
 Amanita muscaria Info
Myco-pharmacological Outline and Personal Experiences by Francesco Festi and Antonio Bianchi from PM&E Volume Five
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 history 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 profiles 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 poisoning 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 complementary but
different approaches to the same topic. The first study, presented by
Francesco Festi, presents a critical overview of the mycological,
ethnobotanical, chemical and pharmacological 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.
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 muscarius and originally introduced it into the genus. He
included it along with other gill fungi he classified and which were
classified by most Northern European botanists. These same botanists
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 characteristic of the genus Amanita) It
retains this shape more completely 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 whitish)
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 discontinuous (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 relation (a commensalistic symbiosis
shared with many other species 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, however, 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 different from Amanita muscaria with its slender stalk with fibril
becoming brown at the end and the lighter cap (being pale to yellow-
orange (ibid.). Another species of
genus Amanita also worth remembering here is Amanita pantherina (DC ex
Fr.) Seer., which is certain to contain the same psychotropic agents as
Amanita muscaria [see following references]. Amanita pantherina
produces a more toxic than hallucinogenic syndrome, however, when
ingested. A predominance of nonspecific confusional effects,
psychomotor excitement 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].
Amanita 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 discontinuous at 6-15 cm. X 2-20 mm. It is white, stuffed and
then hollow. 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.(1)
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 hallucinogenic 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 contributed 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 activities 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 characteristics
represent(ed) the ideal support for consciousness alteration --
including hallucinogenic plant use. This made connections with an
animistic conception of the world stronger and more widespread. Let's
suppose proto-Indoeuropean man had already discovered 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
Amanita muscaria were transferred cross-culturally to the proto-Uralic
people, maybe with the use(s) of the mushroom itself (which later were
carried 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
connections 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 serpent or toads, etc. Among
the characteristics of the West (as opposed to the Test of the globe --
like America, where shamanism has persisted to the present) was the
speed of socio-economic development and the relatively sudden changes
in lifestyle. This historical evolution contained a base mode of
property ownership 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 connection with these natural, totemic
forces remained. These remained alive, above and beyond the new taboos.
These elements 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 inexplicable. In this way we might
understand our culture's connections 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 mycophobia proposed by Wasson seems to complete
itself in a convincing 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 shamanistic 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.
Even
from the point of view of the chemical and pharmacological research,
the Amanita muscaria takes up a place which distinguishes it from the
many other hallucinogenic mushrooms. 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 ingestion 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 concurrent 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 methodological 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 isolated by Eugster and others, etc.). Or they have turned
out to be inactive at the quantities actually contained in the mushroom
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.
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 concentration 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
muscarine on the central nervous system is demonstrated(4) [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 hallucinatory) 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 compIetely lacking in
pharmacological data [Waser, 1967; Eugster, 1968; Helm, 1978; Bresinsky
and Besl Regensburg, 1985; Festi, 1985].
Tropane Alkaloids and Bufotenine: In
investigating a compound named Pilzatropine by Kolbert in 1881 because
of pharmacological similarities, some authors (Lewis in 1955 and
Manikowsky & Niezdodzki in 1962) reported the presence of
hyoscyamine, atropine and scopolamine in the Amanita muscaria,
(Salemink et al., 1963, Tyler and Groger, 1964). This suggests a
mistake due to substances with the same chromategraphic 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 carpophores 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 pharmacological 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 hallucinogenic P-carboline. Such
are active compounds within the psychotropic species of the genus
Banisteriopsis [Schultes and Hofmann, 1980]. Chilton and Ott [1976],
nevertheless, 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]. In
the early sixties a remarkable contribution to our knowledge 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,1967; 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 percentages ranging
from 0.08 to 0.1%. Greater concentrations were in the ripe mushrooms
grown in the summer. These concentrations focused in the cap more than
the stalk.(7) 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 cumulative 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 origin). In an American pantherina sample, this percentage
was 0.46% [Benedict et al., 1966; Chilton and Ott, 1976]. 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 psychological effects inducted by the
Amanita muscaria are focused in two main research studies. The first
one was carried 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 possible 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 several psychological symptoms. Regarding
these last symptoms: 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 acting directly on the
structure responsible for the psychotropic effects, or, perhaps, by
modulating some of their pharmacological variables tied to the
