international program on chemical safety- amanita muscaria and related species

8/3/2019 International Program on Chemical Safety- Amanita Muscaria and Related Species

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Amanita muscaria and related species 1

AMANITA MUSCARIAAND RELATED SPECIES

MONOGRAPH FOR THE I.P.C.S.

(International Program on Chemical Safety)


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SECTION 1 NAME

1.1 Scientific name :

Amanita muscaria(L.ex Fr.) Hooker

1.2 Family :

1.2.1. AgaricaceaeGenus: Amanita

1.2.2. Other mushrooms: Other Amanitamushrooms containthe same toxins and induce similar toxicity:

- Amanita muscariavar. KamtschaticaLangsdorff ex. Fr.- Amanita regalis(Fr.) R.Mre. (A.muscaria var.umbrina Fr.)- Amanita muscariavar. formosa- Amanita muscariavar. alba- Amanita velatipesAtk.- Amanita cothurnataAtk.- Amanita flavivolvataSing.- A.pantherina(DC ex Fr.) Secr.- A.strobiliformis(Vitt.)Quel.

1.3 Common name :

-Amanita muscaria

:

English: Fly AgaricGerman: Fliegenpilz, Roter fliegenpilz.Spanish: Falsa oronja, amanita matamoscas.French: Amanite tue-mouche, Agaric aux mouches, fausse oronge.Italian: Ovulo malefico, Uovolaccio.

- Amanita pantherina:

English: Panther cap.

German: Pantherpilz, Braunner Knollenbltter pilz.Spanish: Amanita pantera, galipiermo falso.French: Amanite phantre, Fausse golmelle.Italian: Tignosa bigia, Tignosa rigata, Agarico panterino.

These mushrooms are mostly species of Amanita, primarily the Fly-Agaric, Amanitamuscaria, and the Panther, Amanita pantherina, but their toxins are not relatedchemically to the toxins in the more deadly Amanitas such as A.phalloides andA.virosa. Nor do these mushrooms present a symptomatology typical of muscarinepoisoning, in spite of the fact that minute amounts of muscarine occur in some of thespecies. Rather, the Fly Agaric, and to a lesser extent the other species in this

group, contain toxic compounds that produce a characteristic set of symptoms, inclu-ding enebriation, confusion of the senses, manic behaviour, delirium, and deep


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sleep, from which all but a very few persons recover rather quickly. These symptomsare very similar to those produced by the so called "Tropanic plants" - Daturastramonium, Atropa belladonna, Hyoscyamus niger ...-. This poisoning could beappropriately named "Mycoatropinic". However, tropanic alkaloids (atropine,hyoscyamine) are not present in the Fly Agaric.

SECTION 2. SUMMARY

2.1 Main risk and target organs:

Experiments in animal and man support a central nervous system (CNS) role formuscimol and ibotenic acid, probably as false neurotransmitters: The localization ofthe action of the isoxazole toxins is in the brain, and the central nervous system maybe considered their target organ. Muscimol and ibotenic acid presumably cross theblood-brain barrier via some active transport system. Inefficient removal of thesefalse neurotransmitters once they have passed the blood-brain barrier may be animportant contributing factor to their CNS effects.

2.2 Summary of clinical effects:

The Fly-Agaric's effects start about 30 minutes after ingestion and last for hours.First it acts as soporific, and induces to sleep for about two hours with vivid dreams.After waking from this sleep, some persons enjoy a feeling of elation that can lastthree or four hours, during which they can enjoy performing extraordinary feats orphysical effort:

* Onset within 30 to 90 minutes, most marked at 2 or 3 hours.* Drowsiness* Confusion resembling alcoholic intoxication.* Dizziness.* Ataxia.* Euphoria may progress into hyperkinetic activity.* Muscle cramps and spasms.* Delirium.* Convulsions are only observed sometimes in children.* Visual and auditory disturbances. Seldom real hallucinations* Gastrointestinal disturbances were often present in our experience, althoughmany authors state vomiting usually does not take place. Drowsiness to deepsleep or even coma terminates the episode, which usually lasts 4 to 8 h.

2.3 Relevant laboratory analysis/sample collection:

The only specific analytic determination that could be performed is the urinemeasurement of muscimol and ibotenic acid. Specific reagents are based on anundefined reaction between pentacyanoferriate ion and the heterocycle of theseamino acids. In particular the pentacyanoaquoferriate reagent of Smith is a readilyprepared, storable and reasonably sensitive reagent. The closely related Grote'sreagent and other cyanoferriate methods can be used to detect ibotenic acid and

muscimol To our knowledge, neither serum nor urine levels have value in order totake decisions on therapeutic. These determinations are only diagnostic.The diagnosis may be confirmed by the examination of the mushrooms or their


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remnants. If available, they have to be studied by a mycologist. However, oneshould take into account that the absence of toxic specimens in the material broughtby relatives, does not necessarily imply the lack of ingestion of toxic mushrooms.

2.4 First-aid measures and management principles:

The general measures to prevent absorption and enhance excretion areparticulary important in these intoxications:a) Reduction of absorption: emesis, gastric lavage, catharsis.b) Enhancement of excretion: Forced diuresis is usually

not needed.General supportive measures are of great importance.Antidotes have to be used according to symptoms: If anticholinergicsymptoms, especially at CNS level (agitation, excitement, hallucinations, or onthe contrary, deep sleep or coma) occur, physostigmine might be considered.Cholinergic symptoms are rarely seen, only in the case of the very infrequentstrains of mushrooms that probably have an unusual concentration ofmuscarine. If these symptoms occur, atropine might be considered.

2.5 Poisonous parts:

All parts of the fruiting bodies of A.muscariaand A. pantherina are toxic. Theisoxazoles are not distributed uniformly in the mushroom but, at least inA.muscariaare in highest concentration in the yellow tissue immediately belowthe red skin.

2.6 Main toxins :

The toxic constituents of these amanitas have been identified as theIsoxazoles Ibotenic Acid and its decarboxylation product Muscimol. Thereare also some irritants of the gastrointestinal tract, which have not beenidentified yet.


