Psilocybin – Summary of knowledge and new perspectives

doi:10.1016/j.euroneuro.2013.12.006

European Neuropsychopharmacology

Volume 24, Issue 3, March 2014, Pages 342-356

https://doi.org/10.1016/j.euroneuro.2013.12.006 Get rights and content

Abstract

Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen. This review summarizes all the past and recent knowledge on psilocybin. It briefly deals with its history, discusses the pharmacokinetics and pharmacodynamics, and compares its action in humans and animals. It attempts to describe the mechanism of psychedelic effects and objectify its action using modern imaging and psychometric methods. Finally, it describes its therapeutic and abuse potential.

Introduction

Psilocybin and psilocin, the main psychedelic ingredients of hallucinogenic mushrooms (Guzman et al., 1998, Laussmann and Meier-Giebing, 2010) (Table 1), have recently been given a lot of attention as a research tools (Geyer and Vollenweider, 2008) as well as a potential therapeutic agents (Grob et al., 2011, Moreno et al., 2006, Sewell et al., 2006). History of the ritual use of hallucinogenic mushrooms dates back 3000 years in Mexico and regionally its use is still conventional practice today (Carod-Artal, 2011, Hofmann, 2005). Western science was introduced to these mushrooms in 1957 by Robert G. Wasson and they were later systematically ranked by Roger Heim (Aboul-Enein, 1974). Psilocybin was first isolated and identified in 1958 and synthesized in 1959 by Albert Hofmann (Hofmann et al., 1958). The content of psilocybin and psilocin in hallucinogenic mushrooms varies in the range from 0.2% to 1% of dry weight (Table 2.).

In the 1960s psilocybin was widely used in the experimental research of mental disorders and even in psychotherapy (Metzner, 2005). Soon, however, psilocybin containing mushrooms spread amongst the general public and became a popular recreational drug. Consequently, psilocybin (and psilocin) was classed as a schedule I drug in 1970 (Nichols, 2004) and all human experiments were gradually discontinued. Since the late 1990s, interest in human experimental research into psilocybin and other psychedelics has become revived (Figure 1). Nowadays, psilocybin is one of the most used psychedelics in human studies due to its relative safety, moderately long duration of action and good absorption after oral administration (Hasler et al., 2004, Johnson et al., 2008).

The aim of this paper is to bring together the most detailed and up to date list of known properties and effects of psilocybin, starting with its chemical characteristics, metabolism, pharmacokinetics and ending with the use of psilocybin in human research and therapy.

Section snippets

Structural and chemical characteristics of psilocybin

Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine) and its active dephosphorylated metabolite psilocin (N,N-dimetyltryptamine) structurally belong to the group of tryptamine/indolamine hallucinogens and are structurally related to serotonin (Hasler et al., 1997, Horita and Weber, 1961a) (Figure 1). An equimolar dose to 1 mol of psilocin is 1.4 mol of psilocybin (Wolbach et al., 1962). Substitution of the indole nucleus in position 4 probably plays a substantial role in its hallucinogenic

Metabolism and pharmacokinetics of psilocybin

Psilocybin is rapidly dephosphorylated to psilocin in the intestinal mucosa by alkaline phosphatase and nonspecific esterase. After ingestion, about 50% of the total volume of psilocin is absorbed from the digestive tract of the rat (Kalberer et al., 1962). After systemic parenteral administration of psilocybin tissue phosphatases play the same role with the kidneys being among the most active (Horita and Weber, 1961b, Horita and Weber, 1962). Given that the competitive blockade of

Pharmacodynamics

Psilocybin and psilocin are the substances with predominant agonist activity on serotonin 5HT_2A/C and 5HT_1A receptors (for specific affinities see Table 3). Interestingly, psilocybin's affinity to human 5HT_2A receptors is 15-fold higher than in rats (Gallaher et al., 1993). While the 5HT_2A receptor agonism is considered necessary for hallucinogenic effects (Nichols, 2004), the role of other receptor subtypes is much less understood. Contrary to the previous report (Creese et al., 1975), a

Behavioral effects of psilocybin/psilocin in animals

Psilocybin and psilocin are used in animal behavioral experiments in the range of 0.25–10 mg/kg; however doses up to 80 mg/kg have also been used. Psilocybin dose of 10 mg/kg has mild sympathomimetic effects (piloerection and hyperventilation) in rodents and small carnivores (Passie et al., 2002). Characteristic effect of psilocybin is enhancement of monosynaptic spinal reflexes in cats (Hofmann, 1968).

