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

criticality; diffusion‐weighted imaging (DWI); disorders of consciousness; functional magnetic resonance imaging (fMRI); psychedelics; whole‐brain modeling

Abstract :

[en] 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.

Disciplines :

Neurosciences & behavior

Author, co-author :

Alnagger, Naji ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Coma Science Group

Cardone, Paolo ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Coma Science Group

Martial, Charlotte ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Coma Science Group

Perl, Yonatan Sanz ; Institut du Cerveau - Paris Brain Institute - ICM, Inserm CNRS, Sorbonne Université, Paris, 75013, France ; Department of Information and Communication Technologies, Centre for Brain and Cognition, Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, 08005, Spain

Mindlin, Iván ; Institut du Cerveau - Paris Brain Institute - ICM, Inserm CNRS, Sorbonne Université, Paris, 75013, France

Sitt, Jacobo D ; Institut du Cerveau - Paris Brain Institute - ICM, Inserm CNRS, Sorbonne Université, Paris, 75013, France

Roseman, Leor ; Department of Psychology, University of Exeter, Exeter, EX4 4QG, UK ; Centre for Psychedelic Research, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, W12 0HS, UK

Carhart-Harris, Robin ; Centre for Psychedelic Research, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, W12 0HS, UK ; Psychedelics Division, Neuroscape, University of California, San Francisco, San Francisco, CA, CA 94158, USA

Nutt, David ; Centre for Psychedelic Research, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, W12 0HS, UK

Mallaroni, Pablo ; Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, 6229 ER, The Netherlands

More authors (8 more)

^✱ These authors have contributed equally to this work.

Language :

English

Title :

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

Publication date :

20 November 2025

Journal title :

Advanced Science

eISSN :

2198-3844

Publisher :

Wiley, Germany

Pages :

e11780

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://advanced.onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202511780

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique

Available on ORBi :

since 22 December 2025

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