Do the therapeutic effects of psilocybin involve actions in the gut?
Trends in pharmacological sciences – February 01, 2024
Source: PubMed
Summary
Psilocybin's therapeutic benefits may start in an unexpected place: your gut. New evidence suggests this psychedelic compound works along the gut-brain axis, activating serotonin receptors in both the digestive system and brain. Through the vagus nerve pathway, these actions may enhance neuroplasticity and improve mental health. The gut's high concentration of serotonin receptors could be key to understanding how psychedelics create positive changes.
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.