Aminita muscaria, Amanita pantherina and others
| 1. NAME |
| 1.1 Scientific name |
| 1.2 Family |
| 1.3 Common name(s) and synonym(s) |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First aid measures and management principles |
| 2.5 Poisonous parts |
| 2.6 Main toxins |
| 3. CHARACTERISTICS |
| 3.1 Description of the fungus |
| 3.1.1 Special identification features |
| 3.1.2 Habitat |
| 3.1.3 Distribution |
| 3.2 Poisonous parts of the fungus |
| 3.3 The toxin(s) |
| 3.3.1 Name(s) |
| 3.3.2 Description, chemical structure, stability |
| 3.3.3 Other physico-chemical characteristics |
| 3.4 Other chemical contents of the fungus |
| 4. USES/CIRCUMSTANCES OF POISONING |
| 4.1 Uses |
| 4.1.1 Uses |
| 4.1.2 Description |
| 4.2 High risk circumstances |
| 4.3 High risk geographical areas |
| 5. ROUTES OF EXPOSURE |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Others |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological halflife by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination and excretion |
| 7. TOXINOLOGY |
| 7.1 Mode of action |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant Animal data |
| 7.2.3 Relevant in vitro data |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
| 8.1 Material sampling plan |
| 8.1.1 Sampling and specimen collection |
| 8.1.1.1 Toxicological analyses |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological analyses |
| 8.1.1.5 Other (unspecified) analyses |
| 8.1.2 Storage of laboratory samples and specimens |
| 8.1.2.1 Toxicological analyses |
| 8.1.2.2 Biomedical analyses |
| 8.1.2.3 Arterial blood gas analysis |
| 8.1.2.4 Haematological analyses |
| 8.1.2.5 Other (unspecified) analyses |
| 8.1.3 Transport of laboratory samples and specimens |
| 8.1.3.1 Toxicological analyses |
| 8.1.3.2 Biomedical analyses |
| 8.1.3.3 Arterial blood gas analysis |
| 8.1.3.4 Haematological analyses |
| 8.1.3.5 Other (unspecified) analyses |
| 8.2 Toxicological Analyses and Their Interpretation |
| 8.2.1 Tests on toxic ingredient(s) of material |
| 8.2.1.1 Simple Qualitative Test(s) |
| 8.2.1.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.1.3 Simple Quantitative Method(s) |
| 8.2.1.4 Advanced Quantitative Method(s) |
| 8.2.2 Tests for biological specimens |
| 8.2.2.1 Simple Qualitative Test(s) |
| 8.2.2.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.2.3 Simple Quantitative Method(s) |
| 8.2.2.4 Advanced Quantitative Method(s) |
| 8.2.2.5 Other Dedicated Method(s) |
| 8.2.3 Interpretation of toxicological analyses |
| 8.3 Biomedical investigations and their interpretation |
| 8.3.1 Biochemical analysis |
| 8.3.1.1 Blood, plasma or serum |
| 8.3.1.2 Urine |
| 8.3.1.3 Other fluids |
| 8.3.2 Arterial blood gas analyses |
| 8.3.3 Haematological analyses |
| 8.3.4 Interpretation of biomedical investigations |
| 8.4 Other biomedical (diagnostic) investigations and their interpretation |
| 8.5 Overall interpretation of all toxicological analyses and toxicological investigations |
| 8.6 References |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 Central nervous system (CNS) |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Other |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ear, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Other |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Life supportive procedures and symptomatic/specific treatment |
| 10.3 Decontamination |
| 10.4 Enhanced elimination |
| 10.5 Antidote/antitoxin treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. Additional information |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UPDATING), COMPLETE ADDRESSES |
AMINITA MUSCARIA & AMANITA PANTHERINA
AND OTHERS
International Programme on Chemical Safety
Poisons Information Monograph (Group monograph) G026
Fungi
Please note that further information on Sections 1, 3.1, 3.2 and 8 is
pending.
1. NAME
1.1 Scientific name
Species of the genus Amanita. The species known to
cause the majority of toxic exposures are: Amanita muscaria
and Amanita pantherina.
The toxins are all isoxazole derivatives.
Other Amanita mushrooms contain the same toxins and
induce similar toxicity:
Amanita muscaria var. Kamtschatica Langsdorff ex. Fr.
Amanita regalis (Fr.) R. Mre. (A. muscaria var. umbrina Fr.)
Amanita muscaria var. formosa
Amanita muscaria var. alba
Amanita gemmata (Fr.) Bertillon
Amanita velatipes Atk.
Amanita cothurnata Atk.
Amanita flavovolvata Sing.
Amanita strobiliformis (Vitt.) Quel.
Amanita pantherina (DC ex Fr.) Secr.
Amanita pantherina multisquamosa
Amanita pantherina velatipes
Amanita pantherina pantherinoides
Tricholoma muscaria
1.2 Family
Agaricaceae ( Agaricales)
The genus is Amanita (Amanitaceae)
1.3 Common name(s) and synonym(s)
Amanita muscaria
English Fly Agaric
German Fliegenpilz, Roter fliegenpilz
Spanish Falsa oronja, Amanita matamoscas
French Amanite tue-mouche,
Agaric aux mouches,
fausse oronge
Italian Ovulo malefico, Uovolaccio
Polish Muchomor czerwony
Amanita pantherina
English Panther cap.