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SECTION 3. CHARACTERISTICS

3.1 Description of the plant:

3.1.1 Special Identification features:

3.1.1.1 Identification:A.muscaria (the fly agaric) is easily identifiable. Its red cap with withe wartsare usually clear enough to made the right recognition. However, completeand precise identification of the mushrooms (if available), should beperformed by a mycologist. Identification is more difficult in remnants of dishes,when the mushrooms have been altered by cooking.

3.1.1.2 Description of A.muscaria:

CAP:

Size : 8 - 12 cm acrossoccasionally over 20 cm

Shape and colour: Ovoid or hemispherical when young, becoming convex,finally plane. Viscid, striate on margin. At first covered by thick whitish or paleyellow warts and hanging marginal veil remains. Cap dull to bright yellow,orange, orange-red, blood-red or scarlet, rarely white. Darkest at centre.The yellow, orange to orange-red caps (A.muscariavar. formosa) occurs ineastern North America. The scarlet cap (A.muscariavar. muscaria) occurs inwestern North America, throughout Europe and in Asia.

GILLS:

Free or just touching stalk, close, white to yellowish, edges even or floccose.

STALK:

Size: 7 - 15 x 0.8 - 1.5 cm

Shape and colour: equal or enlarging down to bulbous base. Whitish and

silky or floccose near apex. White to pale yellow and fibrillose-scaly belowring.

ANNULUS: (Ring; partial veil)

Large, membranous, white to yellowish, median to superior, persistentthough margin usually frayed.

VOLVA: (Cup)

Present as two or three concentric rings just above bulb. White to straw.


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SPORES:

White spore print (in mass). (8)9-11 x (6)7-8 m. Elliptical, smooth, non-amyloid.

3.1.2. Habitat:

Scattered to abundant, some times in fairy rings. On ground under hardwoodsand conifers. Among others, the Fly-Agaric can be found in conifers forests ofhigh mountains (Abies, Picea), and also in Fagusforests.

Season: Spring, summer, autumn.

3.1.3. Distribution: These species are widely distributed throughout theplanet. Amanita muscariagrows in summer and autumn under coniferous and

deciduous trees, from the lowland up to the subalpine zone. It occurspractically all over the temperate and subtropical zones in Europe, NorthAfrica, South Africa, Asia, Japan, Australia, North America (in the WesternStates of the USA more often than in the Eastern States) and in SouthAmerica. A.pantherinagrows from summer until autumn (in some areas inSpring and autumn) under conifers and hardwood, especially in the pinewoodsof the lowland, and also in submountainous and mountainous regions. Itoccurs in North, Central and Southern Europe down to North Africa, inIndochina, Japan and in North America (Seeger & Stijve, 1978).

3.2 Poisonous part of the plant:

All parts of the fruiting bodies of A.muscaria and A. pantherina are toxic. Theisoxazoles are not distributed uniformly in the mushroom but, at least in A.muscariaare in highest concentration in the yellow tissue immediately below the red skin(Lampe, 1978). Although the dry mushroom is psychoactive, the content of ibotenicacid gradually diminishes with time (Benedict et al, 1966).

3.3 Toxins:

3.3.1 Names:

When Schmiedeberg and Koppe extracted a toxic compound from thismushroom in 1869 (Singer, 1978), it was assumed to be the activecomponent responsible for its effects, and it was named muscarine. When itwas found that atropine quickly and effectively counteracted the effects ofmuscarine, it was assumed that atropine was the perfect remedy for Fly-Agaric poisoning. This is still believed by many practising physicians, despitemore than 80 years of medical research to the contrary. Muscarine is nowknown to be found in only insignificant amounts in the Fly-Agaric (3 p.p.m offresh weight (Eugster, 1979)). More importantly, muscarine do not produce apsychotropic action, probably by its difficulty, as a quaternary amine inpassing the blood brain barrier (Waser 1979). By 1903 it was known that the

Fly-Agaric contained other toxins as well, and that atropine was not anantidote (Lincoff & Mitchel, 1977): in fact atropine has been shown toexacerbate symptoms of Fly-Agaric poisoning. On the other hand, if one


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genus is characterized by its muscarine-containing species, this is the genusInocybe. In fact, muscarine could have been more appropriately namedInocybine.Actually, it was not until the 1960' that the toxin believed to be primarilyresponsible for this mushroom's characteristic intoxication syndrome wereisolated and described. Three related compounds, ibotenic acid, muscimoland muscazone, all isoxazole derivatives, have been found in the Fly-Agaric(Eugster, 1979). Among them, Ibotenic acid and muscimol are responsible toa significant degree for the toxicity of draw and cooked Amanita muscariaand A.pantherinaand of aqueous extracts of these species.

IBOTENIC ACID and MUSCIMOL

Ibotenic acid and muscimol were isolated independently in Switzerland,England and Japan between 1960 and 1964. Although each group workedcompletely independently, they all involved very similar fly-killing (Takemotoet al., 1964), fly-stunning (Bowden & Mogey, 1965) and mouse narcosispotentiating tests (Eugster et al., 1965; Mller & Eugster, 1965).

3.3.2 Description, chemical structure (formula, molecu-lar weight), stability:

Molecular weight: - Ibotenic acid: 168 daltons- Muscimol : 124 daltons

Ibotenic acid and muscimol are respectively, conformationaly restrictedderivatives of glutamic acid and GABA. The X-ray Crystallographiccomparison of muscimol to GABA has been made (Brehm et al, 1972),CNDO-calculated conformations of ibotenic acid have been compared tosolution conformations of glutamic acid (Borthwick & Stewart, 1976). GABA isrelated to glutamic acid in the same way that muscimol is related to ibotenicacid, by decarboxylation. The decarboxylation of glutamic acid does notoccur in the absence of L-glutamate-1-cocarboxylase. However, ibotenic aciddecarboxylates readily, and almost any step of manipulations in acidicsolvents, even chromatography of recrystallization, is accompanied by partialdecarboxylation to give muscimol. The analogy between glutamic andibotenic acids extend to the taste-intensifying properties of monosodiumglutamate: ibotenic acid has been patented as a flavour enhancer.


