Mind Over Matter: The Microbial Mindscapes of Psychedelics and the Gut-Brain Axis

Abstract

Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss alternative mechanistic models and ways in which the microbiome should be accounted for in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota. eTOC blurbDrawing on their structural similarity to serotonin, we argue that the effect of psychedelics on the brain is partly mediated by the gut microbiota. Recognising psychedelic-microbe interactions can facilitate the implementation of precision medicine, by mapping the heterogeneity of a patient’s microbiome to the variability in responses to psychedelic-based therapies.