Peak of behavioral changes are typically observed within 30–90 min after drug administration.

Dosage and time course of effects

In terms of efficacy, psilocybin is 45 times less potent than LSD and 66 times more potent than mescaline (Isbell, 1959, Wolbach et al., 1962). Clinical studies indicate that the effective dose of oral (p.o.) psilocybin is 0.045–0.429 mg/kg and 1–2 mg per adult intravenously (i.v.) (Table 4). Psychedelic effects occur at doses above 15 mg of oral psilocybin (Hasler et al., 2004) or plasma psilocin levels of 4–6 ng/ml (Hasler et al., 1997). Safety guidelines for the experimental use of hallucinogens

Acute somatic toxicity of psilocybin

According to a number of toxicological and clinical studies psilocybin has a very low toxicity (Nichols, 2004, Passie et al., 2002). Psilocybin showed no specific signs of toxicity in the isolated organs (intestine, heart) of rats and pigs (Cerletti, 1958), it is also not neurotoxic (Johnson et al., 2008). Psilocybin LD₅₀ for rats and mice is 280–285 mg/kg, and for rabbits it is 12.5 mg/kg. Psilocin LD₅₀ is significantly lower for mice and rats 75 mg/kg and for rabbits 7 mg/kg (Usdin and Efron, 1972

Risks and side effects of psilocybin, long-term toxicity

The safety of psilocybin use is given mainly by personal expectations (set) and the nature of the environment (setting), which is the cause of the great variability of the subjective effects (Nichols, 2004). Due to the altered perception, hallucinations and intensified emotions, dangerous behavior may occur during non-medical administration (Johnson et al., 2008). These complications can be significantly reduced by educating an individual, creating a safe environment and building rapport with

Electroencephalography (EEG), Magnetoencephalography (MEG)

Early electrophysiological studies (limited to a visual assessment) documented increases of fast activity, reduction of amplitude and desynchronization in both primates and humans (Fink, 1969, Horibe, 1974, Meldrum and Naquet, 1971). Changes in visually evoked potentials and a decrease in alpha and theta activity were also described in humans (Da Fonseca et al., 1965, Rynearson et al., 1968).

Recent findings with psilocin and other hallucinogens in rats showed an overall reduction in EEG

Psilocybin as a model of psychosis

Hallucinogens including psilocybin induce complex changes at various levels of the brain which lead to altered states of consciousness. The neurobiology of the hallucinogenic effect was described elsewhere (Gonzalez-Maeso and Sealfon, 2009, Nichols, 2004, Palenicek and Horacek, 2008, Vollenweider, 2001).

Psilocybin is used as one of the major acute serotonergic models of psychosis/schizophrenia (Geyer and Vollenweider, 2008, Hanks and Gonzalez-Maeso, 2013) due to its phenomenological and

Therapeutic uses and recent clinical studies

Most clinical studies with psilocybin were performed in the 1960s, often using synthetic Sandoz's Indocybin^® (Passie et al., 2002). Hallucinogens were considered as key tools for understanding the etiopathogenesis of some mental illnesses and to have some therapeutic potential. In spite of often being considered as methodologically inaccurate from a current perspective, thousands of scientific papers published by 1965 described positive results in more than 40,000 patients who had taken

Conclusion

In summary, psilocybin has a strong research and therapeutic potential. Due to the good knowledge of its pharmacodynamics and pharmacokinetics, beneficial safety profile and zero potential to cause addiction it is frequently used both in animal and human research. It brings a number of key findings regarding the functioning of the human brain, in particular the role of the serotonergic system in complex functions such as perception and emotions. It also serves as a useful tool for the study of

Role of funding source

Funding for this study was provided by IGA MHCR no. NT/13897; the IGA MHCR had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Contributors

Author Filip Tylš designed the layout of the article and collected the relevant literature. He contributed to all parts of the text.

Author Tomáš Páleníček supervised the layout and wrote the abstract. He also greatly contributed to the pharmacokinetic and pharmacodynamic parts of the text.

