Abstract
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.
Highlights
Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood
Excessive movement or other artefact meant that three patients were removed from the Arterial spin labelling (ASL) analyses and four from the resting-state functional connectivity (RSFC) (SI Appendix), leaving sample sizes of 16 and 15 for the ASL and blood oxygen-level dependent (BOLD) analyses, respectively
The present study goes some way to addressing an important knowledge gap concerning the post-acute brain effects of serotonergic psychedelics
Summary
Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. 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. Findings from healthy volunteer studies[10] and trials with other psychedelics[11,12,13] supplement those from clinical studies showing that these drugs can have a rapid and lasting positive impact on mental health, often after just one or two doses Such outcomes raise a number of important questions, including: what brain mechanisms mediate these effects?. The present study focused on changes in brain function before versus after psilocybin in patients with treatment-resistant depression who received two doses of the drug (10 mg followed by 25 mg, one-week apart) as part of an open-label clinical trial. We predicted that resting-state CBF and FC would be altered post treatment and correlate with immediate and longer-term clinical improvements
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