eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Mushroom - Ibotenic Acid

Author: Peter A Chyka, PharmD, FAACT, DABAT, Professor and Executive Associate Dean, College of Pharmacy, University of Tennessee Health Science Center
Coauthor(s): William Banner Jr, MD, PhD,, Medical Director, Oklahoma Poison Control Center; Clinical Professor of Pharmacy, Oklahoma University College of Pharmacy-Tulsa; Adjunct Clinical Professor of Pediatrics, Oklahoma State University College of Osteopathic Medicine
Contributor Information and Disclosures

Updated: Oct 8, 2009

Introduction

Background

Amanita muscaria, also called fly agaric or soma, and Amanita pantherina, also called panther or panther amanita, are representative of the mushrooms in the ibotenic acid and muscimol mushroom group that produce ethanol-like intoxication and jerking movements. Symptoms typically occur within 90 minutes of ingestion, last for 4-8 hours, and resolve in most cases without drug therapy.

The genus name (Amanita) and species name (muscaria) can be confusing because the names imply a type of toxin, whereas the true toxins might not be obvious. The toxin muscarine produces muscarinic pharmacologic effects (eg, salivation, bradycardia, diarrhea, miosis); this toxin was first extracted from A muscaria in 1869, but it is not a significant toxin in A muscaria. Ibotenic acid and muscimol are the major toxins in this mushroom; these substances are psychoactive, inducing a state of intoxication similar to that induced by ethanol, with a mix of excitation, sedation, and mild hallucinations. Although this mushroom is in the genus Amanita, it does not contain amatoxin, which is responsible for the serious and life-threatening nature of cyclopeptide-type mushroom poisoning.
 
Amanita muscaria is also known as fly agaric based on the olden European practice of sprinkling the mushrooms in milk as an insecticide to kill flies presumably due to the actions of ibotenic acid.

Several general types of mushrooms can cause poisoning:^1,2,3  

• Cyclopeptides (Amanita phalloides) - Hepatotoxic
• Orellanine and orelline (Cortinarius mushrooms) - Nephrotoxic
• Ibotenic acid and muscimol (A muscaria, A pantherina), also termed isoxazoles - Intoxication and jerking movements
• Gyromitrin or monomethylhydrazine (Gyromitra mushrooms) - Hemolytic
• Muscarine (Inocybe and Clitocybe mushrooms) - Cholinergic
• Coprine (Coprinus atramentarius, inky cap) - Disulfiramlike reaction
• Psilocybin (Psilocybe and Paneolus mushrooms, magic mushrooms) - Hallucinogenic
• GI irritants
• Allenic norleucine (Amanita smithiana) - Nephrotoxic

A classification of 14 syndromic categories of mushroom poisoning has been proposed, but this classification system has yet to be widely adopted.^4,5

Mushrooms in the ibotenic acid group are commonly found throughout the United States, Europe, and Asia. They are found in wooded areas, especially among conifer forests, in the spring and fall seasons of North America. The young specimens emerge with patches of membrane left covering the cap and forming a cup (volva) at the base. The mature specimens often have brilliant cap colors and delicate skirts and cups. Many everyday representations of mushrooms depict the A muscaria because of its shape and bright coloring.

Mushroom poisoning in children is an infrequent but perennial problem for parents and clinicians. Parental anxiety is generally high because of fears of unknown or untoward effects. Clinicians are challenged to identify such poisonings, to discern whether poisoning has taken place, to order appropriate diagnostic studies, and to prescribe reasonable therapy. The varied nature of mushroom toxicities, their ubiquitous distribution, and the relative infrequency of the ingestions make the task difficult.

Dried mushrooms have been promoted on the Internet because of their various properties, and their ingestion might lead to serious toxicity from the mushroom or from unknown adulterants added to them.⁶

Various cultures throughout the world have used fungi for ceremonies and for divinatory purposes, practices that date back 3000 years. In North America, the Algonquin people used A muscaria for religious and ritualistic ceremonies. In some European and Asian cultures, the urine of a person or a deer ingesting these mushrooms is consumed to achieve secondary intoxication.

