such as genes, proteins and microRNAs in the pathogenesis of neurological disorders and in the field of drug addiction, specifically methamphetamine abuse. Over the last six years, my lab has been extensively studying the role of extracellular vesicles (EVs) which express a repertoire of cargo (cf. proteins, miRNA, lipids etc.) in an array of neurodegenerative and neurodevelopmental disorders. My lab uses various model systems including human biospecimens, rhesus macaques in addition to rodent models and in vitro based approaches to study brain dysfunction associated with chronic drug use. On these lines, my own research program focuses on investigating the role of extracellular vesicles in chronic methamphetamine (meth) abuse as well as sex differences associated with meth relapse. My lab has also shown significant success in standardizing EV isolation and characterizing the role of brain derived EVs (BDEs) in an array of neurological disorders cf. NeuroAIDS, Traumatic Brain Injury and in Methamphetamine/ Prescription opioid/Nicotine use disorders.

Full Sowmya Yelamanchili bio

Feasibility of Assessing the Effects of Substance Use on Auditory and Vestibular Function

Led by Dr. Amanda Rodriguez & Dr. Michelle HughesUniversity of Nebraska-Lincoln

Study Overview:

This pilot project aims to evaluate the feasibility of obtaining auditory and vestibular (balance) function outcomes in a substance-misuse population.

Specific Aims:

(Aim 1): To establish recruitment sources for participants who chronically misuse substances and are in different stages of use (i.e., active, recovery, relapsed).

(Aim 2): To determine the feasibility of implementing a comprehensive auditory and vestibular test battery for people who misuse substances.

Study Sample Population:

We seek to enroll a minimum of 30 adults with a substance use history. Participant groups will include people: (1) in the community with active substance use, (2) who are diagnosed with a substance use disorder and currently in treatment, and (3) who have relapsed after having active recovery either on their own or through a treatment program.

Unique Study Procedures:

This project will be the first to systematically assess both auditory and vestibular function within a substance use population using a comprehensive battery of physiological and behavioral metrics that assess both peripheral and central functions, so that site-of-lesions can be identified.

Long-Term Goals:

This project’s results will provide pilot data for a subsequent larger-scale study to characterize auditory and vestibular function in people who chronically use substances and determine how health and use factors might exacerbate hearing and vestibular loss. Results will reveal the magnitude of alcohol and drug-induced hearing or vestibular loss and justify the need for diagnostic monitoring for people seeking treatment for substance-use disorder. Furthermore, this work will inform specific rehabilitative strategies that could also be implemented through telehealth to better reach rural communities where social and economic impacts of untreated hearing or vestibular loss are compounded by other healthcare disparities.

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Michelle Hughes

Dr. Michelle HughesPROJECT Director

Michelle Hughes, PhD, CCC-A is an Associate Professor and Director of the Cochlear Implant Research Laboratory (CIRL) at the University of Nebraska-Lincoln in the Department of Special Education and Communication Disorders. She received her MA in Audiology and PhD in Hearing Science from the University of Iowa, and completed her clinical fellowship in the Department of Otolaryngology—Head and Neck Surgery at the University of Iowa Hospitals and Clinics. Research interests involve examining the relation between physiology and perception in cochlear implants, investigating ways to incorporate telepractice into cochlear implant service delivery, and exploring ototoxicity effects secondary to substance misuse.

Full Michelle Hughes bio

Photo of Amanda Rodriguez title=
Amanda Rodriguez

Dr. Amanda RodriguezPROJECT Director

Amanda Rodriguez, AuD, PhD, CCC-A is an Assistant Professor and Director of the Concussion and Vestibular Evaluation (CAVE) Laboratory at the University of Nebraska-Lincoln in the Department of Special Education and Communication Disorders. She is also a Resident Faculty member in the Center of Brain, Biology and Behavior. She received her AuD/PhD in Audiology and Vestibular Function-Assessment from Texas Tech University Health Sciences Center. She then completed a T32 post-doc fellowship at Boys Town National Research Hospital. Her research interests include examining the effects of sports concussion on the vestibular system and identifying modifiable health risk factors associated with vestibular loss. Dr. Rodriguez is also a practicing vestibular audiologist in the community.

Full Amanda Rodriguez bio

A Critical Examination of the Incidence of Neonatal Opioid Exposure in Rural Nebraska

Led by Dr. Ann Anderson BerryUniversity of Nebraska Medical Center

Study Overview:

This pilot project aims to elucidate rural Nebraska incidence of intrauterine opioid and substances of abuse exposure to identify evidence based educational interventions and treatment opportunities.

Specific Aims:

(Aim 1): Assess the risk of intrauterine opioid exposure and NOWS from opioids prescribed during pregnancy in rural Nebraska newborns.

(Aim 2): Develop a method to survey polysubstance exposure in late pregnancy across rural Nebraska.

Study Sample Population:

This project will use innovative methods with NEHII (Nebraska’s Health Information Initiative) to enumerate opioid prescriptions to women during pregnancy and compare those rates with local diagnoses of NOWS.

Unique Study Procedures:

This project will utilize an educational module with rural delivery health care providers (physicians, nurses, pharmacists) to ensure staff have an evidenced based process to: minimize maternal opioid prescriptions, identify and initiate treatment for maternal opiate use disorder, recognize and diagnose neonates impacted by maternal opiate use, and care for them accordingly.

Long-Term Goals:

Findings from this proposal with inform our long-term goal of decreasing use and increasing access to care. Results from this project will further inform outreach, prevention and treatment efforts in the perinatal population of rural Nebraska. Additionally, we will disseminate our results (success and failures) to the medical community so that other rural states can utilize similar methodology to impact their rural perinatal populations.

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Ann Anderson Berry

Dr. Ann Anderson BerryPROJECT Director

Dr. Ann Anderson Berry is the Vice-Chair of Research and Professor in the Department of Pediatrics, Interim Executive Director of the Child Health Research Institute (CHRI) at UNMC, Division Chief of Neonatology, and the medical director of a high acuity level III NICU and newborn nursery. Her long-term goal is to understand the implications of perinatal health research findings in communities.

Full Ann Anderson Berry bio