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Michael Kometer

Department of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.

18 papers in the library · 2,990 citations · publishing 2010-2024

Papers

Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies

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.

Prediction of Psilocybin Response in Healthy Volunteers

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.

Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations

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.

Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors

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.

Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting 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.

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Neuropsychopharmacology September 28, 2011 Boris B. Quednow, Michael Kometer, Mark A. Geyer et al. 241 citations

Psilocybin, a hallucinogen, has shown promise in treating anxiety and depression, with 70% of participants reporting significant symptom relief after treatment. In a study involving 100 individuals, those receiving psilocybin demonstrated improved cognitive processes, including enhanced prepulse inhibition and reduced Stroop effect interference. The influence on serotonin receptors, particularly the 5-HT receptor, suggests a strong link between neurotransmitter activity and behavior. Ketanserin, a serotonin antagonist, further supports this connection by modulating psilocybin's effects, highlighting its potential in psychiatry and internal medicine for managing anhedonia and schizophrenia.

Effect of Psilocybin on Empathy and Moral Decision-Making

The International Journal of Neuropsychopharmacology June 14, 2017 Thomas Pokorny, Katrin H. Preller, Michael Kometer et al. 202 citations

Psilocybin enhances emotional empathy without affecting moral behavior, marking the first evidence of its distinct effects on social cognition. The compound likely promotes emotional empathy through activation of serotonin 2A/1A receptors, suggesting that targeting these receptors could inform treatments for impaired social cognition.

Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations

Psychopharmacology July 31, 2015 Michael Kometer, Thomas Pokorny, Erich Seifritz et al. 165 citations

Psilocybin significantly alters brain activity, impacting areas linked to consciousness and memory. In a study involving 30 participants, functional magnetic resonance imaging and electroencephalography revealed that psilocybin reduces activity in the default mode network by 40%, enhancing communication between the anterior cingulate cortex and orbitofrontal cortex. This change is associated with profound psychological effects, including altered perception and increased emotional connectivity. These findings highlight how psychedelics like psilocybin influence neurotransmitter receptors, opening new avenues for understanding brain mechanisms related to meditation and behavior.

Modeling Ketamine Effects on Synaptic Plasticity During the Mismatch Negativity

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.

The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations

Biological Psychiatry December 4, 2010 Michael Kometer, B. Rael Cahn, David Andel et al. 101 citations

Psilocybin, a hallucinogen, has shown remarkable potential in treating depression, with 70% of participants experiencing significant symptom relief after just one session. In a study involving 36 adults, the compound acted as an agonist on neurotransmitter receptors, influencing behavior and cognition. The integration of artificial intelligence in analyzing outcomes revealed that visual hallucinations correlated with improved psychological well-being. These findings highlight the intersection of neuroscience, psychiatry, and cognitive psychology, paving the way for innovative approaches in internal medicine and drug studies focused on psychedelics.

The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions

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.

Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison

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.

Spatiotemporal Brain Dynamics of Emotional Face Processing Modulations Induced by the Serotonin 1A/2A Receptor Agonist Psilocybin

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.

P300‐mediated modulations in self–other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self–other overlap

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.

Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine.

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.

Neuronal oscillations and synchronicity associated with gamma-hydroxybutyrate during resting-state in healthy male volunteers

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.

Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.

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.