Summary:

Amanita muscaria, also known as Fly Agaric, is a yellow-to-orange

capped wild mushroom. It grows in symbiosis with arboreal trees

such as Birch, Pine or Fir, in both Europe and the Americas. Its his-

tory has it associated with both shamanic and magical practices for at

least the last 2,000 years, and it is probably the Soma intoxicant

spoken of in the Indian Rig-Vedas. The following piece details both

the generic as well as the esoteric history and pharmacological pro-

files of the Amanita muscaria. It also introduces research which

shows that psychoactivity related to this species is seasonally-

determinant. This determinant can mean the difference between poi-

soning and pleasant, healing applications, which include psychedelic

experiences. Connections between the physiology of sleep and the

plant's inner chemistry is also outlined.

This study is divided into two parts, reflecting two comple-

mentary but different approaches to the same topic. The first

study, presented by Francesco Festi, presents a critical over-

view of the mycological, ethnobotanical, chemical and phar-

macological data which are referred to the Amanita muscaria

(through 1986). In the second part, also Italian author and

mycologist Antonio Bianchi reports on personal experiences

with the Amanita muscaria taken from European samples. The

following experimental data -- far from constituting any final

answers -- are only a proposal and (hopefully) an excitement

for further investigations.

Part One: Mycological, Chemical and

Neuropharmacological Aspects

1) Mycological Outline

Amanita muscaria (L. ex Fr.) Pers. ex Hooker -- The Fly

Agaric -- is one of the oldest classifications of fungi known.

It has consistently appeared in all the naturalistic fields

throughout history. Linnaeus identified it as Agaricus muscar-

ius and originally introduced it into the genus. He included it

along with other gill fungi he classified and which were classi-

fied by most Northern European botanists. These same bota-

nists were traditionally mycophobic. This, unfortunately, led

to the bypassing of other important mushrooms and fungi in

their studies.

The generic name, coined by Persoon, derives from the

Greek amanitai, means "fungi without any details" (or from

Amanos, a mountain place between Cicilia and Syria). The

specific epithet re-proposes a connection for which we will

spend some words later. One will be able to recognize these in

the popular names of the fungus: Fliegenpilz or

Fliegenschwamm in German; Mukhomor in Russian; Amanite

tue-Mouche in French, and The FIy Agaric in English.

The typus of the species has a cap of between 5-25 cm. It is

at first globe-shaped (in the embryonic stage it is bred from the

cloth of the universal veil in typical egg-shape that is charac-

teristic of the genus Amanita) It retains this shape more com-

pletely until reaching an applanate or lightly depressed area

around the center form, with the margin more or less streaked.

The skin of the cap is peelable, bright red or leaning to orange

(sometimes with yellow colors, especially near the margin). It

is shiny and viscous when moist, strewn with white (or whit-

ish) warts (sometimes absent in mature specimens because of

washing away). The flesh is white into the cap and stripe, but

yellow or yellowish in the stripe just under the cuticle, having

no special taste or smell to humans. After drying it puts on a

darker color (from dark cream to pale brown) and an acrid,

nauseating taste. The stalk is white, cylindrical and discontinu-

ous (easily discemable from the cap), with a bulbous base and

a volva typically fragmented in warts arranged in a concentric

circle; white (to whitish), broad and membranaceous, in a more

or less streaked ring.

The spore print is white, with the spore 9-11 X 6-9 microns,

elliptical-ovate, smooth and not amyloid (Ricken, 1915;

Gilbert, 1918; Bresadola, 1927-41; Kuhner & Romagnesi,

1953; Moser, 1967; Wasson, 1967b; Cetto, 1970-87; Heim,

1969, 1978; Flammer and Horak, 1983; Roth, et al., 1984;

Bresinsky and Besl Regensburg, 1985, and many others).

Amanita muscaria is a typical species of the septentrional

latitudes. At lesser latitudes it is present particularly in the

mountain areas. It is broadly spread throughout Europe, North

(in a different form) and Central America, North Africa, Asia

and Australia. The Amanita has a preference for acidic soil,

and a condition for sprouting includes the presence of arboreal

species such as Pine, Fir or, infrequently, Larch and other

trees. This inter-plant bond comes from the mycorrhizic rela-

tion (a commensalistic symbiosis shared with many other spe-

cies of fungi. This is very important, among other things, for

the ecology) between trees and fungi.

Strictly tied to muscaria are other similar species (A. emilii

Riel., A. aureola Kalch., A. regalis Fries, etc.) These, how-

ever, probably don't go beyond the subspecific rankings of

fungi. Probably the most interesting in this context would be

A. americana Helm, typical of Canada and the U.S. It's differ-

ent from A. muscaria with its slender stalk with fibril becom-

ing brown at the end and the lighter cap (being pale to yellow-

orange (ibid.).

Another species of genus Amanita also worth remembering

here is A. pantherina (DC ex Fr.) Seer., which is certain to

contain the same psychotropic agents as A. muscaria [see fol-

lowing references]. A. pantherina produces a more toxic than

hallucinogenic syndrome, however, when ingested. A predom-

inance of nonspecific confusional effects, psychomotor excite-

ment and serious anxious (or anxiety-laden) states generally

occur [John, 1935; Bosman, et al., 1965; Gerault & Girre,

1977; Lincoff & Mitchel, 1977; Helm, 1978; Rumack and

Saltman, 1978; Flammer, 1980; Gelfand and Harris, 1982;

Flammer & Horak, 1983; Roth et al., 1984; Bresinsky & Besl

Regensburg, 1985]. A. pantherina has a cap of 6-12 cm. wide

at first, then globe-shaped. It is then slightly flattened or

depressed near the center. The colors are from chestnut brown

to gray-olive green, with a striated margin and a cuticle which

is peelable. This is strewn with white or greyish warts which

are easily removed through washing. The stalk is discontinu-

ous at 6-15 cm. X 2-20 mm. It is white, stuffed and then hol-

low. It is fibrillose or glabrous, bulbose at the base where it is

ornamented with a volva of 2-3 membranaceous girdles which

are superimposed. These are white and narrow, with annules

slightly (or not at all) streaked. The flesh has a sweetish taste

without special smell (to humans). This is white or brownish

so far as the subcuticule layers. The gills are free or just

adnexed. These are white or mealy at the margin. The spore

print is white, the spores measuring 8-12 X 7.8 microns. They

are elliptical-ovate, smooth and not amyloid (see the references

for Amanita muscaria, etc.) . It grows with conifers trees, in

the wood, in Europe, North America, North Africa and Asia.'

