Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine

The paper traces Amanita muscaria from its shamanistic use and the isolation of four active compounds (muscarine, muscimol, muscazone and ibotenic acid) to Henry Dale and Otto Loewi’s demonstration that the parasympathetic transmitter is acetylcholine, which defined muscarinic/cholinergic receptors and paved the way for drugs such as pilocarpine and ipratropium.

Authors

  • Lee, M. R.
  • Dukan, E.
  • Milne, I.

Published

Journal of the Royal College of Physicians of Edinburgh
meta Study

Abstract

The mushroom Amanita muscaria (fly agaric) is widely distributed throughout continental Europe and the UK. Its common name suggests that it had been used to kill flies, until superseded by arsenic. The bioactive compounds occurring in the mushroom remained a mystery for long periods of time, but eventually four hallucinogens were isolated from the fungus: muscarine, muscimol, muscazone and ibotenic acid. The shamans of Eastern Siberia used the mushroom as an inebriant and a hallucinogen. In 1912, Henry Dale suggested that muscarine (or a closely related substance) was the transmitter at the parasympathetic nerve endings, where it would produce lacrimation, salivation, sweating, bronchoconstriction and increased intestinal motility. He and Otto Loewi eventually isolated the transmitter and showed that it was not muscarine but acetylcholine. The receptor is now known variously as cholinergic or muscarinic. From this basic knowledge, drugs such as pilocarpine (cholinergic) and ipratropium (anticholinergic) have been shown to be of value in glaucoma and diseases of the lungs, respectively.

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Research Summary of 'Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine'

Introduction

Amanita muscaria (fly agaric) is presented as a culturally prominent and readily recognisable mushroom in Europe and the UK, notable for its scarlet cap with white scales and association with birch forests. Earlier research and ethnographic reports established its long-standing use as an inebriant and hallucinogen among Siberian shamans, while 19th- and 20th-century pharmacological work identified multiple bioactive alkaloids; nonetheless, the mushroom's precise contribution to understanding parasympathetic pharmacology and the identity of the endogenous parasympathetic transmitter remained a historically important puzzle. This paper traces that historical and pharmacological trajectory. It aims to recount the ethnographic accounts of shamanistic use, summarise the isolation and characterisation of the mushroom's active constituents (including muscarine, ibotenic acid, muscimol and muscazone), and to describe how those findings, together with work on other alkaloids such as pilocarpine and physostigmine, contributed to the discovery of acetylcholine and to the development of therapeutics for glaucoma and respiratory disease. The article is framed as a narrative historical review rather than an empirical study with a formal experimental protocol.

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Study Details

  • Study Type
    meta
  • Journal
  • APA Citation

    Lee, M., Dukan, E., & Milne, I. (2018). Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine. Journal of the Royal College of Physicians of Edinburgh, 48(1), 85-91. https://doi.org/10.4997/jrcpe.2018.119

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Amanita muscaria (fly agaric): from a shamanistic... — Research Summary & Context | Blossom