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.
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.
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.
Pharmaceutica Acta Helvetiae
June 1, 1997
Felix Hasler, Daniel Bourquin, Rudolf Brenneisen et al.
231 citations
After oral ingestion of psilocybin, the main psychoactive compound in Psilocybe mushrooms, peak plasma levels of its metabolite psilocin occur around 105 minutes, averaging 8.2 ng/ml. Another metabolite, 4HIAA, peaks at about 113 minutes at 150 ng/ml. Intravenous administration produces psilocin peaks within roughly 2 minutes at 12.9 ng/ml, indicating rapid dephosphorylation of psilocybin. 4HIAA was not detected after intravenous dosing. The absolute oral bioavailability of psilocin from psilocybin is estimated at about 53%.
Psychopharmacology
September 13, 2007
Olivia Carter, Felix Hasler, John D. Pettigrew et al.
150 citations
Binocular rivalry, where each eye sees a different image and perception alternates between them, was slowed by psilocybin (215 µg/kg) in ten healthy adults. Pretreatment with ketanserin (50 mg), a 5-HT2A receptor blocker, prevented most of psilocybin's hallucinogenic symptoms but did not reverse the slowing of rivalry switching or the drug's negative-type symptoms such as reduced arousal and vigilance. These findings link slower binocular rivalry switching to subjective levels of arousal and attention, and suggest that psilocybin's effect on rivalry is not mediated by the 5-HT2A receptor.
Neuropsychopharmacology
January 26, 2005
Olivia Carter, John D. Pettigrew, Felix Hasler et al.
122 citations
Binocular rivalry, where each eye sees a different image and perception alternates between them, is influenced by psilocybin. In 12 healthy volunteers, both low (115 µg/kg) and high (250 µg/kg) doses of psilocybin significantly reduced the rate and rhythmicity of perceptual alternations 90 minutes after administration, compared to placebo. Over time, switch rates increased, with some exceeding pretest levels at 360 minutes, though mean phase duration did not significantly differ from placebo. Drug-induced changes in rivalry phase durations corresponded to altered states of consciousness measured by the 5D-ASC scale. The findings implicate serotonergic pathways and support a brainstem oscillator's role in perceptual rivalry and psychosis symptoms.
Journal of Pharmaceutical and Biomedical Analysis
August 26, 2002
Felix Hasler, Daniel Bourquin, Rudolf Brenneisen et al.
100 citations
After oral doses of psilocybin (212 ± 25 µg/kg body weight), the metabolite psilocin appears in urine, peaking at 870 µg/L between 2 and 4 hours. Within 24 hours, 3.4 ± 0.9% of the dose is excreted as free psilocin. Adding beta-glucuronidase doubles measured psilocin levels, indicating partial excretion as psilocin-O-glucuronide, though 18 ± 7% of unconjugated psilocin decomposes during incubation. Enzymatic hydrolysis extends detectability in urine.
Neuroscience Letters
February 13, 2008
Jiřı́ Wackermann, Marc Wittmann, Felix Hasler et al.
95 citations
Psilocybin, a hallucinogenic substance, alters the internal representation of time by increasing the loss rate of the internal duration representation. In two double-blind, placebo-controlled experiments—one with 12 subjects receiving graded doses and another with 9 subjects receiving a very low dose—participants repeatedly reproduced time intervals between 1.5 and 5 seconds. The parameter kappa from the 'dual klepsydra' model was used to assess effects. At 90 minutes after intake, psilocybin significantly increased kappa, indicating a higher loss rate of internal time representation. These findings may relate to qualitative changes in subjective time during altered states of consciousness.
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 Psychopharmacology
July 17, 2008
Felix Hasler, Erich Studerus, Karl‐johan Lindner et al.
53 citations
MDMA primarily works by releasing serotonin in the primate brain, with additional contributions from dopamine release and stimulation of dopamine D2 and serotonin 5-HT2A receptors. The role of serotonin 5-HT1A receptors in MDMA's effects in humans was unclear. In a double-blind, placebo-controlled study, 15 healthy men received placebo, the 5-HT1A antagonist pindolol, MDMA alone, or MDMA after pindolol. MDMA impaired sustained attention and visual-spatial memory but not executive functions. Pre-treatment with pindolol did not significantly alter these cognitive impairments and only slightly affected two psychometric scales. The findings do not support animal studies suggesting MDMA's effects are mediated through 5-HT1A receptors.
Journal of Vision
March 19, 2010
O. Carter, John D. Pettigrew, Felix Hasler et al.
3 citations
Binocular rivalry, the fluctuation in visual awareness when different images are shown to each eye, is slowed by the hallucinogenic compound psilocybin, the active ingredient in magic mushrooms. In ten healthy human subjects, psilocybin reduced the rate of switching between percepts and increased the experience of mixed or transitional percepts. Pretreatment with ketanserin, a selective 5-HT2A receptor antagonist, blocked most of psilocybin's positive psychotic-like symptoms but did not affect the slowing of binocular rivalry switching or negative symptoms related to reduced arousal and vigilance. This suggests that the slowing of binocular rivalry by psilocybin is not mediated by 5-HT2A receptors but may instead involve 5-HT1A receptor activation reducing serotonin release from the brainstem raphe nuclei, linking rivalry switching rate to arousal and attention.