2. A Short Ethnomycological Account

A review of the anthropological and historical data on the Fly

agaric is impossible herein due to the tremendous bulk of work

on this very subject. Nevertheless, it is possible to try to build a

hypothesis which connects traditions and the roles of hallucin-

ogenic fungi in man's history. This starts from the fascinating

proposals of R. G. Wasson [Wasson & Wasson, 1957; Wasson,

1967a, 1967b, 1978] and those who, simultaneously also con-

tributed to the growth of the subject of ethnomycology [La

Barre, 1970; Harner, 1973; Furst, 1976; Ott, 1976; Schultes &

Hofmann, 1979, and many others].

One can begin by supposing that primitive man, in his activ-

ities as food gatherer, had discovered plants (and fungi) with

useful properties but not directly connected with hunger and

eating and alimentary use.2 It's likely that, in this way, man

had his first contacts with hallucinogenic plants. Mushrooms,

no doubt, had a very particular role herein.

The fact that they apparently are born "from nothing" with

rapid development, the beautiful strangeness of their shapes,

and all the other characteristics which distinguish them from

other plants surely struck the hunter-gatherer man. This surely

led him to discover the mushroom's amazing properties. The

structure of the Mesolithic-Neolithic society -- surely one of

the shamanic type 3 -- had no doubt a catalyptic effect in

developing these theme characteristics. Such societal charac-

teristics represent(ed) the ideal support for consciousness alter-

ation -- including hallucinogenic plant use. This made connec-

tions with an animistic conception of the world stronger and

more widespread.

Let's suppose proto-Indoeuropean man had already discov-

ered the psychotropic properties of Amanita muscaria (and

other plants) while these people were still living in the original

region of the plants. This supposition is under discussion in

order to revise the hypothesis accepted so far. This probably

also included the lowlands of central Siberia. During this

period the linguistic roots connected with the A. muscaria were

transferred cross-culturally to the proto-Uralic people, maybe

with the use(s) of the mushroom itself (which later were car-

ried on to the Siberian peoples, at least until the beginnings of

this century). Along with Amanita might have come Fomes

fomentarius, used as tinder for fire.

A few millennia before this, man's migrations through the

Bering Straits had come to an end. These were the peoples

who would eventually originate the American peoples. These

original explorers took with them the traditions connected with

the original uses of cultural planning, the shamanism, etc.

They did not, however, openly carry the traditions connected

with use(s) of hallucinogens. It was because of the presence of

societies originally based on the shamanic structure (including

fungi) that the use of hallucinogens developed and continued

in the Americas.

In Eurasia, when the Indo-Europeans moved towards Iran and

India, they took with them the cult of the sacred fungus. This

later became the Indian Soma (the God-plant of the Rig-Veda)

and the Persian Haoma. Also carried were the fungi's relation

to the Birch tree, sealed by the ancient shamanic religion. It's

not impossible that the Tree of Divine Knowledge named in

Genesis in the Bible was an echo of the original Tree of life

(the Birch). The serpent might have been a metaphor for the

sacred Mushroom, bestower of divine knowledge and wisdom.

Also, the Indo-European fringe which spread over Europe

took with them at least a part of the religious-social structure,

characterizing the life in their original lands. The fusion

between their animistic totemism and those of the preexisting

peoples produced a religion with a shamanistic background.

The train of elements include the following which are most

interesting: the ritual ingestion of the Amanita muscaria (and

maybe other psychotropic vegetables), the deep spiritual ties

with nature, the consequent worship of nature spirits (among

which were terrestrial ones, such as the toad and the serpent),

and the magic interpretation of many events. The links

between the many natural-supernatural fusion penetrated into

the life of these ancient Europeans, cementing deep connec-

tions with their "cultural unconscious."

A particular element of this social structure, also present in

the Siberian and Mexican peoples, was the taboo that only the

shaman (or the one who took his place as mediator with the

divine world) could use with impunity the sacred elements.

All the other peoples were prevented from doing this because

of the dread of the supernatural. In other religions this tie also

involved the name of the sacred plant, and in this way some

metaphorical, but self-referential, epithets could have been

originated. These words contained reference to some more or

less obvious characteristics of the fungus. These included

fusion with other animals such as the fly, other insects, the ser-

Pent or toads, etc.

Among the characteristics of the West (as opposed to the

Test of the globe -- like America, where shamanism has per-

sisted to the present) was the speed of socio-economic devel-

opment and the relatively sudden changes in lifestyle. This

historical evolution contained a base mode of property owner-

ship and rigid role divisions, and class distinctions. The old

religions, no longer functional to the powers-that-be, were

replaced by new models of worship. These were modeled with

ritual symbolism rather than direct share of the divine world.

As a consequence, the ancient usages of the psychoactive

plants able to modify consciousness was hampered and in

some cases forsaken. This is the core of Wasson's hypothesis.

He supposed that not all the Gods of these old religions were

completely obscured when new religions (and new Gods) took

over.

