Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals

A single dose of psilocybin in 10 healthy volunteers who had never used psychedelics produced a significant decrease in resting-state functional connectivity within the executive control network (ECN) one week later, an effect that was no longer present at three months. No other changes in brain connectivity were observed at either time point. Exploratory analyses suggested that the decreased ECN connectivity at one week predicted increased mindfulness at three months. The findings point to modulation of the ECN during the psychedelic 'afterglow' period as a possible neural pathway for lasting positive effects on well-being, though the neural basis of personality changes seen at three months remains unknown.

Study at a glance

Abstract

Background: Psilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans. Aim: Evaluate changes in resting-state functional connectivity (RSFC) at 1 week and 3 months after one psilocybin dose in 10 healthy psychedelic-naïve volunteers and explore associations between change in RSFC and related measures. Methods: Participants received 0.2–0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state functional magnetic resonance imaging (fMRI) scans at baseline, 1-week and 3-month post-administration and [11C]Cimbi-36 PET scans at baseline and 1 week. We examined changes in within-network, between-network and region-to-region RSFC. We explored associations between changes in RSFC and psilocybin-induced phenomenology as well as changes in psychological measures and neocortex serotonin 2A receptor binding. Results: Psilocybin was well tolerated and produced positive changes in well-being. At 1 week only, executive control network (ECN) RSFC was significantly decreased (Cohen’s d = −1.73, pFWE = 0.010). We observed no other significant changes in RSFC at 1 week or 3 months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at 1 week predicted increased mindfulness at 3 months ( r = −0.65). Conclusions: These findings in a small cohort indicate that psilocybin affects ECN function within the psychedelic ‘afterglow’ period. Our findings implicate ECN modulation as mediating psilocybin-induced, long-lasting increases in mindfulness. Although our findings implicate a neural pathway mediating lasting psilocybin effects, it is notable that changes in neuroimaging measures at 3 months, when personality changes are observed, remain to be identified.