Psychedelics and schizophrenia: Distinct alterations to Bayesian inference

This analysis of neuroimaging (M/EEG) compares data from patients with schizophrenia (n=29) and healthy volunteers under the influence of LSD (75μg, n=17) or ketamine (n=19). It finds that although both show increased neural signal diversity, only for those with schizophrenia did it increase the precision (weighting) of sensory information. Both groups increase ‘bottom-up’ signalling, but of a different kind.


“Schizophrenia and states induced by certain psychotomimetic drugs may share some physiological and phenomenological properties, but they differ in fundamental ways: one is a crippling chronic mental disease, while the others are temporary, pharmacologically-induced states presently being explored as treatments for mental illnesses. Building towards a deeper understanding of these different alterations of normal consciousness, here we compare the changes in neural dynamics induced by LSD and ketamine (in healthy volunteers) against those associated with schizophrenia, as observed in resting-state M/EEG recordings. While both conditions exhibit increased neural signal diversity, our findings reveal that this is accompanied by an increased transfer entropy from the front to the back of the brain in schizophrenia, versus an overall reduction under the two drugs. Furthermore, we show that these effects can be reproduced via different alterations of standard Bayesian inference applied on a computational model based on the predictive processing framework. In particular, the effects observed under the drugs are modelled as a reduction of the precision of the priors, while the effects of schizophrenia correspond to an increased precision of sensory information. These findings shed new light on the similarities and differences between schizophrenia and two psychotomimetic drug states, and have potential implications for the study of consciousness and future mental health treatments.”

Authors: Hardik Rajpal, Pedro A. M. Mediano, Fernando E. Rosas, Christopher B. Timmermann, Stefan Brugger, Suresh Muthukumaraswamy, Anil K. Seth, Daniel Bor, Robin L. Carhart-Harris & Henrik J. Jensen

Study details

Compounds studied
LSD Ketamine

Topics studied

Study characteristics
Re-analysis Bio/Neuro

67 Humans


Authors associated with this publication with profiles on Blossom

Fernando Rosas
Dr. Fernando E. Rosas is a Postdoctoral Researcher at Imperial College London, based at the Centre For Psychedelic Research.

Chris Timmermann
Chris Timmerman is a postdoc at Imperial College London. His research is mostly focussed on DMT.

Suresh Muthukumaraswamy
Suresh Muthukumaraswamy (Ph.D.) is a Principal Investigator in the Centre for Brain Research and the Auckland Neuropsychopharmacology Research Group. His main research interests are in understanding how therapies alter brain activity and in developing methodologies to measure these changes in both healthy individuals and patient groups. His previous studies investigated a range of compounds including hallucinogens (ketamine, LSD, psilocybin), anesthetics, anti-epileptics, and GABA-enhancers using a wide range of neuroimaging techniques. His current work investigates ketamine and midazolam using simultaneous EEG/fMRI recordings, and the effects of ketamine, scopolamine, and rTMS in depression.

Anil Seth
Anil Seth (Ph.D.) is Professor of Cognitive and Computational Neuroscience at the University of Sussex, where he co-directs the Sackler Centre for Consciousness Science. He is also a Senior Fellow of the Canadian Institute for Advanced Research and a Wellcome Trust Engagement Fellow. His work on psilocybin, LSD, and ketamine has revealed that psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.

Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.

Compound Details

The psychedelics given at which dose and how many times

LSD 75 - 75
μg | 1x Ketamine 17.5 - 17.5
mg | 1x

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