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

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.

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

“…Previous studies in HCs showed that psilocybin (2 mg) IV destabilized a frontoparietal subsystem (293), whereas IV LSD (75 µg) and IV psilocybin increased the fractal dimension of bold blood oxygen level dependent (BOLD) time-series from regions assigned to the dorsal-attention network (294). Furthermore, a recent rsFC fMRI study in 10 healthy volunteers showed that the executive control network was decreased at 1-week, which was associated with increased mindfulness at 3 months, but there were no other significant changes in other networks (295).…”

Rediscovering Psilocybin as an Antidepressive Treatment Strategy

“…Whereas most of these studies investigated acute effects of psilocybin on functional network connectivity, one study on 10 healthy volunteers evaluated the effects of a single psilocybin administration on functional connectivity of the executive control network (ECN) one week and three months after intake. The significant decrease in ECN functional connectivity after one week of administration of psilocybin was not evident after three months [62].…”

Psilocybin modulation of dynamic functional connectivity is associated with plasma psilocin and subjective effects

“…The current study examined only acute psilocybin effects on dynamic functional connectivity, while previous studies indicate that psilocybin induces lasting changes in clinical symptoms, mood, and core personality traits. To date, three studies have examined long-term psilocybin effects on functional brain imaging, both primarily examining static connectivity measures (Barrett et al, 2020;Doss et al, 2021;McCulloch et al, 2021b). Two of these studies analyzed dynamic conditional correlation (Engle, 2002) as a variance measure of edge-specific correlation coefficients (Barrett et al, 2020;Doss et al, 2021).…”