A Virtual Clinical Trial of Psychedelics to Treat Patients With Disorders of Consciousness
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.
Authors
- Jacobo Diego Sitt (ORCID: https://orcid.org/0000-0002-3878-4846)
- David Nutt (ORCID: https://orcid.org/0000-0002-1286-1401)
- Leor Roseman (ORCID: https://orcid.org/0000-0001-9990-6029)
- Olivia Gosseries (ORCID: https://orcid.org/0000-0001-9011-7496)
- Steven Laureys (ORCID: https://orcid.org/0000-0002-3096-3807)
- Charlotte Martial (ORCID: https://orcid.org/0000-0001-6291-3460)
- Johannes G. Ramaekers (ORCID: https://orcid.org/0000-0003-4553-376X)
- Iván Mindlin (ORCID: https://orcid.org/0000-0001-6041-6081)
- Natasha L. Mason (ORCID: https://orcid.org/0000-0001-7115-0389)
- Vincent Bonhomme (ORCID: https://orcid.org/0000-0001-6356-547X)
- Gustavo Deco (ORCID: https://orcid.org/0000-0002-8995-7583)
- Pablo Núñez (ORCID: https://orcid.org/0000-0002-5898-6664)
- Pablo Mallaroni (ORCID: https://orcid.org/0000-0002-0959-2837)
- Paolo Cardone (ORCID: https://orcid.org/0000-0002-8537-2123)
- Naji Alnagger (ORCID: https://orcid.org/0000-0002-7880-6237)
- Robin Carhart‐Harris (ORCID: https://orcid.org/0000-0002-6062-7150)
- Jitka Annen (ORCID: https://orcid.org/0000-0002-7459-4345)
- Yonatan Sanz Perl (ORCID: https://orcid.org/0000-0002-1270-5564)
Institutions
- Universidad de Valladolid (ES)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Liège (BE)
- Universitat Pompeu Fabra (ES)
- University of California, San Francisco (US)
- University of Exeter (GB)
- Ghent University Hospital (BE)
- Ghent University (BE)
- Maastricht University (NL)
- Sorbonne Université (FR)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Institut du Cerveau (FR)
- Université Laval (CA)
- Imperial College London (GB)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-11-20
- DOI
- https://doi.org/10.1002/advs.202511780
- Citations
- 1
- Primary Topic
- Psychedelics and Drug Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.31
Funders
- Mind Science Foundation
- Fonds De La Recherche Scientifique - FNRS
- Fonds Wetenschappelijk Onderzoek
- Fundação Bial
- Koning Boudewijnstichting
- Fonds Léon Fredericq