Ibotenic Acid Mushroom Toxicity 

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.

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 2009, 5902 mushroom ingestions were reported to the National Poison Data System of the American Association of Poison Control Centers (AAPCC).^[8] Of these cases, 77% involved mushrooms of unknown type. Mushrooms containing ibotenic acid accounted for 61 cases with 52 as single-substance exposures, of which 5 (10%) involved children younger than 6 years. About 60% of all cases involving ibotenic acid mushrooms were intentional ingestions and 71% 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 5 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]

Mortality/Morbidity

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

• From 1999-2009, 35 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 52 single-substance exposures to ibotenic mushrooms reported by US poison control centers through the AAPCC, 27% of cases had no or minor effects, 37% had moderate effects, 7% suffered major effects, and the outcome was unknown in 29% during 2009.^[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); coma-like 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]}