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How Muscarine Works: Effects, Toxicity, Safety, and Legality
How Muscarine Works: Effects, Toxicity, Safety, and Legality
- Chemical Overview of Muscarine
- Muscarine in Mushrooms
- Mechanism of Action: How Muscarine Affects the Body
- Toxicological Risks
- Muscarine’s Potency Levels in Amanita
- Guidelines for Safe Consumption of Amanita Muscaria
- Legal Status and Public Safety
- A Glimmer of Research Potential
- Bottom Line
Muscarine is a natural alkaloid found in some wild mushrooms, including Amanita muscaria. Its name derives from Amanita muscaria, the iconic red-and-white-spotted mushroom known for its delirium qualities and therapeutic potential. Scientists isolated the compound in the late 1800s as the first parasympathomimetic substance.
Muscarine’s parasympathomimetic qualities mean it activates muscarinic receptors in the nervous system. At specific concentrations, this activation can cause adverse effects, from blurry vision and stomach cramps to convulsions and even death. At the same time, muscarine also has pharmacological potential, with research indicating it could help treat specific brain and lung conditions.
This article explores muscarine's chemical structure, actions in the body, toxicological risks, and safe consumption practices for Amanita mushrooms.
Chemical Overview of Muscarine
Muscarine (2-methyl-3-hydroxy-5-(N,N,N-trimethylammonium) methylente-trahydrofuran chloride) is a quaternary trimethyl ammonium salt compound. Structurally, it is similar to acetylcholine, a neurotransmitter in the mammalian nervous system.
The molecule has a three-dimensional structure and a five-membered ring in the molecular skeleton that contains a quaternary nitrogen important for activating receptors throughout the nervous system.
Muscarine was one of the first known substances that could reproduce some of the effects of stimulating the autonomic nervous system (ANS). This ANS is a network of nerves that regulates involuntary physiologic processes, including heart rate, blood pressure, breathing, and digestion.
The compound predominantly affects the autonomic nervous system by stimulating muscarinic acetylcholine receptors. Binding to these receptors can induce parasympathetic-like responses, including bradycardia (slowed heart rate), miosis (pupil constriction), and increased secretion from glands like the salivary and sweat glands. It can also stimulate smooth muscle contractions, affecting the respiratory and gastrointestinal systems.
Muscarine in Mushrooms
About 100 mushroom species potentially harm humans, and most contain alkaloids like muscarine. Muscarine-containing mushrooms grow worldwide, most commonly in forests throughout the United States, Europe, and Asia.
- Amanita muscaria
- Clitocybe (funnel caps, blewits)
- Inocybe (fiber caps)
- Omphalotus
- Boletus
- Mycena pura
- Entoloma rhodopolium
- Russula
- Lactarius
- Hygrocybe
Muscarine in Amanita muscaria
Scientists first isolated muscarine from the Amanita muscaria mushroom species in the late 1800s. The mushroom’s name comes from the Latin word “musca,” meaning “fly,” referring to how people used it to attract and kill flies. Because of its toxic qualities, Amanita muscaria works well as an insecticide.
However, muscarine is not the primary psychoactive compound in Amanita muscaria. Ibotenic acid and muscimol are. Muscarine’s content in Amanita mushrooms is generally low, often insufficient to produce the parasympathetic effects commonly associated with muscarine.
Mechanism of Action: How Muscarine Affects the Body
Muscarine is chemically similar to acetylcholine, a neurotransmitter that plays a role in memory, muscle contractions, and movement.
Upon ingestion, muscarine activates muscarinic acetylcholine receptors (mAChRs), which are named because they are sensitive to muscarine. Their counterparts, nicotinic receptors, are comparatively unresponsive to muscarine. Together, muscarinic and nicotinic receptors are called cholinergic receptors. They help brain cells grow and stay alive, become specialized, and create connections with other brain cells.
Muscarinic receptors occur throughout the brain, with the highest concentrations in cortical regions, including the hippocampus. These areas are essential in learning and memory. Because of their location and function, these receptors play a role in mental and neurological health issues.
However, overstimulating these receptors can be a problem.
Studies show that simply activating central nervous system muscarinic receptors in animals increases blood pressure, heart rate, and sympathetic outflow (the fight or flight response that increases heart rate and stress).
Muscarinic acetylcholine receptors also occur in:
- Blood vessels
- Heart
- Eyes
- Lungs
- Smooth muscle of the gastrointestinal and urinary tracts
Toxicological Risks
Muscarinic agonists like muscarine can have side effects in humans.
Overstimulating muscarinic receptors at neuromuscular junctions can cause a health issue called a “cholinergic crisis,” also known by the mnemonic “SLUDGE” syndrome, which stands for “salivation, lacrimation, urination, defecation, gastrointestinal distress, and emesis.”
Muscarine overdose is typically rapid, with effects occurring within 30 minutes to two hours. Patients often experience symptoms such as:
- Nausea and vomiting
- Cramps
- Excessive salivation
- Muscular weakness
- Paralysis
- Diarrhea
- Blurry vision
If a high level of muscarine reaches the brain, it can cause severe symptoms, including:
- Tremor
- Convulsions
- Hypothermia
- Hypotension, possibly leading to severe problems associated with reduced coronary blood flow.
Most Amanita muscaria mushrooms do not contain enough muscarine to cause damage. However, ingesting muscarine-rich varieties in rare cases could result in circulatory collapse.