German Pantherpilz, Braunner Knollenblätterpilz
Spanish Amanita pantera, galipiermo falso
French Amanite panthère, Fausse golmelle
Italian Tignosa bigia, Tignosa regata, Agarico panterino
Polish Muchomor plamisty
2. SUMMARY
2.1 Main risks and target organs
The most frequent cause of intoxication is the
consumption of Amanita muscaria by people who mistake it
and ignore its toxicity. Amanita muscaria might also be
ingested in order to obtain mind-altering effects. The
central nervous system is the major target organ.
2.2 Summary of clinical effects
Symptoms appear 30 to 90 minutes after ingestion and
last usually for 6 hours but may persist for 12 to 24 hours.
The primary effects are central nervous system depression and
stimulation, which may alternate. Symptoms usually begin
with drowsiness followed by a state of confusion, with
ataxia, dizziness, euphoria resembling alcohol intoxication
and may proceed to increased activity, illusions, or even
manic excitement.
These periods of excitement may alternate with periods of
somnolence, deep sleep or stupor. The illusions are
primarily a misinterpretation of sensory stimuli. The
prognosis is usually good with symptomatic treatment. Death
from these mushrooms is extremely rare.
2.3 Diagnosis
Based upon history of ingestion and clinical features.
2.4 First aid measures and management principles
Treatment includes prevention of absorption of the
toxins and treatment of the signs and symptoms of
intoxication as they occur. Atropine is not recommended.
Induction of emesis is NOT recommended because of the
potential central nervous system depression and seizures.
There is no specific antidote for Amantia muscaria and
Amanita pantherina poisoning.
2.5 Poisonous parts
All parts of the fruiting body of Amanita muscaria and
Amanita pantherina are toxic.
2.6 Main toxins
The main toxins are: ibotenic acid, muscimol and
muscazone. These three toxins are found in certain species of
mushrooms throughout the world. They are related and are all
isoxazole derivatives.
3. CHARACTERISTICS
3.1 Description of the fungus
3.1.1 Special identification features
Identification: Complete and precise
identification of the mushroom (if available) should
be accomplished by a mycologist. If no mycologist is
available, colour photographs may be helpful for a
first identification. Identification is difficult when
the mushrooms have been altered by cooking, eating or
storage.
Description of Amanita muscaria
Cap: 8 to 12 cm diameter, occasionally over 20 cm;
conical when young, flattening in age;
viscid, adorned with white to pale yellow
warts or small patches. This mushroom has a
variety of color variants, ranging from
yellow through orange, orange-red to
blood-red or scarlet.
The yellow, orange or orange-red caps
(A. muscaria var. formosa) occurs in eastern
North America. The scarlet cap
(A. muscaria var. muscaria) occurs in western
North America, throughout Europe and
Asia.
Flesh firm, white throughout.
Gills (lamellae): crowded, free or just touching
stalk, broad, white, minutely hairy
edges.
Stalk: 8 to 15 cm long, 20 to 30 mm thick enlarging
towards base and becoming bulbous; white,
covered with silky hairs.
Ring: (annulus): large, membranous, white to
yellowish, median to superior, resistant
though margin usually frayed.
Cup (volva): the remains of the volva are often
only 2 or 3 concentric rings above the bulb;
white to straw.
Spores: white spore print (in mass); 8 - 11 by 6 - 8
microns, ellipsoid, thin walled, no amyloid
reaction.
Description of Amanita pantherina
3.1.2 Habitat
Scattered or abundant, sometimes in fairy rings
under hardwoods and conifers from spring to
autumn.
3.1.3 Distribution
These species are widely distributed throughout
the planet. Amanita muscaria grows in summer and
autumn under coniferous and deciduous trees, from the
lowland up to the subalpine zone. It occurs
practically all over the temperate and subtropical
zones in Europe, North Africa, South Africa, Asia,
Japan, Australia, North America (in the Western States
of the USA more often than in the Eastern States) and
in South America. (Seeger & Stijve, 1978).
3.2 Poisonous parts of the fungus
All parts of the fruit body of A. muscaria are toxic.
The isoxazoles are NOT distributed uniformly in the mushroom.
Most are detected in the cap of the fruit, then in the base,
with the smallest amount in the stalk (Lampe, 1978; Tsunoda
et al., 1993). Drying A. muscaria in the sun or with
heater caused an increase of muscimol in the mushroom, though
a lot of precursors of ibotenic acid was lost. Ibotenic acid
and muscimol in the mushroom were stable on storage under dry
or salt conditions (Benedict et al., 1966; Tsunoda et al.,
1993).
Whilst ibotenic acid and muscimol are rapidly released from
the mushrooms by cooking and boiling, these processes do not
eliminate all toxic substances.
3.3 The toxin(s)
3.3.1 Name(s)
The main toxins are: ibotenic acid, muscimol
and muscazone.
These three toxins are found in certain species of
mushrooms throughout the world. They are related and
are all isoxazole derivatives (Eugster, 1979).
Ibotenic acid and muscinol are mainly responsible for
the toxic effects (Takemoto et al., 1964; Bowden and
Mogey, 1965; Eugster et al., 1965; Muller and Eugster,
1965).