resorption or distribution. It might be interesting, so far as this
idea, to study the ingestion, in controlled conditions, of Muscimol,
Ibotenic Acid and Muscazone. These would be studied in varying
proportions or in combination. In this way, the Isoxazoles and those
other more recently isolated substances could be studied
synergistically. Ibotenic Acid is far less
active than Muscimol (the activity of Muscazone is practically
negligible). At the average concentration 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 muscaria that has proven not to be irrelevant so far as
psychotropic activity. Also, there is a plethora of solid
psychopharmacological data and neurophysiological studies surrounding
this compound. 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 interesting aspects are worth considering. If
we compare Muscimol with other psychotropic substances, 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
desynchronization. In rabbits, the EEG tracings (with Muscimol) are
synchronized. It contains a dramatic reduction of the desynchronizing
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 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
involvement 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 hallucinogens 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 desynchronized 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 neurotransmitter 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 chemical 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, 1983]. Many studies with
radioactive Muscimol have shown several binding sites (in the nervous
system). It is very active in displacing 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 ionophore level [Snodgrass, 1983]. Muscimol is subject
to metabolic 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, 1985]. 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 process [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
especially 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. 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 system 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 developed. This is in reference to the hallucinogens of the
indole group (psilocybin, psilocin, LSD, DMT, etc.) and other compounds
with similar neurophysiological actions (such as mescaline). 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 nearby reticular
formations. Tendency to cortical and subcortical activation. Increase,
as compared to the normal state of active waking, 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 different 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
disinhibition by the "normal" pathways, or by the opening of some
alternative ones. These also would be under the influence of our
postulated serotoninergic inhibition resulting in direct facilitatory
actions, etc. The results of such cortex
processings are felt as hallucinations. The subcortical structures, and
particularly the limbic system (this also being activated by the fall
of tonic inhibibtion) 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
considering only the interrelation between serotonin and noradrenaline,
it is possible that the action of this latter system (more marked,
e.g., for psilocin than for LSD, being the second most powerful
hallucinogen) counterbalances the alterations on the raphe nuclei (and
surely on other parts of the brain), and modulates the strength of the
described psychetropic agent. In
attempting to relate this model to aspects of the Muscimol action, it
is worth noting that there are pharmacological references 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.
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 beginning. 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 motivation, 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 interested 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 analyzed the importance of the
expectations and beliefs but it's important that the experience closer
to religious or transpersonal "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 nausea and vomiting
predominate (vomiting is very rare while a strong sense of nausea is
always present); a second stage when the narcotic effect predominates,
a 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 middie 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. 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: - The filtering of sunlight into the mushroom, bearing its magical powers from the heavens,
- The woolen cloth through which the juices were strained,
- 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). I'm
speak-ing about the "particular" one because in the Amanita experience
you can have highly colorful, bright dreams with a particular 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 persons in this stage have reported being sleeping
and simultaneously 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 conversing 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 perspective with a
feeling of being split in two, with a part of himself remaining on the
left side of his body. Dizziness and a sense of being disoriented, with
some difficulty in motor coordination, 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 experiencing 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 transformed into images. This has happened to
six people. During the Amanita experience people complained of a lack
of attention 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 emotional 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 muscaria
is 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 maintained 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.
- Even
without entering into the subject, it's worth mentioning the other
three species of the genus Amanita which are somehow 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].
- 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].
- Already Neanderthal men might have had a proto-religion with shaman characters [Furst, 1976].
- Well
enough known to give the name to cholinergic receptors tied to the
effecters (and its parasympathomimetic activity at post-ganglionic
levels).
- 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].
- 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.
- 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].
- A benzodiazepine which, as we will see below, potentiates the effects of Muscimol and, in general, of GABA-agonists.
- der
to be exhaustive, we can say that the behavioral and EEG effects of
ibotenic acid re practically the same as muscimol, yet 5-10 times less
powerful.
- One among GABA-antagonists at the CNS level.
- On
the other hand, the lack of neurobiological relationship between
hallucinogenic drugs of different psychotropic families demonstrates
the baselessness of one among the hypotheses 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].
|