In the traditions fused with Amanita muscaria use, a connec-

tion with these natural, totemic forces remained. These

remained alive, above and beyond the new taboos. These ele-

ments were, at first, only connected to the sacred uses of the

mushroom, however. As time went on, this melting together

of ideas, both terrifying and divine, lost all the connections

with their original source. It soon spread on to the whole of

the fungi's' world (and also to the original entities connected

with the mushroom). Only the fear truly retained its potency,

staying alive through our unconscious as maleficient and inex-

plicable. In this way we might understand our culture's con-

nections between the evil or harmful and the fly, the serpent

and the toad. Mycophobia and its corollaries are thusly

explained.

This dichotomic division between mycophilia and mycopho-

bia proposed by Wasson seems to complete itself in a convinc-

ing way with the hypothesis of J. Ott (1976). According to this

author, the malefic character attributed to the mushroom the

survivor of the old animistic religion -- was not the result of

the survival of the taboo. Rather it was derived from the events

linked to the establishment of a new cult. In fact, when a new

religion replaces preexisting ones, consequences occur. One is

the change of the social orders which restrict or hamper the

previous cults (usually by any means possible). In this way,

things not willing to adapt to the new creed become, by neces-

sity, malefic or demonic.

In our opinion, therefore, and after taking for granted the

close bonds between shamanism and the use of hallucinogenic

mushrooms, different cultural attitudes relating to fungi can be

explained.

Speaking of the European peoples, and taking into account

several variables, we propose: the substitutive dynamic

referred to the religions after its inception within shamanism;

its impacts on the preexisting cultural heritages; the more-or-

less distant age in which the passing from cults with shamanis-

tic qualities to those of a dogmatic-fideistic kind occurred; the

geographical proximity with people for whom this passing

occurred; the geographical proximity for which this passing

occurred in relatively recent times (for example, the Slavs); the

kind of economic-social development and its bonds with the

natural world.

It's certainly true that checks on these matters would request

ethnological data newer and more precise than the ones we

possess. We think, however, that it is correct to attempt it,

with the serene objectivity that this subject deserves.

3. Chemistry and Pharmacology

Even from the point of view of the chemical and pharmaco-

logical research, the Amanita muscaria takes up a place which

distinguishes it from the many other hallucinogenic mush-

rooms. In fact, in the species of the Psilocybian group (up

until now including parts of the genus Psilocybe, Conocybe,

Stropharia, Panaeolus, Gymnopilus and Pluteus [Helm, 1978;

Schultes and Hofmann, 1980; Bresinsky and Besl Regensburg,

1985; Festi, 1985]), the isolation of the psilocybin and inges-

tion experiments led to the belief that this substance (or, more

exactly, to Psilocin, its active metabolite) were responsible for

all the hallucinogenic effects. For the Amanita muscaria it's

not the same.

On different occasions several different compounds have

been isolated -- each having psychotropic Properties concur-

rent with the hallucinogenic properties of the Amanita in toto.

Apart from the large number of principal chemicals, the view

of the whole is obscured by other factors.

Some reports actually seem to be the result of methodologi-

cal mistakes (e.g., the ones concerning tropane alkaloids and

Bufotenine). The substances at issue would be, in any case, too

minimal in the species mentioned in the tropane/Bufotenine

references to produce the described effects.

Other compounds, which certainly are of the metabolic store

of the Amanita muscaria, have not been submitted, as yet, to

any pharmacological studies (i.e.., the indolic substances iso-

lated by Eugster and others, etc.). Or they have turned out to

be inactive at the quantities actually contained in the mush-

room itself (i.e.., the Muscarine). Though Ibotenic Acid and

Muscimol, finally, are at the center of the present hypothesis

(so far as the active principal of the Amanita), they don t quite

explain all of the psychoactivity. In this context, in order to

see our way clear through the mine of substances making up

the Amanita muscaria, we prefer to consider all the different

compounds within. Thus, we will be able to determine exactly

what contributes to the psychoactive nature of the Amanita,

what does not, and the relationship of everything to the main

psychoactive constituent, Muscimol.

3a. Miscellaneous Chemical Compounds

Muscarine: Muscarine (or 4-hydroxy-5- methyl-tetrahydro-

furfuryl-trimethyl-ammonium salt) was isolated from Amanita

muscaria, from which the mushroom took its name. This

occurred in the nineteenth century [Salemink et al., 1963;

Waser, 1967; Eugster, 1968; Waser, 1958, 1961; Helm, 1978;

Bresinsky and Besl Regensburg, 1985]. The actual concentra-

tion of this compound (on the average) is very low (0.0002-

0.0003% with reference to the fresh weight [Eugster, 1968;

Helm, 1978; Schultes and Hofmann, 1980], and in any case

much lower than in other species (i.e., Inocybe mixtilis Sacc,

with 1.33% of dry weight). Although the activity of musca-

rine on the central nervous system is demonstrated4 [Waser,

1967; Bloom, 1980], its resorption through the intestinal wall

is very slow and it is almost completely blocked by the blood-

brain barrier (the passage is possible only with the combination

of an amino acid or Lecithin [Waser, 1967]). Furthermore, the

psychological effects shown after poisoning with Muscarine

fungi are different from the effects of Amanita muscaria [Festi,

1985].

It is impossible to demonstrate any direct action of

Muscarine. Its low concentration in the mushroom itself is

enough to leave it out of the origin of psychic (or hallucina-

tory) effects. Only some of the somatic disturbances caused by

the mushroom's ingestion can be attributed to the action of the

Muscarine, probably combined with the one of Muscimole.

Other Quaternary Ammonium Bases: In the Fly Agaric was

found, several times over, Choline, Acetylcholine, and buten-

(I)-yl-(4)-trimethylammonium and "muscaridine." While the

first substance is psychotropically inactive and the second is

contained in very low quantity in the Amanita muscaria, the

last two (even those found with little concentration) are com-

pIeteEy lacking in pharmacological data [Waser, 1967; Eugster,

1968; Helm, 1978; Bresinsky and Besl Regensburg, 1985;

Festi, 1985].