3.3.2 Description, chemical structure, stability
Ibotenic acid and muscimol have similar
structure to glutamic acid and GABA (Krogsgaard-Larsen
P. et al., 2000).
Muscimol
CHEMICAL NAME: 3-Isoxazolol, 5-(aminomethyl)-
CAS REGISTRY NUMBER: 2763-96-4
SYNONYMS:
3(2H)-ISOXAZOLONE, 5-(AMINOMETHYL)-3-
HYDROXY-5-AMINOMETHYLISOXAZOLE
3-Hydroxy-5-aminomethylisoxazole-agarin
3-HYDROXY-5-AMINOMETHYLISOXAZOLE-AGARIN
AGARIN
5-(Aminomethyl)-3(2H)-isoxazolone
5-(Aminomethyl)-3-isoxazolol
5-Aminomethyl-3-hydroxyisoxazole
5-Aminomethyl-3-isoxyzole
Agarin
AGARINE
Muscimol
Pantherin
PANTHERINE
RCRA waste number P007
OTHER NUMBERS: 6036
NIOSH/NY3325000
NY3325000
(Ref: IPCS INTOX CD-ROM, 2000, 1)
Ibotenic acid
CHEMICAL NAME: 5-Isoxazoleacetic acid,
alpha-amino-3-hydroxy-, monohydrate
CAS REGISTRY NUMBER: 60573-88-8
SYNONYMS
alpha-Amino-2,3-dihydro-3-oxo-5-
isoxazoleacetic acid
alpha-Amino-3-hydroxy-5-isoxazoleacetic acid
hydrate
alpha-Amino-3-hydroxy-5-isoxazolessigsaure
hydrat
Amino-(3-hydroxy-5-isoxazolyl)acetic acid
Ibotenic acid
Ibotensaeure
Isotenic acid
Pramuscimol
OTHER NUMBERS
NY2100000
(Ref: IPCS INTOX CD-ROM, 2000, 1)
The toxins are thermostable and are NOT destroyed by
cooking.
3.3.3 Other physico-chemical characteristics
Molecular weight:
Ibotenic acid: 176.15
Muscimol 114.12
3.4 Other chemical contents of the fungus
Bufotenine (Waser, 1979)
Amavadin: a vanadium compound (Kneifel et al, 1986).
Stizolobic and Stizolobinic acid: L-DOPA oxidation products
(Chilton et al. 1974; Bresinsky & Besl, 1985).
Muscaflavin, Muscaurin: colorant principles (Depovere & Moens
1984)
Muscarine (Eugster, 1979)
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.1.1 Uses
4.1.2 Description
Amanita muscaria and Amanita pantherina are
not and have not been used in medical practice.
In the past it has been used in different populations
and cultures as a fly-killer and an inebriant
(Siberia), an ecstasy agent (India), and a
hallucinogenic (Indian peoples of Meso-America). In
Japan, a derivative of muscinol is presently being
used as a pesticide. An extract of ibotenic acid has
been found to be some 20 times more powerful than
monosodium glutamate as a flavour enhancer (Wasson,
1964, 1968, 1972, 1979).
4.2 High risk circumstances
The most frequent course of intoxication is the
consumption of Amanita muscaria and Amanita pantherina by
people who mistake it and ignore its toxicity. Amanita
muscaria and Amanita pantherina might also be ingested in
order to obtain psychotic effects and especially to expand or
alter spatio-temporal awareness.
Death from this kind of mushroom is rare, or rarely reported.
If so, it is due to complications. However, it would be
unwise to consider eating them because the toxins are
complex, variable in quantity, and not completely
understood.
4.3 High risk geographical areas
These species are widely distributed throughout the
planet.
5. ROUTES OF EXPOSURE
5.1 Oral
Ingestion of mushrooms is the most common cause of
intoxication.
5.2 Inhalation
No data available
5.3 Dermal
No data available
5.4 Eye
No data available
5.5 Parenteral
No data available
5.6 Others
No data available
6. KINETICS
6.1 Absorption by route of exposure
Based on the time of onset of clinical symptoms, the
rate of absorption of the toxins of Amanita muscaria and
pantherina from the gastro-intestinal tract seems to be
rapid. However, the exact rate and the proportion of
absorption is still unknown.
6.2 Distribution by route of exposure
Muscimol and ibotenic acid, presumably cross the
blood-brain barrier via some active transport system.
Neither muscimol nor ibotenic acid is removed from the
receptor by the GABA or glutamate active uptake system.
Inefficient removal of these false neurotransmitters once
they have passed the blood-brain barrier may be an important
contributing factor to their central nervous system effect
(Balcar & Johnston, 1972; Kronsgaard-Larsen & Johnston, 1975,
2000).
6.3 Biological halflife by route of exposure
Both ibotenic acid and muscimol may be detected in human
urine within one hour after the ingestion of the mushrooms.
The peak of excretion of ibotenic acid appears at the second
hour after the ingestion.
6.4 Metabolism
Metabolites include pantherin, tricholomic acid and
solitaric acid.
In humans, a substantial amount of ingested ibotenic acid is
excreted in urine unmetabolized. Some is converted to
muscimol which is more pharmacologically active.
6.5 Elimination and excretion
In human beings, a substantial fraction of ingested
ibotenic acid is excreted in the urine unmetabolized.
Virtually no muscimol is excreted when pure ibotenic acid is
eaten, but muscimol is detectable in the urine after eating
A. muscaria, which contains both, ibotenic acid and
muscimol. The ibotenic acid that does pass through the body
is excreted rapidly, between 20 and 90 minutes after
ingestion (Chilton, 1975). It should be noted that major
symptoms appear after the first 60 minutes to 2 hours and
reach their greatest intensity after the excretion of
ibotenic acid. Major signs and symptoms of major or severe
intoxication lasts more than 5 hours after the peak in
excretion of ibotenic acid.
