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PubMed2003

Effects of the 5-HT2A agonist psilocybin on mismatch negativity generation and AX-continuous performance task: implications for the neuropharmacology of cognitive deficits in schizophrenia.

Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an 'AX'-type continuous performance test (AX-CPT)--measures of auditory and visual context-dependent information processing--in a similar manner as observed in schizophrenia. This placebo-controlled study investigated effects of the 5-HT(2A) receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin administration induced significant performance deficits in the AX-CPT, but failed to reduce MMN generation significantly. These results indirectly support evidence that deficient MMN generation in schizophrenia may be a relatively distinct manifestation of deficient NMDAR functioning. In contrast, secondary pharmacological effects shared by NMDAR antagonists and the 5-HT(2A) agonist (ie disruption of glutamatergic neurotransmission) may be the mechanism underlying impairments in AX-CPT performance observed during both psilocybin and ketamine administration. Comparable deficits in schizophrenia may result from independent dysfunctions of 5-HT(2A) and NMDAR-related neurotransmission.

Adult↗

PubMed2002

The pharmacology of psilocybin.

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.

Agaricales↗

PubMed1998

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

Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics.

Adult↗

PubMed2002

Effects of the hallucinogen psilocybin on covert orienting of visual attention in humans.

Hallucinogenic drug-induced states are considered as models for acute schizophrenic disorders (experimental psychoses). In a double-blind study with healthy volunteers we investigated the influence of the serotonergic hallucinogen psilocybin, the ecstasy-like drug 3,4-methylenedioxyethylamphetamine (MDE), the stimulant d- methamphetamine and placebo on covert orienting of spatial attention (n = 8 in each group). Reaction times were prolonged after ingestion of psilocybin > MDE, but not after d-methamphetamine. In addition, subjects on psilocybin exhibited particularly slow reaction times in invalid trials at short cue target intervals and failure of response inhibition in valid trials at long cue target intervals for right visual field targets. Despite some methodological limitations, these results are in line with both bilateral impairment of disengagement of attention and a lateralized impairment of inhibition of return (IOR) in productive psychotic states. Additional investigations with larger samples, different hallucinogenic substances (serotonergic agonists vs. NMDA antagonists) and different dose regimens are needed in order to further explore the suggested relationship between visuospatial attentional dysfunction and acute psychotic conditions.

3,4-Methylenedioxyamphetamine↗

PubMed2003

[Levels of psilocybin and psilocin in various types of mushrooms].

Psilocin and psilocybin are psychoactive components of mushrooms of the genus Psilocybe and many others (Panaeolus, Inocybe, Pluteus etc.). In our republic, several species of Psilocybe with a high content of these components can be found. In the present study, we give a semiquantitative content of psilocin and psilocybin in some of our mushrooms in dry substance (Psilocybe semilanceata, Psilocybe bohemica, Psilocybe arcana, Psilocybe cyanescens, Panaeolus acuminatus sensu Ricken, Inocybe haemacta and Pluteus salicinus). For quantification, the GC/MS instrumentation was applied. Psilocin and psilocybin were silylated by the derivatization agent N-methyl-N-trimet-hylsilyltrifluoroacetamide. As an internal standard, 5-methoxytryptamin was used. The results of this study prove the presence of at least three species of Psilocybe with a high content of psychoactive components growing in our republic: Psilocybe semilanceata, Psilocybe bohemica and Psilocybe arcana.

Agaricales↗

PubMed1983

The quantitation of psilocybin in hallucinogenic mushrooms using high performance liquid chromatography.

A method using high performance liquid chromatography (HPLC) with an acetonitrile, water, and phosphoric acid mobile phase and a bonded cyano-amino-type polar phase column has been developed for the rapid, selective, and accurate quantitation of psilocybin in dry mushroom material. A simple one-step procedure is used for the quantitative extraction of psilocybin in under 60 min. The 267:254 nm absorbance ratio is used as a check on peak purity for the psilocybin response.

Basidiomycota↗

PubMed1999

Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers. Results of an experimental double-blind placebo-controlled study.