Tropane Alkaloids and Bufotenine: In investigating a com-

pound named Pilzatropine by Kolbert in 1881 because of phar-

macological similarities, some authors (Lewis in 1955 and

Manikowsky & Niezdodzki in 1962) reported the presence of

hyoscyamine, atropine and scopolamine in the Amanita mus-

caria, (Salemink et al., 1963, Tyler and Groger, 1964). This

suggests a mistake due to substances with the same chromate-

graphic behaviors as the tropane alkaloids. Furthermore, the

percentage of content reported by Lewis would be, in any way,

too low to contribute to the psychoactive activity of the fungus

(Waser, 1965,1968)5.

As well, so far as Bufotenine goes, there is a report by

Wieland and Motzel (1953) pertaining to Amanita muscaria,

pantherina, and citrina. The presence of Bufotenine was then

verified only for the species citrina, porphyria, and tomentelIa

[Catalfolmo and Tyler, 1961; Tyler, 1961; Tyler and Groger,

1964b; Hoffer and Osmond, 1967; Eugster, 1968; Andary et

al., 1978a, 1978b; Stijve, 1979; Perez-Silva and Aroche

Alfonso, 1983; Bresinsky and Besl Regensburg, 1985]. There

is probably a mistake due to contamination caused by carpo-

phores of Amanita citrina. Bufotenine should be left out any-

way because it is not orally active [Fabing and Hawkins,

1956; Hoffer and Osmond, 1967; Schultes and Hofmann,

1980], and, according to some authors, not active at all.

Other Compounds. We list here some substances isolated

from the Amanita muscaria, to which accurate pharmacologi-

cal data are missing. Only the first two (respectively based on

the narcotic-antagonist activity and the indolic structure), we

suppose could contribute to the psychoactivity of the

mushroom.

R4-hydroxy-pyrrolidone-(2): Isolated from butanolic

extract of non-isoxazolic fractions during the isolation of

Muscimol [Eugester 1968; Theobald, et al., 1968; Matsumoto

et al., 1969; Schultes and Hofmann, 1980].

1,2,3,4-tetrahydro-I -methyl-B-carboline-carboxylic

acid: Extracted from the same fractions [Eugster, 1968;

Matsumoto et al., 1969] and chemically related to the hallu-

cinogenic P-carboline. Such are active compounds within

the psychotropic species of the genus Banisteriopsis

[Schultes and Hofmann, 1980]. Chilton and Ott [1976], nev-

ertheless, didn't find MTC in Amanita muscaria samples

from America.

B-N-Butyl-D-glucopyranosid [Matsumoto et al., 1969].

Stizolobic and Stizolobinic Acid, so far found in Amanita

muscaria, pantherina and corthunata [Chilton et al., 1974;

Chilton and Ott, 1976].

3b Muscimol and Isoxazoles

In the early sixties a remarkable contribution to our knowl-

edge of Amanita muscaria was brought forth. This dealt with

the isolation of three substances, independently carried on by

Swiss and Japanese authors and researchers. At least one of

these would turn out to be the main psychotropic agent within

the mushroom itself.6

Muscimol or enoI-betaine of 5-amino-methyl3- hydroxy-

isoxazole [Gagneux et al., 1965a; Miiller and Eugster, 1965;

Eugster, 1967, 1968; Eugster and Takemoto,l967; Theobald

et al., 1968; Brehm et al., 1972; Lund, 1979; Schultes and

Hofmann, 1980; Stijve, 1982].

Ibotenic Acid or the zwitterion of amino- (3-hydroxy-

isoxazolil-(5)-acetic acid monohydrate [Eugster et al., 1965;

Gagneux et al., 1956b; Good ER al., 1965; Sirakawa et al.,

1966; Eugster, 1967; Eugster & Takemoto, 1967; Eugster,

1968; Lund, 1979; Schultes & Hofmann, 1980].

Muscazone or (a)-amino -(2, 3H)-oxazolonyl-(5)-acetic

acid [Eugster et al., 1965; Fritz et al., 1965; Good et al.,

1965; Eugster, 1967; Reiner & Eugster, 1967; Eugster, 1968;

Schultes and Hofmann, 1980].

In the Swiss specimens, Ibotenic Acid was found in a per-

centages ranging from 0.08 to 0.1%. Greater concentrations

were in the ripe mushrooms grown in the summer. These con-

centrations focused in the cap more than the stalk. Takemoto

isolated it in small quantities also from Amanita pantherina

and Amanita strobiliformis. This sample was from Japan

[Eugster, 1968]. The compound easily transforms itself

through decarboxylation into the most active Muscimol.

Because of this, some authors have preferred to give the cumu-

lative percentage of the two compounds together. Benedict

and others [1966] found this to be 0.17-0.18% (both for the

typus and for the varieties formosa and alba of American ori-

gin). In an American pantherina sample, this percentage was

0.46% [Benedict et al., 1966; Chilton and Ott, 19763.

Muscazone, finally, is found in all the species in very small

quantities. The data available to estimate how much these

compounds contribute to the psychoactive syndromes and psy-

chological effects inducted by the Amanita muscaria are

focused in two main research studies. The first one was car-

ried on by Waser [1967] with 20 mg. of Ibotenic Acid and 5,

10, and 15 mg. of Muscimol; the second from Theobald and

others [1968] with 7.5-10 mg. of Muscimol and 75 mg. of

Ibotenic Acid on ten (10) normal subjects. If we can consider

the result of these studies, the following emphasis is shown:

To the Isoxazoles, and in particular to Muscimol, it is pos-

sible to attribute most of the effects by the fungus in tote.