According to animal experiments, most of the muscimol
delivered by intra peritoneal injection in the mouse is
excreted in the urine as muscimol or metabolites of muscimol
within 6 hours. About 1/3 is excreted as muscimol, 1/3 as a
cationic conjugate, and 1/3 as an oxidation product (Ott J.
et al, 1975).
In fact, the urine retains the pharmacological activity of
the Fly Agaric, and in the sacred rituals in eastern Siberia,
the urine of the Shamans and their acolytes was ingested by
some followers and considered a better inebriant or
hallucinogen (Efron et al 1979).
7. TOXINOLOGY
7.1 Mode of action
Ibotenic acid is structurally similar to glutaminic acid
and mimics its effects in animals. Ibotenic acid is rapidly
converted to muscimol, which structurally resembles GABA.
Muscimol has a high affinity for GABA receptor sites and
imitates the action of GABAB in animals and humans,
inhibiting and controlling the recruitment and multiplication
of nerve impulses mediated by many positive neurotrasmitters
(Page, 1984).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
The threshold for observation of
central nervous system disturbances in human
is about 6 mg of muscimol or 30 to 600 mg of
ibotenic acid (Waser, 1979). This dose is
potentially available in a single
A. muscaria or A. pantherina
mushroom.
In human volunteers, effects were measurable
about 1 hour after ingestion of 7.5 to 10 mg
of muscimol, or 50 to 90 mg of ibotenic acid.
These effects continued for 3 to 4 hours,
with some residual effects lasting as much as
10 to 24 hours in some subjects. Hangover
was noted the next day (Chilton, 1975;
Eugster, 1979).
Purified ibotenic acid and muscimol produced
hallucinations, delirium, muscular spasm, and
sleep in volunteers (Theobald et al., 1968,
Waser, 1979).
7.2.1.2 Children
No data available.
7.2.2 Relevant Animal data
Muscimol lacks cholinergic effect at the
neuromuscular junction. It inhibits tremor induced by
tremorin but does not stop the associated salivation
and lacrimation. A low dose of muscimol affects the
EEG of cats and rabbits (Scotti et al., 1969; Theobald
et al., 1968). These observations further support a
localization of action of muscimol in the brain rather
than in the peripheral nervous system.
Muscimol and ibotenic acid administered to rats and
mice intraperitoneally affects brain in the levels of
serotonin (5-hydroxytryptamine), noradrenaline and
dopamine as do LSD, psilocybin and mescaline
(Koenig-Bersin et al., 1970; Waser, 1979).
Ibotenic acid and glutamic acid produce convulsions in
immature rats, in which the blood-brain barrier is not
completely developed (Johnston, 1973). Muscinol has
been shown to produce electroencephalographic
alterations distinct from hallucinogens such as LSD or
mescaline (which is in accord with the clinical
observations). Neither ibotenic acid nor muscimol
appears to act on receptors acetylcholine, dopamine,
or 5-hydroxytryptamine receptors in the central
nervous system. It has been suggested that both
muscimol and ibotenic acid act similarly by activation
of the gamma-aminobutyric acid (GABA) receptor (Brehm
et al., 1972; Walker et al., 1971).
The acute LD50 of muscimol in rats ranges from 4.5
mg/kg intravenously to 45 mg/kg, p.o. Experiments in
dogs suggest that the effects of 20 mg/kg/day, p.o.
are not cumulative (Waser, 1979).
7.2.3 Relevant in vitro data
No data available.
7.3 Carcinogenicity
No data available.
7.4 Teratogenicity
No data available.
7.5 Mutagenicity
No data available.
7.6 Interactions
Muscimol-treated animals, administered small doses of
diazepam or phenobarbital, displayed flaccid paralysis and an
electroencephalographic pattern similar to deep anesthesia
Theobald et al. (1968) and Scotti de Carolis et al. (1969).
These data cannot be extrapolated to humans.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
A convenient analytical method for
ibotenic acid (IBO) and muscimol (MUS) in a
toxic mushroom, Amanita muscaria
(A. muscaria), was developed. IBO and MUS in
the mushroom were extracted with 70%
methanol. After filtration, IBO and MUS in
the extract were determined by high
performance liquid chromatography (HPLC) with
a UV detector set at 210 nm. The HPLC system
adopted was ion-pair chromatography in the
reverse-phase mode on an IRICA RP-18 (C18)
column (4.0 mm with sodium dodecyl sulfate
as a counter ion. Recoveries of IBO and MUS
added to the sample were more than 98% and
the minimum detectable concentration of IBO
or MUS was about 1 ppm. The concentrations
of IBO and MUS in A. muscaria ranged from
258 and 471 ppm and from 18 to 27 ppm,
respectively. Neither of the compounds was
detected in commercial edible mushrooms
(Abstract: Tsunoda K, Inoue N, Aoyagi Y,
Sugahara T, J Food Hyg Soc Jpn; 34(1). 1993.
12-17).
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall interpretation of all toxicological analyses and
toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Symptoms appear within 30 to 90 minutes and are
most marked at 2 or 3 hours. They may include:
drowsiness, confusion, dizziness, ataxia, euphoria,
delirium, visual and auditory disturbances with
hallucinations, muscle cramps and spasms.
