Do the therapeutic effects of psilocybin involve actions in the gut?
TIPS - Trends in Pharmacological Sciences February 1, 2024 DOI: 10.1016/j.tips.2023.12.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Neuroplasticity Psilocybin Serotonin |
| Keywords | Gut–brain axis Mental health Vagus nerve Psychedelics hallucinogens Entheogens Gut-brain connection Neuroscience neuroplast |
| Citations | 22 |
| Key points | Argues that peripheral actions of psilocybin in the gastrointestinal tract may contribute to rapid and long-term therapeutic effects in mental health conditions. |
Abstract
The psychedelic compound psilocybin has recently emerged as a therapeutic intervention for various mental health conditions. Psilocybin is a potent agonist of serotonin (5-HT) receptors (5-HTRs), which are expressed in the brain and throughout peripheral tissues, with particularly high expression in the gastrointestinal (GI) tract. However, no studies have investigated the possibility that peripheral actions of psilocybin may contribute to improvements in mental health outcomes. This is despite strong evidence for disturbed gut-brain signalling in conditions in which psilocybin is being tested clinically. In this Opinion, we highlight the likely actions of psychedelics in the gut and provide initial support for the premise that peripheral actions may be involved in rapid and long-term therapeutic effects. A greater understanding of all sites and modes of action will guide more targeted approaches to drug development.
Comparable studies
Other theoretical and historical papers on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics | 2019 | Theoretical or philosophical paper | |
| Psychedelics as Medicines: An Emerging New Paradigm General population | 2016 | Theoretical or philosophical paper | |
| Theorizing that Psychedelic Assisted Therapy May Play a Role in the Treatment of Trauma-Induced Personality Disorders. | 2024 | Theoretical or philosophical paper | |
| What Geometric Visual Hallucinations Tell Us about the Visual Cortex | 2002 | Theoretical or philosophical paper | |
| Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame | 2020 | Theoretical or philosophical paper |
Citations in the library
Cited by 21
- Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics. Progress in Neuro-Psychopharmacology and Biological Psychiatry August 30, 2024
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
- Early psilocybin intervention alleviates behavioral despair and cognitive impairment in stressed Wistar rats Progress in Neuro-Psychopharmacology and Biological Psychiatry 2025
- Chronic psilocybin administration increases sociability and alters the gut microbiome in male wild-type mice but not in a preclinical model of obsessive-compulsive disorder Neuropharmacology August 21, 2025
- Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning‐Based Advanced Perspectives Advanced Science March 20, 2025
and 16 more in the library
Cites 43
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
and 38 more in the library