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The various pharmacologically active substances from these mushroomshave been only partially determined (Eugster, 1979), and additionalconstituents continue to be found (Chilton & Ott, 1976). Future work shouldtake into account that the Fly mushroom group is taxonomically complex, andconcentration of chemical substances may be variable in differentpopulations, races, and stages of the fungus. (Singer, 1978).

3.3.3 Other physico-chemical characteristics

Muscimol is a very polar and extremately water soluble substance. It is theenol-betaine of 5-aminomethyl-3-hydroxy-isoxazol. It is an unsaturated cyclichydroxamic acid. Muscimol is easily formed by decarboxylation and loss ofwater from ibotenic acid.

3.4 Other chemical contents:

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).Tropane alkaloids are NOT present in A.muscariaor A.pantherina. (This isgenerally accepted, by it seems that there are a few reports on the contrary.According to Depovere et Moens (1984) atropine and scopolamine havebeen isolated from A.muscaria.)


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SECTION 4. USES/CIRCUMSTANCES OF THE POISONING

4.1 Uses

Amanita muscaria, the Fly-Agaric, has attracted attention among Europeans atleast since the appearance in the early eighteenth century of the first travellers' talesrecounting the use of this mushroom among Siberian Tribesmen. Its name is thoughto have derived from its use as a fly-killer, hence, muscariafrom musca, the Latinword for the fly. Wasson (1968) has suggested another explanation for its name,from the mythical association of madness with the fly. He states that, in the MiddleAges and earlier, people who were possessed were believed to be infested by flies.So, the "Mad Mushroom", the "Bolond Gomba"of the Hungarians, the "NarrenSchwamm" of the Germans, those were the Fly Agaric.In Japan, a derivative of muscimol is presently being used as a pesticide. Thisparallels the folk use of the Fly-Agaric as a fly killer. Of some peripheral interest, thepenetrating taste of the Fly-Agaric has also been put to modern use. An extract ofibotenic acid has been found to be some 20 times more powerful than monosodiumglutamate as a flavour enhancer.There has been much speculation recently on the historical use of the Fly-Agaric.R.Gordon Wasson (1972) has suggested that it might have been used by Stone Agehuman beings both as a relief from the rigors and monotony of overdaylife as avehicle by which to communicate with the gods and to travel through space andtime. In an intricate linguistic argument, Wasson reasoned that the Fly-Agaric wasused by Vedic priests some 3.000 years ago to attain ecstasy and see life-everlasting. He has interpreted the soma hymns of the Sacred Indian book, the Rigveda, as being the glorification of the physical beauty of the Fly-Agaric andbeatification of the experience under its influence (Wasson, 1968).Another linguistic case has been advanced by the Sanskrit scholar John Allegro(1971), whose argument suggests that a Fly-Agaric cult may have been the sourceor inspiration for major religions of the Near East. A recent hypothesis has been thatthe Indian peoples of Meso-America might have used the Fly-Agaric in the mannerthey still used other mushrooms, seeking their hallucinogenic effects. This notion isbased on the abundance of this species in the area and the finding of a Mayapainting of a mushroom offering in which the stylized mushroom cap suggests thewarted cap of the Fly-Agaric (Lowy, 1968).The only historically documented use of A.muscaria comes to us in the form ofdiaries and articles written over the past 300 years by Europeans who had been toSiberia where many native tribes used this mushroom as either a sacred or asecular intoxicant. In far-western Siberia, where it retained its religious importance, a"taboo" on its general use was imposed on all but the Chaman and his acolytes. Innortheastern Siberia, on the other hand, the use of the Fly-Agaric becomeessentially recreational, and it was used as an inebriant until it was replaced byvodka. Some people there are said to prefer the mushroom to this day (Lincoff &Mitchel, 1977).It is interesting to note that a few people in Europe and North America eatA.muscariaas a food mushroom. Traditionally they select young mushrooms, peelthe skin of the cap and discard the peeling, and boil the mushrooms, discarding theboiling water. Perhaps experience has thought the advisability of removing the

pigment as well (Lampe, 1978).


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4.2 High risk circumstances

The toxins contained in this groups of mushrooms are capable of eliciting pleasureor fear in the same experience. Which one of these opposite reactions will occurseems to depend upon such factors as the potency of the toxin in the mushrooms,the number of mushrooms eaten, the manner in which are prepared and presented,and the environment in which the experience occurs. Not everyone experiences thesame set of symptoms, and even a person who is strongly affected by a singlemushroom can remain completely unaffected another time after eating many ofthem. Seasonal differences on toxicity of these fungi have been confirmed, and onehave to take into account the possibility of Geographical differences too. Also to beconsidered is the importance of "setting" and "set" in determining the subject'sreaction ("set" is a person's expectations of what a drug will do to him, considered inthe context of his whole personality. "Setting" is the environment, both physical andsocial, in which a drug is taken).Today, because many people are experimenting with various synthetic and naturaldrugs, most poisoning from the Fly-Agaric are probably self-inflicted, although thereaction is not always as expected.Whether or not Fly-Agaric is really psychotropic (it is thought by some not to causehallucinosis), it has been and still is being used in an attempt to expand or alterspatio-temporal awareness. But, in quantity it can be drastic sickener.Dead from this kind of mushrooms is rare, or rarely reported. However, it would beunwise to consider eating them because the toxins are complex, variable in quantity,and not completely understood.

4.3 High risk geographical areas: See 3.1.3 item.

SECTION 5. ROUTES OF ENTRY

5.1 Oral : Intoxications by muscimol-ibotenic acid containing mushrooms are alwaysdue to the oral absorbtion of the toxins.

