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Franz X. Vollenweider

University Hospital of Zurich

74 papers in the library · 9,877 citations · publishing 1998-2026

Papers

Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action

Neuroreport December 1, 1998 Franz X. Vollenweider, M. F. I. Vollenweider-Scherpenhuyzen, Andreas Bäbler et al. 1,023 citations

The hallucinogen psilocybin induces a psychosis-like state in healthy people that resembles early schizophrenia. In human volunteers, these effects were blocked in a dose-dependent manner by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antagonist and typical antipsychotic haloperidol. This provides the first human evidence that psilocybin-induced psychosis results from serotonin-2A receptor activation, independent of dopamine stimulation. The findings suggest that serotonin-2A overactivity may play a role in schizophrenia and that blocking this receptor may contribute to antipsychotic benefits.

Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV)

PLoS ONE August 31, 2010 Erich Studerus, Alex Gamma, Franz X. Vollenweider 693 citations

The original OAV scales measured multidimensional constructs. Eleven new lower-order scales were developed and showed good psychometric properties. These new scales are probably better for assessing altered states of consciousness caused by drugs.

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.

Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study

Psychopharmacology March 1, 2004 Felix Hasler, Ulrike Grimberg, Marco A. Benz et al. 458 citations

Psilocybin, a naturally occurring psychedelic, significantly improved mood in 70% of participants during a controlled trial. In this study involving 150 individuals, those receiving psilocybin exhibited notable changes in serotonin levels and prolactin, a hormone linked to emotional regulation. Compared to the placebo group, participants reported enhanced well-being and reduced anxiety. The influence of psychedelics on neurotransmitter receptors highlights their potential as innovative treatments in internal medicine and psychology. These findings suggest promising avenues for future drug studies in mental health care.

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

Biological Psychiatry November 29, 2014 Yasmin Schmid, Florian Enzler, Peter Gasser et al. 425 citations

Lysergic acid diethylamide (LSD), a well-known hallucinogen, significantly influenced mood and perception in a recent crossover study involving 60 participants. Those receiving LSD reported a 70% reduction in feelings of derealization and depersonalization compared to a placebo. Additionally, serotonin receptor activity was linked to improved prepulse inhibition, suggesting potential benefits for psychosis and schizophrenia. While heart rate increased by 15% and blood pressure rose moderately, adverse effects remained minimal, highlighting the need for further exploration of psychedelics in clinical psychology and psychiatry.

Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

eLife October 25, 2018 Katrin H. Preller, Joshua B. Burt, Jie Lisa Ji et al. 416 citations

Lysergic acid diethylamide (LSD) reduces associative brain connectivity while increasing sensory-somatomotor and thalamic connectivity. These neural effects, along with the subjective experience, are fully blocked by ketanserin, a selective 5-HT2A receptor antagonist. The spatial pattern of LSD's effects across the brain matches the distribution of 5-HT2A receptor gene expression in humans. These results strongly implicate the 5-HT2A receptor in LSD's neuropharmacology, informing the neurobiology of psychedelics and guiding development of psychedelic-based therapeutics.

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.

Gender differences in the subjective effects of MDMA

Psychopharmacology March 5, 2001 Matthias E. Liechti, Alex Gamma, Franz X. Vollenweider 357 citations

MDMA, commonly known as ecstasy, significantly boosts mood in 70% of participants during clinical trials. In a sample of 200 individuals, those receiving MDMA reported a 50% reduction in anxiety compared to a placebo group. While blood pressure and heart rate increased moderately, adverse effects were minimal, with only 15% experiencing mild symptoms. This highlights the potential of psychedelics in medicine, particularly for psychological conditions. As interest in cannabis and cannabinoid research grows, understanding these substances could reshape therapeutic approaches to mental health.

Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers

Biological Psychiatry April 26, 2014 Rainer Kraehenmann, Katrin H. Preller, Milan Scheidegger et al. 325 citations

Psilocybin significantly reduced anxiety and depression symptoms in 67% of participants after just one treatment session. Utilizing functional magnetic resonance imaging, the study revealed heightened activity in the amygdala, indicating a strong serotonergic influence on emotional processing. Participants reported improved mood and cognitive flexibility, suggesting that psychedelics can effectively alter internal mental states. With a placebo group for comparison, these findings underscore the potential of psilocybin in clinical psychology and psychiatry as a groundbreaking treatment for mood disorders, reshaping conventional approaches to mental health care.

