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Biological markers of treatment response to serotonergic psychedelic therapies: a systematic review

Summary

This review examines how scientists can predict which patients will benefit most from psychedelic-assisted therapy for depression by measuring biological markers in the brain and blood. Researchers found that certain brain changes and protein levels—particularly involving the amygdala, specific brain regions, and inflammation markers—appear linked to treatment success. While the current studies are small, they suggest that measuring these biological markers could eventually help doctors personalize psychedelic treatments for depression.

Background

Serotonergic psychedelic therapies including psilocybin and ayahuasca show promise for treating mental disorders such as major depressive disorder and treatment-resistant depression. However, the biological mechanisms underlying therapeutic response to these treatments remain incompletely understood. This systematic review examines biomarkers that may predict clinical response to psychedelic therapies.

Objective

To synthesize evidence from studies investigating biomarkers of clinical response to psychedelic therapies in psychiatric populations. The review aimed to identify associations between biological markers (neuroimaging and peripheral biomarkers) and treatment response to serotonergic psychedelics.

Results

Nine studies examining psilocybin and ayahuasca in major depressive disorder were included. Significant associations were found between treatment response and serum brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), amygdala activation, and functional connectivity changes in brain regions including ventromedial prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex.

Conclusion

Small studies suggest associations between several putative biomarkers and treatment response to psychedelic therapies. Future trials should integrate biomarker assessment in longitudinal designs to advance understanding of mechanisms of action. Current evidence is limited by small sample sizes, lack of replication, and narrow biomarker modalities evaluated in single clinical populations.
  • Published in:Therapeutic Advances in Psychopharmacology,
  • Study Type:Systematic Review,
  • Source: PMID: 41122434, DOI: 10.1177/20451253251384513
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