Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals
In a small sample of 10 healthy volunteers, a single 0.2–0.3 mg/kg dose of psilocybin produced a significant decrease in executive control network resting-state functional connectivity at one week but not at three months. This transient ECN reduction predicted increased mindfulness at three months, suggesting short‑term ECN modulation during the psychedelic “afterglow” may mediate lasting psychological benefits.
Authors
- Gitte Knudsen
- Patrick Fisher
- Dea Stenbæk
Published
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.
Aims
Evaluate changes in resting-state functional connectivity (RSFC) at one-week and three-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 fMRI scans at baseline, one-week and three-months post-administration and [ 11 C]Cimbi-36 PET scans at baseline and one-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 one-week only, executive control network (ECN) RSFC was significantly decreased (Cohen’s d=-1.73, p FWE =0.010). We observed no other significant changes in RSFC at one-week or three-months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at one-week predicted increased mindfulness at three-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 three-months, when personality changes are observed, remain to be identified.
Research Summary of 'Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals'
Introduction
Psilocybin is a serotonergic psychedelic whose acute effects include profound alterations in consciousness lasting about six hours and characterised by sensory and affective changes. Previous clinical and healthy-volunteer studies have reported persistent improvements in mood, well-being and personality traits (for example, increased openness and mindfulness) after one or a few moderate-to-high doses. Although acute effects on resting-state functional connectivity (RSFC) have been documented — including transient disruption of the default mode network (DMN) and increased between-network coupling during the drug experience — there is limited and mixed evidence regarding persistent changes in brain connectivity after the acute effects subside. Few studies have imaged the brain beyond the immediate post-session period, and none, according to the authors, have robustly linked longer-term RSFC changes to concomitant psychological changes or PET measures of 5-HT2A receptor binding. Drummond and colleagues therefore set out to evaluate lasting changes in RSFC following a single psilocybin dose in a small cohort of healthy, psychedelic-naïve volunteers. The study measured within-network and between-network RSFC at baseline, one-week and three-months post-administration, attempted to replicate a prior region-to-region analysis, and explored whether RSFC changes related to acute phenomenology, persisting psychological measures (for example, personality and mindfulness), and neocortex 5-HT2A receptor binding assessed with [11C]Cimbi-36 PET. The aim was to identify candidate brain-system changes that might mediate lasting behavioural effects of psilocybin.
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Study Details
- Study Typeindividual
- Journal
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- APA Citation
McCulloch, D. E., Madsen, M. K., Stenbæk, D. S., Kristiansen, S., Ozenne, B., Jensen, P. S., Knudsen, G. M., & Fisher, P. M. (2021). Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals. https://doi.org/10.1101/2021.01.28.428377
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