This within-subjects fMRI study (n=19) investigated changes in brain function before versus after psilocybin (with psychological support) in patients with treatment-resistant depression. After treatment, all patients showed decreased depressive symptoms and changes in brain functioning.
“Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.”
Authors: Robin L. Carhart-Harris, Leor Roseman, Mark Bolstridge, Lysia Demetriou, J. Nienke Pannekoek, Matthew B. Wall, Mark Tanner, Mendel Kaelen, John McGonigle, Kevin Murphy, Robert Leech, H. Valerie Curran & David J. Nutt
This paper is included in our ‘Top 10 Articles on Psychedelics in the Treatment of Depression‘