Poisonous and Hallucinogenic Mushrooms

for quiz 4

Should You Eat the Mushroom?

• There is no simple rule that helps you identify poisonous and nonpoisonous mushrooms.

• Due to cultural differences, people in North America are much less likely to eat wild mushrooms than people in Europe, so Europeans experience more

poisonings.

• 50% of all serious poisonings and 95% of all fatalities are caused by a few species in the genus Amanita, which fruit in the late summer and fall.

Amanitin Poisoning

• The basidiomata of several species of the agaric genera Amanita, Gelerina,

and Conocybe contain toxins lethal to humans in extremely small doses. These toxins are also found in Lepiota, Omphalotus, and Clitocybe.

• Examples: Amanita abrupta, A. arocheae, A. bisporigera (eastern North American destroying angel), A. exitialis (Guangzhou destroying angel), A. phalloides (death cap), A. subjunuillea (East Asian death cap), A. verna (fool’s mushroom), and A. virosa (European destroying angel).

Amanitin Poisoning, continued

• The toxins are amino acids in a double ring, called cyclic oligopeptides or cyclopeptides.

• Amatoxins (amanitins) contain eight amino acid molecules;

• Phallotoxins (phalloidins) contain seven amino acid molecules.

Amatoxins rapidly damage the intestines, kidney, and liver

• Alpha-amanitin binds to RNA polymerase II, the enzyme that transcribes DNA and produces messenger RNA.

• Since synthesis of RNA stops, so does synthesis of protein.

• Cell turnover is quick in the intestinal lining, liver, and kidney, so the nonreplacement of cells becomes an issue fast.

• There is no specific antidote.

• Symptoms are not noticeable until a great amount of internal damage is already done.

Treatment

• Since Amanita poisoning is rare in North America, doctors don’t think of it

first.

• New treatment: Legalon SIL (silybinin), extract of milk thistle, given intravenously.

Typical treatment:

• Removal of toxin

• Increase excretion of toxin

• Supportive measures

Removal of Toxin

• If it has only been an hour or two since the patient ate the mushrooms, the stomach is emptied by emesis and gastric lavage (throwing up, then washing out the stomach).

• If it has been longer, this step is useless and is skipped.

• Hemodialysis (circulating the blood through a semipermeable membrane bathed in an isotonic medium) might be tried, but amanitin is a large enough molecule (and it often becomes complexed with even larger molecules, such as proteins), that this may be ineffective.

• Hemoperfusion (circulating the blood over activated charcoal) has been used experimentally recently and might be a little bit effective.

Increase Excretion of Toxin

• Research has shown that amanitin concentrations are higher in the urine than in the blood of poisoned people, so a diuretic might be helpful, although this doesn’t seem to have been tried often yet.

Supportive Measures

• Careful monitoring of electrolytes, fluid balance, blood sugar, with adjustments

made as necessary.

• If kidney or liver failure occurs, hemodialysis or hemoperfusion should be started.

• Intravenous infusion of B vitamins, vitamin K, penicillin-G, corticosteroids, and thioctic acid might support the damaged liver or kidneys.

• Not supported by much research, but it could be worth a shot in an emergency!

The Bastien Treatment

• Dr. P. Bastien developed this treatment for Amanita poisoning.

• Steps:

1. Intravenous injections of 1 gram vitamin C twice a day.

2. Two capsules of nifuroxazide three times a day.

3. Two tablets of dihydrostreptomycin three times a day.

4. Other measures to control fluid and electrolyte balance; also, penicillin.

• 15 cases of A. phalloides poisoning were successfully treated 1957-1969.

• Dr. Bastien also ate 70 grams of A. phalloides in 1981 and successfully treated himself.

• This treatment is now used throughout France. It seems not to be common in North America.

Fruit Flies

• Several species of Drosophila (the fruit fly genus, but these species are

mycophagous) eat amanitas with no symptoms of poisoning.

• We don’t know how they deal with the toxin.

• These flies can breed on mushrooms that are toxic to competing fly species.

• The larvae are never parasitized by the nematode Howardula.

• This is useful, because infected adults (up to 35% of the population) are sterile or at least reduced in reproductive success.

Monomethylhydrazine Poisoning

• The false morel, Gyromitra esculenta, fruits at the same time as morels, and is responsible for 2-4% of all fatal mushroom poisonings.

