Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals. (January 2022)

• Record Type: Journal Article
• Authors: McCulloch, Drummond E-Wen; Madsen, Martin Korsbak; Stenbæk, Dea Siggaard; Kristiansen, Sara; Ozenne, Brice; Jensen, Peter Steen; Knudsen, Gitte Moos; Fisher, Patrick MacDonald
• Is Part Of: Journal of psychopharmacology. Volume 36:Number 1(2022)
• Page Start: 74
• Page End: 84
• Publication Date: 2022-01
• Subjects: Functional magnetic resonance imaging -- resting-state connectivity -- psilocybin -- psychedelic -- executive control network; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/02698811211026454
• Languages: English
• ISSNs: 0269-8811

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.