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The case for reverse engineering ketamine and psychedelics: lessons from translational oncology. A Response to Miller et al. “Burning down the house: reinventing drug discovery in psychiatry for the development of targeted therapies”

Molecular Psychiatry volume 28, pages 3164–3166 (2023)Cite this article

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We appreciate the view of Miller et al. [1] in advocating for greater pathophysiologic specificity in psychiatric research. Doubtlessly, moving beyond current diagnostic and outcomes impediments will be vital to advancing the field. Moreover, we strongly support the authors advocation to draw on lessons from the cancer model in restructuring psychiatric translational research.

Precisely for this reason, we are surprised by their dismissal of efforts to reverse engineer therapeutic mechanisms from ketamine and psychedelics as “a low-yield strategy.” We suggest that discounting this approach lacks sufficient recognition for the historical progress of translational oncology and the relative pathophysiologic complexity of central nervous system (CNS) disorders.

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References

  1. Miller AH, Raison CL. Burning down the house: reinventing drug discovery in psychiatry for the development of targeted therapies. Mol Psychiatry. 2022 https://doi.org/10.1038/S41380-022-01887-Y.

  2. Abhyankar D. Ipilimumab: a tale of twists and turns. South Asian J Cancer. 2018;7:193.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer. 2019;19:133–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8:1069–86.

    Article  PubMed  Google Scholar 

  5. Seligson ND, Knepper TC, Ragg S, Walko CM. Developing drugs for tissue‐agnostic indications: a paradigm shift in leveraging cancer biology for precision medicine. Clin Pharm Ther. 2021;109:334.

    Article  CAS  Google Scholar 

  6. Photopoulos J. The future of tissue-agnostic drugs. Nature. 2020;585:S16–S18.

    Article  CAS  Google Scholar 

  7. DeVita VT, Chu E. A history of cancer chemotherapy. Cancer Res. 2008;68:8643–53.

    Article  CAS  PubMed  Google Scholar 

  8. Dressel R, Greinix HT, Holler E, Dickinson AM. Editorial: Cellular therapies: past, present and future. Front Immunol. 2018;9:1966.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Miller KD, Ostrom QT, Kruchko C, Patil N, Tihan T, Cioffi G, et al. Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin. 2021;71:381–406.

    Article  PubMed  Google Scholar 

  10. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.

    Article  CAS  PubMed  Google Scholar 

  11. le Rhun E, Preusser M, Roth P, Reardon DA, van den Bent M, Wen P, et al. Molecular targeted therapy of glioblastoma. Cancer Treatment Rev. 2019;80:101896.

  12. Davola ME, Mossman KL. Oncolytic viruses: how “lytic” must they be for therapeutic efficacy? 2019;8. https://doi.org/10.1080/2162402X.2019.1596006.

  13. Zhang S, Rabkin SD. The discovery and development of oncolytic viruses: are they the future of cancer immunotherapy? 2020;16:391–410. https://doi.org/10.1080/17460441.2021.1850689.

  14. Daws RE, Timmermann C, Giribaldi B, Sexton JD, Wall MB, Erritzoe D, et al. Increased global integration in the brain after psilocybin therapy for depression. Nat Med. 2022;28:844–51.

  15. Farmer CA, Gilbert JR, Moaddel R, George J, Adeojo L, Lovett J, et al. Ketamine metabolites, clinical response, and gamma power in a randomized, placebo-controlled, crossover trial for treatment-resistant major depression. Neuropsychopharmacology. 2020;45:1398–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Center to Study Psychedelics for Treatment of Depression, Anxiety | Dell Medical School. https://dellmed.utexas.edu/news/dell-med-launches-center-to-study-psychedelics-for-treatment-of-depression-anxiety-ptsd.

  17. Garber K. Delix therapeutics: psychedelics without the trip. Nat Biotechnol. 2022. https://doi.org/10.1038/D41587-022-00006-0.

  18. Grunebaum MF, Mann JJ, Galfalvy HC, Gibbons RD. Computerized-adaptive vs. traditional ratings of depression and suicidal thoughts: an assay sensitivity pilot study in a ketamine clinical trial. Front Psychiatry. 2021;12:450.

    Article  Google Scholar 

  19. Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27:1025–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA

    Gregory Jones & Rodrigo Machado-Vieira

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  1. Gregory Jones
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  2. Rodrigo Machado-Vieira
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Correspondence to Rodrigo Machado-Vieira.

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Jones, G., Machado-Vieira, R. The case for reverse engineering ketamine and psychedelics: lessons from translational oncology. A Response to Miller et al. “Burning down the house: reinventing drug discovery in psychiatry for the development of targeted therapies”. Mol Psychiatry 28, 3164–3166 (2023). https://doi.org/10.1038/s41380-023-02102-2

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