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Glutamatergic Agents for the Treatment of Cocaine Use Disorder

  • Addictions (M Potenza and E DeVito, Section Editors)
  • Published:
Current Behavioral Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Disruptions in glutamate hemostasis have been implicated in cocaine use disorder (CUD). This manuscript reviews novel agents that influence glutamate neurotransmission with respect to their potential for the treatment of CUD. Among glutamatergic receptors/transporters, we focused on NMDA and AMPA/kainate receptors, mGluR1/5, mGluR2/3, and xCT and GLT-1 transporters.

Recent Findings

This review suggests that beta-lactam antibiotics, propentofylline, metabotropic glutamate-receptor-5 antagonists, and ketamine may alter neuroplastic processes related to chronic cocaine use. Among novel agents targeting glutamatergic systems, arguably the agent with the most preclinical and clinical support is ketamine, although the route of administration and potential for misuse are limitations. The beta-lactam antibiotics clavulanic acid and ceftriaxone have significant preclinical support, but ceftriaxone has limitations relating to the route of administration and safety profile. Among other agents with promising preclinical data, there exists ongoing (e.g., mavoglurant and clavulanic acid) or completed (e.g., clavulanic acid) clinical trials.

Summary

Given the potential of targeting glutamatergic systems, further study is needed of these agents. Gaps and limitations when it comes to translation of preclinical work to clinical settings are being reduced and addressed with promising candidates such as ketamine, newer beta-lactam agents with better safety profiles, and ongoing trials with agents targeting metabotropic glutamate receptors.

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Funding

This work was supported by grants R21 DA040914 (GAA), R21 DA043055 (GAA), R01 DA052454 (GAA), R01 DA039136 (MNP), and K01 DA042998 (PDW) from the National Institute on Drug Abuse (NIDA). HH received funding from the Fredrick C. and Herta G. Redlich Research Fund, and JMF received funding from the Daniel X and Mary Freedman Foundation and the Neuroscience Research Training Program at Yale University. The work described in this article was also funded in part by the State of Connecticut, Department of Mental Health and Addiction Services, but this publication does not express the views of the Department of Mental Health and Addiction Services or the State of Connecticut. The views and opinions expressed are those of the authors. The funding sources had no involvement in the literature search, interpretation of the literature, writing of the manuscript, or in the decision to submit the article for publication.

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  1. Hasti Hadizadeh and José M. Flores contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT, 06511, USA

    Hasti Hadizadeh, José M. Flores, Talia Mayerson, Patrick D. Worhunsky, Marc N. Potenza & Gustavo A. Angarita

  2. Clinical Neuroscience Research Unit, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519, USA

    Hasti Hadizadeh, José M. Flores & Gustavo A. Angarita

  3. Department of Psychiatry and Behavioral Sciences, University of Minnesota, F282/2A West, 2450 Riverside Avenue, Minneapolis, MN, 55454, USA

    Hasti Hadizadeh

  4. Department of Neuroscience, Yale University, New Haven, CT, 06510, USA

    Marc N. Potenza

  5. Child Study Center, Yale University School of Medicine, New Haven, CT, 06510, USA

    Marc N. Potenza

  6. Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519, USA

    Marc N. Potenza

  7. Connecticut Council on Problem Gambling, Wethersfield, CT, 06109, USA

    Marc N. Potenza

  8. Wu Tsai Institute, Yale University, New Haven, CT, 06510, USA

    Marc N. Potenza

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The authors report that they have no financial conflicts of interest with respect to the content of this manuscript. Dr. Potenza has the following relationships to disclose: Dr. Potenza has consulted for and advised Game Day Data, Opiant Pharmaceuticals, Idorsia, BariaTek, the Addiction Policy Forum, and AXA; has been involved in a patent application with Yale University and Novartis; has received research support from the Mohegan Sun Casino and the Connecticut Council on Problem Gambling; has participated in surveys, mailings, or telephone consultations related to addictive disorders or other health topics; has consulted for or advised law offices and gambling entities on issues related to addictive disorders and behaviors; has provided clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; has performed grant reviews; has edited journals and journal sections; has given academic lectures in grand rounds, CME events, and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts. All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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Hadizadeh, H., Flores, J.M., Mayerson, T. et al. Glutamatergic Agents for the Treatment of Cocaine Use Disorder. Curr Behav Neurosci Rep 9, 101–112 (2022). https://doi.org/10.1007/s40473-022-00252-1

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