Kappa opioid receptor influences naltrexone's effects on drinking alcohol

August 06, 2019

Philadelphia, August 6, 2019 - Researchers at Yale University have identified how naltrexone, a medication used to treat alcohol use disorder, reduces craving and consumption in heavy drinkers. The findings appear in Biological Psychiatry published by Elsevier. Although naltrexone is an approved treatment for alcohol use disorder, it only works in some people, which has led doctors to stop prescribing the drug. The new findings provide a better understanding of how naltrexone works in the brain, which could help identify people who would benefit from the treatment.

Although naltrexone binds to multiple molecules in the brain, first author Bart de Laat, PhD, and his senior colleagues Evan D. Morris, PhD, and Suchitra Krishnan-Sarin, PhD, in the Department of Radiology and Biomedical Imaging, and the Department of Psychiatry, focused on one of its targets, the kappa opioid receptor, to see if the molecule influences alcohol drinking and how much people want to drink alcohol.

Heavy drinkers with more kappa opioid receptors in the brain experienced a greater urge to drink alcohol. They also responded less to naltrexone treatment, meaning they continued to drink the same amount after receiving naltrexone.

"Kappa opioid receptor activation has been implicated in the 'dark side of addiction', in this case the motivation to drink even when alcohol is no longer rewarding. This innovative study makes the case that some therapeutic effects of naltrexone may be mediated by its effects on this target," said John Krystal, MD, Editor of Biological Psychiatry.

The researchers performed the study in non-treatment-seeking heavy drinkers who were allowed to self-administer alcoholic drinks before and after a week of naltrexone treatment. The findings are the first to reveal the role of the kappa opioid receptor in naltrexone's effect on craving and drinking in people with alcohol dependence.

"These results are an important step forward in our understanding of alcohol-related behaviors and how naltrexone functions. They highlight the importance of the kappa opioid receptor in alcohol use disorders and its treatment," said Dr. De Laat.

Other biological variables likely affect how well naltrexone works in different people, and more research is needed to discover who will or will not benefit from naltrexone treatment, Dr. De Laat added. But the new findings help advance understanding of the neurobiology of drinking problems and how to better treat them.
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Notes for editors

The article is "The kappa opioid receptor is associated with naltrexone-induced reduction of drinking and craving," by Bart de Laat, Alissa Goldberg, Julia Shi, Jeanette M. Tetrault, Nabeel Nabulsi, Ming-Qiang Zheng, Soheila Najafzadeh, Hong Gao, Michael Kapinos, Jim Ropchan, Stephanie S. O'Malley, Yiyun Huang, Evan D. Morris, and Suchitra Krishnan-Sarin (https://doi.org/10.1016/j.biopsych.2019.05.021). It appears in Biological Psychiatry, published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at Biol.Psych@sobp.org or +1 214 648 0880. Journalists wishing to interview the authors may contact Bart de Laat, PhD, at bart.delaat@yale.edu or +1 203 974 7595.

The authors' affiliations and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry

Biological Psychiatry
is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 7th out of 146 Psychiatry titles and 12th out of 267 Neurosciences titles in the Journal Citations Reports® published by Clarivate Analytics. The 2018 Impact Factor score for Biological Psychiatry is 11.501. http://www.sobp.org/journal

About Elsevier

Elsevier is a global information analytics business that helps scientists and clinicians to find new answers, reshape human knowledge, and tackle the most urgent human crises. For 140 years, we have partnered with the research world to curate and verify scientific knowledge. Today, we're committed to bringing that rigor to a new generation of platforms. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, 39,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers. http://www.elsevier.com

Media contact

Rhiannon Bugno
Editorial Office, Biological Psychiatry
+1 214 648 0880
Biol.Psych@sobp.org

Elsevier

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