Review of blood and brain markers linked to response to psilocybin and ayahuasca therapy

The question

Can measurable biological signals in the blood or brain help explain, or predict, who responds to psychedelic therapy for a diagnosed mental disorder?

What they did

The authors searched four research databases (MedLine, PsycInfo, EMBASE and Web of Science) on 10 January 2024 for prospective clinical trials of psychedelics in people with a diagnosed mental disorder. To be included, a study had to report both a clinical outcome and a related biological marker. Nine studies met the criteria, all involving ayahuasca or psilocybin in people with major depressive disorder or treatment-resistant depression. The review protocol was registered in advance (PROSPERO CRD42021291171).

What they found

The nine studies looked at markers from brain imaging and blood samples. Significant associations with treatment response were reported for two blood markers — brain-derived neurotrophic factor (a protein involved in the growth and maintenance of nerve cells) and C-reactive protein (a marker of inflammation). Brain imaging findings included activity in the amygdala, a region involved in processing emotion, and the strength of communication between the ventromedial prefrontal cortex, anterior cingulate cortex and posterior cingulate cortex. The authors stressed that all of these came from small studies.

The fine print

Only nine studies were found and all were small, so the associations may not hold up in larger samples. All involved depression, so the findings may not apply to other conditions, and only ayahuasca and psilocybin were covered. An association between a marker and improvement does not show the marker causes or reliably predicts that improvement, and the abstract gives no pooled numbers or effect sizes. This summary is based on the abstract only.

What it means

Early research hints that certain blood proteins and patterns of brain activity may track with how people respond to psilocybin or ayahuasca therapy for depression, but the evidence base is small and preliminary.

Evidence grade: Low. A systematic review that found only nine small trials and did not pool their results statistically, so the underlying evidence is limited and exploratory.

This summary is based on the study’s published abstract.