Addiction Treatment Development and Testing

Mission

Our mission is to develop and test interventions to address gaps in evidence-based treatment and to optimize outcomes for individuals struggling with addiction.

Leadership

Dr. Andrew Norman is Professor of Pharmacology. He received a B.Sc. with honors in Pharmacology in 1980 and a Ph.D. in Pharmacology in 1983 from King’s College London. Dr. Norman was a postdoctoral scientist with the Department of Neurosciences at the University of California, San Diego from 1983-1986. A major focus of Dr. Norman's research is the development of quantitative pharmacological models of addictive behavior. These models can then be used to predict the clinical efficacy of potential medications for the treatment of cocaine and other addictions. Dr. Norman leads a multidisciplinary team that is developing human anti-cocaine monoclonal antibodies suitable for use as therapeutic agents for the prevention of relapse in individuals addicted to cocaine.

Addiction Treatment Development and Testing Faculty

Dr. Amato combines a broad number of methods including in vivo imaging and ex vivo electrophysiology to study the molecular and neural mechanisms of psychotropic drugs (specifically psychostimulants and antipsychotic medications) and to understand how glutamate-dopamine co-regulation at cortico-accumbal synapses impacts D2 receptor medium spiny neurons (D2-MSNs) and contributes to pre, post and perisynaptic plasticity to alter behavior. My most significant contributions in this field include: 1) individuation of a subpopulation of accumbens core D2-MSNs that actively promote cocaine and antipsychotic cross-sensitization. These data are relevant to understanding precise mechanisms of a critical side effect following chronic antipsychotic treatment, behavioral supersensitivity. 2) Development of an animal model of deficient extinction learning and enhanced relapse using a classic instrumental behavioral protocol, revealing a new potential side effect of abrupt discontinuation of antipsychotic treatment. 3) Individuation of new molecular mechanisms underlying antipsychotic efficacy and failure, describing the dopamine transporter as a therapeutic target to rescue antipsychotic failure. Therefore my current work describes the basic functions of D2-MSNs, their regulation by different inputs, and their relevance for drug addiction, neurological disorders and psychiatric conditions. 

Dr. Burlew serves as a consulting psychologist at the Crossroads Center. She received her PhD in social psychology from the University of Michigan. She later retrained in clinical psychology. She is the co-author/co-editor of four books and has published over 70 journal articles and book chapters. She previously served as the Editor-In-Chief of the Journal of Black Psychology and currently is an Associate Editor of the Journal of Ethnicity in Substance Abuse. Her research primarily focuses on two areas (1) Evaluation of evidence-based interventions to determine their effectiveness for reducing Black substance use (2) Cultural adaptation of HIV interventions to be more appropriate for Black substance users. She employs a community engagement approach to her cultural adaptation work. She serves as chair of the Minority Interest Group of NIDA’s National Drug Abuse Treatment Clinical Trials Network. In that role, she has first-authored four guidance papers and one commentary on best practices for conducting health disparities research.  

Dr. Kirley’s laboratory has been involved, in collaboration with Dr. Norman, in the development and pre-clinical testing of his anti-cocaine mAb, to be used as a treatment for cocaine use disorders. We have characterized the post-translational modifications and analyzed the heterogeneity of this h2E2 monoclonal antibody, as well as developed methods for generation and purification of antibody fragments, including the therapeutically relevant Fab fragment (the part of the antibody that binds that binds cocaine). We also developed fluorescence quenching methods and differential scanning fluorescence techniques to measure binding affinities of the antibody and its fragments for cocaine and its metabolites and derivatives. In addition, we have characterized the stability of the intact antibody and the Fab fragment using multiple methodologies, crystalized the Fab fragment, and determined batch to batch glycosylation heterogeneities using mass spectral analyses. We continue to analyze and characterize the large scale GMP mAb batch prepared for use in Phase 1 Clinical Trials, as well as to develop novel analysis techniques to further characterize this monoclonal antibody.

Most research to date has focused on transcriptional, epigenetic, electrophysiological and morphological adaptations within neurons to understand drug addiction and relapse. Instead, Dr. Kruyer and her lab use single cell approaches to characterize astroglial subpopulations within the basal ganglia, the collection of brain nuclei that orchestrate motivated behaviors, including drug seeking. The principal findings of this work demonstrate a dynamic role for astrocytes in suppression of relapse-like behavior through regulation of synaptic activity in multiple basal ganglia nuclei. The ultimate goal of this research is to identify druggable targets that can be targeted to restore synaptic homeostasis and reduce relapse rates in patients with substance use disorders and in other vulnerable populations.

Dr. McReynolds conducts NIDA-funded pre-clinical research investigating the influence of stress on cocaine addiction with the goal of identifying unique neurobiological mechanisms that underlie the effect of stress and may provide potential therapeutic targets, especially for whom stress is a contributing factor to their substance use disorder. Her lab’s research specifically focuses on how acute and chronic stress contribute to drug use and relapse and the underlying neurobiological mechanisms. Her research has identified how glucocorticoid and endocannabinoid signaling interacts to mediate the effects of acute and chronic stress on cocaine use and relapse-like behavior in rodents.

Dr. Montgomery's research focuses on the prevention and treatment of marijuana and tobacco use and co-use (especially via blunts), medical marijuana and racial/ethnic disparities in substance use and prevention. She is an Associate Editor for the Journal of Substance Abuse Treatment and serves on the editorial board for several other health journals (e.g., Psychology of Addictive Behaviors, Ethnicity & Disease). Dr. Montgomery currently has a career development award (K23) from the National Institute on Drug Abuse to develop and pilot test a Twitter-based intervention to reduce blunt use among young African American adults.