Almost all the somatic symptoms (for which we have seen

the possible contribution of Muscarine) coincide, as do sev-

eral psychological symptoms. Regarding these last symp-

toms: It's nevertheless noticeable that the lack of "structured"

hallucinations occurs. Such are usually reported after usage

of Amanita muscaria. This fact suggests that a collateral

action exists with other compounds (some of these already

considered) contained in the mushroom. They could act (in

respect to the Isoxazoles) by strengthening, modifying or act-

ing directly on the structure responsible for the psychotropic

effects, or, perhaps, by modulating some of their pharmaco-

logical variables tied to the resorption or distribution. It

might be interesting, so far as this idea, to study the inges-

tion, in controlled conditions, of Muscimol, Ibotenic Acid

and Muscazone. These would be studied in varying proper-

tions or in combination. In this way, the Isoxazoles and

those other more recently isolated substances could be stud-

led synergistically.

Ibotenic Acid is far less active than Muscimol (the activity of

Muscazone is practically negligible). At the average con-

centration found in the mushroom, it would produce barely

perceptible effects.

Estimating content for an Amanita muscaria specimen of

autumnal growth, Muscimol can be found at around 0.05%.

This is based on an estimate of a mushroom with a cap 10-15

cm. broad and which weighs approximately 60-70 g. There

is a good correspondence between an effective dose of the

mushroom (1-10 caps of medium size) and the ones of the

isolated compound.

In summary, therefore, it seems correct to focus attention on

the Muscimol. This is the only compound in the Amanita mus-

caria that has proven not to be irrelevant so far as psychotropic

activity. Also, there is a plethora of solid psychopharma-

cological data and neurophysiological studies surrounding this

compound.

3.c The Pharmacology of Muscimol

Even without considering all the pharmacological studies

with animals concerning (see the following: Waser, 1967;

Theobald et al., 1968; Scotti de Carolis et al., 1969; Biggio et

al., 1977; Kulcsar et al., 1977; Jobert et al., 1979; Worms et

al., 1979; Festi, 1985 and the references below), other interest-

ing aspects are worth considering.

If we compare Muscimol with other psychotropic sub-

stances, we can observe that its electroencephalographic

effects are considerably different from those induced by

indolic compounds (psilocybin, psilocin, LSD, etc.), These

usually produce effects characterized by EEG desynchroni-

zation. In rabbits, the EEG tracings (with Muscimol) are syn-

chronized. It contains a dramatic reduction of the desynchro-

nizing response to acoustical or electrical stimulation of the

midbrain reticular substance. This effect is elicited with 0.25

mg./kg. i.v. With 1 mg./kg. the EEG awakening is totally

Continued after following page

blocked. With higher (2 mg./kg.) doses, characteristic spikes

(in the EEG) appear. A further injection of 1 mg./kg. of

Diazepam makes the EEG tracing practically isoelectric, even

though some spikes are still present.

This EEG syndrome is also the same in rats and cats

[Theobald et al., 1968; Scotti de Carolis et al., 1969]. It seems

to be closer to readings caused by anticholinergic deliriants

than by indolic hallucinogens. However, Physiostigmine (an

acetylcholinesterase inhibitor) produced a slight effect on the

EEG pattern of Muscimol. This suggests a secondary involve-

ment of the acetylcholinergic system [Scotti de Carolis et al.,

1969].

Also interesting, but difficult to understand, are the EEG

spikes which appear also after the administration of hallucino-

gens such as Dimethoxy-Methyl-Amphetamine (DOM) [Florio

et al., 1969], Harmine, /\-8 and d-9-transtetra-

hydrocannabinol (active principles of Cannabis indica)

[Lipparini et al., 1969]. These spikes have turned out to be the

most resistant to the depressant action of Diazepam.8

As well, the relationships between Muscimol and de-

synchronized sleep appear interesting. In cats, doses (of

Muscimol) 0.3 and 1 mg i.p. cause 20% and 40% reductions,

respectively, in the whole length of paradoxical sleep. One

mg./kg. i.p. increases by 30% the incidence of non-REM PGO

(Ponto-Genilo-Occipital) waves [Kulcsar et al., 1977].9

From a biochemical-pharmacological point of view, it was

shown in 1968 that Muscimol had an antagonism towards

GABA (Y-aminobutyric acid -- one of the main CNS neuro-

transmitter amino acids). This was determined right after

Muscimol had first been isolated. Muscimol has been shown to

be particularly effective on Bicuculline -sensitive receptors.

This was discovered by Johnston et al. (1968). In effect,

Muscimol is chemically very close to GABA, both in its chem-

ical conformation [Curtis et al., 1970; Kier and Truitt, 1970;

Johnston, 1971; Brehm et al., 1972; Curds and Johnston, 1974;

Andrews and Johnston, 1979], and for the distributions of the

charged molecule regions [Kier and Truitt, 1970]. It differs

from the latter in its greater rigidity due to the Isoxazole ring

[Snodgrass, 19833.

Many studies with radioactive Muscimol have shown several

binding sites (in the nervous system). It is very active in dis-

placing Bicuculline or GABA [Iverson, 1978; Mao and Costa,

1978; Andrew and Johnston, 1979; Wang et al., 1979;

Schaeffer, 1980; Snodgrass, 1983].

Furthermore, as a GABA-agonist, it stimulates the binding

of benzodiazepines and the reinforcement of its effects by

Diazepam may be explained with this stimulation. The slighter

strengthening (of its effects) by barbiturates (Penthobarbital

and others) is probably due to synergistic actions at the iono-

phore level [Snodgrass, 1983]. Muscimol is subject to meta-

bolic degradation after systemic administration. However,

none of its metabolites has GABAergic activity, or the ability

to replace Muscimol itself at receptor sites. Further evidence

of this includes the fact that only the active agent itself -- not

any transaminated molecule -- correlates with Bicuculline-

induced seizures as an antagonist. This has been correlated

with the Muscimol concentrations in the brain [ibid.; Baraldi

et al., 1979; Maggi and Enna, 1979; Matthews et al., 1981].

