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.