Gastrointestinal disturbances and convulsions may also
be seen.
9.1.2 Inhalation
No data available.
9.1.3 Skin exposure
No data available.
9.1.4 Eye contact
No data available.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
No data about chronic toxicity available.
9.2.2 Inhalation
No data available.
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
Toxic effects appear 30 to 90 minutes after ingestion
and last usually for 6 hours but may persist for 12 to 24
hours. Hangover is often observed the following day. The
prognosis is usually good with symptomatic treatment. Death
from these mushrooms is extremely rare (Chilton, 1978).
Although they sometimes produce dramatic intoxications with
extensive psychological and neurological effects these
mushrooms have a totally unwarranted reputation for being
"deadly poisonous".
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Pulse and blood pressure are usually normal.
In one case, the patient developed cardiac
fibrillation (Lincoff & Mitchel, 1977), also
bradycardia was observed (Benjamin, 1992).
9.4.2 Respiratory
Respiration is not usually affected (Bosman et
al., 1965); but respiratory depression is possible as
a result of over treatment (Benjamin, 1992).
9.4.3 Neurological
9.4.3.1 Central nervous system (CNS)
The primary effects are CNS
depression and stimulation, which may
alternate. Symptoms usually begin with
drowsiness followed by a state of confusion,
with ataxia, dizziness, euphoria resembling
alcohol intoxication and may proceed to
increase activity, illusions, or even manic
excitement.
These periods of excitement may alternate
with periods of somnolence, deep sleep or
stupor (Ammirati et al., 1985; Benjamin,
1992).
The illusions are primarily a
misinterpretation of sensory stimuli such as
changes in color vision, echo images (seeing
through walls), identification of hospital
personnel as divine figures, and the like,
rather than true hallucinations caused by
Psilocybe, or Paneolus.
However, vivid hallucinations associated with
accidental poisoning by this Amanitas have
been reported occasionally (McDonald, 1980;
Carter et al., 1983).
Seizures are observed primarily in children
(Benjamin, 1992).
9.4.3.2 Peripheral nervous system
Muscimol lacks cholinergic effects
at the neuromuscular junction
9.4.3.3 Autonomic nervous system
Neither muscarinic nor atropinic
effects have been observed in poisoning due
to A. muscaria or A. pantherina.
Occasionally, sweating and salivation have
been reported (Lampe, 1978; Waser, 1979;
Benjamin, 1992).
9.4.3.4 Skeletal and smooth muscle
Muscle jerks, fasciculation and
spasms in the extremities are observed
(Chilton, 1978; Benjamin, 1992).
9.4.4 Gastrointestinal
Dyspepsia and vomiting may occur (Chilton,
1978, own data).
9.4.5 Hepatic
Amanita muscaria has no hepatotoxic effects.
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Other
No data available.
9.4.7 Endocrine and reproductive systems
No data available.
9.4.8 Dermatological
Skin may be warm and flushed (Benjamin, 1992).
9.4.9 Eye, ear, nose, throat: local effects
Miosis as well as mydriasis or intermittent
mydriasis were observed in children (Benjamin,
1992)
9.4.10 Haematological
No data available.
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
No data available.
9.4.12.2 Fluid and electrolyte disturbances
Light or mild dehydration may be
observed, as a consequence of
vomiting.
9.4.12.3 Others
No data available.
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
No data available.
9.5 Other
No data available.
9.6 Summary
Symptoms onset is usually within 30 to 90 minutes,
peaking at 2 to 3 hours. Initial drowsiness is followed by
ataxia, confusion, agitation, illusions or even manic
excitement. These periods of excitement may alternate with
periods of somnolence, deep sleep or stupor. Muscle jerks,
fasiculations and spasms in the extremities were
observed.
10. MANAGEMENT
10.1 General principles
Treatment includes prevention of absorption of the
toxins and treatment of the signs and symptoms of
intoxication as they occur, especially sedation.
Induction of emesis is NOT recommended because of the
potential CNS depression and seizures.
10.2 Life supportive procedures and symptomatic/specific
treatment
Make a proper assessment of airway, breathing,
circulation and neurological status of the patient.
Control convulsions with appropriate drug regimen, sedation
with benzodiazepines is required (see IPCS Treatment
Guidelines).
10.3 Decontamination
Emesis is not recommended.
Administer activated charcoal, most effective when
administered within one hour of ingestion.
Gastrointestinal emptying and/or charcoal is however, rarely
indicated and only in very recent ingestion, while the
patient is asymptomatic.
10.4 Enhanced elimination
Forced diuresis
Not necessary, although possibly effective on
theoretical grounds.
Hemodialysis
Although the toxins may be removed by hemodialysis (Mitchell
and Lumack, 1978) this procedure is considered unnecessary in
view of the good prognosis of clinical cases.
10.5 Antidote/antitoxin treatment
10.5.1 Adults
There is no specific antidote for Amanita
muscaria and Amanita pantherina poisoning.
10.5.2 Children
There is no specific antidote for Amanita
muscaria and Amanita pantherina
poisoning.
10.6 Management discussion
Treatment includes prevention of absorption, with
activated charcoal, of the toxins and treatment of the signs
and symptoms of intoxication as they occur.
Induction of emesis is not recommended because of the
potential central nervous system depression and seizures.
