A systematic review of neuroimaging studies on psychedelics for major depressive disorder found that psilocybin, ayahuasca, and LSD alter brain activity and connectivity in ways linked to antidepressant response. Key changes include amygdala activity and functional connectivity alterations, shifts in medial and ventromedial prefrontal cortex connectivity, and decreased global brain network modularity. One ayahuasca study reported increased limbic activity. The evidence, based on only four datasets, suggests the default mode and limbic networks may be important targets for future research, but more data are needed to confirm these preliminary findings.
In a retrospective chart review of 209 adults with treatment-resistant depression treated with intravenous ketamine, depressive and anxiety symptoms improved significantly over four or six infusions, but the improvements were modest and highly variable across individuals. Anxiety symptoms improved more slowly and less robustly than depressive symptoms. End-of-treatment response and remission rates were numerically higher after six infusions than after four, but the difference was not statistically significant. Four distinct patterns of symptom change emerged for both depression and anxiety, highlighting the heterogeneity of treatment response. Durability after six infusions could not be assessed because follow-up data were available only for the four-infusion group.