In summary, we can say that the oral administration, as well

as administration through other routes, activates most

GABAergic receptors in the CNS [Johnston et al., 1968; Curtis

et al., 1970; Johnston, 1971; Curtis and Johnston, 1974;

Kulcsar et al., 1977; Chan-Palay, 1978a, 1978b; Iversen,

1978; Johnston et al., 1978; Mao and Costa, 1978; Olpe and

Koella, 1978; Snodgrass, 1978; Amt et al., 1979; Andrew and

Johnston, 1979; Matsui and Kamioka, 1979; Waddington and

Cross, 1979; Wang et al., 1979; Worms et al., 1979; DeFeudis,

1980; De Feudis et al.; Schaefer, 1980; Snodgrass, 1983; Festi,

19853. However, the syndrome produced by Muscimol can be

slightly different from the one produced by other GABA-

agonists. In particular, it causes myoclonic jerks and seizures.

From this it is possible to suppose the restriction of inhibitory

pathways [Menon and Vivovia, 1981; Snodgrass, 1983] could

involve a non-uniform activity on some cerebral area or pro-

cess [Snodgrass, 1983].

Also, the administration of Muscimol induces metabolic

modifications for other neurotransmitters. The level of 5-

Hydroxytriptamine (Serotonin) [Konig-Bersin et al., 1970],

Dopamine [ibid.; Biggio et al., 1977; Iverson, 1978; Gundlach

and Beart, 1980] and Acetylcholine [Scatton and Bartholini,

1982] is increased, while Noradrenaline is decreased [Kunig-

Bersin, et al., 1970]. In some cases the concentration is espe-

cially changed in particular zones. In others the changes are

uniform in the whole brain. Several pharmacological

researches suggest, however, that these effects are indirect and

pass through the GABAergic system rather than directly on the

respective neurotransmitter systems.

3d Possible Mode of Action of Muscimol

It seems clear, therefore, that the main activity (maybe the

only one) of Muscimol is as GABA-agonist. However, the

broad distribution and the complexity of the GABAergic sys-

tem don't make it easy to interpret so far as its mechanisms of

action. It may be possible to attribute ataxia, dizziness and

other vestibular symptoms to the GABA-mimetic action on

cerebrovestibular pathways. The decrease of motor activity

and catalepsy can be tied to the interface with the GABAergic

control of dopaminergic (and probably also acetylcholinergic)

neurons in the nigro-strio-pallidal complex.

Nevertheless, the matter is far more difficult when we try to

analyze typical psychic symptoms such as hallucinations,

mood changes, etc. This is because specific studies on these

topics are lacking. After discovering the strong GABA-agonist

activity of Muscimol, neurophysiologists and pharmacologists

preferred using it in classic researches on GABA itself rather

than investigate its mechanisms as a psychotropic agent. The

hypothesis that we can produce on this possible mode of action

are therefore necessarily reduced and partially speculative,

while awaiting further studies on this subject.

It seems possible, however, to try an approach between the

available data on Muscimol and an attempt at an integrative

hypothesis that one of us [Francesco Festi, 1985] has devel-

oped. This is in reference to the hallucinogens of the indole

group (psilocybin, psilocin, LSD, DMT, etc.) and other com-

pounds with similar neurophysiological actions (such as mes-

caline). This proposal takes inspiration from the connections

between hallucinations and dreams (suggested by Jacobs and

Trulson, 1979). This is founded on the similarity between

some physiological states tied to the oneiric process and to the

action of indole hallucinogens. These parallel situations can be

gauged as follows (see Festi, 1985 for a review of the

neuropharmacological data on this topic).

Decrease or inhibition of the rate in the serotoninergic

midbrain raphe neurons.

Increase of the discharge rate in the neurons of the near-

by reticular formations.

Tendency to cortical and subcortical activation.

Increase, as compared to the normal state of active wak-

ing, in the number of rapid-eye movements (REM) both

in humans and monkeys.

Therefore, taking as a reference frame the convincing

hypothesis of Hobson and McCarley [1982; McCarley and

Hobson, 1975; Hobson, 1977; McCarley, 1978] relating to the

oneiric mechanism, we can suppose certain actions. These are

that under the effects of hallucinogenic drugs, the brain is in an

anomalous situation so far as the "normal" consciousness states

and the oneiric one. Disorganized information reaches the

encephalic structures, superimposed over the sensorial ones.

These inputs can be either of bulbar origin (and thus, according

to Hobson and McCarley's model, tied to eye movements) or

due to false interpretation of exogenous information, maybe

for interference derived from the fall of serotoninergic inhibi-

tion (or from the complementary facilitation of excitation) on

some elaborating or leading structures.

The anomalous data can't be analyzed as normal sensations,

because the temporal-spatial coordinates are lacking. Nor can

they follow the oneiric iter, because the whole situation is dif-

ferent from desynchronized Sleep and requires coordination

with motor activities, which are not blocked out and indeed are

even more sensitive! However, like activities during dreams,

the proencephalon tries to make what Hobson and McCarley

have defined as "the best of bad work." The disorganized

inputs are structured by deriving information from mnemonic

engrams to which the access is facilitated either by dis-

inhibition by the "normal" pathways, or by the opening of

some alternative ones. These also would be under the influ-

ence of our postulated serotoninergic inhibition resulting in

direct facilitatory actions, etc.

The results of such cortex processings are felt as hallucina-

tions. The subcortical structures, and particularly the limbic

system (this also being activated by the fall of tonic inhibib-

tion) could be responsible for the concurrent emotional

experiences.

