Exploring the In Vitro Effect of Psilocybin on the Composition and Metabolic Activity of Gut Microbiota in Individuals with Severe Anxiety
M. Salgaço, D. D. Farias, Mariela Zucolo de Souza, A. Sartoratto, Flavia Bottino, H. Barud, Fellipe Lopes de Oliveira, A. Medeiros, Breno Vilas Boas Raimundo, Victor Hugo Nascimento, Taynah P Galdino, Suédina M L Silva, Marcus V L Fook, Katia Sivieri
Drugs and Drug Candidates August 12, 2026 DOI: 10.3390/ddc5030046 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Fecal microbiota from individuals with severe anxiety |
| Intervention | Psilocybe cubensis extract |
| Dose | 35 mg/L |
| Duration | 20 hours and 15 days of fermentation |
| Topics | Anxiety Psilocybin |
| Key findings | Psilocybin-containing P. cubensis extract reduced ammonia by 19–25% and GABA, increased acetic, propionic, and butyric acids by 2.26-, 2.69-, and 2.21-fold, and raised Bifidobacterium and Lactobacillus abundances after 20 hours and 15 days, with a slight reduction in α-diversity. Cytokine and intestinal barrier responses showed a complex immunomodulatory pattern, not a uniform anti-inflammatory effect. |
Abstract
Background/Objectives: This study investigated the effects of a single dose of psilocybin-containing Psilocybe cubensis extract on gut microbiota composition, microbial metabolism, and intestinal immune-related responses.
Methods: A single dose of P. cubensis extract (35 mg/L) was subjected to colonic fermentation using the SHIME® model inoculated with fecal microbiota from individuals with severe anxiety. Psilocybin and psilocin concentrations, microbial metabolites, gut microbiota composition, intestinal barrier integrity, and cytokine responses were evaluated.
Results: During colonic fermentation, the concentrations of both psilocybin and psilocin decreased significantly, suggesting their metabolism or degradation within the gut microbial environment. Treatment reduced ammonia production by 19–25% and decreased gamma-aminobutyric acid (GABA) levels. By contrast, the concentrations of the short-chain fatty acids acetic, propionic, and butyric increased by 2.26-, 2.69-, and 2.21-fold, respectively, after 20 h of fermentation. Microbial profiling revealed marked increases in the relative abundances of Bifidobacterium and Lactobacillus after 20 h and 15 days, together with a slight reduction in α-diversity. Fermentation supernatants also altered cytokine profiles and influenced intestinal barrier-related responses, although these effects reflected a complex immunomodulatory pattern rather than a uniform anti-inflammatory response.
Conclusions: These findings indicate that psilocybin-containing P. cubensis extract can modulate gut microbiota composition and metabolic activity under in vitro colonic conditions. The observed changes in microbial metabolites, bacterial taxa, and host-related responses support the hypothesis that gut-microbiota-mediated mechanisms may contribute to the broader biological effects of psilocybin. However, these in vitro findings do not establish clinical benefits for intestinal or mental health, and further validation in animal models and well-controlled clinical studies is required.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Psilocybe cubensis extract altered gut microbiota composition and metabolism, reducing ammonia and GABA while increasing short-chain fatty acids and Bifidobacterium/Lactobacillus, with a complex immunomodulatory pattern.
Synthesized
Comparable studies
Other preclinical and animal studies on psilocybin for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats Wistar rats | 2018 | Experimental study | n = 40 |
| Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming SAPAP3 knockout mice | 2024 | Randomized controlled trial | n = 50 |
| Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder. Male rats | 2024 | Preclinical study | |
| Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor Mice | 2024 | Experimental study |