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Shrinking the know–do gap in psychedelic-assisted therapy

Nature Human Behaviour volume 9, pages 665–672 (2025)Cite this article

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Abstract

There is a push to shrink the anticipated 17-year research-to-practice gap for psychedelic-assisted therapy (PAT), offering precarious hope to those with disabling mental health conditions. However, numerous questions regarding how PAT works, how well it works, for whom and in what context remain. Substantial changes to current systems of care, including regulatory approvals, clinical training and access will all be required to accommodate PAT, a multimodal therapy that combines pharmacological and psychotherapy components that are not routinely available outside clinical research settings. Implementation science can help to reduce the gap in a way that maintains scientific rigour by simultaneously examining the safety, effectiveness and implementation of PAT. Specifically, precision implementation science methods (for example, sequential multiple assignment randomized trial (SMART) designs), hybrid study designs, valid measurement of fidelity and use of theory-based models and frameworks for treatment development will accelerate the process of implementation while balancing safety and quality. The time to proceed, with accelerated caution, is now.

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Fig. 1: Integration of implementation science methods in the drug discovery and testing process.

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Acknowledgements

This work was made possible by National Institutes of Health (NIH) grants T32MH019960 and R25 MH112473, as well as the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. This work was also supported by research grants from the Center for Brain Research in Mood Disorders and the Taylor Family Foundation for Innovative Psychiatric Research, the Mallinckrodt Institute of Radiology, the McDonnell Center for Systems Neuroscience and the Institute for Clinical and Translational Sciences at Washington University School of Medicine in St Louis, and by the Barnes Jewish Hospital Foundation and Usona Institute.

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Authors and Affiliations

  1. Healthy Mind Lab, Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA

    Ginger E. Nicol & Eric J. Lenze

  2. School of Social Work, College of Health Sciences, University of Missouri, Columbia, MO, USA

    Danielle R. Adams & Leopoldo J. Cabassa

  3. Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA

    Eric J. Lenze

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  4. Leopoldo J. Cabassa
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Contributions

G.E.N. developed the overall concept for the manuscript, conducted an extensive review of the existing literature, created the content for figures, tables and text boxes, drafted the initial manuscript, and substantively revised it based on reviewer and editorial feedback. D.R.A. contributed extensively to the manuscript by providing explanatory details and historical background, and provided substantial revisions to improve its readability for a diverse readership. E.J.L. contributed to the overall conceptual design of the manuscript and provided substantial edits regarding pharmacological and regulatory content. L.J.C. worked closely with G.E.N. to devise the overall concept, providing guidance and content relevant to implementation science methods. All authors have reviewed, revised and approved the submitted version. All authors agree to be personally accountable for their contributions to this work and will ensure that questions related to accuracy or integrity are appropriately investigated, resolved and documented in the literature.

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Correspondence to Ginger E. Nicol.

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Competing interests

G.E.N. has received salary support from institutional grants supported by the National Center for Translational Sciences (NCATS) and the National Institute of Digestive and Diabetes and Kidney Diseases (NIDDK), research support from the National Institute of Mental Health (NIMH), the Health Resources and Services Administration (HRSA), the Patient Centered Outcomes Research Institute (PCORI), the Barnes Jewish Hospital Foundation and the Institute for Clinical Translational Sciences, the Taylor Family Institute for Innovative Psychiatric Research, the Mallinckrodt Institute of Radiology, the McDonnell Center for Systems Neuroscience and the Center for Holistic Interdisciplinary Research in Psychedelics (CHIRP), funded by a Transcend Initiative Grant through the Here & Next Research Grants programme at Washington University. She has served as a co-investigator or principal investigator for studies funded by COMPASS Pathways, LB Pharmaceuticals, Inc., Usona Institute and Alkermes, Inc., and has received personal fees as a consultant from Carelon, Novartis and Alkermes, Inc. D.R.A. has received grant support from the NIMH (T32MH019960). E.J.L. has received grant support from Fast grants and Jansen, has consulting relationships with Pritikin ICR, Boehringer Ingelheim, Merck, IngenioRX and Prodeo and a patent pending for the use of fluvoxamine for COVID-19. L.J.C. has received research support from NIMH (T32MH019960), the Washington University in St Louis Institute for Public Health and the Center for Dissemination and Implementation (D&I) and the Center for Mental Health Services Research in the Brown School at Washington University.

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Nicol, G.E., Adams, D.R., Lenze, E.J. et al. Shrinking the know–do gap in psychedelic-assisted therapy. Nat Hum Behav 9, 665–672 (2025). https://doi.org/10.1038/s41562-025-02103-x

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