The hallucinations, therefore, could be produced by a lack of

balance among the connections of the neurotransmitter system.

These connections are not completely responsible for and

superimposable for what occurs during REM sleep. In consid-

ering only the interrelation between serotonin and nor-

adrenaline, it is possible that the action of this latter system

(more marked, e.g., for psilocin than for LSD, being the sec-

ond most powerful hallucinogen) counterbalances the altera-

tions on the raphe nuclei (and surely on other parts of the

brain), and modulates the strength of the described psyche-

tropic agent.

In attempting to relate this model to aspects of the Muscimol

action, it is worth noting that there are pharmacological refer-

ences which point to Muscimol's ability to depress the rate of

serotoninergic raphe neurons. It has been demonstrated that

there is a picrotoxin-sensitive inhibition of these neurons after

iontophoretic application of GABA. It seems, furthermore,

that the afferent adrenergic pathways to the dorsal raphe are

mediated by GABAergic interneurons [Gallager and

Aghajanian, 1976; Wang et al., 1976; Aghajanian and Wang,

1978; Sulser, 1978; Aghajanian, 1982; Aghajanian, 1984;

Hamon, 1984]. Another very significant fact is that Muscimol,

in non-toxic doses, can produce interferences on physiological

processes tied to oneiric events [Kulcsar et al., 1977; vide

supra].

According to this hypothesis we can also assume that the

strengthening of action following the soporific effect of the

Amanita muscaria (reported so far as the Siberian peoples and

sometimes also verified after auto-experience of ingestion

[Waser, 1967; Wasson and Wasson, 1957; Doanlies and Volt,

1460; Wasson, 1967a, 1967b; Arietti and Tomasi, 1975;

Lincoff and Mitchel, 1977; Helm, 1978; Rumack and Saltman,

1978; Flammer, 1980; Schultes and Hofmann, 1980; Bresinsky

and Besl Regensburg, 1985; see also below]) are due to a

greater interferencial power when the CNS is in the sleeping

biochemical-physiological states. In fact, because this is the

natural background for "endogenous" dreams, the state of sleep

may produce an amplifying action on the effectiveness of the

compound. This possibly may act just on the structures active

during the oneiric process [Festi, 1985].

However, the same mode of action for indole hallucinogens

and Muscimol are not proposable, not even on a hypothetical

basis.11 The active principle of Amanita certainly has broad

activity. This is as broad as the spreading of the GABAergic

system itself. It could have possible interferences on several

levels. So far as this subject, it is worth considering also the

non-identity of the symptomatological complexes, the first

being the practically opposite effects on EEG readings.

The future of our knowledge about Muscimol is indissolubly

tied to the development of the acquisition of information on the

GABAergic systems in man. The Muscimol/GABA system

interactions must certainly give favorable results. This is in

regard to the mechanisms of actions of psychoactive drugs, and

also in connection with our knowledge about higher nervous

system processes in man.

Part II. Personal Experience with Amanita muscaria.

Speaking about experience with Amanita muscaria is very

difficult because it depends on the mushroom, on the person

who is undergoing the experience, and on the environment

where the experience takes place. We have had a very small

number of experiments (six times) with a small group (five

people). At the beginning there were six but one withdrew

after the first experience because it was too unpleasant for him.

We have found, according to the data reported in many texts,

that the most important variable is the time of the season when

the mushroom is picked. The most powerful mushrooms were

picked in the middle of August when the season was begin-

ning. In the mushroom picked in September the narcotic and

physical effects were predominant whereas in August the

"visionary" and psychedelic effects were more highlighted.

Obviously the personality of the single person, his motiva-

tion, attitude, mood and past experience are important in all

psychedelic experiences. In fact, people who are interested in

"meditative" or introspective experiences have found the

Amanita muscaria closer to this feeling, while people inter-

ested only in a "trip" have found it "too unpleasant." Group

interaction has been found to be meaningless because the

effect of the drug is very individual and each person wants to

be alone with himself. Perhaps this is determined by the

absence of a guide, a person with some familiarity with the

drug, and this lack has been underlined by all. We haven't ana-

lyzed the importance of the expectations and beliefs but it's

important that the experience closer to religious or transper-

sonal "insight" has been experienced by people with stronger

expectations of a "religious vision" and with some knowledge

of "shamanic belief." Another very important aspect of this

mushroom is diet (fasting before taking it): light food two or

three days before and a day of fasting help to reduce the nausea

in the first stage and to permit a "relaxed" course.

The experience with Amanita muscaria can be split into

three stages: a first stage when the physical symptoms of nau-

sea and vomiting predominate (vomiting is very rare while a

strong sense of nausea is always present); a second stage when

the narcotic effect predominates, and a third when there could

be visions and hallucinations. The amount of the drug changes

from 1-2 mushrooms in August to 4-5 mushrooms in the mid-

die of September. This is because the August mushrooms are

more powerful, so you have to increase the quantity. But even

with the higher amount the experience is not the same: in

September the physical symptom of nausea is more marked

and the narcotic and visionary experience is less. The most

particular trait of the Amanita experience is the second stage.

In this stage you can have different levels of narcotic effect,

including sleep with normal or "particular" dreams. I'm speak-

Continued after following page

--------------------------------------------------------

SOMA AND THE RIG VEDAS

"Like a stag, come here to drink!

Drink Soma, as much as you like.

Pissing it out day by day, O generous one,

You have assumed your most mighty

force. "

VIII 4.10

Rig Veda

"Soma, storm cloud filled with life,

Milked with mild and butter,

Navel of the Path; immortal Concept,

Which springs to life far from here

In unison those charged with the task,

The blessed do honor to Soma.

In flowing movements swollen men piss

Soma."

