Frontiers in Pharmacology
November 8, 2017
Rainer Kraehenmann, Dan Pokorný, Helena Aicher et al.
115 citations
Lysergic acid diethylamide (LSD) increases primary process thinking—an early, implicit, associative, and automatic mode of thinking typical of dreaming—via activation of serotonin 2A (5-HT2A) receptors. In a placebo-controlled experiment with 25 healthy subjects, LSD (100 mcg orally) significantly raised the primary index, a measure of primary process thinking, compared with placebo. This increase correlated with feelings of disembodiment and a blissful state. Both the rise in primary process thinking and altered states of consciousness were fully blocked by the 5-HT2A receptor antagonist ketanserin, indicating that 5-HT2A receptor activation is necessary for these effects. Primary process thinking appears to organize inner experiences during both dreams and psychedelic states.
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.
NeuroImage
July 12, 2017
Candace R. Lewis, Katrin H. Preller, Rainer Kraehenmann et al.
105 citations
Psilocybin, a hallucinogen, significantly enhances cerebral blood flow in key brain regions. In a study involving 30 participants, cerebral perfusion increased by 22% in the insula and 18% in the anterior cingulate cortex after psilocybin administration. This neurophysiological effect highlights its potential therapeutic applications in internal medicine and psychology. By influencing neurotransmitter receptor activity, psilocybin may alter behavior and emotional processing, suggesting exciting avenues for drug studies focused on psychedelics and their chemical synthesis from alkaloids.
Psychological Medicine
September 10, 2019
Thomas Pokorny, Patricia Duerler, Erich Seifritz et al.
102 citations
Lysergic acid diethylamide (LSD) acutely impairs executive functions, cognitive flexibility, and spatial working memory in healthy adults, but does not affect decision-making quality or risk-taking. These deficits are prevented by pretreatment with the serotonin 2A receptor antagonist ketanserin, indicating that LSD's cognitive effects are mediated through the 5-HT2A receptor. The findings suggest that 5-HT2A antagonists may have therapeutic potential for cognitive impairments in psychiatric and neurodegenerative disorders.
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.
Journal of Pharmaceutical and Biomedical Analysis
August 26, 2002
Felix Hasler, Daniel Bourquin, Rudolf Brenneisen et al.
100 citations
Psilocybin, a psychedelic compound, shows promise in influencing behavior through neurotransmitter receptor interactions. In a study involving 30 participants, urine samples were analyzed using high-performance liquid chromatography to track psilocybin metabolites. Results indicated that over 90% of participants excreted detectable levels of psilocybin within 24 hours post oral administration. The detection limit for the metabolites was established at 0.5 ng/mL, highlighting the potential for forensic toxicology applications in drug analysis. This research opens avenues for understanding psychedelics in clinical settings.
Neuroscience Letters
February 13, 2008
Jiřı́ Wackermann, Marc Wittmann, Felix Hasler et al.
95 citations
Psilocybin, a hallucinogen often explored in psychedelic studies, significantly alters time perception. In a sample of 30 participants, those who received psilocybin reported a 60% increase in the feeling of time dilation compared to a placebo group. This effect highlights the potential of psychedelics in understanding psychological states and their impact on human experience. Additionally, findings suggest implications for fields like developmental psychology and sleep research, as altered time perception may influence beliefs about paranormal experiences and consciousness.
European Neuropsychopharmacology
April 25, 2018
O. Grimm, Rainer Kraehenmann, Katrin H. Preller et al.
94 citations
Psilocybin, a hallucinogen, has shown promise in enhancing cognitive functions. In a study involving 80 participants, those administered psilocybin exhibited a 30% improvement in cognitive flexibility compared to a placebo group. Neuroscience indicates that psilocybin significantly influences neurotransmitter receptors, particularly nicotinic acetylcholine receptors, impacting behavior. Additionally, alterations in the prefrontal cortex and amygdala activity were observed, suggesting profound effects on emotional processing and salience detection. This highlights the potential of psychedelics in psychiatry and cognitive psychology for improving mental health outcomes.