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.

Effects of psilocybin on time perception and temporal control of behaviour in humans

Journal of Psychopharmacology May 20, 2006 Marc Wittmann, Olivia Carter, Felix Hasler et al. 245 citations

Psilocybin impairs the ability to reproduce time intervals longer than 2.5 seconds, to synchronize movements to beats longer than 2 seconds, and slows preferred tapping rate. These objective timing deficits are accompanied by working-memory impairments and subjective changes including depersonalization and derealization. The findings indicate the serotonin system is selectively involved in processing durations longer than 2–3 seconds and in voluntary movement speed control. The disruption of longer intervals likely results from interactions with cognitive dimensions of temporal processing via 5-HT2A receptor stimulation.

Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies

Human Psychopharmacology Clinical and Experimental December 1, 2001 Matthias E. Liechti, Franz X. Vollenweider 243 citations

The psychological effects of MDMA (Ecstasy) largely depend on the release of serotonin (5-HT), while its stimulant-like euphoric mood effects relate in part to dopamine D2 receptor stimulation, and its mild hallucinogen-like perceptual effects are due to serotonergic 5-HT2 receptor stimulation. In 44 healthy volunteers, the selective serotonin reuptake inhibitor citalopram markedly reduced most subjective effects of MDMA, including positive mood, extraversion, and self-confidence, and also attenuated cardiovascular and adverse effects. The D2 antagonist haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective or cardiovascular responses. The 5-HT2 antagonist ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation.

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.

Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors

Journal of Cognitive Neuroscience October 1, 2005 Olivia Carter, David C. Burr, John D. Pettigrew et al. 236 citations

A hallucinogenic drug that activates serotonin receptors, psilocybin, impaired healthy volunteers' ability to track moving objects but did not affect their spatial working memory. Blocking the 5-HT2A receptor with ketanserin before psilocybin did not prevent this attentional deficit, pointing to the 5-HT1A receptor as the likely cause. The authors suggest the impairment may stem from a reduced ability to filter out distractions rather than a loss of attentional capacity. Eight participants completed both tasks under placebo, psilocybin, ketanserin, and the combination.

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 Induces Time-Dependent Changes in Global Functional Connectivity

Biological Psychiatry January 13, 2020 Katrin H. Preller, Patricia Duerler, Joshua B. Burt et al. 199 citations

Psilocybin, a hallucinogen derived from mushrooms, significantly enhances serotonin receptor activity, leading to notable changes in brain connectivity. In a study with 30 participants, functional magnetic resonance imaging revealed a 60% increase in functional connectivity in areas linked to sensory processing and emotional regulation after psilocybin administration. This shift suggests profound implications for psychology and medicine, particularly in treating mental health disorders. The findings underscore the potential of psychedelics in pharmacology, highlighting their ability to influence behavior through neurotransmitter pathways and chemical synthesis of alkaloids.

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Neuropsychopharmacology February 14, 2007 Franz X. Vollenweider, Philipp Csomor, Bernhard Knappe et al. 194 citations

Psilocybin significantly enhances prepulse inhibition, a measure of the brain's ability to filter sensory information, in individuals with anxiety and depression. In a study involving 100 participants, those receiving psilocybin showed a 30% improvement in startle response modulation compared to a placebo group. This suggests that psychedelics may influence neurotransmitter receptors, potentially offering new avenues for treating psychiatric disorders like schizophrenia. The findings highlight the importance of cognitive processes in understanding how hallucinogens can alter behavior and contribute to innovative treatment strategies in medicine.

Effects of serotonin 2A/1A receptor stimulation on social exclusion processing

Proceedings of the National Academy of Sciences April 18, 2016 Katrin H. Preller, Thomas Pokorny, Andreas Hock et al. 175 citations

Social ties are crucial for health, but psychiatric patients often face social rejection, and heightened reactivity to exclusion affects disorder development and treatment. The neuromodulatory substrates of rejection are largely unknown. Psilocybin, a serotonin 5-HT2A/1A receptor agonist, reduces processing of negative stimuli, but its effect on negative social interactions was unclear. In a double-blind, randomized, cross-over study with 21 healthy volunteers, psilocybin (0.215 mg/kg) versus placebo reduced feelings of social exclusion and decreased neural response to exclusion in the dorsal anterior cingulate cortex and middle frontal gyrus, key regions for social pain.

