Introduction to Amanita Muscaria

Amanita Muscaria in history

The original name Amanita Muscaria comes from the ancient Greek Amanítis, modern amanitai - Amanita (a fungus) + latin musca (fly). The Amanita muscaria (AM) has a surprising equivalent all over the world and is connected to the "flykiller": fly agaric (English); Haetorimodashi (Japanese); Hongomosquero, Ho Hongomosquero, and Hongo Matamoscas (Spanish); Amanite Tue-mouches (French); Fliegenpils (German); Mukhomor (Russian); and Moscario (Italian).

Amanita Muscaria is widespread throughout the Earth and is present on all continents from far north to south, occurring in Europe, Asia, Africa, Australia, New Zealand, North America, Central America, and South America.

A growing number of molecular studies show that Amanita Muscaria has phylogeographic structures and that its distinct lineages are usually limited to different continents. Phylogenetic work indicates three geographic clades (Eurasian, Eurasian-alpine, and North American groups) within Amanita Muscaria. Nested clade analyses (NCA) confirmed that the ancestral population of Amanita Muscaria likely evolved in the Siberian - Beringian region and expanded their range in North America and Eurasia. In addition to range expansions, populations of all three species remained in Beringia and adapted to the cooling climate.

Amanita Muscaria is the oldest entheogen mushroom known to humans. The fungus was used before the Common Era (BCE) by distant ancestors, confirmed by a caveman's text carved in stone for descendants and the folklore world.

Use of the Amanita Muscaria mushroom started in ancient times and is connected with mysticism. Amanita goes back 50,000 years, painted by Aboriginals in Australian caves. Mushrooms and toadstools were believed to be fallen stars endowed with magic. As such, they were considered taboo, and their consumption was forbidden.

Representations of Amanita mushrooms, most prominently Amanita Muscaria, have been reported in polychromatic rock paintings in the Sahara, dating from the Paleolithic era from 9,000 - 7,000 BCE. Amanita Muscaria has had a reputation for killing flies at least as far back as the De Vegetabilibus of Albertus Magnus in the thirteenth century. The psychoactive Amanita mushrooms have a well-attested entheogenic use among Siberian, European, and Pan-American shamanic peoples and are specifically implicated in the mysteries of ancient Greece (the Mysteries of Dionysus) and Rome (Mithraic Mysteries), and as the original Vedic plant-God Soma, and the Avestan haoma among the gnostic Manicheans and early and mystically inclined Christians of later periods.

Besides various symbols that might correspond to Amanita Muscaria and originate from northern and southern Asian traditions, some may also be discerned in Buddhist myths. In the legendary biographies of some Buddhist adepts from the second and ninth centuries, there are some clues that can be interpreted to reveal that the adepts were consuming psychedelic Amanita Muscaria - fly agaric - mushrooms to achieve enlightenment. They appear to be echoed in Germanic tradition, possibly in some characteristics related to the God Odin.

A few publications argue that Christianity originates from a cult of Amanita Muscaria. Jesus was supposedly being invested with the energy of the mushroom, but other religious and secular biblical scholars discredit this.

P. J. Von Strahlenberg, a Swedish colonel who was in a Siberian prisoner of war camp for twelve years, wrote the first published documentation of the effects of Amanita Muscaria on humans. In written observations Von Strahlenberg noted this:

The Russians who trade with them (Koryak), carry thither a kind of mushrooms, called in the Russian tongue, Muchumur, which they exchange for squirrels, fox, hermin, sable and other furs: those who are rich among them lay up large provisions of these mushrooms, for the winter. When they make a feast, they pour water upon some of these mushrooms and boil them. They then drink the liquor, which intoxicates them: the poorer sort, on these occasions, post themselves round the huts of the rich, and watch the opportunity of the guests coming down to make water; And then hold a wooden bowl to receive the urine, which they drink off greedily, as having still some virtue of the mushroom in it, and by this way they also get drunk.

Known as mukhomor in Russian, the Amanita Muscaria toadstool is the center of iconic myths and legends of the indigenous peoples of Siberian tribes - Chukchi, Koryaks, Kamchadals, Yakuts, and Yukagirs.

