Muscimol
Encyclopedia
Muscimol is the major psychoactive alkaloid present in many mushrooms of the Amanita
genus. Unlike psilocin
(the active metabolite of psilocybin
, found in psilocybin mushroom
s), which is a serotonergic psychedelic
and agonist for the 5-HT2A receptor
set, muscimol is a potent, selective agonist
for the GABAA receptor set and is a deliriant
as a opposed to a psychedelic
(see hallucinogens).
and its derivative muscimol. Muscimol is the product of the decarboxylation
or drying of ibotenic acid and it is thought that muscimol is as much as ten times as potent as ibotenic acid.
, Amanita pantherina, and Amanita gemmata
, along with muscarine
, muscazone
, and ibotenic acid
. A. muscaria and A. pantherina are not considered safe for human consumption; poisonings have occurred from A. muscaria and A. pantherina as well. In A. muscaria
, the layer just below the skin of the cap contains the highest amount of muscimol, and is therefore the most psychoactive portion.
agonist
, activating the receptor
for the brain's major inhibitory neurotransmitter
, GABA
. Muscimol actually binds to the same site on the GABAA receptor complex as GABA itself, as opposed to other GABAergic drugs such as barbiturates and benzodiazepines which bind to separate regulatory sites. GABAA receptors are widely distributed in the brain, and so when muscimol is administered, it alters neuronal activity in multiple regions including the cerebral cortex
, hippocampus
, and cerebellum
.
While muscimol is conventionally thought of as a selective GABAA agonist, it is also a potent partial agonist at the GABAC receptor, and so its range of effects results from a combined action at both targets.
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.
During a test involving rabbits connected to an EEG
, muscimol showed a distinctly synchronized EEG tracing. This is substantially different from indolic
psychedelics, as brainwave patterns will generally show a desynchronization. In higher doses (2 mg/kg), the EEG will show characteristic spikes.
If consumed, muscimol will pass through the human body, and be excreted unchanged in the subject's urine.
The psychoactive dose of muscimol is around 10–15 mg for a normal person. A Guide to British Psilocybin Mushrooms by Richard Cooper published in 1977 recommends a smaller dose, 8.5 mg, and suggests that it is possible for this amount to be present in as little as 1 g of dried A. muscaria. A correct dose may be difficult to determine because potency varies dramatically from one mushroom to the next.
state. The hallucinogenic effect produced by muscimol is most closely comparable to the hallucinogenic side effects produced by some other GABAergic drugs such as zolpidem
.http://www.ncbi.nlm.nih.gov/pubmed/21093461
Amanita
The genus Amanita contains about 600 species of agarics including some of the most toxic known mushrooms found worldwide. This genus is responsible for approximately 95% of the fatalities resulting from mushroom poisoning, with the death cap accounting for about 50% on its own...
genus. Unlike psilocin
Psilocin
Psilocin , an aromatic compound, sometimes also spelled psilocine, psilocyn, or psilotsin, is a psychedelic mushroom alkaloid. It is found in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin...
(the active metabolite of psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...
, found in psilocybin mushroom
Psilocybin mushroom
Psilocybin mushrooms are fungi that contain the psychoactive compounds psilocybin and psilocin. There are multiple colloquial terms for psilocybin mushrooms, the most common being shrooms or magic mushrooms....
s), which is a serotonergic psychedelic
Serotonergic psychedelic
Serotonergic psychedelics are a class of hallucinogenic drugs with a method of action strongly tied to the serotonin neurotransmitter...
and agonist for the 5-HT2A receptor
5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
set, muscimol is a potent, selective agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
for the GABAA receptor set and is a deliriant
Deliriant
The deliriants are a special class of acetylcholine-inhibitor hallucinogen. The term was introduced by David F. Duncan and Robert S...
as a opposed to a psychedelic
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...
(see hallucinogens).
Chemistry
Amanita muscaria contains two main active ingredients, ibotenic acidIbotenic acid
Ibotenic acid is a chemical compound that is naturally occurring in the mushrooms Amanita muscaria and Amanita pantherina, among others...
and its derivative muscimol. Muscimol is the product of the decarboxylation
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
or drying of ibotenic acid and it is thought that muscimol is as much as ten times as potent as ibotenic acid.
