Psilocybin is a naturally occurring psychedelic compound found in certain species of mushrooms, commonly referred to as "magic mushrooms." For centuries, various cultures and spiritual practices have used these mushrooms for their hallucinogenic properties. Recently, increasing interest in psilocybin has led to a growing body of research and a push for its legalization and use in medical settings. Modern scientific research has focused on the potential therapeutic benefits of psilocybin for a range of mental health conditions, including depression, anxiety, and addiction. 

In this blog, we will explore the history, science, and potential benefits of psilocybin and its potential risks and legal status.

What Is Psilocybin?

Psilocybin is a naturally occurring psychedelic compound. It is the primary active ingredient in psilocybin mushrooms, also known as psychedelic mushrooms or magic mushrooms, capable of producing powerful hallucinations and mystical experiences. 

Psilocybin is a prodrug that is converted into the pharmacologically active compound psilocin in the body by a dephosphorylation reaction.

Psilocybin belongs to a class of psychedelics called tryptamine alkaloids. While some tryptamines are naturally occurring neurotransmitters found in the brains of animals and people (such as serotonin and melatonin), most are psychoactive hallucinogens found in plants and fungi. 

Archaeological evidence suggests that humans have used psilocybin mushrooms as psychedelics for 7,000 years, including Mesoamerican spiritual and religious rituals. Today, psilocybin mushrooms are still some of the most commonly used entheogenic compounds in the U.S. and Europe. 

Mycelial Sources of Psilocybin

Mushrooms, commonly known as magic mushrooms or “shrooms,” are the principal source of psilocybin in nature. More than 180 species of mushrooms contain psilocybin or its derivative, psilocin.

Psilocybin Mushrooms

The most popular psilocybin-containing magic mushrooms include.

• Psilocybe cubensis (Gold Caps, Golden Teachers): The most well-known and widely cultivated psilocybin mushroom
• Psilocybe azurescens (Flying Saucer Mushrooms): Noted as the most potent psilocybin mushroom in the world
• Psilocybe cyanescens (Wavy Caps)
• Psilocybe natalensis (Natal Super Strength)
• Psilocybe baeocystis (Bottle Caps, Knobby Tops, Blue Bells, and Olive Caps)
• Psilocybe semilanceata (Liberty Caps)
• Psilocybe mexicana (Conical Caps)
• Copelandia cyanescens (Panaeolus cyanescens, Blue Meanies)

Psilocybin Chemistry and Mechanisms

Psilocybin  (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine, 4-PO-Psilocin, or 4-PO-HO-DMT) is a prodrug, which means it is a biologically inactive compound that gets converted into an active drug (psilocin) in the body through metabolic processes. 

Psilocybin can be converted into a crystalline powder soluble in water and other polar solvents. Its molecular formula is C12H17N2O4P, indicating that it contains 12 carbon atoms, 17 hydrogen atoms, two nitrogen atoms, four oxygen atoms, and one phosphorus atom. 

Psilocybin and psilocin primarily interact with serotonin receptors in the brain and have an incredibly high affinity for the 5-HT (serotonin) 2A subtype receptors. These brain hubs help integrate sensory experiences, which could explain altered senses and “mystical-like” hallucinatory effects during mushroom trips. 

Psilocybin also deactivates or normalizes hyperactivity of the medial prefrontal cortex (mPFC), which can lead to anti-depressant and anti-anxiety effects.

Psilocybin Effects

Psilocybin’s effects depend on the mushroom species and vary based on an individual’s weight, metabolism, tolerance level, and mindset.

Psilocybin mushrooms cause psychedelic mental effects that include:

• Euphoria
• Visual and mental hallucinations, such as a sense of the world breathing around you
• Distorted vision with vivid colors and tracers
• Perceptual changes, such as halos around objects and geometric patterns 
• Distorted sense of time
• Perceived spiritual experiences
• Ego-loss or self-transcendence

Physical side effects can include:

• Feeling deeply relaxed and calm
• Changes in heart rate (up or down)
• Changes in blood pressure (up or down)
• Nausea
• Increased tendon reflexes
• Tremors
• Dilated pupils
• Restlessness or arousal
• Trouble with coordinated movement

Psilocybin Experience

Brain-imaging studies show that a typical psilocybin mushroom experience (mushroom trip)  is similar to dreaming and occurs in the transitory state between wakefulness and sleep. Users often experience:

• Increased intensity of emotional experiences
• Increased introspection
• Changes in thoughts and emotions
• Openness to usually avoided thoughts and feelings
• Sense of wonder and delight with surroundings
• Sense of peace and connection with the world

A mushroom trip contains four phases, each with its own set of perceptions and observations:

• Ingestion
• Onset
• The trip (peak)
• The comedown

The trip peak typically occurs about two hours after ingestion, resulting in the most intense sensory and psychological shifts. 

After a psilocybin experience, people often report a greater appreciation of music, art, and nature, increased creativity and imagination, and more tolerance for others.

How to Consume Psilocybin Mushrooms

Most people consume psilocybin mushrooms in whole, dried form and would say that they don’t taste great. There are several options to mask the flavor, such as

• Brewing the mushrooms into a tea
• Mixing them with Nutella or peanut butter
• Blend them with a juice or smoothie
• Mixing them with citrus juice (known as Lemon Tekking)
• Grinding them up into capsules

Each of these methods will change the onset of effects. For example, drinking the mushrooms in tea will have faster effects than eating whole mushrooms, while mushroom capsules will take effect later. 

