Navigating the chaos of psychedelic fMRI brain-entropy via multi-metric evaluations of acute psilocybin effects
Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne, Dea Siggaard Stenbæk, Sophia Armand, M. Madsen, Gitte M. Knudsen, Patrick M. Fisher
medRxiv July 3, 2023 preprint DOI: 10.1101/2023.07.03.23292164 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort |
|---|---|
| Sample size | 28 |
| Population | Healthy adults |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Sample entropy Artificial intelligence Cognitive psychology Pattern recognition psychology Hallucinogen |
| Citations | 20 |
| Key findings | Psilocybin had significant positive associations with some entropy metrics (Shannon entropy of path-length and instantaneous correlation distributions) but not with most metrics, indicating a nuanced effect on brain entropy. |
Abstract
A prominent theory of psychedelics is that they increase brain entropy. Twelve studies have evaluated psychedelic effects on fMRI brain entropy quantifications, no findings have been replicated. Here we evaluated these metrics in an independent 28-participant healthy cohort with 121 pre- and post-psilocybin fMRI scans. We assessed relations between brain entropy and plasma psilocin, brain serotonin 2A receptor occupancy, and a subjective drug intensity rating using linear mixed-effects models. We observed significant positive associations for Shannon entropy of path-length, instantaneous correlation distributions, and divergent associations of sample entropy at varying time-scales. We did not observe significant effects for 8 of 13 entropy metrics. Brain entropy quantifications showed limited inter-measure correlations. Our observations support a nuanced acute psychedelic effect on brain entropy, underscoring the need for replication and that these metrics do not reflect a singular construct. Our findings highlight candidate brain entropy metrics that may mediate clinical effects of psychedelics.
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 |
Citations in the library
Cited by 14
- Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation. Scientific Reports March 26, 2024
- The serotonergic psychedelic N,N-dipropyltryptamine alters information-processing dynamics in in vitro cortical neural circuits. Network Neuroscience December 10, 2024
- Acute psilocybin and ketanserin effects on cerebral blood flow: 5-HT2AR neuromodulation in healthy humans. Journal of Cerebral Blood Flow & Metabolism February 26, 2025
- What fMRI studies say about the nature of the psychedelic effect: a scoping review Frontiers in Neuroscience July 1, 2025
- Neuroimaging and the Investigation of Drug-Drug Interactions Involving Psychedelics. Neuroscience Insights October 8, 2024
and 9 more in the library
Cites 32
- 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
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology December 1, 2011
and 27 more in the library