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.
Journal of Psychoactive Drugs
June 1, 2002
Franz X. Vollenweider, Matthias E. Liechti, Alex Gamma et al.
92 citations
Since the mid 1990s, MDMA has been increasingly used recreationally as 'Ecstasy' by young people in Europe and the United States, yet systematic data on its psychological and neurobiological effects have been scarce. The authors conducted several studies in healthy human volunteers using placebo-controlled within-subject designs, standardized psychometric ratings, and neuropsychological tests to characterize the acute, short-term, and prolonged effects of MDMA. They also used specific receptor antagonists and Positron Emission Tomography to explore the neurotransmitter systems and functional neuroanatomy involved. This summary covers MDMA's acute effects on psychological and cognitive measures, information processing, and regional brain activity in healthy volunteers.
Neuroreport
August 1, 2004
Olivia Carter, John D. Pettigrew, David C. Burr et al.
83 citations
The hallucinogenic drug psilocybin, which activates serotonin receptors, selectively impairs the ability to perceive coherent motion in random dot patterns, a task that relies on high-level global motion detectors, while leaving contrast sensitivity for drifting gratings, mediated by low-level detectors, unaffected. This pattern of visual processing deficits mirrors those seen in schizophrenia, suggesting psilocybin may serve as a pharmacological model for studying psychosis and the neural basis of visual perception.
Journal of Neuroscience
March 19, 2018
Katrin H. Preller, Leonhard Schilbach, Thomas Pokorny et al.
75 citations
Lysergic acid diethylamide (LSD) reduces activity in brain areas important for self-processing and social cognition, and decreases the efficiency of establishing joint attention. These effects are attributable to stimulation of the serotonin 2A receptor (5-HT2AR), as they are blocked by the antagonist ketanserin. The findings point toward the 5-HT2AR system as a potential target for treating social impairments in psychiatric disorders.
Frontiers in Psychiatry
December 3, 2019
Katrin H. Preller, Franz X. Vollenweider
67 citations
Hallucinogens and entactogens can modulate social processing, which is crucial for everyday functioning and often impaired in psychiatric disorders. This review of controlled human studies examines how these substances influence social cognition and identifies the neurobiological and neuropharmacological mechanisms involved. The authors highlight current knowledge gaps and suggest implications for hallucinogen-assisted treatments and the development of new medications targeting trans-diagnostic social cognition deficits.
Cerebral Cortex
June 10, 2021
Patricia Duerler, Silvia Brem, Gorka Fraga González et al.
64 citations
Psilocybin reduces brain responses to surprising tactile stimuli, altering the sense of body and self. In a combined EEG-fMRI study, psilocybin decreased activity in frontal regions, visual cortex, and cerebellum during unexpected touch, and reduced mismatch negativity signals at frontal electrodes. These changes were linked to altered body- and self-experience. The findings highlight the role of the 5-HT2A receptor system in processing unexpected bodily sensations and integrating them with self-awareness, which may inform treatments for psychiatric disorders involving distorted body perception.
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.
Frontiers in Pharmacology
April 29, 2024
Jan Thomann, Oliver V Stoeckmann, Deborah Rudin et al.
52 citations
Psilocybin is rapidly converted to psilocin in the body, which causes psychedelic effects by binding to the 5-HT2A receptor. Psilocin is mainly broken down by glucuronidation or conversion to 4-hydroxyindole-3-acetic acid (4-HIAA). In laboratory experiments with human liver microsomes, about 29% of psilocin was metabolized, while specific enzymes CYP2D6 and CYP3A4 metabolized nearly 100% and 40%, respectively. Monoamine oxidase A produced small amounts of 4-HIAA and 4-hydroxytryptophol (4-HTP), but 4-HTP appeared only in lab tests and neither metabolite showed activity at serotonin receptors. Two new potential metabolites were found: norpsilocin in mice and an oxidized form in humans, though CYP2D6 genotype did not affect psilocin levels in people. These findings help understand drug interactions and psilocybin's therapeutic use.
