Unmixing the Psychedelic Connectome: Brain Network Traits of Psilocybin
Krishna Prasad Bhavaraju, Natasha L. Mason, Pablo Mallaroni, Dietmar Heinke, Stefan W. Toennes, Johannes G. Ramaekers, Enrico Amico
November 17, 2025 preprint DOI: 10.1101/2025.11.17.688834 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study |
|---|---|
| Population | Healthy volunteers |
| Intervention | Psilocybin |
| Topics | Neuroplasticity Psilocybin |
| Keywords | Trait Cognition Neuroimaging Functional connectivity Nerve net Human connectome project Cognitive psychology Brain mapping Biological neural network Artificial neural network Independent component analysis Perspective graphical Neural activity Neurocognitive |
| Key findings | The acute psilocybin state is a composite of co-occurring neural processes, with one functional connectivity trait linked to plasma psilocin concentration and another independently associated with impaired visual divergent thinking performance. |
Abstract
Abstract Psilocybin induces profound alterations in consciousness, yet prevailing neural models often describe a monolithic change in brain connectivity that may not fully capture the multifaceted nature of the psychedelic state. To test the hypothesis of a composite neural state, this study applied a robust, data-driven framework, Connectome Independent Component Analysis (connICA) with multi-level resampling, to resting-state fMRI data from healthy volunteers. The analysis decomposed connectomes into statistically independent functional connectivity traits ("FC-Traits"), revealing a primary trait whose expression was significantly modulated by plasma psilocin concentration, providing a whole-cortical signature of the drug’s physiological action. Crucially, a second, distinct trait was also isolated, which independently associated with impaired performance on a visual divergent thinking task. These findings demonstrate that the acute psilocybin state is a composite of co-occurring neural processes. This validates the application of a decompositional connectomic framework to move beyond global descriptions and successfully disentangle the specific neural patterns underlying distinct pharmacological and cognitive correlates.
Comparable studies
Other observational and cohort studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Patients with treatment-resistant depression | 2017 | Observational cohort | n = 19 |
| Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Healthy volunteers | 2019 | Observational cohort | n = 8 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Prediction of Psilocybin Response in Healthy Volunteers Healthy volunteers | 2012 | Observational cohort | n = 409 |