A Virtual Clinical Trial of Psychedelics to Treat Patients With Disorders of Consciousness
Paolo Cardone, Charlotte Martial, Yonatan Sanz Perl, Iván Mindlin, Leor Roseman, David Nutt, Pablo Mallaroni, Vincent Bonhomme, Steven Laureys, Gustavo Deco, Olivia Gosseries, Pablo Núñez, Jitka Annen, Naji Alnagger, Jacobo Sitt, Robin Carhart‐Harris, Natasha L. Mason, Johannes G. Ramaekers
Advanced Science November 20, 2025 DOI: 10.1002/advs.202511780 via OpenAlex
Summary
AI-generated from the abstractSimulated administration of LSD and psilocybin in computational models of patients with disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), shifted brain activity closer to criticality—the phase transition between order and chaos. The effect was greater in MCS patients. In UWS patients, the treatment response correlated with structural connectivity, while in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for using psychedelics in DoC treatment and highlight the potential role of computational modeling in drug discovery and personalized medicine.
Study at a glance
| Characteristics | Computational modeling study Peer reviewed |
|---|---|
| Population | Patients with disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) |
| Interventions | LSD psilocybin |
| Topics | Psilocybin |
| Keywords | Persistent vegetative state Wakefulness Minimally conscious state Clinical trial |
| Citations | 2 |
| Key finding | Simulated LSD and psilocybin shifted brain activity of patients with DoC closer to criticality, with greater effect in MCS patients and treatment response correlating with structural or functional connectivity depending on diagnosis. |
Abstract
Abstract 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.