Pub Date : 2025-12-04DOI: 10.1016/j.biopsych.2025.11.021
Marjorie R. Levinstein, Ingrid Schoenborn, Peter Manza, Alan F. Schatzberg, Carlos A. Zarate, Jordi Bonaventura, Michael Michaelides
Certain medications carry a risk by providing therapeutic benefits at the expense of misuse potential. Ketamine is being used with increasing prevalence for the treatment of depression and studies indicate it may also have utility for substance use disorder (SUD) treatment. However, it has recreational appeal and known misuse potential. Driven by the ongoing expansion of its use in clinical settings, concerns for misuse of ketamine are escalating. This review summarizes neurochemical, molecular, and brain circuit mechanisms associated with ketamine reinforcement and misuse potential and discusses their relevance towards its potential for SUD treatment. We focus on ketamine's direct actions on opioid and glutamatergic systems, highlighting recent discoveries on its interactions with μ opioid receptors (MORs) and N-methyl-D-aspartate receptors (NMDARs) in addiction-relevant brain circuits. We propose that ketamine's reinforcing properties and misuse potential stem from its bifunctional engagement with these receptors, with its (S)-ketamine enantiomer, compared to (R)-ketamine, being ketamine's primary risk driver. We contextualize this bifunctional NMDAR/MOR mechanism within ketamine's known efficacy for treatment of depression and other mental health conditions, including its potential for SUD treatment. We conclude that the brain mechanisms contributing to ketamine reinforcement, its recreational appeal, and misuse potential are intertwined with its antidepressant properties and potential for SUD treatment.
某些药物以潜在的误用为代价提供治疗益处，这是有风险的。氯胺酮被越来越多地用于治疗抑郁症，研究表明它也可能用于治疗物质使用障碍（SUD）。然而，它具有娱乐吸引力和已知的滥用潜力。在临床使用氯胺酮不断扩大的推动下，对氯胺酮滥用的担忧正在加剧。本文综述了与氯胺酮强化和滥用相关的神经化学、分子和脑回路机制，并讨论了它们与氯胺酮治疗SUD潜力的相关性。我们关注氯胺酮对阿片和谷氨酸系统的直接作用，重点介绍了其在成瘾相关脑回路中与μ阿片受体（MORs）和n-甲基- d -天冬氨酸受体（NMDARs）相互作用的最新发现。我们提出氯胺酮的强化特性和滥用潜力源于其与这些受体的双功能作用，与(R)-氯胺酮相比，(S)-氯胺酮对映体是氯胺酮的主要风险驱动因素。我们将这种双功能NMDAR/MOR机制置于氯胺酮治疗抑郁症和其他精神健康状况的已知疗效中，包括其治疗SUD的潜力。我们得出的结论是，氯胺酮强化的大脑机制、其娱乐性的吸引力和滥用的可能性与它的抗抑郁特性和治疗SUD的潜力交织在一起。
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Pub Date : 2025-12-01DOI: 10.1016/j.biopsych.2025.11.019
Hangbin Zhang, Jacob Green, Shraddha Dwivedi, Ying-hui Chou
{"title":"Domain-Specific Efficacy of Accelerated Repetitive Transcranial Magnetic Stimulation in Neuropsychiatric Disorders: A Systematic Review and Meta-Analysis","authors":"Hangbin Zhang, Jacob Green, Shraddha Dwivedi, Ying-hui Chou","doi":"10.1016/j.biopsych.2025.11.019","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.11.019","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"68 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.biopsych.2025.11.018
Ruth H. Asch, Siyan Fan, Ryan Cool, Sarah Boster, Nicole DellaGioia, Mika Naganawa, Nabeel Nabulsi, Cheryl Lacadie, Robert H. Pietrzak, Irina Esterlis
{"title":"Neural Signatures of Bipolar Disorder and Psychotropic Medication Effects: A Multimodal PET–MRI Study","authors":"Ruth H. Asch, Siyan Fan, Ryan Cool, Sarah Boster, Nicole DellaGioia, Mika Naganawa, Nabeel Nabulsi, Cheryl Lacadie, Robert H. Pietrzak, Irina Esterlis","doi":"10.1016/j.biopsych.2025.11.018","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.11.018","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"24 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.biopsych.2025.11.016
Ziv Ben-Zion, Erin Z. Basol, Alexander J. Simon, Maayan Abargil, Katherine Samonek, Megan Patterson, Tobias R. Spiller, Or Duek, Stefan Just, Katrin Preller, Jakcob N. Keynan, Roee Admon, Israel Liberzon, Arieh Y. Shalev, Talma Hendler, Ifat Levy, Jutta Joormann, Dustin Scheinost, Ilan Harpaz-Rotem
{"title":"Dissecting Fear and Emotional Pain in PTSD: From Symptom Networks to Neural Signatures","authors":"Ziv Ben-Zion, Erin Z. Basol, Alexander J. Simon, Maayan Abargil, Katherine Samonek, Megan Patterson, Tobias R. Spiller, Or Duek, Stefan Just, Katrin Preller, Jakcob N. Keynan, Roee Admon, Israel Liberzon, Arieh Y. Shalev, Talma Hendler, Ifat Levy, Jutta Joormann, Dustin Scheinost, Ilan Harpaz-Rotem","doi":"10.1016/j.biopsych.2025.11.016","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.11.016","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"19 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.biopsych.2025.11.017
John H. Krystal , Deanna M. Barch , Rhiannon M. Bugno , Cameron S. Carter
{"title":"Addressing New Challenges to Scientific Integrity Including Paper Mills, Citation Cartels, Coercive Citation Practices, Fake Reviewers, and Artificial Intelligence–Generated Papers","authors":"John H. Krystal , Deanna M. Barch , Rhiannon M. Bugno , Cameron S. Carter","doi":"10.1016/j.biopsych.2025.11.017","DOIUrl":"10.1016/j.biopsych.2025.11.017","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"99 4","pages":"Pages 262-263"},"PeriodicalIF":9.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.biopsych.2025.09.017
Kazutaka Ohi
{"title":"Substance Use Disorders as Genetic Bridges Across Psychiatric Disorders in Diverse Ancestries","authors":"Kazutaka Ohi","doi":"10.1016/j.biopsych.2025.09.017","DOIUrl":"10.1016/j.biopsych.2025.09.017","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"99 1","pages":"Pages 6-8"},"PeriodicalIF":9.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.biopsych.2025.10.011
Mark S. Brodie
{"title":"Elucidating Noradrenergic Neuroadaptations of the Central Amygdala in Alcohol Use Disorder","authors":"Mark S. Brodie","doi":"10.1016/j.biopsych.2025.10.011","DOIUrl":"10.1016/j.biopsych.2025.10.011","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"99 1","pages":"Pages 2-3"},"PeriodicalIF":9.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.biopsych.2025.10.012
Sierra A. Codeluppi-Arrowsmith, Gustavo Turecki
{"title":"Glia in the Spotlight: The Cellular Basis of Alcohol Use Disorder","authors":"Sierra A. Codeluppi-Arrowsmith, Gustavo Turecki","doi":"10.1016/j.biopsych.2025.10.012","DOIUrl":"10.1016/j.biopsych.2025.10.012","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"99 1","pages":"Pages 4-5"},"PeriodicalIF":9.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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