• The toxin precursor is gyromitrin. When hydrolyzed, this becomes monomethylhydrazine (MMH), which is used as rocket fuel and is extremely toxic.

• There is a narrow margin between a small, safe dose and a slightly less small, lethal dose, so sometimes several people eat false morels but not everyone gets sick.

• Also, in some cases the people who ate the false morels were fine but the cook became sick, because monomethylhydrazine has a boiling point of 87.5 °C and its vapors are toxic.

Monomethylhydrazine Poisoning, continued

• Symptoms: first a bloated feeling, then nausea, vomiting, diarrhea, abdominal cramps. Often faintness, loss of muscular control, fever. In severe cases: jaundice, convulsions, coma, death in 2-7 days.

• The toxin is hemolytic, toxic to the central nervous system, irritates the gastrointestinal tract, damages the liver.

• Treatment: pyridoxine hydrochloride (a specific physiological antagonist of MMH).

• Blood sugar, liver and kidney function, and free hemoglobin level should be monitored.

• Intravenous glucose, forced diuresis if free hemoglobin rises, hemodialysis in severe cases.

Orellanine Poisoning

• Eating Cortinarius orellanus led to 132 poisonings in Poland in 1957. 19 people died due to kidney failure.

• The symptoms were extremely delayed, never sooner than 3-4 days after eating the mushrooms, even in fatal cases.

• Symptoms: intense thirst, burning and dryness of the mouth, headache, chills, loin or abdominal pain, nausea, vomiting. Urination was initially stimulated, then greatly reduced or ceased. In severe cases, blood urea nitrogen rose (as would typically happen after kidney damage).

• Similar cases were later reported in France, Germany, Switzerland, and Czechoslovakia. No confirmed cases in North America.

• The toxin is orellanine. It is also produced by Cortinarius orellanoides (in Europe) and C. rainierensis (in North America).

• Kidney transplants would probably be necessary.

Coprine (Antabuse-like) Poisoning

• Coprinopsis atramentaria

• The mushrooms aren’t actually toxic by themselves.

• After eating the mushrooms, if the person drinks alcohol, they will develop symptoms 30-60 minutes later.

• Symptoms: hot flushes of the face and neck, a metallic taste in the mouth, tingling sensations in the limbs, numbness in the hands, palpitations, a throbbing headache, nausea, and vomiting. Not fatal.

• Treatment is mainly focused on controlling irregular heartbeat.

• Symptoms stop when the alcohol is no longer in the person’s system (2-4 hours).

• The toxin is coprine, an amino acid that blocks the metabolism of ethyl alcohol at the acetaldehyde stage. Coprine poisoning is really acetaldehyde poisoning.

• Antabuse (disulfiram) is prescribed to help overcome alcohol addiction, and it works the same way.

Muscarine Poisoning: PSL Syndrome

• Clitocybe and Inocybe mushrooms contain lots of muscarine.

• This toxin stimulates exocrine glands (producing sweat, saliva, and tears) within 30 min to two hours of eating the mushrooms.

• PSL syndrome: perspiration, salivation, lachrymation.

• Also causes constriction of the pupils, blurred vision, muscle spasms, diarrhea, slow heartbeat, and lowered blood pressure.

• Typically not fatal, although if someone has a heart condition, and they have eaten enough mushrooms, their heart might stop.

• Treatment: intravenous atropine.

Ibotenic Acid-Muscimol Poisoning

• Amanita gemmata, A. pantherina, and A. muscaria

• Symptoms: muscle spasms, dizziness, vomiting if many mushrooms have been eaten, deep sleep with odd dreams for ~ 2 hours.

• Then feelings of elation, hyperactivity, compulsive and uncoordinated movements, sometimes nonstop talking and altered perceptions of reality.

• These species have been used in religious or recreational activities for thousands of years by several different cultures, e.g., in Siberia.

• The body doesn’t break down the toxin; it passes unaltered in the urine, so drinking the urine of someone who has eaten mushrooms (humans, reindeer) still produces effects.

Ibotenic Acid-Muscimol Poisoning, continued

• Fresh mushrooms contain ibotenic acid, which affects the nervous system, but dried mushrooms are more potent because ibotenic acid degrades to muscimol when dried.

• People tend not to overdose on thismushroom, but > 10 mushrooms could kill someone.

• Typically, no treatment is needed.

• Atropine should never be given, as it would exacerbate the symptoms.