5.2 InhalationUnknown

5.3 DermalUnknown

5.4 EyeUnknown

5.5 ParenteralUnknown

5.6 OthersUnknown


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SECTION 7. TOXICOLOGY/PHARMACOLOGY

7.1 Mode of action:

Experiments in animal and man support a central nervous system role formuscimol and ibotenic acid, probably as a false neurotransmitter. Unlike GABA,the natural neurotransmitter it mimics, muscimol exerts pronounced centraleffects when administered systematically.Muscimol lacks cholinergic effect at the neuromuscular junction. It inhibitstremor induced by tremorin but does not stop the associated salivation andlachrymation. A low dose of muscimol affects the EEG of cats and rabbits (Scottiet al., 1969; Theobald et al., 1968). These observations further support alocalization of action of muscimol in the brain rather than in the peripheralnervous system.Muscimol and ibotenic acid administered to rats and mice intraperitoneally affectlevels of serotonin, noradrenaline and dopamine in their brain, as LSD,psilocybin and mescaline do (Koenig-Bersin et al., 1970; Waser, 1971). Ibotenicacid administered electrophoretically is, like its isomorph glutamic acid, anexcitant of isolated spinal interneurones and Renshaw cells, while muscimol andGABA are powerful inhibitors of firing of central neurones (Johnston et al., 1968;Johnston, 1971).Ibotenic acid and glutamic acid produce convulsions in immature rats in whichthe blood-brain barrier is not completely developed (Johnston, 1973). Matureanimals are protected from CNS effects of dietary glutamic acid and GABA, butnot from muscimol and ibotenic acid, which presumably cross the barrier viasome active transport system. Neither muscimol nor ibotenic acid is removedfrom the environment of the receptor by the GABA or glutamate active uptakesystem. Inefficient removal of these false neurotransmitters once they havepassed the blood-brain barrier may be an important contributing factor to theirCNS effects (Balcar & Johnston, 1972; Kronsgaard-Larsen & Johnston, 1975).The effect of ibotenic acid on the glutamate-mediated peripheral nervoussystem of snails (Walker et al., 1971) and insects (Lea & Usherwood, 1973) hasalso been studied.Of these compounds, although this action is qualitatively similar, muscimol isthought most likely to be responsible for the central excitement in actual into-xications on the basis of this concentration and potency. This substance hasbeen shown to produce electroencephalographic alterations distinct fromhallucinogens such as LSD or mescaline, which is in accord with the clinicalobservations. The EEG pattern is more like that evoked by anticholinergicdrugs, such as atropine (Scotti de Carolis et al., 1969). Muscimol, however,possess no peripheral atropinic-like activity, nor was physostigmine found tohave a significant effect on the EEG changes induced by muscimol, in completecontrast to its ability to counteract the change induced by the atropine class ofdrugs. Neither ibotenic acid nor muscimol appears to act on central nervoussystem acetylcholine, dopamine, or 5-hydroxytryptamine receptors. It has beensuggested that both muscimol and ibotenic acid act similarly by activation of thegamma-aminobutyric acid (GABA) receptor (Brehm et al., 1972; Walker et al.,1971).

Purified ibotenic acid and muscimol evoke hallucination, delirium, muscularspasm, and sleep in volunteers (Theobald et al, 1968, Waser 1979).


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7.2 Range of toxicity:

7.2.1 Human data:

The threshold for observation of CNS disturbances in human is about 6mg of muscimol or five to ten times that amount of ibotenic acid (Waser,1979). This dose is potentially available in a single A.muscaria orA.pantherina. The ready decarboxylation of ibotenic acid complicatesinterpretation, since the ibotenic /muscimol ratio may change duringexperiments. A major portion of the activity of administered ibotenic acidmay actually be due to muscimol generated in situ.In human volunteers, effects were measurable about 1 hour afteringestion of 7.5 to 10 mg of muscimol or 50 to 90 mg of ibotenic acid andcontinued 3 to 4 h, with some residual effects as much as 10 h later, andin some subjects, hangover on the next day (Chilton 1975, Eugster1979).

7.2.1.1 Adults

7.2.1.2 Children

7.2.2 Animal data

The acute LD50 of muscimol in rats ranges from 4.5 mg/kg i.v. to 45mg/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

7.3 Carcinogenicity:No data

7.4 Teratogenicity:No data

7.5 Mutagenicity:No data

7.6 Interactions:

A finding of particular importance in the investigations by Theobald et al.(1968) and Scotti de Carolis et al. (1969) was that in muscimol-treatedanimals, the administration of small doses of diazepam or phenobarbitalinduced a flaccid paralysis and an electroencephalographic pattern similar todeep anesthesia. This experiment needs to be repeated in human beings

because of its obvious implication for the selection of therapeutic agents inthe management of severe manic excitement or convulsive activity that canbe induced by these mushrooms.


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SECTION 8. TOXICOLOGICAL ANALYSES

8.1 Methods

Ibotenic acid and muscimol are readily detected by the transient yellow colourproduced on treatment with ninhydrin. Several other components ofA.muscaria and A.pantherina give related ninhydrin reactions, includingstizolobic acid (Chilton et al., 1974; Chilton & Ott, 1976). More specificreagents are based on an undefined reaction between pentacyanoferriate ionand the heterocycle of these amino acids.In particular thepentacyanoaquoferriate reagent of Smith (1960; Chilton 1978) is a readilyprepared, storable and reasonably sensitive reagent. The closely relatedGrote's reagent (Eugster et al., 1965) and other cyanoferriate methods can beused to detect ibotenic acid and muscimol (Benedict et al., 1966). None ofthem, however, gives a colour stable enough for spectrophotometricquantitation. Ibotenic acid and muscimol can be readily and rapidly detected inthe presence of other amino acids by electrophoresis at pH 2. Muscimol andibotenic acid have also been quantitated by amino acid analyzer, and by gaschromatography of their trimethylsilyl derivatives (Chilton, 1978). Muscimolwas detected in urine by ion exchange separation and thin layerchromatography (Eugster et al., 1965).

8.2 Toxic concentrations

To our knowledge, neither serum nor urine levels have any value in order totake decisions on therapeutic. These determinations are only diagnostic.


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SECTION 9. CLINICAL EFFECTS

9.1 Acute poisoning by:

9.1.1 Ingestion: Symptoms of acute intoxication appear30 to 90 min. after the ingestion of the mushrooms. The only way oftoxin entrance in human poisoning is the oral one. The ingestion isfrequently a voluntary trying to obtain a "trip".