There is no specific antidote for Amantia muscaria and
pantherina poisoning.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Accidental poisoning
There are numerous reports in the medical literature of this
type of intoxication. Intoxication with A. muscaria and
pantherina have more recently become more common as the
result of deliberate attempts by individuals to induce
hallucinations. Special recipes are even now appearing for
ways to prepare a broth from these mushrooms so that one can
retain their psychoactive effects without the
gastrointestinal irritating effects.
Voluntary ingestion
Agnus McDonald experimented the self-administration of whole
A. muscaria (1978). He prepared capsules with dried and
powdered mushrooms, collected in Northern California. With 12
g of dried A. muscaria a noticeable effect was felt.
"In summary, 12 g of dry red A. muscaria produced mainly
these following symptoms: a marked nausea that tapered off
over the first three hours; 2) a conspicuous absence of
reflective thought combined with a sense of tiredness, and 3)
a slight transient euphoria around the fourth hour that
alternate with and finally was overwhelmed by a general sense
of fatigue. It was not an inspiring experience, and the
initial nausea was so great that I had no desire to repeat
it. I decided on a compromise. I made an infusion by
soaking 30 g of dried mushrooms in a cup of water. Within one
hour I was obviously feeling a greater effect than I had from
eating 12 g. I felt again as if I were in a state of
suspended animation, this time with a much stronger desire to
sleep. Although my environment seemed somehow "bright", there
were no hallucinations of obvious visual distortions. My
stream of consciousness seemed notably empty, and when I
contemplated writing down something about how I felt, I could
think of nothing to say. I noticed a marked increase in my
usual level of saliva production. By 5 1/2 hours after
ingestion, the effects were waning. By 7 hours later, they
were nearly gone, and I succumbed to my desire to sleep.
There were no sequelae the following morning".
McDonald conducted also an assay with six human volunteers
who ate the 12 g does of dried-powdered Fly Agaric. All
experimented nausea, although only two of them vomited. All
six experienced tiredness, and three of the six reported
increased salivation. Only two of the subjects related
visual distortions that might pass for low-grade
hallucinations.
The experiences of Waser (1979), who experimented himself the
effects of pure substances (ibotenic acid and muscimol),
merit to be mentioned here:
"A 20 mg ibotenic acid dose ingested in water tastes like
mushrooms, but produces little immediate action. Within half
an hour a warm and slightly flushed face was noticed, without
changes in blood pressure or heart rate, with no physic
stimulation, but lassitude followed by sleep. A day later a
migraine with classical one-sided visual disturbance
developed for the first time in my life. The occipitally
localized headache continued in a milder form for two
weeks.
Next I turned to muscimol. A dose of 5 mg in water orally
ingested had little effect except a feeling of laziness. Ten
mg produced a slight intoxication after 90 minutes with
dizziness, ataxia and elevated mood, psychic stimulation (in
psychological tests), no hallucinations but slight changes in
taste and color vision. Some myoclonic muscle twitching
followed, then sleep with dreams. After two to three hours I
felt normal, rested and able to undertake anything, even
work. During the next night I slept well, deep and long. No
other signs followed.
With 15 mg of muscimol administered orally the intoxication
started after 40 minutes and was more pronounced. Dizziness
made walking with closed eyes impossible, but reflexes were
not changed. Speech was sometimes inarticulate and
dysarthric. Appetite and taste were diminished. After a
phase of stimulation, concentration became more difficult.
Vision was altered by endlessly repetitioned echopictures of
situations a few minutes before. Hearing became noisy and
sometimes was followed by echo. Most disturbing were
repeated myoclonic cramps of different muscle groups. I felt
sometimes as if I had lost my legs, but never had
hallucinations as vivid and colorful as with LSD. The pupils
remained always the same size. After 2 hours I fell asleep,
but I cannot remember any dreams. Two hours later I awoke
again and was glad that the muscle twitching was less
frequent. I did not feel relaxed and fresh as after 10 mg
muscimol but rather dull and uncertain. Blood pressure was
only a little elevated during the psychoactive phase".
Muscimol induces a state of psychosis with confusions,
dysarthria, disturbance of visual perception, illusions of
colour vision, myoclonia, disorientation in place and time,
weariness, fatigue and sleep. Concentration tests showed
improved performance with small doses (5 mg) but diminished
performance and learning with an increased number of errors
with higher doses (10 to 15 mg).
12. Additional information
12.1 Specific preventive measures
12.2 Other
13. REFERENCES
Allegro J (1971). The Sacred Mushroom and the Cross. New
York, Bantam eds.
Ammirati JF, Traquair JA, Horgen PA (1985) Poisonous mushrooms of
the Northern United States and Canada. Univ. of Minn Press,
Mineapolis.
Balcar VJ, & Johnston GAR (1972). Glutamate Uptake by brain slices
and its relation to the depolarization of neurones by amino acids.
J. Neurobiol, 3:295 (Ref. by Chilton, 1978).
Benedict, PW, Tyler VE, & Brady LR (1966). Chemotaxonomic
significance of isoxazole derivatives in Amanita species. Lloydia,
29: 333-341.
Benjamin DR (1992) Mushroom poisoning in infants and children: the
Amanita pantherina/muscaria group. J Toxicol Clin Toxicol.
30(1):13-22.
Borthwick PW, & Steward EG (1976). Ibotenic acid: Further
observations on its conformational models. Journal of Molecular
Structure, 33:141 (Ref by Chilton, 1978).
Bosman CK, Berman L, Isaacson M, Wolfowitz B & Parkes J (1965).