Pathophysiology

A muscaria and A pantherina contain ibotenic acid, muscimol, and muscazone. These isoxazole derivatives are present in various concentrations depending on the environmental conditions, the maturity of the fungus, and the season of the year. Ibotenic acid and muscimol are relatively stable; for instance, toxic activity has been maintained in dried plants for as long as 7 years. Other toxins are likely present in these mushrooms because pure extracts of ibotenic acid or muscimol do not account for all of the symptoms observed after their ingestion. Ibotenic acid resembles glutamic acid, and, in animals, it acts on glutaminergic receptors to produce excitatory effects. Muscimol, formed by decarboxylation of ibotenic acid, is similar to gamma-aminobutyric acid (GABA). Both of these chemicals can cross the blood-brain barrier.⁷

Demonstrating high affinity for GABA receptors, muscimol activates GABA receptors and, thereby, can act as a sedative. Many of the CNS effects of muscimol are ascribed to its ability to act as a GABA agonist. By comparison, ibotenic acid is more of a CNS stimulant, acting on glutamic acid receptors. In humans, most of the ibotenic acid ingested is excreted unchanged in the urine. Some ibotenic acid is metabolized to muscimol. About one third of the amount of muscimol ingested is excreted unchanged, one-third is conjugated, and the rest is oxidized.⁷

Frequency

United States

In 2007, 7351 mushroom ingestions were reported to the National Poison Data System of the American Association of Poison Control Centers (AAPCC).⁸ Of these cases, 86% involved mushrooms of unknown type. Mushrooms containing ibotenic acid accounted for 43 cases, with 10 (23%) involving children younger than 6 years. About 67% of all cases involving ibotenic acid mushrooms were intentional ingestions and 77% were treated at a healthcare facility. One death was attributed to ibotenic acid mushrooms in 2004, whereas no deaths were reported in the preceding 12 years or subsequent 3 years of data collection by the AAPCC. The manner of confirming A muscaria involvement in this fatality was not described, and the fact that it was purchased on the Internet raises questions about the integrity of the contents.⁶

International

The incidence of all types of toxic mushroom poisonings, including those from the ibotenic acid group, appears to be increasing in Europe and Asia. Estimates of the actual incidence are not available.^4,5

Mortality/Morbidity

Fatalities from ibotenic acid-muscimol containing mushrooms are rare, and symptoms typically are mild to moderate in severity and self-limiting.

• From 1999-2007, 28 deaths due to mushrooms were reported to US poison control centers through the AAPCC, and one death was attributed to mushrooms containing ibotenic acid.⁶ That death in 2004 involved a 44-year-old man who ate 6-10 freeze-dried mushrooms, purported to be A muscaria, which he obtained from the Internet. Paramedics found him in cardiac arrest, and he eventually died 10 days later with anoxic brain injury. Whether the mushroom was confirmed to be A muscaria was not mentioned.
• For the 43 exposures to ibotenic mushrooms reported by US poison control centers through the AAPCC, 35% of cases had no or minor effects, 28% had moderate effects, 14% suffered severe effects, and the outcome was unknown in 23% during 2007.⁸
• Most toxic effects of mushrooms containing ibotenic acid are temporary and self-limiting, lasting 2-6 hours. Some effects, particularly headache, may take 2 days or more to resolve.^9,10
• In Slovenia, a 48-year-old man consumed several A muscaria mushrooms and, within 30 minutes, developed vomiting and lethargy.¹¹ He was found comatose, having a seizurelike episode. He awoke and was oriented 10 hours after ingestion. His condition deteriorated 18 hours after ingestion, and he became confused and uncooperative. Paranoid psychosis with visual and auditory hallucinations appeared, persisted for 5 days, and resolved with short-term drug therapy without later recurrence.
• In Poland, 5 young adults (aged 18-21 y) consumed dried A muscaria and a can of beer, and 4 of them experienced heightened visual and auditory perceptions with an onset of approximately 20 minutes. One person had severe hallucinations and a loss of consciousness according to the others. They induced vomiting and gave her liquids. The next day, she came to a hospital complaining of tiredness and gastric pain. She was evaluated, observed for several days, and sent home. No confirmation of the mushrooms was performed.¹²
• In Poland, 2 women ate 5 fried mushroom caps of Amanita pantherina (later confirmed) and developed nausea, stomachache, diarrhea, and vomiting within 2 hours. They subsequently developed ataxia, waxing and waning obtundation, altered perceptions and hyperkinetic movements, and speech. One patient's symptoms lingered for several days while the other had no symptoms at 6 hours after ingestion. The latter patient received activated charcoal and intravenous fluids.¹³
• A series of 9 children aged 1-6 years who ingested A muscaria or A pantherina were treated at a hospital in Seattle, Washington. Symptoms developed within 30-180 minutes (median, 45 min) after ingestion and lasted for 4-14 hours (median, 9 h). Typical symptoms included lethargy (4 children); unresponsiveness (1); comalike sleep (1); ataxia (2); abnormal movements (3); tonic-clonic seizures (3); and agitation, babbling, or hysteria (5). All children recovered uneventfully within 12 hours after admission.⁹
• Descriptions of cases reported to the North American Mycological Association, toxicology section, illustrate the typical course of many mushroom poisonings; however, these cases were not necessarily observed by health care professionals.¹⁴

