Starting with Psilocybin
Psilocybin containing mushrooms have emerged as a leading contender in the forefront of cutting-edge psychedelic research, capturing attention with groundbreaking studies showcasing its potential to transform mental health. In the public view, psilocin is often left out by the general public discussion which is something of an oversight. Psilocin is the bio-active active version of psilocybin responsible for much of the hallucinogenic properties of psilocybin mushrooms. Psilocybin is the prodrug of psilocin. When people consume magic mushrooms, the body converts psilocybin into psilocin (the bioactive compound) through metabolic processes.
Psilocin Chemistry and Active Mechanisms
Psilocin (also known as 4-HO-DMT, 4-hydroxy DMT, 4-hydroxy-N,N-dimethyltryptamine) and psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) are similar forms of tryptamine alkaloids.
These compounds work in the brain as serotonin "activators," which means they bind to and interact with serotonin receptors. Specifically, they attach to receptors like 5-HT2A, 5-HT2C, and 5-HT1A, which are all involved in regulating things like visual stimulation, decision-making, and mood. To use a metaphor, the receptors are like light-switches and the neurotransmitters flip these switches that control how you see things, make choices, and your mood.
Psilocybin isn’t active on its own. That’s because it has a phosphate chain attached to it. When you eat it, your body will work on the chemical through this process called dephosphorylation which removes that phosphate group. That’s when it converts into psilocin, which is the compound responsible for the psychoactive effects.
Dosing
Dried mushrooms are the most common way to consume psilocybin containing mushrooms. Dosing ranges from micro-dosing to macro-dosing often referred to as a “heroic” dose. Most psilocybin mushrooms are at appromiately a 1% potency, with that assumption dosing is typically as follows:
- Microdose: 0.1-0.3 gram
- Low dose: about 1 gram (10 mg of psilocybin)
- Medium dose: about 1.75 grams (17.5 mg of psilocybin)
- High dose: about 3.5 grams (35 mg of psilocybin)
- Mega (maco) dose: 5 grams or more (50 mg of psilocybin)
Psilocybin and Psilocin Effects
Psilocin reacts with the mentioned excitatory and inhibitory receptors. The most common effects on a person are:
- Euphoria
- Increased heartbeat
- Dilated pupils
- Restlessness
- Visuals with eyes open and closed
- Hearing colors and seeing sounds
Psilocin Strength and Effects
As with all psychedelics there are a great number of myths about psilocybin and psilocin. Referencing the 2017 Global Drug Survey, psilocybin is one of the safest psychoactive substances available, with only 0.2% of users needing emergency medical treatment a rate five times lower than that for MDMA, LSD and cocaine.
Risks from psilocin and psilocybin are few and usually related to adverse yet temporary physical reactions, such as:
- Headache
- Sweating
- Chills
- Nausea
- Anxiety
Anyone who has ever heard of psilocybin mushrooms has also heard of “a bad trip”. Effects of a bad trip might look like:
- Dysphoric hallucinations
- Uncontrollable paranoia
- Reckless behavior
Legality
The DEA lists both psilocybin and psilocin as Schedule 1 substances under the Controlled Substances Act. This makes the compounds and the mushrooms that contain them federally banned in the United States. However, it is now legal to possess and grow psilocybin containing mushrooms in certain cities and states around the country such as Oregon, Colorado, Washington DC and Oakland, California.
The clandestine Amanita muscaria
Amanita muscaria, known for its iconic red cap adorned with white spots has captured the interest of humanity for centuries and yet has maintained a clandestine relationship with Western Culture; it is only relatively recently that it is becoming more well known. Even with its popularity being the subject of Disney's "Fantasia Dancing Mushroom" as well as as being the mushroom of the Nintendo Mario universe, it has maintained a high level of obscurity and it is frequently mischaracterized having more myths and misconceptions about it than any other member of the fungal kingdom. Even still, in scientific circles it has been the subject of a great deal of research primarily due to its two naturally occurring psychoactive compounds: muscimol and ibotenic acid and their therapeutic potential.
How does Muscimol work - is it psychedelic?
Muscimol, the primary psychoactive compound found in Amanita muscaria, was first isolated in the 1960s. This colorless, highly water-soluble crystalline substance functions as a selective GABA agonist, activating both the GABA-A and GABA-C receptors. GABA, a neurotransmitter renowned for its calming effects, regulates various bodily functions including mood, anxiety, sleep, and pain-management. If GABA were personified, it would embody the serene presence of a "yogi," nurturing inner tranquility through calm meditation.
Muscimol distinguishes itself from psilocin by primarily interacting with the neurotransmitter GABA many psychedelics such as psilocin interact with the earlier mentioned serotonin transmitter, 5-HT2A receptor. When muscimol interacts with your GABA receptors it reduces central nervous system activity, specifically it blocks the neuronal and glial uptake of GABA resulting in increased serotonin and acetylcholine levels and lowered norepinephrine. That's a lot of big words about neurotransmitters, let me further explain what that means.
