Posttreatment Brain Effects of Psilocybin in Patients With Treatment-Resistant Depression

woman laying down on bed
woman laying down on bed
Researchers documented changes in brain blood flow and connectivity following the use of psilocybin in patients with treatment-resistant depression.

Changes in resting-state brain blood flow and functional connectivity following the use of psilocybin in patients with treatment-resistant depression have been documented for the first time, according to the results of a recent open-label UK study published in Scientific Reports.

Investigators collected functional magnetic resonance imaging (fMRI) data from patients with treatment-resistant depression in order to examine the post-treatment effects of the classic “psychedelic” drug psilocybin in these individuals. They measured cerebral blood flow (CBF), arterial spin labeling (ASL), and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) via the use of functional magnetic resonance imaging (fMRI) prior to and following treatment with the serotonin agonist psilocybin. All participants received 2 doses of psilocybin (10 mg followed by 25 mg 1 week later).

A total of 19 patients with treatment-resistant major depression completed pretreatment and 1-day posttreatment fMRI scans. The investigators collected quality pretreatment and posttreatment data from 16 of the 19 patients. Treatment with psilocybin was significantly associated with rapid and sustained antidepressant effects in the ASL analysis (mean depression score in week prior to pretreatment scan: 16.9±5.1; mean depression score on day of posttreatment scan: 8.8±6.2; change of

–8.1±6; P <.001). Mean QIDS SR16 score at baseline was 18.9±3 and at 5 weeks posttreatment was 10.9±4.8 (change of –8±5.1; P <.001). In patients included in the BOLD analysis, mean change was –7.3±5.3 (change from scan 1 to scan 2) and –8.2±5.2 (change from baseline to 5 weeks posttreatment), with both contrasts highly significant (P <.001).

All of the 19 patients demonstrated some decrease in depressive symptoms at 1 week, with 12 meeting the criteria for response (P <.001). Overall, 47% of participants met the criteria for response at 5 weeks (P <.001).

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Whole-brain analyses showed posttreatment responses in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF was linked to reduced symptoms of depression. RSFC predicted treatment response at 5 weeks.

The investigators concluded that the data derived from this study fill an important knowledge gap concerning the posttreatment brain effects of psilocybin and are the first data to be compiled on the use of the agent in patients with depression. Since the posttreatment brain changes observed in this study differed from previously observed acute effects of psilocybin and other “psychedelic” drugs, but were associated with clinical outcomes, a “reset” therapeutic mechanism is proposed.


Carhart-Harris RL, Roseman L, Bolstridge M, et al. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci Rep. 2017;7(1):13187.