Toxicology
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“More than a beautiful red mushroom with white spots, Amanita muscaria is Soma, Prince of Paradise, divine medicine for spirit, mind and body.”
–Sacred Soma Shamans 
 
Amanita muscaria, commonly referred to as the fly agaric, is a poisonous and psychoactive basidiomycete fungus. Use of the mushroom started in ancient times and is connected with folk lore and mysticism. It is found throughout the temperate and boreal regions of the Northern Hemisphere. This is the quintessential toadstool, with a large white-spotted, crimson red cap. It is one of the most recognizable and widely encountered mushrooms in the wild.

Amanita muscaria poisoning typically occurs in adolescents and young adults ingesting the mushroom for its hallucinogenic properties. Following the outlawing of psilocybin-containing mushrooms, an increased quantity of legal A. muscaria mushrooms began to be sold and consumed recreationally. Although generally considered poisonous, deaths are extremely rare.

Amanita muscaria contains a number of biologically active agents, two of which, muscimol and ibotenic acid, are known to be psychoactive. Muscimol is the primary agent responsible for the majority of the psychoactivity with ibotenic acid acting as a secondary agent. A toxic dose in adults is approximately 6 mg muscimol or 60 mg ibotenic acid—the amount found in one cap of Amanita muscaria. However, the amount and ratio of chemical compounds per mushroom varies widely from region to region and season to season. Spring and summer mushrooms have been reported to contain up to 10 times as much ibotenic acid and muscimol compared to autumn specimens. Toxic components are not distributed uniformly in the mushroom. Most of the muscimol and ibotenic are contained in the cap or pilius, rather than in the base, with the smallest amount in the stalk. A fatal dose has been calculated at approximately 15 caps.

Fly agarics are known for unpredictable clinical effects which can be highly variable between individuals exposed to similar doses. Symptoms typically appear after 30 to 90 minutes and peak within three hours. Certain effects can last for days, but the majority of cases completely recover within 12 to 24 hours. Unlike other toxic mushroom ingestions, vomiting is uncommon. Patients may exhibit ataxia, auditory and visual hallucinations (described as sliding vision and “the ability to see through walls”), as well as hysteria. Central nervous system depression, coma, myoclonic jerking, hyperkinetic behavior, and seizures have been described in larger doses. Retrograde amnesia and somnolence can result following recovery.

This class of mushroom has previously been reported to cause anticholinergic effects. However, more recent analysis shows that effects are predominantly due to GABA and glutamate properties. The mechanism of toxicity is related to ibotenic acid, which is structurally similar to glutamic acid, and muscimol, which is related to GABA.  Effects of glutamate agonism include central nervous system excitation, while GABA agonist effects include CNS depression. In cases of serious poisoning, it causes a delirium, similar in effect to anticholinergic poisoning characterized by bouts of marked agitation with confusion, hallucinations, and irritability followed by periods of central nervous system depression.

Initial treatment consists of early gastric decontamination. If the delay between ingestion and treatment is less than four hours, activated charcoal is recommended. Gastric lavage can be considered if the patient presents within 1 hour of ingestion. Inducing vomiting with syrup of ipecac is no longer recommended.

There is no specific antidote, and supportive care is the mainstay of treatment for intoxication. As discussed, patients can develop symptoms similar to anticholinergic or cholinergic poisoning. However, the use of atropine or physostigmine as an antidote is not recommended as neither muscimol or ibotenic acid produce a true anticholinergic syndrome nor do they have activity at muscarinic receptors. Agitated or delirious patients can be treated with reassurance and, when necessary, physical restraints. Benzodiazepines such as diazepam or lorazepam can be used to control combativeness, agitation, muscular over activity, and seizures. Recurrent vomiting is uncommon, but if present, intravenous rehydration or electrolyte replacement may be required. Serious cases may develop loss of consciousness or coma, and may necessitate airway control, intubation and mechanical ventilation. Hemodialysis can remove the toxic components, although this intervention is generally considered unnecessary. The prognosis is good following vigilant supportive care with little risk of end organ damage or mortality. Deaths from A. muscaria have been reported in historical journal articles and newspaper reports. However, with modern medical intervention, fatalities are highly unlikely. Many older sources mistakenly list this mushroom as deadly, giving the impression that it is far more toxic than it actually is. The North American Mycological Association has noted no reliably documented fatalities from A. muscaria over the past 100 years. In reality, the vast majority of mushroom poisoning deaths (>90%) are associated with another famous Amanita species—Amanita phalloides better known as the Death Cap or Destroying Angel.


EXTRA CREDIT: Where does the term “going berzerk” come from?


In the 11th century, Vikings allegedly used Amanita muscaria to produce their “berserker” rages. The Berserkers ingested tea made from the mushroom prior to battle to give a sensation of becoming big and strong and would commonly drink or recycle one another’s urine. The urine, which still contained psychoactive metabolites, may have been more potent than the parent mushroom itself. As recorded in old Norse writings: “And then hold a wooden bowl to receive the urine, which they drank off greedily, as having still some virtue of the mushroom in it, and by this way they would also get drunk.”

References:
 
Michelot D, Melendez-Howell LM: Amanita muscaria: chemistry, biology, toxicology, and ethnomycology  Mycol Res. 2003;107(Pt 2):131-46.

Fischbein C, Aks S, Mueller R: Mushroom poisoning. In Erickson, T, Ahrens W, Aks, S, et al: eds McGraw-Hill, New York, NY, 1st Ed, 2005; 533-540.

Satora L, Pach D, Ciszowski K, Winnik L: Fly agaric (Amanita muscaria) poisoning, case report and review. Toxicon. 2005; 45(7):941-3.

Davis DP, Williams SR:  Amanita muscaria J Emerg Med 1999; 17(4):739.

Satora L, Pach D, Ciszowski K, Winnik L Panther cap Amanita pantherina poisoning case report and review.. Toxicon. 2006; 47(5):605-7.

Chew KS, Mohidin MA, Ahmad MZ,, et al: Early onset muscarinic manifestations after wild mushroom ingestion Int J Emerg Med. 2008;1(3):205-8.
 
 

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