Dynamic Functional Hyperconnectivity After Psilocybin Intake Is Primarily Associated With Oceanic Boundlessness.
Sepehr Mortaheb, Larry D. Fort, Natasha L. Mason, Pablo Mallaroni, Johannes G. Ramaekers, Athena Demertzi
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging July 1, 2024 DOI: 10.1016/j.bpsc.2024.04.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 49 |
| Population | Healthy participants |
| Intervention | Psilocybin |
| Duration | 6-minute scan at 102 minutes posttreatment, questionnaire at 360 minutes posttreatment |
| Topics | Ego dissolution Psilocybin |
| Keywords | Psychedelics psilocybin Hallucinogens Neuroscience brain connectivity Consciousness altered states 5d-asc Global signal FMRI Scanning Brain imaging Mystical experiences Neural dynamics |
| Citations | 15 |
| Key findings | Psilocybin induces a hyperconnected brain pattern linked to oceanic boundlessness and visionary restructuralization. |
Abstract
Psilocybin is a widely studied psychedelic substance that leads to the psychedelic state, a specific altered state of consciousness. To date, the relationship between the psychedelic state's neurobiological and experiential patterns remains undercharacterized because they are often analyzed separately. We investigated the relationship between neurobiological and experiential patterns after psilocybin by focusing on the link between dynamic cerebral connectivity and retrospective questionnaire assessment. Healthy participants were randomized to receive either psilocybin (n = 22) or placebo (n = 27) and scanned for 6 minutes in an eyes-open resting state during the peak subjective drug effect (102 minutes posttreatment) in ultrahigh field 7T magnetic resonance imaging. The 5-Dimensional Altered States of Consciousness Rating Scale was administered 360 minutes after drug intake. Under psilocybin, there were alterations across all dimensions of the 5-Dimensional Altered States of Consciousness Rating Scale and widespread increases in averaged brain functional connectivity. Time-varying functional connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low blood oxygen level-dependent signal amplitude, suggesting heightened cortical arousal. In terms of neuroexperiential links, canonical correlation analysis showed higher transition probabilities to the hyperconnected pattern with feelings of oceanic boundlessness and secondly with visionary restructuralization. Psilocybin generates profound alterations at both the brain and the experiential levels. We suggest that the brain's tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. These findings illuminate the intricate interplay between brain dynamics and subjective experience under psilocybin, thereby providing insights into the neurophysiology and neuroexperiential qualities of the psychedelic state.
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 16
- Psilocybin in alcohol use disorder and comorbid depressive symptoms: Results from a feasibility randomized clinical trial Addiction July 24, 2025
- Dynamical structure-function correlations provide robust and generalizable signatures of consciousness in humans Communications Biology September 30, 2024
- Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience. Communications Biology April 18, 2025
- Artificial intelligence and psychedelic medicine Annals of the New York Academy of Sciences September 23, 2024
- The emotional architecture of the psychedelic brain Trends in Cognitive Sciences August 18, 2025
and 11 more in the library
Cites 54
- 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 can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
and 49 more in the library