Age

Adults are frequently involved as foragers for edible mushrooms. Because of errors in identification, they may ingest toxin-containing look-alike mushrooms. Adults and adolescents may also be poisoned when they intentionally consume mushrooms, picked from the ground or purchased dried, to achieve intoxication. Young children may be poisoned by mushrooms when they unintentionally eat mushrooms found outside, typically in yards or outdoor play areas. Reports of seizurelike activity have been reported for children but are not typical in adults.^9,10

Clinical

History

Ask the patient about how many mushrooms were consumed, how they were prepared, and when the mushrooms were eaten. The concentration of active substances is low in any one mushroom, but generally about 1 mushroom in young children and 3 or more in adolescents and adults produce toxic symptoms.¹⁰ The effects of mushrooms vary greatly, and cooking may not alter toxicity. An amount as small as a mouthful can cause symptoms.⁹

• Obtain a history of the exposure that includes the following:
  • Quantity of mushrooms ingested
    • Preparation of the mushroom (eg, raw, cooked)
    • Source of the mushroom (eg, outdoors, the Internet)
    • Time of the ingestion
    • Symptoms and time of onset after ingestion
    • Prehospital treatment including home remedies
    • Medications regularly taken and any coingestants
• The timing of symptom onset is a crucial element of the history in differentiating life-threatening or severe mushroom poisonings from those that are less serious and typically have an onset of symptoms well within 5 hours of ingestion such as the mushrooms of the ibotenic acid group.^4,5,1,2,3
  • Mushrooms from the cyclopeptide (Amanita phalloides) or orellanine (Cortinarius mushrooms) groups that can produce hepatic or renal failure, respectively, typically produce symptoms 6-24 h after ingestion.
  • Amanita smithiana (allenic norleucine group) found in the Northwestern states can also be nephrotoxic, but it has an onset of gastrointestinal distress within 1-12 hours.¹⁵ These mushrooms are often confused with edible pine mushrooms.
  • For mushroom ingestions in the Pacific Northwest region of the United States, patients who have early-onset symptoms and remain symptomatic should be fully evaluated in a hospital until the mushroom identity is confirmed to be nontoxic or the patient’s condition improves.³
• Identification of the actual mushroom consumed is important but is typically impossible because the mushroom in question has already been digested.
  • A muscaria has a scarlet cap, is 5-30 cm in diameter and contains white warts. The stalk is white, is frequently hollow, and is often as long as 15-20 cm. A prominent cup (volva) is found at the bottom of the stalk, with numerous rings superiorly. The gills of A muscaria are free and white. The spores are also white. Its appearance can vary depending on the geographic location. The scarlet cap is predominantly found in western North America. Caps that are orange to yellow-orange caps are most frequent in eastern North America.
  • A muscaria can occur alone or in groups on the ground of forests, in grassy areas and lawns, and especially under trees.
  • Different types of mushrooms can be found in the same location, and a single sample can lead to false identification of the mushroom that was ingested. Consider all possible mushrooms in the immediate vicinity of where the ingestion occurred.
  • When no specimen is brought in by a patient with a suspected mushroom ingestion, sending an experienced forager to the site to collect any mushrooms growing in the area might be helpful.
  • When mushrooms are obtained for identification, the entire mushroom should be dug up to preserve the architecture of the bulb, stem, and cap. Place individual mushrooms in a dry paper bag, not a plastic or cloth bag. Transporting the mushrooms in a careful, dry manner minimizes destruction of the natural architecture of the mushrooms, discoloration of the cap or gills, and premature release of the spores. Do not refrigerate or crush the mushrooms.
  • Collecting the patient's gastric contents by means of gastric lavage or after emesis might yield identifiable spores.
  • Remote viewing of the mushroom by digital photography and Internet transmission may aid the identification of unknown mushrooms by mycologists.¹⁶