Amanita Muscaria was used as medicine, an entheogen for rituals, a food source, and a ceremonial drink. Detailed description of the use of Amanita Muscaria by the peoples of the far northeast in the middle of the eighteenth century was carried out by the Imperial Academy of Sciences in St. Perersburg where, in 1975, a two-volume work of professor S.P. Krasheninnikov, a participant of the Great Northern Expedition of 1733 - 1743, was published. In his book Description of the Land of Kamchatka, Krasheninnikov described the mukhomor (Amanita Muscaria) intoxication in entheogen ceremonies of the Koryaks and Kazaks:

The first and usual sign by which one can recognize a man under the influence of the mukhomor is the shaking of the extremities which will follow after an hour or less, after which the persons thus intoxicated have hallucinations... while some might deem a small crack to be as wide as a door, and a tub of water as deep as the sea.

But this applies only to those who overindulge, while those who use a small quantity experience a feeling of extraordinary lightness, joy, courage, and a sense of energetic well being.

An ethnological study of mukhomor as food, medicine, and an intoxicating and hallucinogenic agent was documented by other participants of the previously mentioned expedition — G. Steller, Description of the Land of Kamchatka, Its Inhabitants, Their Culture, Way of Life and Customs (1793) and Y. Lindenau, Description of the Peoples of Siberia in the First Half of the 18th Century (1983) - in which historical and ethnographic materials about the peoples of Siberia and the Northeast were studied. K. Merck was also part of the Northeastern Geographical Expedition of Billings - Sarychev Ethnographic Materials of the Northeastern Geographical Expedition of 1785 - 1795), and the materials he presented must be noted as well.

Oliver Goldsmith in The Citizen of the World (1762) elevates mushroom intoxication to the nobility in order to comment on a moral about excessive flattery, likened to making use of excreted material. However, the central effects he describes are those of mild alcohol intoxication.

In the late nineteenth century through the mid-twentieth century, mukhomor was studied by ethnographers V. G. Bogoraz - Tan (1904) and V.I. Johelson (1900) on the Jesup Northern Pacific Expedition. In 1957, the monumental two-volume Mushrooms, Russia and History by

R. G. Wasson and V. P. Wasson was published, which for the first time combined well known research in the fields of mycology and ethnobotanics, including data on the red mukhomor.

Amanita Muscaria Chemistry

The chemical constituents of Amanita Muscaria have been thoroughly investigated. Ibotenic acid, muscimol, muscarine, and muscazone are the most studied compounds. These four chemicals are found in certain species of Amanita Muscaria throughout the world. The website inchem.org explains that they are related and are all isoxazole derivatives. Detailed mycological data have already been published.

Ibotenic acid (a-amino-3-hydroxy-5-isoxazoloacetic acid 1) is an analog of the neurotransmitter glutamate, which acts as a non-selective glutamate receptor agonist. Ibotenic acid is water-soluble. Any attempt at dehydration leads to decarboxylation of ibotenic acid, turning it to muscimol. Ibotenic acid is decarboxylated to muscimol in the body. The molecular formula is C5H6N2O4.

Muscimol (3-hydroxy-5-aminomethyl-isoxazole) is a GABA analog, a specific agonist of the GABAA receptor. Muscimol is also water-soluble. The molecular formula is C4H6N2O2.

Muscarine (4-hydroxy-5-methyloxolan-2-ylmethyl-trimethylazanium) is the first parasympathomimetic substance ever studied. Muscarine mimics the function of the natural neurotransmitter acetylcholine in the muscarinic part of the cholinergic nervous system. Muscarine is only a trace compound in the Amanita Muscaria. The molecular formula is C9H2ONO2.

Muscazone (a-amino-2,3-dihydro-2-oxo-5-oxazoleoacetic acid 3) is a heterocyclic glycine derivative found only in Amanita Muscaria. The structure was confirmed by synthesis. The molecular formula is C5H6N2O4.

Other active constituents detected in Amanita Muscaria are only in trace amounts, and their contribution to the biological effects of Amanita Muscaria is apparently negligible. Constituents include acetylcholine, amavadin, betain, betalamic acid, choline, quaternary trimethylammonium salt of 6-amino-2,3-dihydroxy-hexan, hercynin, hypoxanthin, (x)-R-hydroxy-4 pyrrolidone, uracile, stizolobic acid, muscaridin, muscarufin, muscaflavin, xanthin, adenosin, a carbolinic derivative, and b-D-n-butylglycopyranoside, muscapurpurin, muscarubin.