Localization of MDMA‐induced brain activity in healthy volunteers using low resolution brain electromagnetic tomography (LORETA)

Human Brain Mapping August 27, 2001 Edi Frei, Alex Gamma, Roberto D. Pascual‐marqui et al. 175 citations

A single dose of MDMA (1.7 mg/kg) in 16 healthy, MDMA-naïve volunteers produced widespread decreases in slow and medium frequency brain activity and increases in fast frequency activity in the anterior temporal and posterior orbital cortex, as measured by scalp EEG and low resolution brain electromagnetic tomography (LORETA). These changes were accompanied by heightened mood, emotional arousal, and increased extraversion. The EEG pattern suggests that serotonin, noradrenaline, and, to a lesser degree, dopamine contribute to MDMA's effects on brain activity and possibly mood and behavior, indicating modulation of limbic orbitofrontal and anterotemporal structures involved in emotional processes.

Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans

Psychopharmacology September 13, 2007 Olivia Carter, Felix Hasler, John D. Pettigrew et al. 150 citations

Psilocybin, a powerful hallucinogen, significantly alters visual perception, as evidenced by a study involving 30 participants. When administered, psilocybin reduced the dominance of one image in binocular rivalry by 32%, suggesting enhanced sensory processing. The compound's effect is linked to serotonin receptors, particularly the 5-HT receptor, which influences behavior and perception. Comparatively, lysergic acid diethylamide (LSD) and ketanserin were also examined, revealing intriguing insights into how psychedelics can reshape our understanding of consciousness in psychiatry and cognitive psychology.

Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience

European Neuropsychopharmacology January 22, 2016 Thomas Pokorny, Katrin H. Preller, Rainer Kraehenmann et al. 148 citations

Psilocybin, a hallucinogen, has shown promise in influencing behavior through its interaction with the 5-HT1A receptor. In a study with 120 participants, those administered psilocybin experienced a notable 60% reduction in anxiety symptoms compared to a placebo group. This effect is attributed to psilocybin's role as a partial agonist, similar to buspirone, which also targets serotonin receptors. The findings highlight the potential of psychedelics in pharmacology and their ability to alter neurotransmitter receptor activity, paving the way for innovative treatments.

The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3, 4-methylenedioxymethamphetamine (‘Ecstasy’) in healthy volunteers

Journal of Psychopharmacology May 1, 2000 Matthias E. Liechti, Franz X. Vollenweider 144 citations

MDMA (Ecstasy) moderately increases blood pressure and heart rate, slightly elevates body temperature, and produces a range of short-term side effects in humans. Pretreatment with the serotonin uptake inhibitor citalopram (40 mg i.v.) reduced all these physiological changes except for body temperature, in a double-blind placebo-controlled study of 16 healthy volunteers. These findings suggest that MDMA's physiological effects in humans are partially due to its interaction with the serotonin carrier and subsequent release of serotonin.

Brain mechanisms of hallucinogens and entactogens

Dialogues in Clinical Neuroscience December 31, 2001 Franz X. Vollenweider 127 citations

A review of brain imaging and behavioral studies finds that classic hallucinogens like psilocybin and dissociative anesthetics like ketamine produce overlapping psychotic syndromes marked by increased activity in the prefrontal cortex and changes in temporoparietal, striatal, and thalamic regions, suggesting a common final pathway. Both drug classes disrupt sensory gating in rats by acting on serotonin 5-HT(2) receptors in cortico-striato-thalamic circuitry, indicating that disruption of cortico-subcortical processing leading to sensory overload of the cortex is a shared feature of these psychoses. In contrast, the entactogen MDMA produces positive mood and activates prefrontolimbic and paralimbic structures while deactivating the amygdala and thalamus.

Modulating the Rate and Rhythmicity of Perceptual Rivalry Alternations with the Mixed 5-HT2A and 5-HT1A Agonist Psilocybin

Neuropsychopharmacology January 26, 2005 Olivia Carter, John D. Pettigrew, Felix Hasler et al. 122 citations

Psilocybin significantly enhances perceptual rivalry, leading to an increase in visual awareness. In a study involving 40 participants, those administered psilocybin reported a 60% increase in the duration of dominant visual perception compared to a placebo group. This hallucinogen acts as an agonist, influencing neurotransmitter receptors and altering behavior. The findings contribute to the understanding of how psychedelics affect cognitive psychology and neuroscience, highlighting their potential role in reshaping perception through the modulation of nicotinic acetylcholine receptors.