Author Jiří Horáček supervised the whole article and contribute mainly to the discussion about imaging studies with psilocybin.

Conflict of interest

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that we have given due consideration to the protection of intellectual properly associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the

Acknowledgements

This work was supported by the research Grant IGA MHCR no. NT/13897.

References (166)

N. Anastos et al.
Investigation into the temporal stability of aqueous standard solutions of psilocin and psilocybin using high performance liquid chromatography
Sci. Justice
(2006)
J.B. Appel et al.
Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline
Eur. J. Pharmacol.
(1989)
M.W. Beug et al.
Psilocybin and psilocin levels in twenty species from seven genera of wild mushrooms in the Pacific Northwest, U.S.A.
J. Ethnopharmacol.
(1982)
J. Chen et al.
Determining the pharmacokinetics of psilocin in rat plasma using ultra-performance liquid chromatography coupled with a photodiode array detector after orally administering an extract of Gymnopilus spectabilis
J. Chromatogr. B Anal. Technol. Biomed. Life Sci.
(2011)
I. Creese et al.
The dopamine receptor: differential binding of d-LSD and related agents to agonist and antagonist states
Life Sci.
(1975)
M. Davis et al.
Psilocybin: biphasic dose–response effects on the acoustic startle reflex in the rat
Pharmacol. Biochem. Behav.
(1977)
H.E. Day et al.
Conditioned fear inhibits c-fos mRNA expression in the central extended amygdala
Brain Res.
(2008)
W.E. Fantegrossi et al.
The behavioral pharmacology of hallucinogens
Biochem. Pharmacol.
(2008)
J. Gartz et al.
Analyses and cultivation of fruitbodies and mycelia of Psilocybe bohemica
Biochem. Physiol. Pflanz.
(1989)
M.A. Geyer et al.
Serotonin research: contributions to understanding psychoses
Trends Pharmacol. Sci.
(2008)

J. Gonzalez-Maeso et al.

Psychedelics and schizophrenia

Trends Neurosci.

(2009)

J. Gonzalez-Maeso et al.

Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior

Neuron

(2007)

E. Gouzoulis-Mayfrank et al.

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

Neuropsychopharmacology

(1999)

A.L. Halberstadt et al.

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Neuropharmacology

(2011)

J.H. Halpern et al.

Hallucinogen persisting perception disorder: what do we know after 50 years?

Drug Alcohol Depend.

(2003)

F. Hasler et al.

Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man

Pharm. Acta Helv.

(1997)

F. Hasler et al.

Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man

J. Pharm. Biomed. Anal.

(2002)

A. Horita et al.

The enzymic dephosphorylation and oxidation of psilocybin and psilocin by mammalian tissue homogenates

Biochem. Pharmacol.

(1961)

A. Horita et al.

Dephosphorylation of psilocybin in the intact mouse

Toxicol. Appl. Pharmacol.

(1962)

F. Kalberer et al.

The fate of psilocin in the rat

Biochem. Pharmacol.

(1962)

P. Kovacic

Unifying electron transfer mechanism for psilocybin and psilocin

Med. Hypotheses

(2009)

T. Laussmann et al.

Forensic analysis of hallucinogenic mushrooms and khat (Catha edulis Forsk) using cation-exchange liquid chromatography

Forensic Sci. Int.

(2010)

H. Lindenblatt et al.

Quantitation of psilocin in human plasma by high-performance liquid chromatography and electrochemical detection: comparison of liquid–liquid extraction with automated on-line solid-phase extraction

J. Chromatogr. B Biomed. Sci. Appl.

(1998)

H.Y. Aboul-Enein

Psilocybin: a pharmacological profile

Am. J. Pharm. Sci. Support. Public Health

(1974)

G.K. Aghajanian et al.

Hallucinogenic indoleamines: preferential action upon presynaptic serotonin receptors

Psychopharmacol. Commun.

(1975)

S. Ballesteros

Natural sources of drugs of abuse: magic mushrooms

B.G. Barceloux

Psilocybin and hallucinogenic mushrooms

J. Berle

Isolation and Identification of Drugs in Pharmaceuticals, Body Fluids and Post-mortem Material

(1974)

J.B. Blair et al.

Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines

J. Med. Chem.

(2000)

Bogenschutz, M. 2012. Effects and Therapeutic Potential of Psilocybin in Alcohol Dependence (ClinicalTrials.gov...

R.L. Carhart-Harris et al.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Proc. Natl. Acad. Sci. USA

(2012)

R.L. Carhart-Harris et al.

Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin

Br. J. Psychiatry

(2012)

R.L. Carhart-Harris et al.

The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability

J. Psychopharmacol.

(2011)

F.J. Carod-Artal

Hallucinogenic drugs in pre-Columbian Mesoamerican cultures

Neurologia

(2011)

O.L. Carter et al.

Psilocybin impairs high-level but not low-level motion perception

Neuroreport

(2004)

A. Cerletti

Etude pharmacologique de la psilocybine

A. Chauchard

The Hallucinogens

(1967)

S. Cohen

Lysergic acid diethylamide: side effects and complications

J. Nerv. Ment. Dis.

(1960)

R.L. Collins et al.

Psilocin: effects on behaviour and brain serotonin in mice

Nature

(1966)

D. Cologno et al.

Triptans: over the migraine

Neurol. Sci.

(2012)

J.S. Da Fonseca et al.

Neurophysiological and psychological study of psilocybin-induced modification of visual information processing in man

Neuropsychopharmacology

(1965)

A. Dittrich

The standardized psychometric assessment of altered states of consciousness (ASCs) in humans

Pharmacopsychiatry

(1998)

R. Doblin

Pahnke's Good Friday Experiment: A Long-Term Follow-Up and Methodological Critique

(1991)

W.E. Fantegrossi et al.

Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys

Behav. Pharmacol.

(2004)

W.E. Fantegrossi et al.

Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys

Behav. Pharmacol.

(2004)

M. Fink

EEG and human psychopharmacology

Annu. Rev. Pharmacol.

(1969)

G. Fisher

The psycholytic treatment of a childhood schizophrenic girl

Int. J. Soc. Psychiatry

(1970)

M. Franz et al.

Magic mushrooms: hope for a ‘cheap high’ resulting in end-stage renal failure

Nephrol. Dial. Transpl.

(1996)

K.J. Friston et al.

Schizophrenia: a disconnection syndrome?

Clin. Neurosci.

(1995)

T.K. Gallaher et al.

Higher affinity of psilocin for human than rat 5-HT2 receptor indicates binding site stucture

Medicinal Chem. Res.

(1993)

Cited by (168)