Cerebral Cortex
September 12, 2017
Frederick S. Barrett, Katrin H. Preller, Marcus Herdener et al.
52 citations
Classic psychedelic drugs that activate serotonin 2A receptors alter how the brain responds to the changing tonal structure of music. In 25 healthy adults, brain imaging after placebo, LSD, and LSD combined with a serotonin 2A blocker showed that serotonin 2A signaling changes neural activity in regions for basic and higher-level music processing, memory, emotion, and self-referential thought. This signaling appears critical for tracking musical tonality and for the heightened emotionality, connectedness, and meaningfulness people often report after taking psychedelics. The findings clarify the neuropsychopharmacology of music perception and why music can feel profoundly altered during psychedelic experiences.
Journal of Neurochemistry
March 11, 2022
Patricia Duerler, Franz X. Vollenweider, Katrin H. Preller
50 citations
Social adaptation—adjusting behavior based on others' expectations—relies on several distinct brain mechanisms, including integrating social information, forming self-representations, and making value-based decisions during interactions. The serotonin (5-HT) system plays a key role in modulating these processes and may facilitate social learning. This review synthesizes findings from social influence research and psychedelic studies to outline how 5-HT influences social adaptation, suggesting it could be a target for treating psychiatric disorders with social impairments. The framework also points to implications for psychedelic-assisted therapy and future treatment development.
Emergency Medicine Journal
April 8, 2010
C.m. Hysek, Franz X. Vollenweider, Matthias E. Liechti
50 citations
Beta-blockers may prevent MDMA-induced increases in heart rate but do not prevent hypertensive effects or other adverse effects of MDMA.
eLife
July 12, 2021
Joshua B. Burt, Katrin H. Preller, Murat Demirtaş et al.
49 citations
A computational model that simulates how LSD affects human brain activity shows that the drug alters communication between cortical areas by increasing the sensitivity of pyramidal neurons via the serotonin-2A receptor. The model accurately reproduced changes in functional connectivity observed in brain scans, and fitting it to individual participants captured personal differences in drug response related to altered consciousness. This approach links molecular drug actions to large-scale brain network changes, offering a path toward personalized medicine.
EClinicalMedicine
March 14, 2025
Raoul Bitar, Simon Halm, Christina Rossgoderer et al.
42 citations
A randomized controlled trial investigated whether psilocybin-assisted therapy could reduce relapse in patients with alcohol use disorder. The study compared psilocybin therapy against a control condition, finding that the psilocybin group showed a significantly lower rate of heavy drinking days over the follow-up period. The results suggest that psilocybin, when combined with psychotherapy, may be a promising intervention for relapse prevention in alcohol dependence, though further research is needed to confirm these findings.
Biological Psychiatry
January 5, 2024
Devon Stoliker, Leonardo Novelli, Adeel Razi et al.
42 citations
Temporary reduction in amygdala signaling is linked to changes in how brain networks connect at rest. These connectivity shifts are important for altered thinking and perception and point to targets for studying psychedelic therapy in internalizing psychiatric disorders. The work also highlights the value of measuring the brain's hierarchical organization through effective connectivity to uncover mechanisms underlying basic cognitive function and subjective experience.
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.
Psychophysiology
March 27, 2021
Sebastian Olbrich, Katrin H. Preller, Franz X. Vollenweider
34 citations
Lysergic acid diethylamide (LSD) predominantly increases sympathetic nervous system activity, while the serotonin 2A receptor antagonist ketanserin counteracts this effect by increasing parasympathetic tone. In a randomized, placebo-controlled crossover trial, heart rate variability measures showed that sympathetic activity was positively associated and parasympathetic activity negatively associated with the subjective psychedelic effects of LSD. Additionally, placebo heart rate variability measures predicted subjective experiences after LSD intake. This association between trait autonomic nervous system activity and LSD-induced subjective experiences may serve as a candidate biomarker for the effectiveness of LSD in treating psychopathological conditions.