Acetylcholine is a neurotransmitter that functions in the nervous system to facilitate communication between neurons and muscle contractions. If it were a character you might think of it as the sure-footed messenger, delivering signals for various physiological processes including memory, attention and learning.
Norepinephrine also known as noradrenaline is a neurotransmitter that plays a significant role in the body’s fight-or-flight response. If it were a character we might imagine it as an alarm-system robot protecting us with automatic responses. In the modern world, individuals often face a multitude of stressors originating from sources such as the workplace or our constant connectivity with information overload. The cumulative effect of these stressors can have significant implications for physical and mental health. While the fight-or-flight response and stress are fundamental aspects of human physiology our understanding of these phenomena continues to evolve shaping how we approach stress management and promote resilience in individuals.
Dosage
A minimal dose of 6 mg is often suggested to elicit symptoms of central nervous system activity from muscimol. In her book "Microdosing with Amanita Muscaria", Dr. Masha, M.D., suggested most of her participants were taking doses typically ranging from 1 to 2 milligrams of muscimol, are commonly associated with subtle calming effects without notable alterations in consciousness.
Muscimol Strength and Effects
Muscimol offers a distinct psychedelic experience that differs from the vivid visual patterns and intense body sensations commonly associated with psilocybin-containing magic mushrooms.
Instead, muscimol tends to induce a subtler yet profound effect on the mind and body. Users often report heightened sensory perception, a deep sense of relaxation, and vivid dreams during sleep.
What sets muscimol apart is its unique mechanism of action, which shares similarities with benzodiazepines such as Valium and Xanax. Like these medications, muscimol acts as a GABA agonist, meaning it enhances the activity of the neurotransmitter GABA in the brain. Studies suggest that muscimol may be 120-140% more effective than GABA itself.
Referencing “Microdosing with Amanita Muscaria” participants attested to several medicinal benefits, including:
- Relaxing euphoria
- Analgesia (pain relief)
- Energy and virility
- Creativity boost
- Improved sleep quality
- Relief for skin conditions
- Depression and anxiety relief
What other compounds does Amanita muscaria contain?
Muscimol isn't the sole psychoactive compound found in Amanita muscaria mushrooms; they also contain ibotenic acid. Ibotenic acid serves as a precursor to muscimol and is classified as a toxin by the FDA. When these mushrooms are dried, processed, or ingested, the ibotenic acid they contain can undergo decarboxylation, a process where the carboxyl group (-COOH) is removed, converting it into muscimol. This transformation can occur through heat, drying, boiling in water, or even the acidic environment of the stomach.
Ibotenic acid activates glutamate NDMA receptors, which play a role in enhancing neural plasticity associated with learning and memory. To use an image these receptors serve as a bridge between our primal instincts (often termed the "lizard brain") and our higher cognitive functions think of those like a thriving metropolis. In small doses, this interaction with glutamate can be beneficial since our bodies naturally require glutamate. However, excessive stimulation from a large amount of ibotenic acid can lead to adverse effects such as confusion, delirium, gastrointestinal issues, and a sense of intoxication.
Fortunately, these symptoms typically diminish as the body converts ibotenic acid to muscimol. It's far more preferable for this conversion to occur through processing methods rather than experiencing the adverse effects directly.
Finally, important to note that there's a great deal of variability in the potency of one Amanita muscaria cap to the next in its concentrations of ibotenic and muscimol. To address this challenge, decarboxylating a larger quantity of dried mushrooms can help achieve greater consistency through an "averaging effect" across the batch.
Legality
Muscimol and ibotenic acid do not appear on the DEA’s controlled substance list, making them federally unregulated. On the state level, only Louisiana regulates muscimol under Louisiana Act 159, which bans the possession and cultivation of Amanita muscaria mushrooms and outlaws preparations intended for human consumption.
The Federal Drug Administration (FDA) does not specifically approve or regulate mushrooms for consumption, such as cremini, portobello, or Amanita muscaria, as they do for other food additives or pharmaceuticals.
Is Muscimol and Ibotenic Acid Safe?
Research for muscimol continues to be looking at it from a therapeutic opportunity. As stated earlier, ibotenic acid is classified as a toxin by the FDA. Fresh Amanita muscaria mushroom contain more ibotenic acid than muscimol. The ratio of ibotenic acid to muscimol is about 9:1 in a fresh mushroom samples and will convert in a ratio of about 1:1 after decarboxylation to muscimol. Producers of Amanita muscaria products employ techniques to convert or ‘decarboxylate’ the ibotenic acid to muscimol for both efficacy and safety processes. When ingesting Amanita muscara in large quantities mainly containing ibotenic acid, one could experience adverse effects, such as:
- Sweating
- Nausea
- Cramps
- Loss of balance
- Involuntary bodily movements
In order to avoid these side-effects, a common practice among those who work with Amanita muscaria is to do what is called a full-decarboxylation in which the ibotenic acid is not present in any test-able quantity. This in general improves both efficacy and safety.
Conclusion
Both mushrooms offer benefits and have incredibly different pharmacological profiles and interact with our brains in unique ways. The remarkable thing that these two mushrooms do share is that they contain novel alkaloids that are not found elsewhere in nature.
