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

This fascinating computational modelling study simulated the effects of LSD and psilocybin on whole-brain models of patients with disorders of consciousness, finding that both psychedelics shifted brain activity closer to criticality with greater effects in minimally conscious state patients, whilst treatment response correlated with structural connectivity in unresponsive wakefulness syndrome and baseline functional connectivity in minimally conscious state.

“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.“

These results provide a computational proof-of-concept that psychedelics can theoretically modulate brain dynamics relevant to consciousness in DoC, and that personalised modelling could help identify candidate patients and mechanisms for future empirical clinical trials.

Alnagger, N. L., Cardone, P., Martial, C., Perl, Y. S., Mindlin, I., Sitt, J. D., ... & Annen, J. (2024). A virtual clinical trial of psychedelics to treat patients with disorders of consciousness. Advanced Science, e11780. Link to paper

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