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Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Alessandro Colasanti, Robin J. Tyacke, Robert Leech, Andrea L. Malizia, Kevin Murphy, Peter Hobden, John Evans, Amanda Feilding, Richard G. Wise, Robin Carhart-Harris, David Erritzøe, Tom A. Williams, James Stone, Laurence Reed, David Nutt

Proceedings of the National Academy of Sciences January 23, 2012 DOI: 10.1073/pnas.1119598109 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Within-subjects, placebo-controlled, task-free fMRI study Peer reviewed
Sample size 30
Population Healthy volunteers
Intervention Psilocybin
Topics Default mode network Psilocybin
Keywords Consciousness Prefrontal cortex Hallucinogen Cerebral blood flow Posterior cingulate Resting State FMRI Anesthesia
Citations 1,191
Key points Psilocybin decreases cerebral blood flow and BOLD signal in hub regions like the thalamus, ACC, and PCC, and reduces mPFC-PCC connectivity, with the magnitude of ACC/mPFC decrease predicting subjective effect intensity.

Abstract

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • State of the evidence: Psilocybin Supports

    Psilocybin decreased cerebral blood flow and BOLD signal in hub regions such as the thalamus, ACC, and PCC, and reduced mPFC-PCC connectivity, with the magnitude of ACC/mPFC decrease predicting subjective effect intensity.

    Synthesized

Comparable studies

Other randomized controlled trials on psilocybin, most cited first.

Study Year Design Participants
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety 2016 Randomized controlled trial n = 51
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression 2016 Double-blind, placebo-controlled, crossover trial n = 29
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... 2006 Double-blind study n = 36
Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression 2021 Randomized controlled trial
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... 2020 Randomized controlled trial n = 24

Citations in the library

Cited by 833

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Cites 16

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Default mode network Psilocybin Addiction Philosophy of mind