Journal of Psychopharmacology
September 20, 2010
Erich Studerus, Michael Kometer, Felix Hasler et al.
529 citations
Psilocybin, a hallucinogenic compound, dose-dependently induced profound changes in mood, perception, thought, and self-experience, but most subjects described the experience as pleasurable, enriching, and non-threatening. Acute adverse drug reactions—strong dysphoria or anxiety—occurred only at the two highest doses in a small proportion of subjects, and were managed with interpersonal support without medication. Follow-up showed no subsequent drug abuse, persisting perception disorders, prolonged psychosis, or long-term impairment. The findings suggest that moderate doses given to healthy, high-functioning, well-prepared subjects in a carefully monitored research setting carry an acceptable level of risk.
PLoS ONE
February 17, 2012
Erich Studerus, Alex Gamma, Michael Kometer et al.
372 citations
Dose is the strongest predictor of how people respond to psilocybin, but non-pharmacological factors also matter. Among 409 administrations to 261 healthy volunteers, pleasant and mystical-type experiences were most strongly associated with high Absorption personality trait, emotional excitement and activity just before the drug, and few recent psychological problems. Unpleasant or anxious reactions were most strongly predicted by high Emotional Excitability, younger age, and undergoing a PET scan during the session. The findings confirm that personality, mood, and setting significantly shape psilocybin's effects, though dose remains the dominant factor.
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 enhanced positive mood and reduced recognition of negative facial expressions in healthy volunteers. It also increased goal-directed behavior toward positive emotional cues while inhibiting negative sequential emotional effects and valence-dependently attenuated the P300 brain response. These emotional shifts occurred across multiple psychological domains and were blocked by the 5-HT2A antagonist ketanserin, indicating that activation of 5-HT2A receptors is central to mood regulation and emotional face recognition. The findings suggest a mechanism for psilocybin's potential antidepressant effects.
NeuroImage
August 1, 2019
Lukasz Smigielski, Milan Scheidegger, Michael Kometer et al.
261 citations
A single dose of psilocybin (315 μg/kg) combined with a 5-day mindfulness retreat altered brain connectivity in the default mode network, particularly decoupling the medial prefrontal and posterior cingulate cortices. This decoupling correlated with the subjective experience of ego dissolution during meditation. The extent of ego dissolution and brain connectivity changes predicted improvements in psycho-social functioning four months later. The findings suggest that psilocybin-assisted meditation facilitates neurodynamic changes in self-referential networks, linking altered self-experience to lasting behavioral changes.
Neuropsychopharmacology
September 28, 2011
Boris B. Quednow, Michael Kometer, Mark A. Geyer et al.
241 citations
The hallucinogen psilocybin disrupts automatic and controlled inhibition processes in healthy humans by stimulating the serotonin-2A receptor (5-HT(2A)R). In a double-blind, randomized study with 16 participants, psilocybin (260 μg/kg) reduced prepulse inhibition of the acoustic startle response at short lead intervals, increased scores on the altered states of consciousness questionnaire, and increased errors and response latencies in the interference condition of the Stroop Test. These effects were attenuated by pretreatment with the 5-HT(2A/2C)R antagonist ketanserin (40 mg), which alone had no significant effects. The findings indicate that sensorimotor gating and attentional control deficits in schizophrenia may involve changes in the 5-HT(2A)R system.
The International Journal of Neuropsychopharmacology
June 14, 2017
Thomas Pokorny, Katrin H. Preller, Michael Kometer et al.
202 citations
A single dose of psilocybin (0.215 mg/kg) increased emotional empathy in healthy adults but did not affect cognitive empathy or moral decision-making. The rise in implicit emotional empathy correlated with psilocybin-induced changes in the meaning of percepts. These results suggest psilocybin selectively enhances emotional empathy, likely through serotonin 2A/1A receptor activation, which may inform treatments for impaired social cognition.
Sci Rep
October 24, 2019
Lukasz Smigielski, Michael Kometer, Milan Scheidegger et al.
174 citations
In a mindfulness group retreat setting, the acute and sustained effects of psilocybin were characterized and predicted. The study examined how individuals responded to the psychedelic during and after the retreat, identifying factors that influenced the strength and duration of the experience. Results showed that certain psychological and contextual variables predicted more profound acute responses, which in turn were associated with greater long-term improvements in well-being. The findings suggest that psilocybin's effects in a group mindfulness context are shaped by individual differences and the retreat environment, offering insights into optimizing therapeutic use.
Psychopharmacology
July 31, 2015
Michael Kometer, Thomas Pokorny, Erich Seifritz et al.
165 citations
A moderate dose of psilocybin, a naturally occurring hallucinogen, decreased brain electrical activity at 1.5-20 Hz in a network involving the anterior and posterior cingulate cortices and parahippocampal regions. The intensity of spiritual experience and insightfulness correlated with the synchronization of delta oscillations (1.5-4 Hz) between the retrosplenial cortex, parahippocampus, and lateral orbitofrontal area. These findings directly link a specific spatiotemporal neuronal mechanism to spiritual experiences and enhanced insight into life, suggesting a pathway for modulating mental health and promoting well-being.
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.
Biological Psychiatry
December 4, 2010
Michael Kometer, B. Rael Cahn, David Andel et al.
101 citations
The hallucinogenic compound psilocybin, which activates 5-HT2A/1A serotonin receptors, alters how the brain processes visual information. In a placebo-controlled experiment with 17 healthy volunteers, psilocybin dose-dependently reduced the N170 brain response, especially when viewing incomplete object figures, while slightly enhancing the P1 component over occipital areas. The reduction in N170-related brain activity in the right extrastriate and posterior parietal regions correlated with the intensity of visual hallucinations. These findings point to a central role of 5-HT2A/1A receptors in visual processing and suggest that a diminished N170 response may be a key mechanism underlying visual hallucinations.
