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Record W4416398262 · doi:10.1002/advs.202511780

A Virtual Clinical Trial of Psychedelics to Treat Patients With Disorders of Consciousness

2025· article· en· W4416398262 on OpenAlexaff
Naji Alnagger, Paolo Cardone, Charlotte Martial, Yonatan Sanz Perl, Iván Mindlin, Jacobo Sitt, Leor Roseman, Robin Carhart‐Harris, David Nutt, Pablo Mallaroni, Natasha L. Mason, Johannes G. Ramaekers, Vincent Bonhomme, Steven Laureys, Gustavo Deco, Olivia Gosseries, Pablo Nùñez, Jitka Annen

Bibliographic record

VenueAdvanced Science · 2025
Typearticle
Languageen
FieldPsychology
TopicPsychedelics and Drug Studies
Canadian institutionsUniversité Laval
FundersFonds Léon FredericqKoning BoudewijnstichtingFundação BialFonds Wetenschappelijk OnderzoekFonds De La Recherche Scientifique - FNRSMind Science Foundation
KeywordsPsilocybinPersistent vegetative stateWakefulnessConsciousnessFunctional magnetic resonance imagingMinimally conscious stateClinical trialUnconsciousnessConsciousness Disorders

Abstract

fetched live from OpenAlex

Disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have limited treatment options and are characterized by low complexity of brain activity. Recent research suggests that psychedelic drugs, which enhance the complexity of brain activity, could offer promising therapies. Here, individualized whole-brain computational models are developed for patients with DoC, optimized with empirical functional magnetic resonance imaging data and diffusion-weighted imaging data, upon which the administration of lysergic acid diethylamide (LSD) and psilocybin is simulated. An in silico perturbation protocol is applied to assess brain dynamics, first distinguishing between different states of consciousness, including DoC, anesthesia, and the psychedelic state. Then, brain dynamics are assessed before and after a simulation of psychedelic drugs on patients with DoC. Findings indicated that the simulation of LSD and psilocybin shifted the brain activity of patients with DoC closer to criticality (the point at a phase transition between order and chaos), with a greater effect in patients in the MCS. In patients with UWS, the treatment response correlated with structural connectivity, while in patients in the MCS, it aligned with baseline functional connectivity. These results offer a computational foundation for using psychedelics in DoC treatment and highlight the potential future role of computational modeling in drug discovery and personalized medicine.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.647
Threshold uncertainty score0.429

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.027
GPT teacher head0.417
Teacher spread0.390 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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