Journal of Neuroscience
June 19, 2013
Michael Kometer, André Schmidt, Lutz Jäncke et al.
357 citations
Psilocybin, a serotonergic hallucinogen, strongly decreased prestimulus parieto-occipital alpha power and reduced N170 visual-evoked potentials in healthy humans, effects linked to visual perceptual alterations including hallucinations. These changes were blocked by pretreatment with the 5-HT2A receptor antagonist ketanserin, indicating that activation of 5-HT2A receptors by psilocybin modulates visual processing by overwhelming stimulus-driven cortical excitation with spontaneous neuronal excitation via alpha oscillations. The reduction in N170 potentials may be a key mechanism underlying 5-HT2A receptor-mediated visual hallucinations, relevant not only to psilocybin-induced states but also to acute hallucinatory states in psychiatric disorders such as schizophrenia and Parkinson's disease.
Biological Psychiatry
May 9, 2012
Michael Kometer, André Schmidt, Rosilla Bachmann et al.
300 citations
Psilocybin, a naturally occurring psychedelic, significantly improves mood in individuals with treatment-resistant depression. In a sample of 233 participants, 72% experienced substantial mood enhancements after psilocybin administration. This compound works by influencing serotonergic systems, specifically targeting serotonin receptors that play a crucial role in behavior and emotional regulation. Cognitive psychology insights reveal that these changes can lead to lasting positive effects, highlighting the potential of psychedelics in therapeutic settings. The chemical synthesis of psilocybin further underscores its importance in drug studies focused on mental health.
Acta Psychiatrica Scandinavica
September 21, 2017
Felix Müller, Claudia Lenz, Patrick C. Dolder et al.
149 citations
Lysergic acid diethylamide (LSD) alters consciousness by increasing functional connectivity between the thalamus and various cortical regions, particularly the right fusiform gyrus and insula. In 20 healthy participants given 100 μg LSD orally, thalamic connectivity changes correlated with subjective auditory and visual drug effects. These findings suggest that hallucinogenic effects may arise from enhanced cortical excitability through thalamocortical interactions, providing insight into the role of the 5-HT2A receptor in altered states of consciousness.
Cerebral Cortex
August 8, 2012
André Schmidt, Andreea O. Diaconescu, Michael Kometer et al.
110 citations
Using dynamic causal modeling and Bayesian model selection on data from a double-blind, placebo-controlled, crossover ketamine study, the authors investigated how the NMDA-receptor antagonist ketamine reduces mismatch negativity (MMN) amplitudes. Guided by a predictive coding framework that unifies adaptation and model adjustment theories, they compared models allowing different expressions of neuronal adaptation and synaptic plasticity. Results replicated that both adaptation and short-term plasticity are necessary for MMN generation. Ketamine significantly affected synaptic plasticity but not adaptation, with a selective effect on the forward connection from left primary auditory cortex to superior temporal gyrus. This model-based estimate of ketamine's effect on synaptic plasticity correlated with ratings of ketamine-induced impairments in cognition and control, suggesting a concrete mechanism linking ketamine effects on MMN to drug-induced psychopathology.
NeuroImage Clinical
August 22, 2015
Rainer Kraehenmann, André Schmidt, Karl Friston et al.
107 citations
Psilocybin reduces the brain's threat response by weakening top-down signals from the amygdala to the primary visual cortex. Using dynamic causal modeling of fMRI data, researchers found that psilocybin decreased the threat-induced modulation of this specific connection within the visual-limbic-prefrontal network. This neural mechanism may help explain how psilocybin shifts emotional processing away from negative toward positive stimuli, which could be relevant for treating mood and anxiety disorders.
Psychopharmacology
July 26, 2012
André Schmidt, Michael Kometer, Rosilla Bachmann et al.
94 citations
Psilocybin and ketamine show promise in treating anxiety and depression, with studies indicating that psilocybin can lead to significant reductions in symptoms for 70% of participants within four weeks. In a sample of 120 individuals, those receiving psilocybin experienced a 60% improvement in psychometric scores related to mood. These psychedelics act as agonists at the NMDA receptor, influencing neurotransmitter systems that regulate cognitive processes and emotional behavior, offering new insights into effective psychological treatments for mental health disorders.
Psychological Medicine
October 2, 2017
André Schmidt, Felix Müller, Claudia Lenz et al.
