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

This fMRI study (n=10) found that a single dose of psilocybin (14-21mg/70kg) decreased the executive control network (ECN) one week later, but didn’t elicit other lasting (neuronal) effects at that time and at 3-months follow-up. The changes correlated with an increase in mindfulness at the 3-month mark. But other changes (in resting-state functional connectivity, RSFC) have yet to be found.


“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 of psilocybin in a controlled setting. Participants completed resting-state fMRI scans at baseline, one week and three months post-administration and [11C]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, the 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 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.

Authors: Drummond E-W. McCulloch, Martin K. Madsen, Dea S. Stenbæk, Sara Kristiansen, Brice Ozenne, Peter S. Jensen, Gitte M. Knudsen & Patrick M. Fisher

Become a psychedelic insider!

With a free Blossom membership you will always be in the know.

📰 Weekly newsletter about the psychedelic research

✔️ Unlimited access to our database and original articles

🖊️ Add (private) notes and comments to each page

Make an account

Study details

Compounds studied

Topics studied

Study characteristics



Institutes associated with this publication

University of Copenhagen
The Neurobiology Research Unit (NRU) at Copenhagen University Hospital have been carrying clinical and preclinical research with psychedelics since 2017.

Inline Feedbacks
View all comments