9.1.2 Inhalation: No data

9.1.3 Skin exposure: No data

9.1.4 Eye contact: No data

9.1.5 Parenteral exposure: No data

9.1.6 Other: No data

9.2 Chronic exposure: No data about chronic toxicity.

9.2.1 Ingestion: No data

9.2.2 Inhalation: No data

9.2.3 Skin exposure: No data

9.2.4 Eye contact: No data

9.2.5 Parenteral exposure: No data

9.2.6 Other: No data

9.3 Course, prognosis, cause of death:

The Fly-Agaric's effects start about 30 minutes after ingestion and last for hours.First it acts as soporific, and induces to sleep for about two hours: vivid dreams

during sleep from which one not can be roused. After waking from this sleep,some persons enjoy a feeling of elation that can last three or four hours.Subjects slow down in performing tasks and appear tired. Subjective changes ofstate are frequent, but, while some individuals are more relaxed, others are moretense. Viewing oneself from outside one's own body and a sense of being freedfrom the effects of gravity are common experiences in both voluntary andaccidental poisonings. Near objects frequently appear remote to the victim; hehas trouble maintaining a grasp on objects in his hand; he believes without aparticular discomfort that he is about to die. Most poisonings do not involvehallucination. However, Leonhardt (1949) reported some vivid hallucinationsassociated with accidental poisoning by A.muscaria and A.pantherina in

Germany.Death from these mushrooms is rare but not unknown (Chilton, 1978). Althoughthey sometimes produce dramatic intoxications with extensive psychological and


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neurological involvement, these mushrooms have a totally unwarrantedreputation for being "deadly poisonous". Of the extremely limited number of fatalincidents in the medical literature in which these species of mushrooms areunequivocally implicated, all of the victims exhibited a precarious state of healthprior to the poisoning. Even an attempted suicide with A.muscariawas dismallyunsuccessful (Donalies & Vltz, 1960).

9.4 Systematic description of clinical effects:

9.4.1 Cardiovascular: There is no significant change in pulse rate of bloodpressure.

9.4.2 RespiratoryNo data

9.4.3 Neurologic:

9.4.3.1 CNS: Mild intoxications are characterized by drowsiness. This may befollowed by elation, increase activity, illusions, or even manic excitement.These periods of excitement may alternate with periods of somnolence orstupor. The illusions are primarily a misinterpretation of sensory stimuli such aschanges in color vision, echo images (seeing trough walls), identification ofhospital personnel as divine figures, and the like, rather than truehallucinations as exhibited by the psychoactive species of Psilocybe, orPaneolus. However, vivid hallucinations associated with accidental poisoningby this Amanitas have been reported occasionally. Convulsive activity, otherthan tremors, is seen primarily in children.

9.4.3.2 Peripheral nervous system: Muscimol lacks cholinergic effect at theneuromuscular junction. PNS affection has rarely been described: In a fewcases the corneal reflex, the abdominal wall and the patellar reflex were lost,and sometimes a Babinsky sign appeared (Waser, 1979).

9.4.3.3 Autonomic nervous system: As far as our experience is concerned,neither muscarinic nor atropinic stimulation were observed in poisoning due toA.muscaria or A.pantherina. Occasionally, however, a strain of A.muscariamay appear which adds sweating and salivation to the usual symptoms ofpoisoning. This has been reported in North America (Lampe, 1978), andEurope (Waser,1979). There are not reports of these muscarinic effects,however, for A.pantherina. Since muscarine does not enter the brain inclinically significant amounts, it cannot be responsible for either thepsychoactive or central neurological action of these mushrooms

9.4.3.4 Skeletal and smooth muscle: Muscle spasms in the extremities aresometimes observed (Chilton, 1978).

9.4.4 Gastrointestinal:

Gastrointestinal disturbances were often present in our experience. Chilton(1978) also states that dyspepsia and vomiting are common. However, other


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authors state vomiting is absent. The irritant substances responsible for thisgastroenteric affection have not been identified.

9.4.5 Hepatic:

No data

9.4.6 Urinary:

9.4.6.1 Renal: No data9.4.6.2 Others: No data

9.4.7 Endocrine and reproductive system

No data

9.4.8 Dermatologic

No data

9.4.9 Eye, ears, nose, throat: local effects

No data

9.4.10 Hematologic

No data

9.4.11 Immunologic

No data

9.4.12 Metabolic

No data

9.4.12.1 Acid base disturbances: No data

9.4.12.2 Fluid and electrolyte disturbances: Light or mild dehydration may beobserved, as a consequence of vomiting and diarrhea.

9.4.12.3 Others: No data


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9.4.13 Allergic reactions

No data

9.4.14 Other clinical effects

No data

9.4.15 Special risks: pregnancy, breast feeding, enzyme deficiencies:

No data

9.5 Others: No data

SECTION 10: MANAGEMENT

10.1 General principles

Despite the apparent severity of these intoxications, they are usually quitetransient, rarely persisting more than 6 h. A delirium or manic phase ispreferably managed without drug intervention. If convulsive activity is severeand appears to become prolonged, it could be suppressed withbenzodiazepines or phenobarbital or the anticonvulsant of choice. Thee useof Physostigmine is limited to severe and threatening CNS involvement(Lincoff & Mitchel, 1977). The use of stimulants during the depressive phaseof the intoxication is obviously contraindicated. Although hemodialysis isrecommended by Mitchel & Rumack (1978) as well-documented withAmanita muscaria to reduce major symptoms, the usual good prognosis ofthis poisoning make unnecessary such aggressive removal procedure.

10.2 Relevant laboratory analysis

See Section 8.

10.2.1 Sample collection

The diagnosis may be confirmed by the examination of the mushrooms or

their remnants. If available, they have to be studied by a mycologist.However, one should take into account that the absence of toxic specimensin the material brought by relatives, does not necessarily imply the lack ofingestion of toxic mushrooms.

10.2.2 Biomedical analysis

10.2.3 Toxicological analysis

10.3 Life supportive procedures and symptomatic treatment

Supportive measures (maintaining blood pressure, electrolyte balance, followup of analytical parameters) and symptomatic treatment (therapy have to be


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made on the basis of clinical symptoms, no empirically) are indicated in allcases of mushroom poisoning indeed.