IX 74.4

Rig Veda

"In the belly of India

Intoxicating Soma is filtered."

IX 80.3

Rig Veda

The Vedic poets speak of three filters involved in

the preparation of Soma:

1)The filtering of sunlight into the mushroom,

bearing its magical powers from the heavens,

2) The woolen cloth through which the juices

were strained,

3) The human body.

The Indian Rig Vedas speak extensively about Soma. believed to be

the Amanita muscaria. `There are over one hundred (out of

one thousand) devoted to this sacrament (from the magical & Ritual

Use of Herbs by Richard A. Miller (Destiny, 1983).

-------------------------------------------------------------------------------

ing about the "particular" one because in the Amanita experi-

ence you can have highly colorful, bright dreams with a partic-

ular sense of "lucidity." This is not always experienced but we

have five cases in two experiences (August) with a percentage

of 45%. In these dreams you know you're dreaming and are

experiencing a reality other than the waking one. Three per-

sons in this stage have reported being sleeping and simultane-

ously being aware of the environment around them, to have

heard every sound and to have remembered everything that

happened in the room during the experience. It's in this stage

that you can experience a particular "strange" sensation of con-

versing with "something" inside yourself. Personally, I

remember having asked about a personal problem of mine and

suddenly a vivid image coming into my mind with a strong

psychological insight. I remember this image with a sense of

importance for an effect on the course of my life even after

years.

In the third stage we experience a more typical altered state

of consciousness. One person in the first session reported in

the passage between stage 1 and stage 2 a "profound sense of

spiritual insight with a dreamlike feeling of a religious identity

with my deep self." This is the only religious feeling which

has been reported. More common were changes in body per-

spective with a feeling of being split in two, with a part of him-

self remaining on the left side of his body. Dizziness and a

sense of being disoriented, with some difficulty in motor coor-

dination, were very common in the third stage. In all cases this

experience occurred in a dreamlike state, which is the most

important aspect of stage 3: a state in which a person is experi-

encing reality as an inner world with a strong feeling of

introspection.

Sometimes there was a sense of a change in objects with

perceptive and sensorial distortion, a sense of bodily expansion

into the environment or of an extraordinary sensory change.

All the people were fully aware of being in an unusual state of

consciousness but the sense of ego was maintained throughout

the experience. The imagery increased at the height of the

experience (interface between stages 1 and 2), with a greater

distinctness and vividness: people experienced a particular

kind of imagination where thoughts were immediately trans-

formed into images. This has happened to six people. During

the Amanita experience people complained of a lack of atten-

tion with a high involvement in inner images and sensations

and great difficulty in directing concentration. No effects were

reported on memory, which was unimpaired in all throughout

the experience. Nobody has reported feelings of irritation,

anger, shame, guilt or other negative feelings. Sexual feelings

and also sensations of love, joy and bliss were absent. Some

people remember a marked sense of detachment and no emo-

tional involvement. Control of the experience, thought and

image was very reduced because of the absence of volition:

the person accepted this situation with detachment and absence

of any criticism. I think that the most powerful quality of

Amanita muscariais this sense of silent talking to oneself; the

kind of internal dialogue where a person has the feeling of

important revelations about his life, a feeling which is main-

tained for a long time after the experience. More research into

this is needed, particularly with selected groups of people: I

think this mushroom could have a lot to teach us about

ourselves.

Notes

1 Even without entering into the subject, it's worth mentioning

the other three species of the genus Amanita which are some-

how connected to the hallucinogenic substances: A. tomentelIa

Kromb., A. citrina (Scheff.) S.F. Gray (= A. mappa (Batsch. ex

Fr.) Quulet) and A. porphyria (A. & S. ex Fr.) Seer. (= A.

recutita (Fr.) Gillet). In this species were found bufotenine

and other compounds such as the psychotropic dimethyl-

byptamine (DMT) [Catalfolmo & Tyler, 1961; Tyler, 1961;

Hofmann, 1964; Tyler and Gr6ger, 1964; Eugster, 1968;

Perez-Silva and Aroche Alfonso, 1983].

2 Traces of plants with known therapeutical value but without

alimentary usefulness are found in caves and burial places

more than 60,000 years old [Furst, 1976].

3 Already Neanderthal men might have had a proto-religion

with shaman characters [Furst, 1976].

4 Well enough known to give the name to cholinergic recep-

tors tied to the effecters (and its parasympathomimetic activity

at post-ganglionic levels).

5 The tropane alkaloids, typical of deliriants of the family

Solanaceae, are generally active after ingestion of higher than

10-30 mg. of pure substance [Hoffer and Osmond, 1967;

Waser, 1967; Schultes and Hofmann, 1980].

6 It's worth remembering here the report of a compound,

named Agarin, found in the mushroom by Bowden and

Drysdale [1965; Bowden et al., 1965] and whose structure is

then shown exactly alike Muscimol.

7 This difference of concentration for different parts of the

mushroom, different picking seasons and different growing

stages can give partial scientific support to the "rules" of

Amanita muscaria gathering among the Siberian people using

it as an inebriant [Wasson, 1967a, 1967b].

8 A benzodiazepine which, as we will see below, potentiates

the effects of Muscimol and, in general, of GABA-agonists.

9 In order to be exhaustive, we can say that the behavioral

and EEG effects of ibotenic acid are practically the same as

muscimol, yet 5-10 times less powerful.

10 One among GABA-antagonists at the CNS level.

11 On the other hand, the lack of neurobiological relationship

between hallucinogenic drugs of different psychotropic fami-

lies demonstrates the baselessness of one among the hypothe-

ses proposed in the early 1970s, which supposed a common

final way for the actions of hallucinogens [Brawley and

Duffield, 1972; Grinspoon and Bakalar, 1979; Jacobs, 1984].

Bibliography
To Be Scanned soon -