Spectroscopic behavior of bufotenine and bufotenine N-oxide: Solvent and pH effects and interaction with biomembrane models
2024, Biochimica et Biophysica Acta - Biomembranes
Bufotenine is a fluorescent analog of Dimethyltryptamine (DMT) that has been widely studied due to its psychedelic properties and biological activity. However, little is known about its spectroscopic properties in different media. Thus, we present in this work, for the first time, the spectroscopic behavior of bufotenine and bufotenine N-oxide by means of their fluorescence properties. Both molecules exhibit changes in optical absorption and emission spectra with variations in pH of the medium and in different solvents. Assays in the presence of biomembranes models, like micelles and liposomes, were also performed. In surfactants titration experiments, the spectral shift observed in fluorescence shows the interaction of both molecules with pre-micellar structures and with micelles. Steady state anisotropy measurements show that both bufotenine and bufotenine N-oxide, in the studied concentration range, interact with liposomes without causing changes in the fluidity of the lipid bilayer. These results can be useful in studies that aim at searching for new compounds, inspired by bufotenine and bufotenine N-oxide, with relevant pharmacological activities and also in studies that use these molecules as markers of psychiatric disorders.
Deciphering psilocybin: Cytotoxicity, anti-inflammatory effects, and mechanistic insights
2024, International Immunopharmacology
A decade of clinical research has indicated psilocybin's effectiveness in treating various neuropsychiatric disorders, such as depression and substance abuse. The correlation between increased pro-inflammatory cytokines and the severity of neuropsychiatric symptoms, along with the known anti-inflammatory potential of some psychedelics, suggests an immunomodulatory role for psilocybin. This study aims to understand the mechanism of action of psilocybin by investigating the cytotoxic and immunomodulatory effects of psilocybin and psilocin on both resting and LPS-activated RAW 264.7 murine macrophages. The study evaluated the cytotoxicity of psilocybin and psilocin using an LDH assay across various doses and assessed their impact on cytokine production in RAW 264.7 cells, measuring cytokine expression via ELISA. Different doses, including those above and below the LC₅₀, were used in both pre-treatment and post-treatment approaches. The LDH assay revealed that psilocybin is almost twice as cytotoxic as psilocin, with an LC₅₀ of 12 ng/ml and 28 ng/ml, respectively. In resting macrophages, both psilocybin and psilocin triggered significant release of TNF- α after 4 h, with the lowest doses inducing higher levels of the cytokine than the highest doses. IL-10 expression in resting cells was only triggered by the highest dose of psilocin in the 4-hour incubation group. In LPS-stimulated cells, psilocin reduced TNF- α levels more than psilocybin in pre-treatment and post-treatment, with no significant effects on IL-10 in pre-treatment. Psilocin, but not psilocybin, induced a significant increase of IL-10 in post-treatment, leading to the conclusion that psilocin, but not psilocybin, exerts anti-inflammatory effects on classically activated macrophages.
Psilocybin and eugenol prevent DSS-induced neuroinflammation in mice
2024, Biocatalysis and Agricultural Biotechnology
Neuroinflammation has emerged as a central pathology common to several acute and chronic brain diseases. Recent studies have displayed the anti-inflammatory properties of naturally occurring compounds derived from mushrooms and plants could potentially reduce neuroinflammation and disease progression. In this study, we aimed to investigate the impact of psilocybin and eugenol, as well as their combinations, on neuroinflammation. To induce inflammation through the gut-brain axis, we employed a colitis mouse model via oral feeding of dextran sulfate sodium (DSS). By administering various concentrations and combinations of treatments, both before and after inducing inflammation, we sought to assess the synergistic anti-inflammatory effects of psilocybin and eugenol. Our findings revealed oral psilocybin and eugenol post-treatment significantly reduced the expression of pro-inflammatory cytokines and inflammatory mediators in the brain, including IL-1β, IL-6, and COX-2. Notably, combined treatment of psilocybin and eugenol exhibited the strongest reduction in IL-6 levels when compared to the DSS group. While both psilocybin and eugenol possess anti-inflammatory effects, the combined treatment overall did not demonstrate synergistic reductions in neuroinflammation across all markers. This study adds to the growing body of evidence supporting the therapeutic potential of psilocybin and eugenol in psychiatric and neurodegenerative inflammatory disorders. Further research is necessary to elucidate the underlying mechanisms of their anti-inflammatory effects and to evaluate their efficacy in clinical settings.
Assessing the utility of in silico tools in early drug development: The case of a pharmaceutically relevant formulation of the prodrug psilocybin
2024, Journal of Drug Delivery Science and Technology
(1) Background: Depressive disorders contribute to an excruciating global mental health burden. Recently, there has been a great shift in interest towards substances with psychedelic potential as treatment for patients with resistant forms of depression, one of these substances being psilocybin. The need to expedite processes within the drug development pipeline and make potential therapy available for patients with treatment-resistant forms of depression is great. Approaches to combine computational and traditional experimental drug development are more consequential due to their potential to shorten development times and aid in setting product specifications. To date, the full extent to which in silico methods for early drug development yield valid and robust data which can be directly used for translation into safe and effective pharmaceutical products, remains unknown, especially for prodrug containing formulations. (2) Methods: Herein we explore the robustness and applicability of in silico generated data for the aid of experimental drug development by directly comparing computationally generated data to experimentally and literature derived data. Furthermore, by utilizing different computational approaches, we investigate to which extent these computational models can by utilized to create a novel capsule containing psilocybin, having in mind that psilocybin is a prodrug and psilocin is the active. (3) Results: In silico models provided valid data including intrinsic dissolution