10.4 Decontamination

Emesis: If not already adequate from the poisoning itself, is indicated in allcases of mushroom poisoning unless the patient is unconscious orconvulsing. Ipecac syrup 15-30 cc followed by large amounts of oral liquids(250 to 500 ml in adults or 15 to 20 ml/kg orally in children) is the mosteffective emetic. Ipecac syrup is not recommended before the sixth month oflife in children. The dose for the 6-18 month old is of 10 ml. Older childrencan take 15 ml. It is a good idea to give a glass of juice fruit after the syrup.

Gastric lavage: with copious amount of liquid is indicated if the patient iscomatous of convulsing.

Activated charcoal: to adsorb toxins - 50 to 100 g in 200 ml of saline orwater orally or through the tube after the lavage.

10.5 Elimination

Forced diuresis: Usually not necessary but may be considered useful,according to the experiences that showed an urinary excretion of ibotenicacid and muscimol in human beings and in animals.

Hemodialysis: Although hemodialysis is recommended by Mitchel &

Rumack (1978) as well-documented with Amanita muscariato reduce majorsymptoms, the usual good prognosis of this poisoning make unnecessarysuch aggressive removal procedure.

10.6 Antidote treatment: This kind of poisoning is in gene-ral well controlled without the use of antidotes. However, according to thesymptoms present and not anticipating them, antidotes could be consideredin a few cases:

* Only when severe CNS symptoms occur, Physostigmine might be

considered:Adults: 2 mg slowly intravenously (in 2 or 3 min).Children: 0.5 mg slowly intravenously.This substance is metabolized between 30 to 60 min, and repeated dosesmay be necessary.


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* If cholinergic symptoms (perspiration, salivation, lacrimation, miosis, andspecially bradycardia) occur, consider Atropine:Adults dose: 2 mg IV or subcutaneously.Children dose: 0.05 mg/kg subcutaneously.

10.6.1 Adults

10.6.2 Children

10.7 Management discussion: alternatives and controversies.

SECTION 11: ILLUSTRATIVE CASES

11.1 Case reports from literature:

11.1.1 Accidental poisoning:

There are numerous reports in the medical literature of this type of intoxication. InEurope and South Africa, A.pantherinais most frequently involved, often affectingwhole families when served as the main dish at a meal. Indeed, in central Europe,this type of mushroom poisoning is known as the pantherine syndrome. Althoughsimilar reports appear in the early North American Journals (Hotson, 1934; Lampe,1978) intoxications with A.muscariahave more recently become far more commonas the result of deliberate attempts by individuals to employ it for inducinghallucinations. This is possibly a result of the popularization of the ethnomycologicalstudies of Wasson, who refers to this species as the "Divine Mushroom ofImmortality" (Wasson, 1968). Special recipes are even now appearing for ways toprepare a broth from this mushroom so that one can retain its psychoactiveproperties but eliminate the gastroenteric irritants also present.A.pantherina tends to produce a more complex intoxication pattern than Amanitamuscaria (Bosman et al., 1965; Pfefferkorn & Kirsten, 1967), which providesadditional evidence for the supposition that unidentified pharmacologically activesubstances remain. The following case condensation is illustrative (Pfefferkorn &Kirsten, 1967):

A twelve years old girl ate some boiled mushrooms (Amanita pantherina). About one hour later

she exhibited increasing drowsiness, severe giddiness and pallor. About three hours after themeal she had generalized tonic-clonic convulsions with loss of consciousness. There was notvomiting or diarrhea. The pupils were dilated and unreactive to light. The corneal reflex wasactive. No increase in salivation or sweating was observed. Respiration was regular.The patient was given phenobarbital to control the convulsions and the stomach was emptied.Additional therapy included the intravenous administration of 40 % fructose, prednisone andcalcium gluconate.Sporadic, violent clonic convulsions reappeared and 9 hours and weakly again and 9

1/2 hours

after the ingestion. Chvostek's sign was well defined and Trousseau's sign appeared. The childwas given 20 ml of 25% magnesium sulfate. About one hour later the sensorium cleared and

the patient showed no neurological deficit. The laboratory findings were unremarkable.


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The other cases given by Pfefferkorn and Kirsten (1967) presented generally similarclinical features. In some, the corneal, abdominal wall, and patellar reflex were lost.In a case a Babinsky sign appeared. Some of the patients had severe delirium, aswould be expected, in addition to the neurological phenomena. Some patients had aresidual headache which persisted for several days, an experience also noted byWaser (1979) following the ingestion of pure ibotenic acid.

Ott (1978) state that there is striking disparity between the experiences of theaccidental poisoning victims and intentional users. This indicate the importance ofthe expectation of the user as a determining factor in the nature of an hallucinogenicexperience. Victims of accidental poisonings became very negative towardmushrooms, and could not understand how some persons could intentionally ingestthese mushrooms. Of nine persons accidentally poisoned by A.pantherinareportedby Ott (1978), three referred nausea, seven drowsiness (of whom five lostconsciousness). Three reported loss of balance and coordination, two reportedmuscle weakness, three reported muscle spasms, and seven reportedhallucinations.

11.1.2 Voluntary ingestion:

In Siberia, the Fly-Agaric experience has been reported to include hearing voicesand seeing visions, as well as a desire for exaggerated physical activity, and eithermacropsia (i.e. misperceiving very small objects as enormous ones, such as a tinytwig appearing as a giant log, requiring a great leap to surmount it) or inappropriatebehaviour (for example leaping over that is correctly perceived as a twig) (Lincoff &Mitchell, 1977).

