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.
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.
Archives of General Psychiatry
December 1, 2000
Daniel Umbricht, Liselotte Schmid, Rene Koller et al.
590 citations
In healthy volunteers, the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine significantly reduced the amplitude of mismatch negativity (MMN) brain responses to pitch and duration changes by 27% and 21%, respectively. Ketamine also impaired performance on a continuous performance test, decreasing hit rates and increasing specific context-dependent errors (BX errors), indicating a failure to form and use transient memory traces. These findings suggest that NMDARs are critically involved in generating MMN and that NMDAR dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia.
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.
Psychopharmacology
March 1, 2004
Felix Hasler, Ulrike Grimberg, Marco A. Benz et al.
458 citations
Psilocybin, a serotonin 5-HT(2A) receptor agonist, dose-dependently altered consciousness, attention, and mood in eight healthy subjects. At medium and high doses (215 and 315 micrograms per kilogram body weight), performance on an attention test dropped by 50%, and participants reported increased emotional excitability, dreaminess, and general inactivation. Only one person experienced transient anxiety at the highest dose. Blood pressure rose modestly after the high dose, and levels of the hormones TSH, ACTH, cortisol, and prolactin increased during peak effects, with prolactin rising after both medium and high doses. No changes occurred in heart rhythm or body temperature. The authors conclude psilocybin affects core dimensions of consciousness and physiology in a dose-dependent manner and found no evidence of harm to physical health.
Biological Psychiatry
November 29, 2014
Yasmin Schmid, Florian Enzler, Peter Gasser et al.
425 citations
In a double-blind, placebo-controlled crossover study, 200 μg of lysergic acid diethylamide (LSD) given to 16 healthy subjects produced pronounced alterations in consciousness lasting 12 hours, including visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization. LSD increased subjective well-being, happiness, closeness to others, openness, and trust, and decreased prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating. It also significantly increased blood pressure, heart rate, body temperature, pupil size, and plasma levels of cortisol, prolactin, oxytocin, and epinephrine. All adverse effects subsided within 72 hours, with no severe acute adverse effects observed. LSD produces empathogenic mood effects similar to methylenedioxymethamphetamine and alters sensorimotor gating in a human model of psychosis, supporting its potential use in psychotherapy and translational psychiatric research.
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.
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.
Psychopharmacology
March 5, 2001
Matthias E. Liechti, Alex Gamma, Franz X. Vollenweider
357 citations
Equal doses of MDMA per kilogram of body weight produce stronger subjective effects in women than in men. Women reported more intense perceptual changes, thought disturbances, and fear of losing body control, and they experienced more acute adverse effects and aftereffects. The dose of MDMA correlated with the intensity of perceptual changes in women. Men showed greater increases in blood pressure. These findings suggest women may be more susceptible to the serotonin-releasing effects of MDMA.
Biological Psychiatry
April 26, 2014
Rainer Kraehenmann, Katrin H. Preller, Milan Scheidegger et al.
325 citations
A double-blind, randomized, crossover study in 25 healthy volunteers found that a single dose of psilocybin (0.16 mg/kg) reduced amygdala reactivity to negative and neutral stimuli, measured with functional magnetic resonance imaging, compared with placebo. The reduction in right amygdala reactivity to negative stimuli was linked to an increase in positive mood, assessed with the Positive and Negative Affect Schedule and the State-Trait Anxiety Inventory. These findings suggest psilocybin may dampen neural responses to negative emotional cues and improve mood, which could be relevant for treating conditions like major depression where amygdala hyperactivity and negative mood states are common.
Proc Natl Acad Sci U S A
January 28, 2019
Katrin H. Preller, Adeel Razi, Peter Zeidman et al.
303 citations
LSD alters communication within brain pathways that filter sensory information, according to a brain imaging study. Using a double-blind, placebo-controlled design with 25 healthy participants, researchers found that LSD increased signaling from the thalamus to the posterior cingulate cortex—an effect dependent on serotonin 2A receptor activation—and decreased signaling from the ventral striatum to the thalamus independently of those receptors. These changes in directed connectivity within cortico-striato-thalamo-cortical loops support the thalamic filter model of psychedelic action, which proposes that psychedelics disrupt the gating of sensory information to the cortex. The findings advance understanding of how psychedelics alter consciousness and may inform development of new therapeutics.
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.
Current topics in behavioral neurosciences
January 1, 2016
Katrin H. Preller, Franz X. Vollenweider
285 citations
Psychedelics produce altered states of consciousness marked by changes in sensory perception, mood, thought, and sense of self. This review describes three primary dimensions of these states—oceanic boundlessness, anxious ego-dissolution, and visionary restructuralization—along with 11 lower-order factors, all measurable by the APZ-OAV questionnaire. The dynamic nature of psychedelic experiences is highlighted, with subjects progressing through stages along a perception-hallucination continuum. Acute effects on sensory perception, emotion, cognition, creativity, and time perception are reviewed, along with neural mechanisms. Non-pharmacological factors like demographics, genetics, personality, mood, and setting influence the experience, and long-term effects are discussed. Neuroscientific models of psychedelic states are presented.
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.
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.
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.
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.
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.
Biological Psychiatry
January 13, 2020
Katrin H. Preller, Patricia Duerler, Joshua B. Burt et al.
199 citations
Psilocybin reduces connectivity in associative brain regions while increasing connectivity in sensory regions, a pattern that emerges over time from administration to peak effects. Baseline connectivity predicts the extent of these changes. The shifts correlate with spatial gene expression patterns of the serotonin 2A and 1A receptors, pinpointing their critical role in the psychedelic state. These findings suggest that sensory integration and associative disintegration may underlie the psychedelic experience, and baseline connectivity could serve as a predictive marker for personalized psychedelic treatment.
Neuropsychopharmacology
February 14, 2007
Franz X. Vollenweider, Philipp Csomor, Bernhard Knappe et al.
194 citations
Psilocybin, a hallucinogenic 5-HT(2A) receptor agonist, produces opposite effects on prepulse inhibition (PPI) of the startle response depending on the time interval between the prepulse and the startle stimulus. In healthy humans, psilocybin dose-dependently reduced PPI at short intervals (30 ms) and increased PPI at long intervals (120-2000 ms), with no effect at medium intervals (60 ms). The reduction in PPI at short intervals correlated with impaired sustained attention, consistent with PPI deficits seen in schizophrenia. Psilocybin also impaired attention and increased altered states of consciousness scores.
Neuropsychopharmacology
January 1, 2003
Daniel Umbricht, Franz X. Vollenweider, Liselotte Schmid et al.
192 citations
The NMDA receptor antagonist ketamine disrupts auditory mismatch negativity (MMN) and performance on an AX-type continuous performance test (AX-CPT), similar to deficits seen in schizophrenia. This placebo-controlled study tested the 5-HT(2A) receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin caused significant performance deficits on the AX-CPT but did not significantly reduce MMN generation. These results suggest that deficient MMN generation in schizophrenia may specifically reflect NMDA receptor dysfunction, while impairments in AX-CPT performance during both psilocybin and ketamine administration may stem from shared disruption of glutamatergic neurotransmission. Comparable deficits in schizophrenia may arise from independent dysfunctions of 5-HT(2A) and NMDA receptor-related neurotransmission.
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.
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.
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.