In most cases, recovery occurs within 12 hours, and doctors can counteract and treat the poisoning with atropine sulfate. Promptly administering the antidote via IV can treat severe muscarinic symptoms, such as wheezing and bradycardia (when the heart does not operate correctly and develops an abnormally slow heart rate of less than 60 beats per minute).
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Muscarine’s Potency Levels in Amanita
Muscarine and muscarine-like compounds are present in varying quantities in some mushroom species.
Inocybe and Clitocybe mushrooms contain the most significant muscarine concentrations (up to 1.6%), resulting in higher chances of mushroom poisoning and potentially fatal results.
- According to the available data, about 500 grams of raw Inocybe or Clitocybe mushrooms contain a human lethal dose of muscarine. As little as 10 to 20 grams can lead to severe illness.
In comparison, the muscarine content in Amanita muscaria is much less (around 0.0003% of the mushroom’s fresh weight). Eating raw, unprocessed Amanita muscaria mushrooms still has the potential to make users sick. However, extreme toxicity and fatalities are improbable due to its trace amounts.
- According to a statement from the North American Mycological Association, there have been no “reliably documented cases of death” from toxins in the past 100 years for Amanita muscaria, A. pantherina, A. gemmata, or Amanita multisquamosa mushrooms.
The Amanita species that account for the most deaths due to poisoning are the Death Cap (Amanita phalloides) and the Destroying Angel (Amanita bisporigera). These mushrooms also contain amatoxin, a natural toxin that can cause liver failure. 95% of deaths from mushroom ingestions worldwide are from amatoxin-containing mushrooms.
Guidelines for Safe Consumption of Amanita Muscaria
Amanita muscaria mushrooms aren't lethal, but depending on the muscarine content, they may cause discomfort and confusion. To safely consume Amanita muscaria, most people dry, boil, and otherwise process the mushroom to inactivate the compound. For instance, parboiling the mushrooms twice weakens their toxicity while maintaining the psychoactive effects.
When buying Amanita muscaria products, consumers should steer toward extracts or dried mushrooms from verified sellers focusing on muscimol, the mushroom’s primary psychoactive component. Muscimol is well-tolerated when consumed as a purified extract.
Testing: Although Amanita muscaria is legal in most of the United States, no authority regulates its products. That means Amanita products have no set testing standards and may be unsafe for consumption. Consumers should only purchase from reputable brands that test their products for alkaloid potency and publish a Certificate of Analysis verifying the results.
Dosing: The intensity of Amanita muscaria effects will vary mainly depending on the amount consumed. As with all psychedelic mushrooms, consumers should start with microdose before increasing to heftier doses. Users should take extracts containing no more than 5 mg of muscimol to achieve mild psychoactive or therapeutic effects like relaxation and pain relief. Doses of 1-2 mg are often acceptable for beginners.
Legal Status and Public Safety
Amanita muscaria mushrooms have grown in popularity because they are legal in many places where other psychedelics are not.
For instance, Amanita muscaria compounds like muscarine and muscimol do not appear on the DEA’s controlled substances list, making these mushrooms and their products federally unregulated and legal to buy in most of the United States. On the state level, only Louisiana regulates Amanita muscaria under Louisiana State Act 159, which bans possessing and cultivating Amanita muscaria mushrooms and outlaws preparations intended for human consumption.
Possessing, selling, cultivating, and consuming Amanita muscaria is legal in countries like Ukraine, Australia, and Sweden. On the other hand, some countries, including Romania, the Netherlands, and Thailand, consider these mushrooms prohibited substances.
A Glimmer of Research Potential
Muscarine itself isn't used as a medicine, but scientists are keen on how it affects the nervous system. It was one of the first substances studied for its ability to mimic the action of acetylcholine. Medicines that work like acetylcholine are called "cholinergic," and studying muscarine helps researchers understand these medicines better and maybe even create new ones.
For instance, acetylcholine is involved in processes that underpin some of the most essential central nervous system functions. The muscarinic and nicotinic receptor families that acetylcholine and muscarine interact with have been a research target for at least a quarter-century.
- Muscarinic receptor agonists produce CNS effects, including learning and memory-improving agents. They have implications in possibly treating psychiatric and neurological disorders, such as schizophrenia, bipolar disorder, major depressive disorder (MDD), and substance abuse, as well as neurological diseases, such as Alzheimer's and Parkinson's disease.
- Ongoing studies seek to determine whether these receptors are viable targets for developing future therapeutic agents and medications.
- Muscarine might also have implications in respiratory research for designing anticholinergic drugs that can effectively inhibit the accelerated decline of lung function in patients with COPD (chronic obstructive pulmonary disease).
Bottom Line
Muscarine is an alkaloid found in several mushrooms. The risk of severe and fatal effects is low because it occurs in trace amounts in Amanita muscaria mushrooms. However, other mushroom speicies with high muscarine concentrations can be dangerous and potentially lead to an overdose.
Muscarine’s interaction with receptors in the central nervous system also has potential for specific research opportunities, such as developing new medications to treat brain and lung issues. More studies into understanding and dealing with muscarine’s action in the body could have considerable implications in treating diseases like Alzheimer's, Parkinson’s, COPD, and more.
ACS Laboratory is a leading innovator in testing mushrooms, including Amanita muscaria mushrooms. Brands interested in offering the highest quality Amanita products should contact us about testing today.
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