Agnus McDonald experimented the self-administration of whole A.muscaria(1978).He prepared capsules with dried and powdered mushrooms, collected in NortherCalifornia. With 12 g of dried A.muscariaa noticeable effect was felt:

In summary, 12 g of dry red A.muscariaproduced mainly these following symtoms: 1) A marked

nausea that tapered off over the first three hours, 2) a conspicuous absence of reflectivethought combined with a sense of tiredness, and 3) a slight transient euphoria around the fourthhour that alternate with and finally was overwhelmed by a general sense of fatigue. It was not aninspiring experience, and the initial nausea was so great that i had not desire to repeat it... Idecided on a compromise. I made an infusion by soaking 30 gr of dried mushroom in a cup ofwater... Within one hour I was obviously feeling a greater effect than I had from eating 12 g. I feltagain as if I were in a state of suspended animation, this time with a much stronger desire tosleep. Although my environment seemed some how "bright", there were no hallucinations ofobvious 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 noticeda marked increase in my usual level of saliva production. By 5

1/2 hr after ingestion, the effects

were waning. By 7 hr later they were nearly gone, and I succumbed to my desire of sleep. Therewere no sequelae the following morning.

McDonald conduced also an assay with six human volunteers who ate the 12 g doseof dried-powdered Fly Agaric. All experimented nausea, although only two of themvomited. All six experimented tiredness, and three of the six reported increasesalivation. Only two of the subjets related visual distortions that might pass for low-grade hallucinations.


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The experiences of Waser (1979), who experimented himself the effects of puresubstances (ibotenic acid and muscimol), merit to be mentioned here:

A 20 mg ibotenic acid dose ingested in water tastes like mushrooms, but produces littleimmediate 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 bysleep. A day later a migraine with classical one sided visual disturbance developed for the firsttime 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 afeeling of laziness. Ten mg produced a slight intoxication after 90 min with dizziness, ataxia andelevated mood, psychic stimulation (in psychological tests), no hallucinations but slight changesin taste and colour 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. Duringthe 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 notchanged. Speech was sometimes inarticulate and dysarthric. Appetite and taste werediminished. After a phase of stimulation, concentration become mare difficult. Vision was altered

by endlessly repetitioned echo-pictures of situations a few minutes before. Hearing becomenoisy and sometimes was followed by echo. Most disturbing were repeated myoclonic crampsof different muscle groups. I felt sometimes as if I had lost my legs, but never had hallucinationsas vivid and colourful as with LSD. The pupils remained always the same size. After 2 hours Ifell 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 mgmuscimol but rather dull and uncertain. Blood pressure was only a little elevated during thepsychoactive phase.Muscimol makes a toxic psychosis with confusions, dysarthria, disturbance of visual perception,

illusions of colour vision, myoclonia, disorientation in place and time, weariness, fatigue andsleep. Concentration tests show and improved performance with small doses (5 mg), butdiminished performance and learning with an increased number of errors with higher doses (10-

15 mg).

11.2 Internally extracted data on cases:

Among 232 cases of mushroom poisoning studied in the Barcelona Area during aseven years period (1982-1988), twelve were produced by the ingestion of IbotenicAcid-Muscimol containing Amanitas. In ten cases by A.muscaria(four of them wereintentional ones), and by A.pantherina in the remainder two. Gastro-intestinaldisturbances were the most frequent and important manifestations, present in all thecases. Signs of CNS affection were present in six patients (50 %), but only severe intwo of them: One patient showed agressivity and maniac behaviour; the other oneshowed deep sleep, poorly reactive. We treated the two patients withphysostigmine, with a good and quick recovery from those symptoms, in spite of thefact that tropane alkaloids are not present in these mushrooms. True hallucinationswere not observed, and only one patient refered feeling sensation of ingravity. Allour cases may be considered light or mild intoxications.

11.3 Internally cases


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SECTION 12: REFERENCES

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BENEDICT, R.G., TYLER, V.E. & BRADY, L.R. (1966) ChemotaxonomicSignificance of Isoxazole Derivatives in Amanitaspecies. Lloydia, 29:333-341.

BORTHWICK, P.W. & STEWARD, E.G. (1976) Ibotenic Acid: Further Observationson its Conformational Models. Journal of Molecular Structure, 33:141. ( Ref. byChilton, 1978).

BOSMAN, C.K., 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, A.C. & MOGEY, G.A. (1965) Constituents of Amanitamuscaria. Nature, 206:1359-1360.

BREHM, L., HJEDS, H. & KROGSGAARD-LARSEN, P. (1972) Structure ofMuscimol, a Gamma-Aminobutiric Analog of Restricted Conformation. Acta Chim.Scand., 26:1298-1299.

BRESINSKY, A. & BESL, H. (1985) Giftpilze [Mushroom Poisoning]. Stuttgart:Wissenschaftliche Verlagsgesellschaft mbH. (In German)

CHILTON, W.S. (1975) The Course of an Intentional Poisoning. MacIlvanea, 2:17. (Ref. by Lincoff & Mitchel 1977, and Chilton, 1978).

CHILTON, W.S. (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. pp:87-124.

CHILTON, W.S., HSU, C.P. & ZDYBAC, W.T. (1974) Stizolobic and StizolobinicAcids in Amanita pantherina. Phytochemistry, 13:1179-1181.

CHILTON, W.S. & OTT, J. (1976) Toxic Metabolites of Amanita pantherina,cothurnata, muscariaand other species. LLoydia, 39:150-157.

DEPOVERE, P. & MOENS, P. (1984) [Active Components and Colorant Substancesin the Fly Agaric Amanita muscaria(Fries) Hooker.] J.Pharm.Belg., 39:238-242. (InFrench)

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EFRON, D.H., HOLMSTEDT, B. & KLINE, N.S. (1979) Ethnopharmacological


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EUGSTER, C.H. (1979) Isolation, Structure, and Synthesis of Central ActiveCompounds from Amanita muscaria(L. ex Fr.) Hooker. In: Efron, D.H., Holmstedt, B.& Kline, N.S.eds. Ethnopharmacological Search for Psychoactive Drugs. U.S. Publichealth Service Publication, No.1645:416-419.

EUGSTER, C.H., MLLER, G.F.R. & GOOD, R. (1965) [Active Principles fromAmanita muscaria: Ibotenic Acid and Muscazone.] Tetrahedron Lett., 1965:1813-1815. (In German)

FISCHER, O. E. (1971) Mushroom Poisoning. In: Kauffman, C.H. ed. The GilledMushrooms of Michigan and the Great Lakes Region. New York: Dover Reprint.

HOTSON, J.W. (1934) Mushroom Poisoning in Seattle. Mycologia, 26:194-195.