Physical

Once ingested, A muscaria produces symptoms within 30-90 minutes. Peak effects occur at 2-3 hours. The initial symptom is drowsiness, followed by confusion, ataxia, dizziness, euphoria, and intoxication. These symptoms can proceed to hyperkinesis, muscle jerks, spasms, and delirium. Deep sleep or coma can occur and generally lasts 4-8 hours.

• If symptoms such as vomiting, diarrhea, and abdominal pain begin 5 hours or more after ingestion, poisoning with the potentially life-threatening or severe mushrooms such as the cyclopeptide (Amanita phalloides) or orellanine (Cortinarius mushrooms) groups, which can produce hepatic or renal failure, respectively, should be considered.^4,5,1,2,3  Amanita smithiana (allenic norleucine group) found in the Northwestern United States can also be nephrotoxic, but it has an onset of gastrointestinal distress within 1-12 hours after ingestion.¹⁵ For mushroom ingestions in the Pacific Northwest region of the United States, patients who have early-onset symptoms and remain symptomatic should be fully evaluated in a hospital until the mushroom identity is confirmed or the patient's condition improves.³
• Vital signs: Pulse and blood pressure are usually unchanged.
• Respiration: Breathing is slow and regular, similar to that in deep sleep.
• GI: GI upset and vomiting occur but are not common. When vomiting or diarrhea does occur, fluid and electrolyte changes are uncommon.
• Integumentary: Skin may be reddened and warm to the touch.
• Musculoskeletal: Muscle spasms may occur.
• Neurologic: Agitation and CNS depression may occur. 
  • Especially in children, tonic-clonic seizures, fasciculations, and myoclonic jerking lasting 6-9 hours have been reported.⁹ Seizures in adults are uncommon.
  • Initial excitation leads to stupor, then coma; severe lethargy alternating with agitation is common, and a deep sleep may occur.
  • Agitation, babbling, confusion, screaming, irritability, hallucinations, dizziness, ataxia, euphoria progressing to muscle jerks, spasms, delirium, racing thoughts, and giddiness may be seen.
  • Headache may last several days.
  • Illusions of sight and sound are produced by misinterpretation of sensory input.

Causes

• Incorrect mushroom identification by a naive forager such as an immigrant who mistakes one of the local poisonous varieties for an edible mushroom native to his or her homeland or a novice mushroom harvester
• Intentional ingestion by a suicidal person
• Unintentional ingestion by a child who found mushrooms growing in yards or outdoor play areas
• Foul play in which an individual is poisoned by someone else
• Inadvertent poisoning from dried mushrooms purchased on the Internet or from other sources where the composition of the mushroom is unreliable or where the mushroom might contaminated with unknown toxic compounds

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