Psilocybin-Psilocin “Poisoning”

• Aztecs in what is now Mexico referred to the sacred mushrooms as teonanacatl, “the flesh of the gods”. The mushrooms were used in religious rites and medical procedures.

• Four agaric genera cause similar hallucinations and feelings of euphoria or divine connectedness: Psilocybe, Panaeolus, Conocybe, and Gymnopilus.

• In Mexico, the most commonly used species are Psilocybe caerulescens, P. zapotecorum, and P. mexicana. In the U.S. and coastal regions of British Columbia, the most commonly used species are P. cyanescens and some species of Panaeolus and Conocybe.

Psilocybin-Psilocin “Poisoning”, continued

• The relevant molecules are psilocybin and psilocin, both indole alkaloids and hydroxyltryptamine derivatives related to the neurotransmitter serotonin.

• If a person eats a lot of the relevant mushrooms, they may be overwhelmed by hallucinogenic effects, but they aren’t likely to be poisoned.

• Unfortunate symptoms: extreme anxiety, paranoia; in children, high fever and convulsions.

• Hallucinations can be reduced with chlorpromazine; convulsions can be reduced with diazepam.

Psilocybin for Treatment of Anxiety and Depression in Cancer Patients

• Clinical trials of psilocybin for reducing anxiety and depression in cancer patients at New York State University started in 2013.

• Results are promising!

• With a single dose of synthetic psilocybin, 80% of patients in those trials showed significant reductions in anxiety and depression for at least seven months.

• One patient reported reduced symptoms three years later.

Rhabdomyolysis

• Rhabdomyolysis: breakdown of skeletal muscle.

• 12 cases occurred in France after people at several consecutive meals of Tricholoma flavovirens. This species used to be considered edible.

• Symptoms: fatigue, weakness, myalgia (muscle pain) (especially in the thighs).

• Symptoms worsened over 3-4 days and progressed to dark urine, facial redness, sweating, nausea, high temperature, myocarditis, arrhythmia, and cardiovascular collapse in three people.

• Autopsy showed lesions on heart muscle and kidneys.

• In Japan, some people died after eating Russula subnigricans. They suffered rhabdomyolysis.

• The muscle breakdown releases myoglobin into the blood, which causes kidney failure.

• The toxin is cycloprop-2-ene carboxylic acid.

• This species is not often eaten, so more cases are unlikely.

Poisoning by Pleurocybella porrigens (Angel Wings)

• In 2004, at least 17 people in Japan died of acute brain damage after eating

Pleurocybella porrigens.

• All the people who died had preexisting kidney disease.

• The fungus does contain toxins, but we don’t understand them.

Poisoning by Paxillus involutus (Poison Pax)

• This species is eaten in China.

• It is the third most common cause of gastrointestinal symptoms in Eastern

Europe.

• If someone eats this species many times, they can eventually develop acute hemolytic anemia, but people tend not to show any symptoms after eating the species a few times, so diagnosis is difficult.

Poisoning by Amanita smithiana

• This species has caused many poisonings in the Pacific Northwest of the U.S. because people think it is the matsutake mushroom (Tricholoma magnivelare).

• We don’t understand the toxin, but it seems not to be an amanitin.

• It causes kidney and liver failure.

Gastrointestinal Irritants

• Caused by fleshy fungi from many different genera.

• Symptoms typically start 30-90 minutes after eating the mushrooms and reduce in 3-4 hours, completely disappearing within a day or so.

• Common symptoms: vomiting, diarrhea, abdominal cramps.

• We don’t know the toxins involved.

• Since the toxin isn’t known, the only treatment option is emptying the stomach and monitoring for dehydration, reduced blood pressure, or impaired kidney function.

• Fatalities aren’t very common, but they do occur.

Four Categories of Poisons:

• Toxins that cause extensive cell destruction but that produce overt symptoms only after a significant, and potentially fatal, delay;

→ E.g., amanitin, orellanine, monomethylhydrazine

• Toxins that act on the autonomic nervous system, causing symptoms either as soon as they have been absorbed or whenever the appropriate substrate enters the system;

→ E.g., muscarine, coprine

• Toxins that act on the central nervous system, causing symptoms as soon as they have been absorbed.

→ E.g., muscimol, psilocybin

• Undetermined toxins that act on the alimentary canal, causing symptoms as soo as they have been absorbed.