Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?
Alanna Kit, Kate Conway, Savannah Makarowski, Grace O'Regan, Josh Allen, Sandy R Shultz, Tamara S Bodnar, Brian R Christie
Neurobiology of Stress May 1, 2025 DOI: 10.1016/j.ynstr.2025.100732 via OpenAlex
Summary
AI-generated from the abstractPsilocybin shows therapeutic potential for stress-related neuropsychiatric disorders like depression, anxiety, PTSD, OCD, addiction, and eating disorders, but its mechanisms are complex, involving multiple body systems. This review explores how psilocybin interacts with the gut microbiota, enteric nervous system, and hypothalamic-pituitary axis, influencing bidirectional communication between peripheral and neuronal systems. Understanding these gut-brain interactions could advance psilocybin-based therapies from preparation through long-term integration, potentially extending benefits beyond psychiatric disorders to inflammatory-related conditions.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Inflammation Neuropsychiatric disorders Psychedelics hallucinogens Gut-brain axis microbiome |
| Citations | 5 |
| Key finding | Psilocybin's therapeutic effects involve complex interactions with the gut-brain axis, including the gut microbiota, enteric nervous system, and hypothalamic-pituitary axis. |
Abstract
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.