JOHNSTON, G.A.R., CURTIS, D.R., DE GROAT, W.C. & DUGGAN, A.W. (1968)Central Actions of Ibotenic Acid and Muscimol. Biochem. Pharmacol., 17:2488. (Ref.by Chilton, 1978 and Lampe 1978).

JOHNSTON, G.A.R. (1971) Muscimol and the Uptake of Gamma-Aminobutyric Acid by Rat Brain Slices. Psychopharmacologia, 22: 230. (Ref. byChilton, 1978 and Lampe, 1978).

JOHNSTON, G.A.R. (1973) Convulsion Induced in 10-days-old rats byIntraperitoneal Injection of Monosodium Glutamate and Related Excitant AminoAcids. 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, P.G., 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, G.A.R. (1975) Inhibition of GABAUptake in Rat Brain Slices by nipecotic acid, various isoxazoles and relatedcompounds. J.Neurochem. 25:797. (Ref. by Chilton, 1978).

LAMPE, K.F. (1978) Pharmacology and Therapy of Mushroom Intoxications. In:Rumack, B.H & Salzman, E. Eds. Mushroom Poisoning: Diagnosis and Treatment.West Palm Beach (Florida), CRC Press Inc. pp:125-169.

LEA, T.J. & USHERWOOD, P.N.R. (1973) Effect of Ibotenic acid on ChloridePermeability of Insect-Muscle Fibers. Comp.Gen. Pharmacol., 4:351. (Ref. byChilton, 1978).

LEONHARDT, W. (1949) [States of Inebration on Amanita pantherinapoisoning].Der Nervenarzt, 20:181-188. (In German).


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LOWY, B. (1972) Mushroom Symbolism in Maya Codices. Mycologia, 64: 816-821.

LINCOFF, G. & MITCHEL, D.H. (1977) Toxic and Hallucinogenic MushroomPoisoninig. New York, Van Nostrand Reinhold Co.

MACDONALD, A. The Present Status of Soma. The Effects of California Amanitamuscaria on Normal Human Volunteers. In: Rumack, B.H & Salzman, E. Eds.Mushroom Poisoning: Diagnosis and Treatment. West Palm Beach (Florida), CRCPress Inc. pp:215-223.

MITCHEL, D.H. & RUMACK, B.H. (1978) Symptomatic Diagnosis and Treatment ofMushroom Poisoning. In: Rumack, B.H & Salzman, E. Eds. Mushroom Poisoning:Diagnosis and Treatment. West Palm Beach (Florida), CRC Press Inc. pp: 171-179.

MLLER, G.F.R. & EUGSTER, C.H. (1965) [Muscimol, a PharmacodinamicSubstance from Amanita muscaria] Helvetica Chimica Acta, 48:910-926. (InGerman)

OTT, J., WHEATON, P.S. & CHILTON, W.S. (1975) Fate of Muscimol in the Mouse.Physiol.Chem.Phys., 7:381-384.

PFEFFERKORN, W. & KIRSTEN, G. (1967) [Pantherine Syndrome Course inChildhood: Panther Mushroom Poisoning]. Kinderrtzl. Praxis, 35:355-364. (InGerman).

REPKE, D.B., LESLIE, D.T. & KISH, N.G. (1978) GLC-Mass Spectral Analysis ofFungal Metabolites. J.Pharm.Sci., 67:485-487.

SCOTTI DE CAROLIS, A., LIPPARINI, F. & LONGO, V.G. (1969)Neuropharmacological Investigations on Muscimol, a psychotropic Drug Extracted ofAmanita 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. pp:3-16.

SINGER, R. Hallucinogenic Mushrooms. In: Rumack, B.H & Salzman, E. Eds.Mushroom Poisoning: Diagnosis and Treatment. West Palm Beach (Florida), CRCPress Inc. pp: 201-214.

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TAKEMOTO, T., NAKAJIMA, T. & SAKUMA, P. (1964) Isolation of a FlycidalConstituent "Ibotenic Acid" from Amanita muscaria and A.pantherina. YakugakuZasshi, 84:1233-1234.

TAKEMOTO, T., NAKAJIMA, T. & YOKOBE, T. (1964) Structure of Ibotenic Acid.Yakugaku Zasshi, 84:1232-1233.


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THEOBALD, W., BCH. O, KUNZ, H.A., KRUPP, P., STENGER, E.G. & HEIMANN,H. (1968) [Pharmacological & Experimental Investigations of Two Components ofthe Fly Agaric.] Arzneim.Forsch., 18:311-315. (In German).

WALKER, R.J., WOODRUFF, G.N. & KERKUT, G.A. (1971) The Effect of IbotenicAcid and Muscimol on single neurones of the snail Helix aspersa.Comp.Gen.Pharmacol., 2:168. (Ref. by Chilton, 1978 and Lampe 1978).

WASER, P.G. (1979) The Pharmacology of Amanita muscaria. In: Efron, D.H.,Holmstedt, B. & Kline, N.S.eds. Ethnopharmacological Search for PsychoactiveDrugs. U.S. Public health Service Publication, No.1645:419-439.

WASSON, R.G.(1964) The Present State of Oloiuhqui and Hallucinogens of Mexico.Psychodellic. Rev., 1:275-301.

WASSON, R.G. (1968) Soma: Divine Mushroom of Immortality. New York: HartcourtBrace Javonovich Inc.

WASSON, R.G. (1972) Soma and The Fly-Agaric. Botanic Museum Eds., HarwardUniversity.

WASSON, R.G. (1979) Fly Agaric and Man. In: Efron, D.H., Holmstedt, B. & Kline,N.S.eds. Ethnopharmacological Search for Psychoactive Drugs. U.S. Public healthService Publication, No.1645: 405-414.

SECTION 13: AUTHOR, DATE:

J.PIQUERASDepartment of Haematology & HaemotherapyGeneral Hospital Vall d'HebronAutonomous University of Barcelona08035 BARCELONA - SPAIN

SECTION 14: ADDITIONAL INFORMATION

14.1 Availability of antidotes

14.2 Other

international program on chemical safety- amanita muscaria and related species

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