Biology
Muscimol is produced naturally in the mushrooms Amanita muscariaAmanita muscaria
Amanita muscaria, commonly known as the fly agaric or fly amanita , is a poisonous and psychoactive basidiomycete fungus, one of many in the genus Amanita...
, Amanita pantherina, and Amanita gemmata
Amanita gemmata
Amanita gemmata, commonly known as the gemmed Amanita or the jonquil Amanita, is a mushroom of the genus Amanita, a genus of fungi including some of the most deadly mushrooms, as well as notably psychoactive mushrooms. A. gemmata resembles the false death cap, tawny grisette and panther cap mushrooms...
, along with muscarine
Muscarine
Muscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested...
, muscazone
Muscazone
Muscazone is a toxic psychoactive chemical compound. It is an amino acid found in European fly agaric mushrooms....
, and ibotenic acid
Ibotenic acid
Ibotenic acid is a chemical compound that is naturally occurring in the mushrooms Amanita muscaria and Amanita pantherina, among others...
. A. muscaria and A. pantherina are not considered safe for human consumption; poisonings have occurred from A. muscaria and A. pantherina as well. In A. muscaria
Amanita muscaria
Amanita muscaria, commonly known as the fly agaric or fly amanita , is a poisonous and psychoactive basidiomycete fungus, one of many in the genus Amanita...
, the layer just below the skin of the cap contains the highest amount of muscimol, and is therefore the most psychoactive portion.
Pharmacology
Muscimol is a potent GABAAGABA A receptor
The GABAA receptor is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid , the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in...
agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
, activating the receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
for the brain's major inhibitory neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
, GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
. Muscimol actually binds to the same site on the GABAA receptor complex as GABA itself, as opposed to other GABAergic drugs such as barbiturates and benzodiazepines which bind to separate regulatory sites. GABAA receptors are widely distributed in the brain, and so when muscimol is administered, it alters neuronal activity in multiple regions including the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
, and cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
.
While muscimol is conventionally thought of as a selective GABAA agonist, it is also a potent partial agonist at the GABAC receptor, and so its range of effects results from a combined action at both targets.
In patients with Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
and chronic schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, oral doses of muscimol have been found to cause a rise of both prolactin and growth hormone.
During a test involving rabbits connected to an EEG
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
, muscimol showed a distinctly synchronized EEG tracing. This is substantially different from indolic
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...
psychedelics, as brainwave patterns will generally show a desynchronization. In higher doses (2 mg/kg), the EEG will show characteristic spikes.
If consumed, muscimol will pass through the human body, and be excreted unchanged in the subject's urine.
The psychoactive dose of muscimol is around 10–15 mg for a normal person. A Guide to British Psilocybin Mushrooms by Richard Cooper published in 1977 recommends a smaller dose, 8.5 mg, and suggests that it is possible for this amount to be present in as little as 1 g of dried A. muscaria. A correct dose may be difficult to determine because potency varies dramatically from one mushroom to the next.
Toxicity
The in mice is 3.8 mg/kg s.c, 2.5 mg/kg i.p. The LD50 rats is 4.5 mg/kg i.v, 45 mg/kg orally.Effects
The effects of muscimol are substantially different from Psilocybe mushroom alkaloids, as the chemicals target separate parts of the brain. Muscimol has been shown to lack "structured" hallucinations in most cases, and the effects are frequently compared to a lucid dreamLucid dreaming
A lucid dream is a dream in which one is aware that one is dreaming. The term was coined by the Dutch psychiatrist and writer Frederik van Eeden . In a lucid dream, the dreamer can actively participate in and manipulate imaginary experiences in the dream environment. Lucid dreams can seem real and...
state. The hallucinogenic effect produced by muscimol is most closely comparable to the hallucinogenic side effects produced by some other GABAergic drugs such as zolpidem
Zolpidem
Zolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
.http://www.ncbi.nlm.nih.gov/pubmed/21093461
See also
- Psychedelic drugPsychedelic drugA psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...
- Psychoactive drugPsychoactive drugA psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...
- Amanita muscariaAmanita muscariaAmanita muscaria, commonly known as the fly agaric or fly amanita , is a poisonous and psychoactive basidiomycete fungus, one of many in the genus Amanita...
- Ibotenic acidIbotenic acidIbotenic acid is a chemical compound that is naturally occurring in the mushrooms Amanita muscaria and Amanita pantherina, among others...
- List of Entheogens