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
Therapeutic Advances in Psychopharmacology October 16, 2025 DOI: 10.1177/20451253251384513 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Longitudinal Peer reviewed |
|---|---|
| Population | Participants diagnosed with major depressive disorder or treatment-resistant depression |
| Interventions | Ayahuasca Psilocybin |
| Topics | Psychedelic-assisted therapy Serotonin |
| Keywords | Psychedelic treatment Mental health interventions Biological markers Biomarkers Key biological indicators Specific biological signals Genetic variations Neurochemical changes Personalized treatment Personalized medicine Individualized therapy Precision medicine Predictive analytics Treatment prediction Forecasting outcomes Prognostic markers |
| Citations | 3 |
| Key findings | 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.
Comparable studies
Other systematic reviews and meta-analyses on serotonin, most cited first.
Citations in the library
Cited by 4
- A critical review of brain entropy as a biomarker of the psychedelic state. Neuroscience & Biobehavioral Reviews July 1, 2026
- Psilocybin-induced behavioral and cellular effects. Journal of neurogenetics July 12, 2026
- Multimodal autonomic arousal tracks dose-dependent affective dynamics during the acute effects of DMT bioRxiv May 4, 2026
- Methodological fragmentation and integration priorities in psychedelic-assisted therapy assessment: a scoping review Frontiers in Psychiatry August 6, 2026
Cites 22
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
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- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology April 26, 2017
and 17 more in the library