Biological markers of treatment response to serotonergic psychedelic therapies: a systematic review.
Stanley Wong, Brett D. M. Jones, Mathura T. Thiyagarajah, Sami G. Sabbah, Chase Thompson, Marco Solmi, Madeha Umer, Christoph Zrenner, Daphne Voineskos, Joshua D. Rosenblat, Benoit H. Mulsant, Daniel M. Blumberger, Muhammad Ishrat Husain
Ther Adv Psychopharmacol October 16, 2025 DOI: 10.1177/20451253251384513 via PubMed Central
Summary
AI-generated from the abstractA review of nine small clinical trials found that ayahuasca and psilocybin, when used to treat major depressive disorder and treatment-resistant depression, are associated with changes in several biological markers. These include increased serum brain-derived neurotrophic factor, decreased serum C-reactive protein, altered amygdala activation, and changes in functional connectivity between brain regions such as the ventromedial prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex. These associations suggest potential mechanisms of clinical response, but larger, longer-term studies are needed to confirm these findings.
Study at a glance
| Characteristics | Systematic review Longitudinal Peer reviewed |
|---|---|
| Population | Participants diagnosed with major depressive disorder or treatment-resistant depression |
| Interventions | Ayahuasca Psilocybin |
| Topics | Psychedelic-assisted therapy |
| Keywords | Psychedelic treatment Mental health interventions Biological markers Biomarkers |
| Citations | 3 |
| Key finding | Several potential biomarkers, including serum brain-derived neurotrophic factor, serum C-reactive protein, and specific patterns of brain activation and connectivity, were associated with clinical response to ayahuasca and psilocybin therapies. |
Abstract
Background: Results from contemporary clinical trials of serotonergic psychedelic therapies have led to an increasing focus on their potential clinical use across mental disorders. However, studies examining mechanisms of clinical response to psychedelic therapy in psychiatric populations are limited. This review aimed to synthesize evidence from studies examining biomarkers of clinical response to psychedelic therapies. Data sources and methods: A systematic search of four databases (MedLine, PsycInfo, EMBASE, and Web of Science) for studies investigating treatment response to psychedelic therapies in psychiatric populations that included both clinical outcomes and a related biomarker was conducted on January 10, 2024. Studies were included if they reported on prospective clinical trials involving the use of a psychedelic in participants diagnosed with any Diagnostic and Statistical Manual or International Classification of Diseases mental disorder, where a biological marker was measured and evaluated in association with treatment response. Results: Nine studies investigating the effects of Ayahuasca and psilocybin in major depressive disorder and treatment-resistant depression were included in this review. Several potential biomarkers of response were explored through neuroimaging and blood samples, with significant associations found for serum brain-derived neurotrophic factor, serum C-reactive protein, cerebral activation of the amygdala, and functional connectivity between regions such as the ventromedial prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex. Conclusion: Results of small studies suggest associations between several putative biomarkers and treatment response to psychedelic therapies. Future trials of psychedelic therapies should integrate biomarker assessment in longitudinal designs to advance the understanding of their mechanism of action in mental disorders. Trial registration: This study protocol was registered to PROSPERO under the number CRD42021291171.