Dr. Murnan is currently conducting a NIDA-funded K23 award with a clinical trial component. The goal of the project is to co-design a family-based intervention to reduce opioid use among women who sell sex. More broadly, Dr. Murnan is focused on leveraging community partnered methods to develop and adapt multi-systemic substance use interventions to better meet the needs of marginalized individuals and families. He has a particular interest in serving families who have been disproportionately impacted by the opioid epidemic and the criminal justice system. His prior clinical and research experiences have contributed to our understanding of best practices to addressing substance use disorders among individuals experiencing homelessness and the long-term effects of prenatal marijuana exposure on children's developmental and behavioral trajectories

Dr. Schultz has conducted NIH/NIDA-, AHA- and PhRMA Foundation-funded studies, spanning 15+ years, focused on the cardiovascular outcomes of acute or chronic opioid/opiate use. She and her PhD graduate mentor are acknowledged as the pioneers in the field of acute opioid use in cardiac ischemia-reperfusion injury, which has resulted multiple “therapeutic use” patents and consulting opportunities. Dr. Schultz’s research has contributed to our understanding of the effects of opioid/opiate use and use disorder in ischemic heart disease or heart failure outcomes.

Dr. Sprunger's research program is focused on understanding the complex mechanisms underlying problematic behavior at the intersection of alcohol/substance use disorders, trauma, and aggression. He is particularly interested in advancing our use of technology to facilitate psychological assessment and intervention to overcome barriers for high-risk populations. Dr. Sprunger has years of experience working on NIAAA-funded grants, including his F31-supported dissertation that investigated an attention-based intervention for mitigating intimate partner aggression risk for acutely intoxicated couples. The ultimate goal of his research program is to develop and disseminate technology that improves our ability to identify who is at risk for negative outcomes, under what conditions they are at greatest risk, and which mechanism-informed interventions are most effective for that person under those conditions.

Dr. Vinks is a pediatric clinical pharmacology and clinical trials expert. He is the director of the Division of Clinical Pharmacology at Cincinnati Children’s Hospital Medical Center. As the principal investigator of the former National Institute of Child Health and Human Development (NICHD) Pediatric Pharmacology Research Unit he has conducted multiple pediatric and adult clinical trials focused on population pharmacokinetics-pharmacodynamics (PK/PD) and pharmacogenetics/genomics. His recent efforts have focused on the development of PK/PD model-informed precision dosing strategies and clinical decision support in a variety of indications including for the management of neonates with opioid withdrawal syndrome (NOWS).

Dr. Wexelblatt is a pediatrician and researcher focused on improving perinatal health outcomes in regional populations.  I am currently the Regional Director of Newborn Services for Cincinnati Children's Hospital Medical Center (CCHMC) Perinatal Institute, which serves eight level 2 hospitals and three level 1 nurseries in our region.  As the regional faculty representative for the Ohio Children’s Hospital Association (OCHA) subcommittee on neonatal abstinence syndrome (NAS), I helped establish a protocol for NAS for twenty Ohio children’s and maternity hospitals.  I led in the reporting of key findings from OCHA demonstrating that improved outcomes for NAS following an infant’s in-utero exposure to opioids could be achieved through the utilization of standard treatment protocols with stringent weaning guidelines. Subsequently, I co-led the analysis and writing of a follow-up study reporting improvement in NAS outcomes after adoption of the collaborative guidelines. Building upon my work with the OCHA collaborative, I served as a primary or co-investigator in several additional regional analyses designed to provide evidence for further optimizing NAS guidelines. Analyses of outcomes following methadone versus buprenorphine weaning and a comparative effectiveness evaluation of conventional methadone weaning versus weaning with a pharmacokinetic modeled methadone protocol were published.  I am currently participating as a faculty member of the Ohio Perinatal Quality Collaboration (OPQC) disseminating our findings to 53 delivery hospitals in Ohio to improve the care of the opioid exposed infant.  Through our statewide collaborations of OCHA and OPQC, we have created a standardized protocol to safely decrease the length of stay.  We have also showed that a pharmacokinetic modeled taper reduced length of stay by three days, and that buprenorphine may be a safe and more effective option for pharmacologic treatment in the setting of NAS.

Dr. Wheeler is an assistant professor of Clinical Psychology. Her research focuses on drug use, treatment for drug use disorders, and associated health disparities among Black Americans. Her work seeks to identify cultural strengths that can facilitate drug use treatment effectiveness, retention, and overall improvement of treatment approaches in the context of structural barriers that disproportionately affect Black Americans. Dr. Wheeler also examines understudied drug use patterns among Black Americans that inform unmet health needs, such as nonmedical use of prescription drugs. Ultimately, Dr. Wheeler aims to utilize this research to develop and implement culturally congruent drug use interventions that will improve drug use outcomes in Black communities.

Dr. Winhusen has conducted NIDA-funded clinical trials for the past 20 years devoted to improving the treatment of substance use disorders including opioid, cocaine, and tobacco use disorders. He is one of the foremost experts in conducting multi-site addiction trials in clinical settings, having served as the national PI for six National Drug Abuse Clinical Trials Network trials. Dr. Winhusen’s research has contributed to our understanding of co-occurring disorders (e.g., tobacco use disorder with ADHD and with stimulant use disorders), the treatment of pregnant substance abusers, and the neurocognitive functioning of individuals with stimulant use disorders.

Dr. Zhang specializes in facilitating and de-risking drug development with integrated mathematical modeling and machine learning.