Mushroom poisoning caused by Amanita pantherina. S Afr Med J,
39:983-986.
Bowden K, Drysdale AC & Mogey GA (1965). Constituents of Amanita
muscaria. Nature, 206:1359-1360.
Brehm L, Hjeds H & Krogsgaard-Larsen P (1972). Structure of
muscimol, a gamma-aminobutiric analog of restricted conformation.
Acta Chim Scand, 26:1298-1299.
Breskinsky A & Besl H (1985). Mushroom poisoning, Stuttgard:
Wissenschaftliche Verlagsgesellschaft mbH. (In German).
Carter CA, Wojciechowski NH & Skoutakis VA (1983) Management of
mushroom poisoning. Clinical Toxicology Consultant 5:103-108.
Chilton WS, (1975). The course of an intentional poisoning.
MacIlvanea, 2:17. (Ref. by Lincoff & Mitchel 1977, and Chilton
1978).
Chilton WS (1978). Chemistry and mode of action of mushroom
toxins. In: Rumack, B.H. & Salzman, E, Eds. Mushroom poisoning:
Diagnosis and Treatment. West Palm Beach (Florida), CRC Press
Inc. 87:124.
Chilton WS, HSU, CP & Zdybac WT (1974). Stizolobic and
Stizolobinic acids in Amanita pantherina. Phytochemistry,
13:1179-1181.
Chilton WS & Ott J (1976). Toxic metabolites of Amanita
pantherina, cothurnata, muscaria and other species. Lloydia,
39:150-157.
Depovere P & Moens P (1984). Active components and colorant
substances in the Fly Agaric Aminita muscaria (Fires) Hooker. J.
Pharm Belg, 39:238-242 (in French).
Donalies G & Volz G (1960). An attempted suicide with the Fly
Agaric Der Nervenartz, 31:182-185 (in German).
Efron DH, Holmstedt B & Kline NS (1979). Ethnopharmacological
Search for Psychoactive Drugs. U.S. Public Health Service
Publication. (First edition was a very limited one in 1967).
Eugster CH (1979). Isolation, structure and synthesis of central
active compounds from Amanita muscaria (L. ex Fr.) Hooker. In:
Efron, DH Holmstedt B & Cline NS eds. Ethnopharmacological Search
for Psychoactive Drugs. U.S. Public Health Service Publication
1645:416-419.
Eugster CH, Müller GFR, & Good R (1965). Active Principles from
Amanita muscaria: Ibotenic Acid and Muscazone. Tetrahedron Lett.
1965:1813-1815 (in German).
Fischer OE (1971). Mushroom poisoning. In: Kauffman, CH, ed. The
gilled mushrooms of Michigan and the Great Lakes Region, New York:
Dover Reprint.
Hotson JW (1934). Mushroom poisoning in Seattle. Mycologia,
26:194-195.
IPCS INTOX CD-ROM, 2000-1
Johnston GAR, Curtis DR, De Groat WC, & Duggan AW (1968). Central
actions of Ibotenic acid and muscimol. Biochem. Pharmacol,
17:2488. (Ref. by Chilton 1978 and Lampe 1978).
Johnston GAR (1971). Muscimol and the uptake of Gamma-Aminobutyric
acid by rat brain slices. Psychopharmacologia, 22:230. (Ref. by
Chilton 1978) and Lampe 1978).
Johnston GAR (1973). Convulsion induced in 10-day-old rats by
intraperitoneal injection of monosodium glutamate and related
excitant amino acids. Byochem. Pharmacol, 22:137 (Ref by Chilton
1978).
Kneifel H & Bayer E (1986). Stereochemistry and total synthesis of
amavadin, the naturally occurring vanadium compound of Amanita
muscaria. J. Am Chem Soc, 108:3075-3077.
Koenig-Bersin P, Waser PG, Langemann H & Lichtensteiger W (1970).
Monoamines in the brain under the influence of muscimol and
ibotenic acid, two psychoactive principles of Amanita muscaria.
Psychopharmacologia, 18:1-10.
Kronsgaard-Larsen P & Johnston GAR (1975). Inhibition of GABA
uptake in rat brain slices by nipecotic acid, various isoxazoles
and related compounds. J Neurochem 25:797 (Ref by Chilton,
1978).
Krogsgaard-Larsen P & Hansen JJ (1992) Naturally-occurring
excitatory amino acids as neurotoxins and leads in drug design.
Toxicol Lett. 64-65 Spec No: 409-16.
Krogsgaard-Larsen P, Frolund B & Frydenvang K (2000) GABA uptake
inhibitors. Design, molecular pharmacology and therapeutic
aspects. Curr Pharm Des 6(12):1193-209.
Lampe KF (1978). Pharmacology and therapy of mushroom
intoxications, In: Rumack BH, & Salzman. E, Eds. Mushroom
poisoning: Diagnosis and treatment. West Palm Beach (Florida),
CRC Press Inc, 125-169.
Lea TJ & Usherwood PNR (1973). Effect of Ibotenic acid on Chloride
Permeability of insect-muscle fibers. Comp Gen Pharmacol 4:351
(Ref by Chilton, 1978).
Leonhardt W (1949). States of Inerbration on Amanita pantherina
poisoning. Der Nervenarzt, 20:181-188 (in German).
Lowy B (1972). Mushroom symbolism in Maya Codices. Mycologia 64:
816-821.
