Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity
Katrin H. Preller, Patricia Duerler, Joshua B. Burt, Jie Lisa Ji, Brendan Adkinson, Philipp Stämpfli, Erich Seifritz, Grega Repovš, John H. Krystal, John D. Murray, Alan Anticevic, Franz X. Vollenweider
Biological Psychiatry January 13, 2020 DOI: 10.1016/j.biopsych.2019.12.027 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, counterbalanced, crossover study Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Healthy human participants |
| Intervention | Psilocybin |
| Dose | 0.2 mg/kg |
| Topics | Psilocybin Serotonin |
| Keywords | Hallucinogen Sensory system Functional connectivity Pharmacology |
| Citations | 199 |
| Key points | Psilocybin reduced associative but increased sensory brain-wide connectivity over time, with changes correlating with serotonin 2A and 1A receptor gene expression patterns. |
Abstract
BackgroundThe use of psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.MethodsWe conducted a double-blind, randomized, counterbalanced, crossover study comprising 23 healthy human participants who received placebo and 0.2 mg/kg of psilocybin orally on 2 different test days. Participants underwent magnetic resonance imaging at 3 time points between administration and peak effects: 20 minutes, 40 minutes, and 70 minutes after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared with cortical gene expression maps.ResultsPsilocybin reduced associative, but concurrently increased sensory, brain-wide connectivity. This pattern emerged over time from administration to peak effects. Furthermore, we showed that baseline connectivity is associated with the extent of psilocybin-induced changes in functional connectivity. Lastly, psilocybin-induced changes correlated in a time-dependent manner with spatial gene expression patterns of the 5-HT2A (5-hydroxytryptamine 2A) and 5-HT1A (5-hydroxytryptamine 1A) receptors.ConclusionsThese results suggest that the integration of functional connectivity in sensory regions and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.
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 156
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine Journal of Neuroscience November 30, 2020
- Psilocybin desynchronizes the human brain. Nature August 1, 2024
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Human brain effects of DMT assessed via EEG-fMRI. Proceedings of the National Academy of Sciences March 28, 2023
and 151 more in the library
Cites 30
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
and 25 more in the library