Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis.

Psychedelics show promise for treating psychiatric disorders, but current explanations focus mainly on their action at serotonin receptors in the brain. This review argues that the gut microbiota, via the gut-brain axis, may also play a role. Evidence suggests psychedelics can alter gut microbiota composition, and microbial metabolism might influence psychedelic effects. The authors call for incorporating microbiome hypotheses into future research, which could lead to personalized psychedelic therapies tailored to individual gut microbiota profiles.

Study at a glance

Abstract

Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A 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 various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome 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.