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Psychedelics and ketamine are a symptom of psychiatry’s woes, not a cure

Molecular Psychiatry volume 28, pages 3167–3168 (2023)Cite this article

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A Response to Jones and Machado-Vieira “The Case for Reverse Engineering Ketamine and Psychedelics: Lessons from Translational Oncology”.

To suggest that psychedelics and ketamine (reverse engineered or not) are akin in any way to immune checkpoint inhibitors or targeted therapies in oncology not only fails to appreciate the painstaking scientific research that led to these discoveries in oncology, but also, more importantly, belies the desperation in psychiatry regarding the lack of progress in drug development and the need for a “win” however conceived. Checkpoint inhibitors were not developed by reverse engineering (as the authors intimate) [1] but arose from an iterative process from bench to bedside and back using the scientific method to make incremental advances based on years of work elucidating the basic cellular and molecular mechanisms of immune cell regulation, tumor-host interactions, and tumor biology [2]. Indeed, pembrolizumab was developed based on elegant research conducted beginning in the 1990s on expression of the programmed death (PD)-1 receptor on T and B cells and its role in multiple aspects of immunity including autoimmunity, infection, and the tumor immune response [2]. This ground-breaking body of work led to the 2018 Nobel Prize in Physiology and Medicine awarded to Drs. Tasuku Honjo and James Allison. That pembrolizumab’s full potential was not realized until after the approval of other checkpoint inhibitors had less to do with its mechanism of action (or reverse engineering as the authors suggest) [1] than the vicissitudes of big pharma [3]. That said, unlike psychedelics or ketamine, checkpoint inhibitors and targeted therapies including the tyrosine kinase inhibitors were designed based on mechanistic understandings of host tumor responses and tumor biology and were refined and further developed based on their outcomes in clinical trials [2, 4]. These are not examples of “embracing what works and continuing to discover why it works” [1], but rather an example of doing the hard scientific research to understand basic mechanisms of pathology, developing drugs that target these mechanisms and then refining their use in clinical trials.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

    Andrew H. Miller

  2. Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA

    Charles L. Raison

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  1. Andrew H. Miller
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Both AHM and CLR contributed to the writing of this correspondence.

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Correspondence to Andrew H. Miller.

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Competing interests

AHM is a paid consultant for Cerevel Therapeutics and Sirtsei Pharmaceuticals, Inc., and CLR is a paid consultant for Novartis, Alfasigma USA Inc., Usona Institute, and Emory Healthcare.

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Miller, A.H., Raison, C.L. Psychedelics and ketamine are a symptom of psychiatry’s woes, not a cure. Mol Psychiatry 28, 3167–3168 (2023). https://doi.org/10.1038/s41380-023-02132-w

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