Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?

There is growing interest in exploring the therapeutic potential and mechanisms of action of psilocybin on stress-related neuropsychiatric disorders, including depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), addiction, and d...

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Main Authors: Alanna Kit, Kate Conway, Savannah Makarowski, Grace O'Regan, Josh Allen, Sandy R. Shultz, Tamara S. Bodnar, Brian R. Christie
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Neurobiology of Stress
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352289525000268
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author Alanna Kit
Kate Conway
Savannah Makarowski
Grace O'Regan
Josh Allen
Sandy R. Shultz
Tamara S. Bodnar
Brian R. Christie
author_facet Alanna Kit
Kate Conway
Savannah Makarowski
Grace O'Regan
Josh Allen
Sandy R. Shultz
Tamara S. Bodnar
Brian R. Christie
author_sort Alanna Kit
collection DOAJ
description There is growing interest in exploring the therapeutic potential and mechanisms of action of psilocybin on stress-related neuropsychiatric disorders, including depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), addiction, and disordered eating. Despite promising progressions in preclinical and clinical research, the neurobiological and physiological mechanisms underlying the therapeutic effects of psilocybin remain complex, involving multiple systems with numerous homeostatic feedback signaling pathways throughout the body. This review paper explores how psilocybin mechanistically interacts with the gut microbiota, enteric nervous system, hypothalamic-pituitary axis, and how psilocybin influences the bidirectional communication between peripheral and neuronal systems. Shifting towards a more integrated paradigm to unravel the mechanisms through which psilocybin affects the bidirectional gut-brain axis holds the promise of significantly advancing our understanding of psilocybin-based therapies from preparation of treatment, administration, to proceeding long-term integration. Such an understanding can extend beyond the treatment of psychiatric disorders, further encompassing a broader spectrum of inflammatory-related disorders.
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issn 2352-2895
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publishDate 2025-05-01
publisher Elsevier
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series Neurobiology of Stress
spelling doaj-art-a8065d6a8d034f0bb1fc6ad40f34134c2025-08-20T02:01:46ZengElsevierNeurobiology of Stress2352-28952025-05-013610073210.1016/j.ynstr.2025.100732Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?Alanna Kit0Kate Conway1Savannah Makarowski2Grace O'Regan3Josh Allen4Sandy R. Shultz5Tamara S. Bodnar6Brian R. Christie7Division of Medical Sciences, University of Victoria, Victoria, BC, CanadaIsland Medical Program, University of British Columbia, Victoria, BC, CanadaDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaDivision of Medical Sciences, University of Victoria, Victoria, BC, CanadaDivision of Medical Sciences, University of Victoria, Victoria, BC, Canada; Centre for Trauma & Mental Health Research, Vancouver Island University, Nanaimo, BC, CanadaDivision of Medical Sciences, University of Victoria, Victoria, BC, Canada; Centre for Trauma & Mental Health Research, Vancouver Island University, Nanaimo, BC, Canada; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, VIC, AustraliaDepartment of Biological Sciences, University of Calgary, Calgary, Alberta, CanadaDivision of Medical Sciences, University of Victoria, Victoria, BC, Canada; Island Medical Program, University of British Columbia, Victoria, BC, Canada; Institute for Aging and Lifelong Health, University of Victoria, 3800 Finnerty Rd, Victoria, BC, V8P 5C2, Canada; Center for Behavioral Teratology, San Diego State University, 6330 Alvarado Ct., San Diego, CA, 92120, USA; Corresponding author. Division of Medical Sciences, University of Victoria, 3800 Finnerty Rd, Victoria, BC, V8P 5C2, Canada.There is growing interest in exploring the therapeutic potential and mechanisms of action of psilocybin on stress-related neuropsychiatric disorders, including depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), addiction, and disordered eating. Despite promising progressions in preclinical and clinical research, the neurobiological and physiological mechanisms underlying the therapeutic effects of psilocybin remain complex, involving multiple systems with numerous homeostatic feedback signaling pathways throughout the body. This review paper explores how psilocybin mechanistically interacts with the gut microbiota, enteric nervous system, hypothalamic-pituitary axis, and how psilocybin influences the bidirectional communication between peripheral and neuronal systems. Shifting towards a more integrated paradigm to unravel the mechanisms through which psilocybin affects the bidirectional gut-brain axis holds the promise of significantly advancing our understanding of psilocybin-based therapies from preparation of treatment, administration, to proceeding long-term integration. Such an understanding can extend beyond the treatment of psychiatric disorders, further encompassing a broader spectrum of inflammatory-related disorders.http://www.sciencedirect.com/science/article/pii/S2352289525000268PsychedelicsHallucinogensMicrobiomeInflammation5-HTNeuropsychiatric disorders
spellingShingle Alanna Kit
Kate Conway
Savannah Makarowski
Grace O'Regan
Josh Allen
Sandy R. Shultz
Tamara S. Bodnar
Brian R. Christie
Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?
Neurobiology of Stress
Psychedelics
Hallucinogens
Microbiome
Inflammation
5-HT
Neuropsychiatric disorders
title Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?
title_full Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?
title_fullStr Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?
title_full_unstemmed Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?
title_short Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?
title_sort can the gut brain axis provide insight into psilocybin s therapeutic value in reducing stress
topic Psychedelics
Hallucinogens
Microbiome
Inflammation
5-HT
Neuropsychiatric disorders
url http://www.sciencedirect.com/science/article/pii/S2352289525000268
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