UK researchers awarded $2.6 million to study new drug combination driving overdose deaths

Grant and Award Announcement

UNIVERSITY OF KENTUCKY

 

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UK RESEARCHERS TERRY HINDS, JR. AND CASSANDRA GIPSON-REICHARDT WILL STUDY HOW XYLAZINE AND FENTANYL COMBINATION CHANGES THE BRAIN'S SIGNALING PATHWAYS.

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CREDIT: MARK CORNELISON | UNIVERSITY OF KENTUCKY PHOTO.

LEXINGTON, Ky. (Oct. 26, 2023) — Cassandra Gipson-Reichardt, Ph.D., and Terry Hinds, Jr., Ph.D., associate professors in the University of Kentucky College of Medicine’s Department of Pharmacology and Nutritional Sciences, have received a $2.65 million five-year grant from the National Institute on Drug Abuse (NIDA) to support research to understand how xylazine and fentanyl change the brain’s signaling pathways.  

Xylazine, a veterinary anesthetic commonly referred to as “tranq,” has recently made its way into the illicit drug supply as a drug adulterant to enhance the effects of fentanyl, a potent opioid that can be lethal even in small amounts. The new drug combination has resulted in a 1,127% increase in xylazine-positive overdose mortalities in the American south from 2020 to 2021, and results in other problematic health effects including tissue necrosis. 

This rapid spread of xylazine is also posing new challenges to addressing the opioid epidemic as it decreases the efficacy of naloxone, the life-saving medication that reverses the effects of an opioid overdose. 

Gipson-Reichardt and Hinds will study the specific brain circuits that are changed when xylazine and fentanyl are used together and see if these changes are responsible for making naloxone less effective. They have already identified unexpected pathways controlled by the combination that may reduce the actions of naloxone. In their work, they will determine if targeting these pathways are potentially therapeutic. 

Their team will utilize advanced PamGene PamStation technology in the Hinds lab to measure activities of hundreds of signaling mechanisms in the brain reward circuitry to identify how the co-use affects pathways and also to identify targets for therapeutic use.  

“By studying these processes in detail, we hope to better understand the ways xylazine and fentanyl interact in the brain and how they affect behavior,” said Gipson-Reichardt. “This knowledge could lead us to new strategies for treating people who are struggling with the combined use of these substances and help make naloxone more effective in saving lives.” 

These are the only preclinical studies currently funded by NIDA to address the xylazine/fentanyl epidemic, and will be the first to determine neurobiological and behavioral impacts of combined xylazine and fentanyl use and identify treatment targets to reverse xylazine’s effects on fentanyl. 

Gipson-Reichardt and Hinds will be collaborating with Kelly Dunn, Ph.D., at Johns Hopkins University to translate findings to inform the public on individual factors that may lead to worse clinical outcomes during withdrawal from the xylazine/fentanyl combination. 

Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA058933. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 

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November issues of American Psychiatric Association journals cover new insights in psychotic disorders, barriers to addiction treatment, bipolar disorder treatment, and more

Peer-Reviewed Publication

AMERICAN PSYCHIATRIC ASSOCIATION

WASHINGTON, D.C., Nov. 1, 2023 — The latest issues of three American Psychiatric Association journals, The American Journal of Psychiatry, Psychiatric Services and Focus, are now available online.

The November issue of The American Journal of Psychiatry provides insights into psychotic disorders, such as the altered neurodevelopment and early symptom presentation associated with the risk of developing schizophrenia; racial and ethnic disparities in diagnosis of psychotic episodes; and predictors of first psychotic episodes and its treatment. Highlights include:

• A Functional Connectome-Based Neural Signature for Individualized Prediction of Antipsychotic Response in First-Episode Psychosis.      
• Are We There Yet? Predicting Conversion to Psychosis Using Machine Learning.
• Rethinking the First Episode of Schizophrenia: Identifying Convergent Mechanisms During Development and Moving Toward Prediction    
• Inequalities in the Incidence of Psychotic Disorders Among Racial and Ethnic Groups. (Lead investigator Winston Chung, M.D., is the featured guest on November’s AJP Audio podcast episode.)

The November issue of Psychiatric Services features:  
 

• Postmarket Surveillance for Effective Regulation of Digital Mental Health Treatments.
• Effect of a Layperson-Delivered Telephone Program for People with Depressive Symptoms.
• Uncovering Barriers to Engagement in Substance Use Disorder Care for Medicaid Enrollees.
• Unconditional Cash Transfers and Association with Clinical Outcomes Among U.S. Veterans with Psychosis or Recent Homelessness.
• Medicaid Costs and Utilization of Collaborative Versus Colocation Care for Patients with Depression. (Featured in the Psychiatric Services “From Pages to Practice” podcast.)

 

Also available online is the latest issue of Focus, Volume 21, Issue 4, a special issue on Bipolar Disorder. Helmed by Guest Editor Trisha Suppes, M.D., Ph.D., the issue features the following:
 

• The CANMAT and ISBD Guidelines for the Treatment of Bipolar Disorder: Summary and a 2023 Update of Evidence.
• Bipolar II Disorder: Understudied and Underdiagnosed.
• Cognition in Bipolar Disorder: An Update for Clinicians.
• Bipolar Disorder Among Older Adults: Newer Evidence to Guide Clinical Practice.
• Suicide Assessment and Prevention in Bipolar Disorder: How Current Evidence Can Inform Clinical Practice.
• Engaging Through the Elation: Forming an Early Therapeutic Rapport With a Patient With Bipolar Disorder.
   

Journalists who wish to access the publications should email press@psych.org.

American Psychiatric Association
The American Psychiatric Association, founded in 1844, is the oldest medical association in the country. The APA  is also the largest psychiatric association in the world with more than 38,000 physician members specializing in the diagnosis, treatment, prevention and research of mental illnesses. APA’s vision is to ensure access to quality psychiatric diagnosis and treatment. For more information, please visit www.psychiatry.org.

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JOURNAL

American Journal of Psychiatry