## Psilocybin – Summary of knowledge and new perspectives

Filip Tylš, Tomáš Páleníček, Jiří Horáček

European Neuropsychopharmacology, 2014, 24, 342–356

Doi : 10.1016/j.euroneuro.2013.12.006

### 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.

### Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . .. . 343
2. Structural and chemical characteristics of psilocybin . . . . . . . . . . . . . . . . . . . . . . . . . . 344
3. Metabolism and pharmacokinetics of psilocybin . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . 345
4. Pharmacodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
5. Behavioral effects of psilocybin/psilocin in animals . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
6. Human studies with psilocybin . . . . . . . . . . . . . . . . . . . . . . . . .  . . . . . . . . . . . . . . . . . . . 346
6.1. Dosage and time course of effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
6.2. Effects on somatic, physiological and endocrine functions. . . . . . . . .. . . . . . . . . . . . 347
6.3. Psychotropic and neuropsychological effects of psilocybin.. . . . . . . . . . . . . . . . . . . . 348

7. Acute somatic toxicity of psilocybin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
8. Risks and side effects of psilocybin, long-term toxicity. . . . . . . . . .  . . . . . . . . . . . . . . . 349
9. Functional brain imaging studies of psilocybin . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . 349
9.1. Electroencephalography (EEG), Magnetoencephalography. . . . . . . . . . . . . . . . . . . . 349
9.2. Positron emission tomography (PET), Functional magnetic resonance imaging (fMRI) .. . 350
10. Psilocybin as a model of psychosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 350
11. Therapeutic uses and recent clinical studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
12. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  . . . . 351
Role of funding source . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . 352
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . 352
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  . . . .  . 352
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  . 352

### 1. 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.

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Psilocybin_-_Summary_of_knowledge_and_ne