Lincoff G & Mitchel DH (1977). Toxic and Hallucinogenic Mushroom
Poisoning, New York. Van Nostrand Reinhold Co.
Mitchel DH & Rumack BH (1978). Symptomatic diagnosis and treatment
of mushroom poisoning. In: Rumack, BH & Salzman E, Eds. Mushroom
poisoning: Diagnosis and Treatment. West Palm Beach (Florida),
CRC Press Inc, 171-179.
Müller GFR & Eugster CH (1965). Muscimol, a pharmacodinamic
substance from Amanita muscaria. Helvetica Chimica. Acta.
48:910-926 (in German).
Ott J, Wheaton PS & Chilton WS (1975). Fate of Muscimol in the
mouse. Physiol. Chem Phys, 7:381-384.
Page LB (1984). Mushroom toxins and the nervous system: some facts
and speculations. McIlvainea, 6, 39-43.
Pfefferkorn W & Kirsten G (1967). Pantherine syndrome course in
childhood: Panther mushroom poisoning. Kinderartzl Praxis,
35:355-364 (in German).
Repke DB, Leslie DT & Kish NG (1978). GLC-maas spectral analysis
of fungal metabolites. J Pharm Sci, 67:485-487.
Scotti de Carolis A, Lipparini F & Longo VG (1969).
Neuropharmacological investigations on muscimol, a psychotropic
drug extracted of Amanita muscaria, Psychopharmacologia,
15:186-195.
Seeger R & Stijve T (1978). In: Faulstich H, Kommerell, B, &
Wieland, T. Eds. Amanita toxins and poisoning. Baden-Baden: Verlag
Gerhard Witzstrock, 3-16.
Smith I, (1960). Chromatography and electrophoretic techniques.
Vol. I. New York: Interscience. (Ref. by Chilton, 1978).
Takemoto T, Nakajima T & Sakuma P (1964). Isolation of a Flycidal
constituent "Ibotenic acid" from Amanita muscaria and
A.pantherina. Yakugaku Zasshi, 84:1233-1234.
Takemoto T, Nakajima T & Yakore T (1964). Structure of Ibotenic
acid. akugaku Zasshi, 84:1232-1233.
Theobald W, Büch O, Kinz HA, Krupp P, Stenger EG, & Heimann H
(1968). Pharmacological & Experimental investigations of two
components of the Fly Agaric. Arzneim Forsch, 18:311-315.
Tsunoda K, Inoue N, Aoyagi Y, & Sugahara T (1993). Simultaneous
analysis of ibotenic acid and muscimol in toxic mushroom, Amanita
muscaria, and analytical survey on edible mushrooms. J Food Hyg
Soc Jpn 34 (1); 12-17.
Tsunoda K, Inoue N, Aoyagi Y, & Sugahara T (1993) Changes in
concentration of ibotenic acid and muscimol in the fruit body of
Amanita muscaria during the reproduction stage: Food hygienic
studies of toxigenic basidiomycotina: II. J Food Hyg Soc Jpn 34
(1); 18-24.
Tsunoda K, Inoue N, Aoyagi Y, & Sugahara T (1993) Change in
ibotenic acid and muscimol contents in Amanita muscaria during
drying, storing or cooking: Food hygienic studies of toxigenic
basidiomycotina: III. J Food Hyg Soc Jpn 34 (2); 153-160.
Walker RJ, Woodruff GN & Kerkut GA (1971). The effect of ibotenic
acid and muscimol on single neurones of the snail Helix aspersa.
Comp Gen Pharmacol, 2: 168 (ref by Chilton, 1978 and Lampe
1978).
Waser FG (1979). The pharmacology of Amanita muscaria. In:
Efron, DH Holmstedt, B & Kline NS eds. Ethnopharmacoplogical
search for psychoactive drugs. U.S. Public Health Service
Publication, No. l645: 419-439.
Wasson RG (1964). The present state of Oloiuhqui and
Hallucinogens of Mexico. Psychodellic. Rev, 1: 275-301.
Wasson RG (1968). Soma: Divine mushroom of immortality. New York:
Hartcourt Brace Javonovich Inc.
Wasson RG (1972). Soma and the Fly Agaric. Botanic' Museum Eds,
Harward University.
Wasson RG (1979). Fly Agaric and Man. In, Efron, DH Holmstedt, B
& Kline, NS eds. Ethnopharmacological search for psychoactive
drugs. U.S. Public Health Service Publication, No. 1645:
405-414.
14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UPDATING), COMPLETE
ADDRESSES
Author: J. Piqueras
Department of Haematology & Haemotherapy
General Hospital Vall d'Hebron
Autonomous University of Barcelona
08035 Barcelona
Spain
Date: 10 January 1990
Reviewer Dr Barbara Groszek
Department of Clinical Toxicology
College of Medicine of the Jagiellonian University
31-826 KRAKOW
POLAND
Tel: +48 12 647 55 85 or +48 12 647 11 05
Fax: +48 12 647 55 85 or +48 12 647 11 05
E-mail: mfgrosze@cyf-kr.edu.pl
Date: 16 October 2000
Reviewed by:
* Dr Barbara Groszek, Dr John Haines, Dr Johan Holmdahl,
Dr Jenny Pronczuk and Dr John Trestrail (Meeting on Mushroom
Poisoning, 19-21 October 2000, Stockholm, Sweden).
* Dr B. Groszek and Dr H. Persson (INTOX-12, 6-11 November
2000), Erfurt, Germany)