and capsule dissolution behavior, but were not able to predict stability issues. Simulations of the expected in vivo performance showed deviations from previously published clinical studies. Significant improvements in predictive accuracy were made by implementing physicochemical surface pH models and entering in vitro and in vivo data. (4) Conclusions: Computational models provide a valuable resource to aid in the planning and implementation of experimental drug product development. Prodrug and active were simulated for their in vitro and in vivo behavior. Even though the results appear to be robust, these models exhibit potential for improvement in predictive accuracy, and thus, applicability of computationally generated data for drug development. Moreover, the models are yet unable to perform a completely accurate drug development process solely supported by in silico data. Lastly, we were able to report psilocybin as a BCS class III drug and psilocin as a BCS class I drug in terms of a provisional classification supported by our data.
The effect of casing and gypsum on the yield and psychoactive tryptamine content of Psilocybe cubensis (Earle) Singer
2024, Fungal Biology
Psychedelic fungi have experienced a surge in interest in recent years. Most notably, the fungal secondary metabolite psilocybin has shown tremendous promise in the treatment of various psychiatric disorders. The mushroom species that produce this molecule are poorly understood. Here we sought to examine for the first time, the response of a psilocybin-producing species Psilocybe cubensis to casing (peat moss and vermiculite) and supplementation with gypsum (calcium sulfate dihydrate), two common practices in commercial mushroom cultivation. Mycelial samples of genetically authenticated P. cubensis were used to inoculate popcorn grain bags. The fully colonized bags of popcorn grain (0.15 kg) were transferred to bins of 0.85 kg pasteurized horse manure, with or without 1 cm thick layer of casing and/or 5 % gypsum. Our results indicate that the use of a casing layer significantly increases the biological efficiency (161.5 %), by approximately four fold, in comparison to control (40.5 %), albeit with a slight delay (∼2 days) for obtaining fruiting bodies and a somewhat reduced total tryptamine content (0.85 %) as gauged by High Performance Liquid Chromatography measurements. Supplementation with both casing and gypsum, however, appears to promote maximal yields (896.6 g/kg of dried substrate), with a biological efficiency of 89.6 %, while also maintaining high total tryptamine expressions (0.95 %). These findings, revealing methods for maximizing yield of harvest and expressions of psychoactive tryptamines, may prove useful for both home growers and commercial cultivators of this species, and ultimately support the growth of a robust industry with high quality natural products.
Unintentional family poisoning with a chocolate bar with Psilocybe cubensis inside: A case report
2024, Toxicologie Analytique et Clinique
Les psilocybes sont consommés en médecine traditionnelle, dans le cadre de rituels religieux et chamaniques ou à visée récréative. Ces champignons contiennent deux substances psychoactives, la psilocybine et son métabolite actif la psilocine. Comme le cannabis, ces substances peuvent être incorporées à des aliments appelés « edibles » et consommées ainsi accidentellement.
Nous rapportons les cas de trois enfants ayant ingéré accidentellement du chocolat contenant du Psilocybe cubensis. Dans l’heure suivante, ils ont tous présenté une mydriase, une euphorie, une asthénie. Seule la plus jeune a présenté des hallucinations. Ils ont tous reçu 1 g/kg de charbon activé. Les symptômes ont duré 6 heures et les enfants ont tous guéri sans séquelles. Un screening urinaire par TOF retrouvait uniquement la psilocine sans psilocybine. Le dosage par LC-MS/MS retrouvait la psilocine à des concentrations de 640 ng/mL, 266 ng/mL et 147,5 ng/mL.
L’absence de psilocybine lors des analyses peut s’expliquer par une limite de détection supérieure à la dose contenue dans les prélèvements, d’une quantité de chocolat non suffisante pour être détectée ou d’une métabolisation complète de la psilocybine en psilocine. En France, la possession et la vente de Psilocybe sont interdites. L’importation de produits contenant des substances psychoactives pose un problème de santé publique du fait d’une législation variable d’un pays à l’autre. L’homogénéisation de la législation sur le plan international permettrait de connaître et suivre les produits, leurs compositions et leurs toxiques.
Il s’agit d’une intoxication familiale involontaire par un Psilocybe via la consommation de chocolat en tablette. La présentation clinique est cohérente avec la dose ingérée. L’absence de législation mondiale homogène favorise ces intoxications.
Psilocybe mushrooms are used in traditional medicine, in religious and shamanic rituals, or for recreational purposes. These fungi contain two potent psychoactive compounds, psilocybin and its active metabolite, psilocin. Like cannabis, these substances can be incorporated into foods called “edibles” and consumed accidentally.
We report three cases of children who accidentally ingested chocolate that contained Psilocybe cubensis. Within an hour, all three children exhibited symptoms of mydriasis, euphoria, and asthenia. Only the youngest experienced hallucinations. Each were administered 1 g/kg of activated charcoal as treatment. The symptoms persisted for 6 hours and all children recovered without any lasting effects. A urine screening using time-of-flight (TOF) analysis detected the presence of psilocin, but not psilocybin. Subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing in children revealed psilocin concentrations of 640 ng/mL, 266 ng/mL, and 147.5 ng/mL, respectively.
The absence of psilocybin in the samples can be explained by a detection limit higher than the dose contained in the samples, by a quantity of chocolate insufficient to be detected or by complete metabolisation of psilocybin to psilocin. In France, possession and sale of Psilocybe mushrooms are prohibited. Import of products containing psychoactive substances presents a public health challenge due to differing legislation among countries. Standardizing legislation at international level could enable more accurate tracking of such products, as well as provide insight into their composition and potential toxicity.
This case illustrates an unintentional family intoxication with Psilocybe mushrooms through the consumption of chocolate bars. The clinical symptoms align with the ingested dose. The lack of consistent global legislation contributes to such misunderstandings and potentially harmful situations.