The aim of this study was to contribute to the characterization of the entactogen (ecstasy) substance group. The psychopathological, neuroendocrine and autonomic effects of common recreational doses of the entactogen 3,4-methylenedioxyethylamphetamine (MDE), the hallucinogen psilocybin, the stimulant d-methamphetamine and placebo were investigated in a double-blind study with healthy volunteers (n = 32). Psychological effects of the drugs were assessed by means of standardized rating scales, self assessment inventories and free descriptions. The most characteristic effects of MDE were pleasant emotional experiences of relaxation, peacefulness, content and closeness to others. However, significant stimulant and hallucinogen-like effects were also present, although the latter were weaker than the effects of psilocybin. MDE elicited the strongest endocrine and autonomic effects among the three drugs, including robust rises of serum cortisol and prolactin, elevations of blood pressure and heart rate, and a moderate, but significant rise of body temperature. The apparent contrast between psychological and autonomic effects (subjective relaxation versus physical activation) was a unique feature of the MDE state. Our findings are in line with both users' reports and results from previous experimental studies, and support the view that entactogens constitute a distinct psychoactive substance class taking an intermediate position between hallucinogens and stimulants.

3,4-Methylenedioxyamphetamine↗

PubMedDate not supplied

Comparison of the discriminative stimulus properties of delta9-THC and psilocybin in rats.

Male albino rats were trained to respond differentially on the left or right lever in a 2-lever chamber on the basis of which drug had been given intra-peritoneally (IP) 30 min before experimentation. In 1 group 1.9 mg/kg of delta9-THC and control injections (vehicle) served as the discriminative stimuli associated with each lever and in another group the drug stimuli were 1.0 mg/kg of delta9-THC and 1.0 mg/kg of psilocybin. The results confirmed those of other experiments using different procedures; that delta9-THC can acquire discriminative control over responding. The fact that delta9-THC and psilocybin were also found to differentially control lever choice demonstrates that these 2 drugs probably produce discriminably different states in rats.

Animals↗

PubMed1982

Variation of psilocybin and psilocin levels with repeated flushes (harvests) of mature sporocarps of Psilocybe cubensis (Earle) Singer.

Analysis of Psilocybe cubensis (Earle) Singer grown in controlled culture showed that the level of psilocin was generally zero in the first (or sometimes even the second) fruiting of the mushroom from a given culture and that the level reached a maximum by the fourth flush. The level of psilocybin, which was nearly always at least twice the level of psilocin, showed no upward or downward trend as fruiting progressed, but was variable over a factor of four. Samples obtained from outside sources had psilocybin levels varying by over a factor of ten from one collection to the next.

Basidiomycota↗

PubMed1981

Quantitative analysis of psilocybin and psilocin in psilocybe baeocystis (Singer and Smith) by high-performance liquid chromatography and by thin-layer chromatography.

Rapid quantification of psilocybin and psilocin in extracts of wild mushrooms is accomplished by reversed-phase high-performance liquid chromatography with paired-ion reagents. Nine solvent systems and three solid supports are evaluated for their efficiency in separating psilocybin, psilocin and other components of crude mushroom extracts by thin-layer chromatography.

Agaricales↗

PubMed1999

Analysis of psilocybin and psilocin in Psilocybe subcubensis Guzmán by ion mobility spectrometry and gas chromatography-mass spectrometry.

A new method has been developed for the rapid analysis of psilocybin and/or psilocin in fungus material using ion mobility spectrometry. Quantitative analysis was performed by gas chromatography-mass spectrometry after a simple one-step extraction involving homogenization of the dried fruit bodies of fungi in chloroform and derivatization with MSTFA. The proposed methods resulted in rapid procedures useful in analyzing psychotropic fungi for psilocybin and psilocin.

Agaricales↗

PubMed1999

Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG.

The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.

3,4-Methylenedioxyamphetamine↗

PubMedDate not supplied

Investigation into the temporal stability of aqueous standard solutions of psilocin and psilocybin using high performance liquid chromatography.

This paper reports an investigation into the temporal stability of aqueous solutions of psilocin and psilocybin reference drug standards over a period of fourteen days. This study was performed using high performance liquid chromatography utilising a (95:5% v/v) methanol: 10 mM ammonium formate, pH 3.5 mobile phase and absorption detection at 269 nm. It was found that the exclusion of light significantly prolonged the useful life of standards, with aqueous solutions of both psilocin and psilocybin being stable over a period of seven days.