Psilocybin Dosing 

Psilocybin is about 100 times less potent than LSD and ten times less potent than mescaline. 

Dosing varies from person to person, but the threshold dose for feeling mild effects of dried mushrooms is typically 0.2-0.5 grams. 

Microdosing (0.1-0.3 grams)

A microdose is typically a sub-perceptvie dose people incorporate into their weekly routines. Individuals who regularly microdose psilocybin mushrooms report many positive effects, including:

• Higher levels of creativity
• Emotional stability
• More energy
• Increased focus
• Improved relational skills
• Reduced anxiety, stress, and depression

Moderate dose (1-2.5 grams)

A moderate dose typically produces effects that last from three to six hours. Users can still grasp their surroundings on a moderate dose. At the same time, they’ll also feel highly altered. Common effects include:

• Visual hallucinations, including patterns and fractals
• Distorted time and depth perception
• Life-changing introspective or philosophical insights
• The increased flow of ideas
• Enhanced appreciation for music, art, etc.
• Amplification of emotions, whether good or bad
• Sensitivity to light
• Disorientation
• Difficulty with cognitive tasks
• Dizziness and nausea

Mega-dose (macro-dosing aka heroic dose) (5 grams or more)

A mega-dose results in complete disconnection from reality. Experts recommend users to have a sitter or companion due to the likelihood of intense hallucinations and extreme difficulty with cognitive tasks. Common effects include:

• Mystical experience and intense feelings of wonder
• Life-changing introspective or philosophical insights
• Ego death
• Memories coming to life
• Time becoming meaningless
• Compromised motor functions and disorientation 
• Extreme difficulty with cognitive tasks
• Dizziness and nausea

Psilocybin Benefits

Psychedelic mushrooms have a long-standing reputation as agents for healing and change. A new wave of psilocybin research over the past two decades has brought psychedelic health benefits back to the forefront.  

To date, over 27,000 scientific articles on psychedelic drugs have been published, with over 1,000 on psilocybin. 

These developments reignited worldwide interest in psilocybin, showing it has promise for treating various ailments, including:

• Obsessive-compulsive disorders
• Anxiety
• Depression
• Post-traumatic stress disorder
• Addiction
• Cluster headaches

Psilocybin to treat mood and anxiety disorders

• Clinical trials testing the effects of psilocybin on patients with depression and life-threatening cancer diagnoses showed significant improvements in stress and anxiety. 

• Another study by a prestigious research group in London shows psilocybin can benefit those with severe treatment-resistant depression.

• In a small study on obsessive-compulsive disorder (OCD) patients who didn’t respond to conventional drug therapy, Psilocybin treatment reduced symptoms by 23% to 100%

• The U.S. Food and Drug Administration (USFDA) granted psilocybin “breakthrough therapy” status, approving several psilocybin trials and drug treatments for treatment-resistant depression and major depressive disorder (MDD), including those by Compass Pathways, Johnson and Johnson, and Usona Institute. 

Psilocybin to treat addiction

• A 2015 study showed psilocybin could help treat alcoholism as part of an assisted treatment plan.

• In a pilot study of 15 tobacco smokers, psilocybin helped 12 (80%) successfully quit. Conventional quitting methods have about a 35% success rate by comparison.

Psilocybin to treat cluster headaches

• A recent survey reported that psilocybin effectively treated cluster headaches—often described as the most painful and disruptive type—in almost 50% of patients. More clinical studies into this use are underway.

Psilocybin Risks & Myths

Myths about psilocybin and magic mushroom claim they can cause permanent brain damage or make people crazy. According to the 2017 Global Drug Survey, psilocybin is one of the safest psychoactive substances available, with only 0.2% of users needing emergency medical treatment. Of course, every drug comes with some risks. 

Psilocybin can cause some physical side effects at the outset and during a trip, such as: 

• Nausea
• Perspiration
• Numbing
• Tremors

A survey published in Substance Abuse and Misuse found that paranoia and anxiety at some point were common in up to 33% of people during their trip.

A “bad trip” can also happen and might cause effects such as:

• Dysphoric hallucinations
• Uncontrollable paranoia
• Reckless behavior

Although rare, Hallucinogen Persisting Perception Disorder (HPPD), commonly known as “flashbacks,” can occur in some users. HPPD is unique to psychedelics and involves perceptual changes in the weeks or months following psilocybin (or other psychedelics). However, it does not cause permanent physical changes or neurological damage.

Psilocybin Legality

The DEA lists psilocybin mushrooms as a Schedule I controlled substance, making the substance federally banned in the U.S. However, it is legal to possess and grow magic mushrooms in certain cities and states around the country, such as Oregon, Denver, Washington, DC, and Oakland. The FDA designating psilocybin as a “breakthrough therapy” for depression and allowing controlled human studies could make it legal by prescription or accelerate changing its federal legal status. 

Bottom Line

The active ingredient in magic mushrooms, psilocybin is one of the world's most well-known and used psychedelics. It causes vivid hallucinations, can open doors to creativity and life-changing insights and is a potential treatment for mood disorders and addiction. 

With magic mushroom use increasing in popularity, mycelial enthusiasts, medicinal patients, and DEA-licensed manufacturers want to be better informed about products and their active ingredients. ACS Laboratory has recently developed a method to test Psilocybin, psilocin and 5 other tryptamines.

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