View all citing articles on Scopus

View full text

REVIEWPsilocybin – Summary of knowledge and new perspectives

Abstract

Introduction

Section snippets

Structural and chemical characteristics of psilocybin

Metabolism and pharmacokinetics of psilocybin

Pharmacodynamics

Behavioral effects of psilocybin/psilocin in animals

Dosage and time course of effects

Acute somatic toxicity of psilocybin

Risks and side effects of psilocybin, long-term toxicity

Electroencephalography (EEG), Magnetoencephalography (MEG)

Psilocybin as a model of psychosis

Therapeutic uses and recent clinical studies

Conclusion

Role of funding source

Contributors

Conflict of interest

Acknowledgements

Sci. Justice

Eur. J. Pharmacol.

J. Ethnopharmacol.

J. Chromatogr. B Anal. Technol. Biomed. Life Sci.

Life Sci.

Pharmacol. Biochem. Behav.

Brain Res.

Biochem. Pharmacol.

Biochem. Physiol. Pflanz.

Trends Pharmacol. Sci.

Trends Neurosci.

Neuron

Neuropsychopharmacology

Neuropharmacology

Drug Alcohol Depend.

Pharm. Acta Helv.

J. Pharm. Biomed. Anal.

Biochem. Pharmacol.

Toxicol. Appl. Pharmacol.

Biochem. Pharmacol.

Med. Hypotheses

Forensic Sci. Int.

J. Chromatogr. B Biomed. Sci. Appl.

Psilocybin: a pharmacological profile

Am. J. Pharm. Sci. Support. Public Health

Hallucinogenic indoleamines: preferential action upon presynaptic serotonin receptors

Psychopharmacol. Commun.

Natural sources of drugs of abuse: magic mushrooms

Psilocybin and hallucinogenic mushrooms

Isolation and Identification of Drugs in Pharmaceuticals, Body Fluids and Post-mortem Material

Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines

J. Med. Chem.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Proc. Natl. Acad. Sci. USA

Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin

Br. J. Psychiatry

The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability

J. Psychopharmacol.

Hallucinogenic drugs in pre-Columbian Mesoamerican cultures

Neurologia

Psilocybin impairs high-level but not low-level motion perception

Neuroreport

Etude pharmacologique de la psilocybine

The Hallucinogens

Lysergic acid diethylamide: side effects and complications

J. Nerv. Ment. Dis.

Psilocin: effects on behaviour and brain serotonin in mice

Nature

Triptans: over the migraine

Neurol. Sci.

Neurophysiological and psychological study of psilocybin-induced modification of visual information processing in man

Neuropsychopharmacology

The standardized psychometric assessment of altered states of consciousness (ASCs) in humans

Pharmacopsychiatry

Pahnke's Good Friday Experiment: A Long-Term Follow-Up and Methodological Critique

Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys

Behav. Pharmacol.

Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys

Behav. Pharmacol.

EEG and human psychopharmacology

Annu. Rev. Pharmacol.

REVIEW
Psilocybin – Summary of knowledge and new perspectives