Chromatography, High Pressure Liquid↗

PubMed1998

Effects of the hallucinogen psilocybin on habituation and prepulse inhibition of the startle reflex in humans.

Schizophrenic patients exhibit deficits in indices of sensorimotor gating, such as habituation and prepulse inhibition (PPI) of the startle reflex. Hallucinogenic drug-induced states are putative models for the early and acute stages of schizophrenic and schizophrenia-spectrum disorders. Hallucinogenic drugs have been shown to disrupt PPI and/or retard habituation of the startle reflex in animal models of schizophrenia, consistent with the view of hallucinogen-induced states as 'model psychoses'. We evaluated the effects of the hallucinogen psilocybin on PPI and habituation of the startle reflex in a double-blind, placebo-controlled human study with 12 healthy subjects. In contrast to animal studies, in our small human sample, psilocybin increased PPI, while having no clear effect on habituation (n = 6). These findings must be considered preliminary because several factors, including dose regimens and experimental parameters, may influence the results of studies on startle plasticity. Further investigations both with psychotic patients in different stages of the disease and with human and animal models of schizophrenia are needed in order to explore the effects of hallucinogens on sensorimotor gating and the relationship between information processing in hallucinogenic drug-induced states and the naturally occurring psychoses.

Adult↗

PubMedDate not supplied

[The morphofunctional changes in the internal organs in the modelling of poisonings by psilocybine-containing mushrooms].

Histological analysis of the viscera in experimental poisoning with psilocybin-containing mushrooms showed nonspecific changes in all examined organs, presenting as expressed hemocirculatory disorders and intracellular dystrophy. Quantitative histochemical analysis showed appreciable shifts in the activities of enzymes involved in the cytoplasmic and mitochondrial redox processes and of specific enzymes involved in nerve tissue metabolism. This may reflect some features in the direct effects of narcotic alkaloids contained in psilocybin-producing mushrooms.

Aggression↗

PubMed1992

[Consumption of psilocybin-containing hallucinogenic mushrooms by young people].

The aim of this questionnaire survey was to investigate the extent of hallucinogenic mushroom consumption among students from a high school in the county of Aarhus, Denmark and among students at the University of Aarhus and students from the Danish school of journalism in Aarhus, Denmark. 3% of the high school students had used psilocybine-containing mushrooms as a hallucinogen. Only 1% had experience with LSD. Of the students at the University of Aarhus, and students from the Danish school of journalism in Aarhus, 333 persons (83%) returned the anonymous questionnaire. 9% had experience with hallucinogenic psilocybine containing mushrooms while only 2% had LSD experience. The use of hallucinogenic mushrooms was surprisingly high. This suggest that mushrooms are the most commonly used hallucinogenic substance in Denmark and that the use has exceeded that of LSD. Compared to non-users mushrooms users had significant more friends with mushroom experience. Furthermore, the study shows that the intention to use mushroom is commoner in persons who have friends with HPS experience. We find that the use of mushroom takes place in minor groups known to each other. Compared to non-users, mushroom-users are significant more experienced with marijuana and other substances. Unfortunately, our data do not permit us to show whether mushroom users are more inclined to try other drugs or whether persons with a high drug experience use mushrooms as well. Further investigation on the subject is recommended.

Adolescent↗

PubMed1977

The effects of psilocybin on primary process content in language.

The hypothesis that psilocybin induced primary process thinking was assessed. On four separate occasions, a subject was asked to write before, during, and after the hallucinogenic experience induced by doses ranging between 80 and 200 microgram/kg of psilocybin. Texts produced at the drug peak contained significantly more primary process content and were significantly more stereotyped on several measures than those written before or after the drug peak.

Humans↗

PubMed1977

GLC-mass spectral analysis of psilocin and psilocybin.

With the combined technique of GLC-mass spectrometry, psilocin and psilocybin, two hallucinogenic indoles, were analyzed as their trimethylsilyl derivatives. The method was applied to these two components in an extract of Psilocybe cubensis (Earle) Sing.

Basidiomycota↗