Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis.
Giorgia Caspani, Simon Ruffell, WaiFung Tsang, Nigel Netzband, Cyrus Rohani-Shukla, Jonathan R Swann, Wilfred A Jefferies
Pharmacological Research September 1, 2024 DOI: 10.1016/j.phrs.2024.107338 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | 5-MeO-DMT Ayahuasca DMT Ketamine Psilocybin Serotonin LSD |
| Keywords | 2 3 5-dimethoxy-4-iodoamphetamine doi Dimethyltryptamine DMT Gut microbiota Gut-brain axis N-Dimethyltryptamine 5-MEO-DMT Personalised medicine Precision medicine Psychedelics hallucinogens Entheogens Gut-brain connection Microbiome |
| Citations | 13 |
| Key findings | The gut microbiota may mediate or modulate the behavioral effects of psychedelics, and future research should consider microbiome contributions. |
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.
Comparable studies
Other narrative reviews on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neuropharmacology of N,N-dimethyltryptamine | 2016 | Review | |
| N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Humans and animals (general) | 2018 | Review | |
| Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Humans (pharmacokinetics) | 2010 | Review | |
| Dark Classics in Chemical Neuroscience:N,N-Dimethyltryptamine (DMT) | 2018 | Review | |
| A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. | 2013 | Review |
Citations in the library
Cited by 10
- Neurobiology of psilocybin: a comprehensive overview and comparative analysis of experimental models Frontiers in Systems Neuroscience August 5, 2025
- Psychedelics and the Gut Microbiome: Unraveling the Interplay and Therapeutic Implications. ACS Chemical Neuroscience July 9, 2025
- The CAnadian Network for Psychedelic-Assisted Cancer Therapy (CAN-PACT): A Multi-Phase Program Overview. Current Oncology December 22, 2025
- Psychedelics in Multiple Sclerosis: Mechanisms, Challenges, and Prospects for Neuroimmune Modulation and Repair. Cells November 26, 2025
- Exploring the importance of bodyset for the psychedelic experience and beyond Journal of Psychedelic Studies September 8, 2025
and 5 more in the library
Cites 78
- A default mode of brain function Proceedings of the National Academy of Sciences January 16, 2001
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
and 73 more in the library