Psychopharmacology
July 26, 2012
André Schmidt, Michael Kometer, Rosilla Bachmann et al.
94 citations
The glutamate NMDA receptor and the serotonin 5-HT receptor system contribute differently to how the brain encodes emotional facial expressions. In healthy volunteers, both S-ketamine (an NMDA receptor antagonist) and psilocybin (a 5-HT receptor agonist) impaired the encoding of fearful faces, as shown by a reduced N170 brain response over parieto-occipital regions. However, only S-ketamine also impaired the encoding of happy faces; psilocybin had no effect on happy-face processing. These findings suggest that early visual evoked responses can detect pharmacologically induced changes in emotional processing biases, offering a framework for studying dysfunctional emotional biases in psychiatric disorders.
Schizophrenia Bulletin
August 5, 2020
Pantelis Leptourgos, Martin Fortier-Davy, Robin Carhart‐Harris et al.
88 citations
A multidisciplinary working group reviewed evidence on the similarities and differences between hallucinations induced by psychedelics and those occurring in schizophrenia-spectrum disorders, examining data from pharmacology, brain imaging, phenomenology, and anthropology. The authors highlight both shared features and distinct characteristics across these scales, and attempt to integrate findings using computational approaches. They conclude with recommendations for future research, emphasizing the need for further study to clarify the relationship between these types of hallucinations.
Journal of Neuroscience
June 19, 2020
Lilian Weber, Andreea O. Diaconescu, Christoph Mathys et al.
82 citations
The auditory mismatch negativity (MMN) is reduced in schizophrenia and can also be reduced by NMDA receptor (NMDAR) antagonists, suggesting impaired predictive coding. This study tested the theory that perceptual inference depends on NMDAR-dependent hierarchical precision-weighted prediction errors (PEs). Using a hierarchical Bayesian model on single-trial EEG data from healthy volunteers given the NMDAR antagonist S-ketamine in a placebo-controlled, double-blind, within-subject design, the analysis showed that low-level PEs (about stimulus transitions) appear early (102-207 ms), while high-level PEs (about transition probability) appear later (152-199 and 215-277 ms). Ketamine significantly diminished high-level PE responses, indicating NMDAR antagonism disrupts inference on abstract statistical regularities and impairs hierarchical Bayesian inference about the world's statistical structure.
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.
Human Brain Mapping
August 21, 2020
Lukasz Smigielski, Michael Kometer, Milan Scheidegger et al.
42 citations
A placebo-controlled, double-blind experiment with 17 participants found that psilocybin, a serotonin receptor agonist, alters self-perception by disrupting the brain's ability to distinguish between self- and other-related stimuli. Participants performed a verbal self-monitoring task while brain activity was recorded. Psilocybin reduced accuracy in identifying whether auditory feedback was their own voice or another's, and it eliminated the typical difference in electrical brain patterns (P300) between self and other stimuli. This effect was linked to changes in the anterior cingulate and insular cortex. The strength of this brain change correlated with feelings of unity and altered meaning. The findings suggest that serotonin signaling modulates how the brain processes self-referential information, offering insight into self-disturbances in mental health conditions.
Frontiers in pharmacology
January 1, 2023
Dario A Dornbierer, Laurenz Marten, Jovin Mueller et al.
32 citations
Ayahuasca, an Amazonian plant medicine containing DMT and harmine, shows promise for mental health disorders but its oral use causes gastrointestinal side effects and unpredictable drug levels. This study tested new ayahuasca-analogue formulations in 10 healthy men: an oral capsule of purified DMT and harmine versus a combined oromucosal harmine tablet with intranasal DMT spray. The combined buccal/intranasal route significantly reduced variations in systemic exposure and attenuated common side effects like nausea, vomiting, and diarrhea compared to traditional oral ayahuasca. All preparations were well tolerated. This approach may enable safer, patient-friendly DMT/harmine administration for affective disorders.
Psychopharmacology
July 1, 2017
Robin Rotz, Michael Kometer, Dario Dornbierer et al.
19 citations
Gamma-hydroxybutyrate (GHB) increases theta oscillations in the posterior cingulate cortex and alpha1 oscillations in the anterior cingulate cortex, while decreasing the global omega complexity of alpha1 oscillations. Higher blood plasma levels of GHB are linked to increased delta oscillation connectivity between the posterior cingulate cortex and the right inferior parietal lobulus. These neural changes in the posterior cingulate cortex may explain the paradoxical dissociation between EEG patterns and behavior that GHB produces, where brain activity resembles sleep during wakefulness. The reduced number of independent neuronal processes is similar to effects seen with other anesthetics.
Scientific reports
March 26, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
15 citations
Brain activity patterns during meditation shift after a psilocybin-assisted retreat, especially when open-monitoring meditation is practiced. Using functional MRI and a topological data analysis method (Mapper), researchers compared experienced meditators who received psilocybin or placebo over five days. The psilocybin group showed a link between positive derealization—an altered perception that can foster insight—and a greater geometric distance between open-monitoring meditation and resting-state brain activity, as measured by optimal transport distance. This suggests that combining psilocybin with open-monitoring practice enhances meta-awareness and insight. The findings point to possible brain markers for synergistic effects between mindfulness and psychedelics.
Scientific Reports
April 23, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
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