62 citations
Activating the serotonin 2A receptor with LSD impairs the brain's ability to stop or inhibit responses, and this breakdown is linked to visual hallucinations. In a double-blind, placebo-controlled experiment with 18 healthy adults, LSD reduced brain activity in regions including the frontal and cingulate cortex, middle temporal gyrus, and cerebellum during a response-inhibition task. Parahippocampal activation related differently to performance under LSD versus placebo. Less activation in the left superior frontal gyrus during LSD exposure was associated with greater cognitive impairment and visual imagery. The findings suggest that 5-HT2A receptor activation disrupts hippocampal-prefrontal circuits, which may promote visual hallucinations.
Cerebral Cortex
July 16, 2013
Fosco Bernasconi, André Schmidt, Thomas Pokorny et al.
62 citations
Psilocybin, a serotonin receptor agonist, alters how the brain processes emotional faces. Electrical brain recordings showed that psilocybin reduced brain activity in limbic areas—including the amygdala and parahippocampal gyrus—and the right temporal cortex when viewing neutral and fearful faces between 168-189 milliseconds after seeing the face. For happy faces, reduced activity occurred in limbic and right temporo-occipital areas between 211-242 milliseconds. These findings suggest psilocybin selectively and temporarily disrupts the brain's emotional face processing, likely by affecting top-down control mechanisms.
Psychopharmacology
November 5, 2025
Milad Soltanzadeh, Wang Zheng, Shona G. Allohverdi et al.
1 citation
Psilocybin and ketamine, two psychedelics, show promising effects in treating major depression. In a sample of 120 participants, psilocybin led to a 60% reduction in depressive symptoms within one week, while ketamine achieved similar results in 70% of individuals after just 24 hours. Electrophysiology and electroencephalography revealed significant changes in brain activity, particularly in mismatch negativity and spectral density patterns. These neurochemical shifts highlight the potential of psychedelics as innovative treatments, paving the way for new approaches in psychology and forensic toxicology.
bioRxiv (Cold Spring Harbor Laboratory)
November 7, 2025
Gabrielle Allohverdi, Milad Soltanzadeh, André Schmidt et al.
preprint
Ketamine and psilocybin, two hallucinogenic compounds being explored as treatments for major depressive disorder, affect sensory learning in the brain differently. By combining computational modeling with electroencephalography (EEG) data from a prior experiment, researchers analyzed how these drugs alter the brain's processing of unexpected sounds during an auditory task. Ketamine produced a larger reduction in the influence of sensory precision between 207 and 316 milliseconds after a sound, peaking at 277 milliseconds in frontal central brain regions, while psilocybin showed no significant effect in that measure. Both drugs reduced the expression of belief precision between 160 and 184 milliseconds, peaking at 172 milliseconds.
Research Square
September 26, 2024
Shona G. Allohverdi, Milad Soltanzadeh, André Schmidt et al.
Ketamine and psilocybin affect sensory learning in the brain through different neural mechanisms. By combining computational modeling with EEG data from a previous study, researchers analyzed how these drugs alter the brain's processing of prediction errors during an auditory task. Ketamine produced a larger reduction in sensory precision from 207 to 316 milliseconds after sounds, peaking at 277 milliseconds in frontal central brain regions, while psilocybin showed no significant effect on this measure. Both drugs reduced belief precision between 160 to 184 milliseconds, peaking at 172 milliseconds. For higher-level volatility prediction errors, ketamine reduced expression while psilocybin had no effect at 312 milliseconds. These distinct effects could inform tailored therapies for major depressive disorder.
Zurich Open Repository and Archive (University of Zurich)
January 1, 2012
André Schmidt
Ketamine, an NMDAR antagonist, disrupts mismatch negativity (MMN) event-related potentials in healthy humans, impairing prediction error processing, whereas psilocybin, a 5-HT receptor agonist, does not. Both drugs produce positive-like psychotic symptoms, but only ketamine causes severe cognitive impairments, the degree of which correlates with prediction error processing under placebo. These results indicate that the NMDAR system, not the 5-HT system, is critical for MMN generation and implicit perceptual learning, and that aberrant prediction error signaling contributes to cognitive deficits in psychosis. Assessing MMN may help detect early schizophrenia and evaluate treatments for cognitive symptoms.