Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?
Neurobiology of Stress – May 01, 2025
Source: OpenAlex
Summary
Psilocybin, a potent hallucinogen, shows profound promise for treating stress-related neuropsychiatric conditions like anxiety and addiction. Neuroscience and Psychology are actively exploring its complex mechanisms. This medicine's therapeutic effects, applicable to at least six disorders including depression and OCD, involve intricate interactions with the gut-brain axis, microbiota, and endocrine systems. Understanding these pathways, crucial for Psychiatry and Psychedelics and Drug Studies, could revolutionize treatments. Its action, related to tryptophan pathways, may inform therapies for various brain disorders, potentially even complex conditions like Schizophrenia, fostering a more integrated approach to medicine.
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.