Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis

Giorgia Caspani; Simon G.D. Ruffell; WaiFung Tsang; Nigel Netzband; Cyrus Rohani-Shukla; Jonathan R. Swann; Wilfred A. Jefferies

Pharmacological Research (Sep 2024)

Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis

Giorgia Caspani,
Simon G.D. Ruffell,
WaiFung Tsang,
Nigel Netzband,
Cyrus Rohani-Shukla,
Jonathan R. Swann,
Wilfred A. Jefferies

Affiliations

Giorgia Caspani: Michael Smith Laboratories, University of British Columbia, 2185 East Mall, East Mall, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Department of Urologic Sciences, University of British Columbia, Gordon & Leslie Diamond Health Care Centre, Level 6, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada; Corresponding authors at: Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada.
Simon G.D. Ruffell: Psychae Institute, Melbourne, Australia; School of Population and Global Health, University of Melbourne, 207 Bouverie St, Carlton, VIC 3053, Australia
WaiFung Tsang: Institute of Psychiatry, Psychology & Neuroscience, King’sCollege London, Department of Psychology, De Crespigny Park, London SE5 8AF, UK
Nigel Netzband: University of West of England, Frenchay Campus, Coldharbour Lane, Bristol BS16 1QY, UK
Cyrus Rohani-Shukla: Centre for Psychedelic Research, Imperial College London, Hammersmith Hospital, Du Cane Rd, London W12 0HS, UK
Jonathan R. Swann: School of Human Development and Health, Faculty of Medicine, University of Southampton, 12 University Rd, Southampton SO17 1BJ, UK; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Wilfred A. Jefferies: Michael Smith Laboratories, University of British Columbia, 2185 East Mall, East Mall, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Department of Urologic Sciences, University of British Columbia, Gordon & Leslie Diamond Health Care Centre, Level 6, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada; Corresponding authors at: Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada.

Journal volume & issue: Vol. 207
p. 107338

Abstract

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Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota.

Published in Pharmacological Research

ISSN: 1096-1186 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/pharmacological-research

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