The caps and stems were studied separately, revealing different metabolic compositions. Compared to the stems, Amanita Muscaria caps exhibited higher concentrations of isoleucine, leucine, valine, alanine, aspartate, asparagine, threonine, lipids (mainly free fatty acids), choline, glycerophosphocholine, acetate, adenosine, uridine, 4-aminobutyrate, 6-hydroxynicotinate, quinolinate, UDP-carbohydrate, and glycerol.

Conversely, stems exhibited lower concentrations of formate, fumarate, trehalose, and α- and β-glucose. Six metabolites — malate, succinate, gluconate, N-acetylated compounds (NAC), tyrosine, and phenylalanine — were detected in whole Amanita Muscaria fruiting bodies but did not show significant differences in their levels between caps and stems.

Fresh Amanita Muscaria contains 258 - 471 ppm of ibotenic acid with the entirety of the fungi. Nearly all the ibotenic acid is concentrated in the caps. Typically, the ibotenic acid to muscimol ratio of fungal cap tissue would be 9:1 or greater in fresh samples. A portion of the ibotenic acid converts to muscimol while drying Amanita Muscaria, so the conversion is incomplete and highly variable depending on conditions. A relatively low conversion rate of only 30% after drying, leaving a concentration of ibotenic acid, is typically 180-1800 ppm. A common ibotenic acid to muscimol ratio would be 3:2 in dried specimens, such that the neurotoxin amounts far exceed the GABA analog.

Additionally, multivariate data analyses of the fungal basidiomata and the types of soil were performed. A biogeochemical study of Amanita Muscaria confirmed that elemental distribution in different parts of fruiting bodies is variable for each element and may change during maturation. Soil properties, species specificity, and the pattern of fruitbody development may all contribute to the various types of elemental distribution and suggest that the results for one species in one location may have only limited potential for generalization.

Amanita Muscaria Toxicology

Amanita Muscaria may concentrate vanadium to 200 ppm (30 times those reported in living organisms). Isolation, structure determination, and synthesis of the pale blue vanadium complex amavadin 18 were confirmed by crystallography. Similarly, unusually high levels of selenium to 17.8 ppm and heavy metals have been reported: cadmium 13.9, cobalt 2.6, chromium 1.7, lead 33.3, mercury 61.3, and nickel 7.5 ppm. Arsenic compounds were identified and quantified in the mushroom Amanita Muscaria collected close to a facility that had roasted arsenic ores.

A prognosis of poisoning is generally minor, and very seldom are lethal cases mentioned. Subsequent gastrointestinal disorders with vomiting are inconsistently reported and not characteristic of the syndrome. Central nervous system dysfunctions primarily characterize this poisoning. No damage to organs has been reported. A study of several poisoning cases in which Amanita Muscaria was consumed to evoke hallucinations showed that the poisoning regressed with no organ complications. The remaining persons who had eaten the fly agaric were free of any complaints.

The onset of symptoms of Amanita Muscaria poisoning is rapid after significant exposure (30 mins - 1.5 hours). Gastrointestinal discomfort is uncommon, and neurologic and psychotropic effects dominate. Inebriation, euphoria alternating with anxiety, confusion, illusions, delusions, hallucinations, agitation, and violent behavior are also common. More uncommon symptoms are myoclonic jerks, muscle fasciculation, and convulsions. CAS depression and unconsciousness may follow heavy exposure, especially in Amanita Pantherina cap poisoning.

If Amanita Muscaria is ingested for a psychoactive experience, manifestations occur within two hours and are characterized by the GABAergic effects of drowsiness, hallucinations, dysphoria, dizziness, delirium, glutaminergic effects of hyperactivity, ataxia, hallucinations, myolonus, and seizures. Since the mushrooms contain both muscimol and ibotenic acid, their ingestion may result in alternating excitatory and inhibitory symptoms. Other than tachycardia, which is nonspecific and may occur due to hypovolemia or hypoxia, adverse cardiac effects with these mushrooms are uncommon.

There is a relationship between the psychochemical properties of the active components and the mode of consumption. For instance, Mexican people eat the carpophore of Amanita Muscaria without the cuticle that has been peeled off and also discard the cooking water. In Italy, after boiling and rejecting excess water, the mushroom is preserved in brine prior to consumption. In North America the red cuticle is peeled off, and the remainder is dried and then smoked. These procedures eliminate or destroy the greater part of the active water-soluble substances. The red skin of the cap and the yellow tissue beneath it contain the highest amounts of these substances, so that might explain the practice of removing it. Russian people eat Amanita Muscaria stems after boiling them twice and frying.

Amanita Muscaria in Pharmaceutical Science

I was not able to find any methodical data, clinical research, or medical tests that relate to the effects on the human body of a regular intake of very small Amanita Muscaria doses. However, I found several studies that show the medicinal properties of Amanita Muscaria components.

It has been proved that muscimol micro-injections in the subthalamic nucleus reverse Parkinsonian symptoms, and muscimol has suppressive effects on essential tremors without impairing speech and coordination.

Possible neuroprotective effects of an extract from Amanita Muscaria that contains high amounts of muscimol have been evaluated, revealing statistically significant neuroprotective effects on in vitro neurotoxicity models.

In patients with Huntington's disease and chronic schizophrenia, oral doses of muscimol have been found to cause a rise of both prolactin and growth hormone. Muscimol is a GABA agonist therapy in schizophrenia. At dose levels below 5 milligrams, many patients experienced a tranquilizing effect from muscimol. These subjects, when receiving the active drug, reported feeling more relaxed and less anxious and claimed a positive drug experience despite their lack of relief from psychotic thinking.

Improvement in tardive dyskinesia was found after muscimol therapy. At oral dose levels from 5 - 9 milligrams, involuntary movements were consistently attenuated, usually in the absence of sedation. Another study showed that ibotenic acid and muscimol both have beneficial effects on human epilepsy, Huntington's disease, and other neurological disorders. Muscimol was involved in synthesis of anticonvulsants such as tiagabine (Gabatril). It was marketed as a therapeutic agent for the treatment of epilepsy.

The chemically related hydroxypyrollidone derivative found in Amanita Muscaria is a known antibiotic and anti-fungal. The hydroxypyrollidone chemical frame is common in some micromycetes, which generally exhibit a potent biological activity against bacteria and other fungi (e.g., aureothrycin, equisetin).

Cycloserine is an antimicrobial tuberculostatic agent that exhibits a carbon backbone similar to muscimol. It is known to induce effects on the central nervous system but with a longer latency period. Somnolence, confusion, and nervousness distinguish untoward effects.

Muscimol is widely used as a ligand to probe GABA receptors and was the lead compound in the development of a range of GABAergic agents, including nipecotic acid, tiagabine, 4,5,6,7-tetrahydroisoxazolo (5,4-c), pyridin-3-ol (gaboxadol), and 4-PIOL. Gaboxadol is currently studied as a potential therapeutic agent in Angelman syndrome. Gaboxadol shows potent, non-opioid analgesic effects. Sedative effects did, however, prevent therapeutic use as an analgesic but were subsequently shown to reflect unique hypnotic properties. Gaboxadol was described as an agent "capable of restoring a normal sleep architecture." Gaboxadol is a conformational analog of muscimol with analgesic and sleep-promoting properties. It was investigated for the treatment of insomnia and has shown activity as an analgesic as well as a novel type of hypnotic that increases non-REM sleep and enhances delta activity.

Transmeningeal muscimol can prevent focal EEG seizures in the rat neocortex without stopping multineural activity in the treated area. Ethanolic extract of Amanita Muscaria shows anti-inflammatory activity and deserves a modern evaluation. Α, β, and β-d-glucan (AM-ASN) isolated from the alkaline extract of the fruiting bodies of Amanita muscaria exhibited significant anti-tumor activity against Sarcoma 180 in mice. The chemical AM-ASN, a beta-glucan, is extremely interesting for its anti-tumor activity.

Fucomannogalactan and glucan isolated from Amanita Muscaria showed inflammatory pain inhibition. Both the homo- and hetero-polysaccharides were evaluated for their anti-inflammatory and anti-nociceptive potential, and they produced potent inhibition of inflammatory pain.

Muscimol has been used to reduce conditioned fear expression in lateral amygdala, to eliminate cortical cell response in ferrets, and to inactivate the lateral magnocellular nucleus of the nidopallium in zebra finches.

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