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Specification
Product Name: 4-PO-DMT
IUPAC Name: 3-[2-(Dimethylamino)ethyl]-1H-indol-4-ol
Other Names: Psilocybin, Psilocybin mushrooms, Magic Mushrooms, Shrooms, 4-PO-DMT
Molecular Formula: None
Molar Mass: 237.26 g·mol−1
Effect: stimulant, psychedelic
Purity of the substance: 99.9%
Physical properties: Crystals, Powder
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Table of Contents

  1. Introduction
  2. Dosage and Preparation
  3. Research
  4. Legal Status
  5. FAQ

Summary

Psilocybin mushrooms, also known as magic mushrooms, psychedelic mushrooms, or shrooms, encompass a diverse family of psychoactive fungi containing psilocybin, a potent psychedelic compound belonging to the tryptamine class. Despite their widespread use and intriguing effects, the precise mechanism of action remains incompletely understood, although it is believed to involve binding activity at serotonin receptors.

History and Classification

Psilocybin mushrooms have a global presence, with over 200 species taxonomically identified, the most potent of which are classified under the genus Psilocybe. Evidence from prehistoric rock art suggests their historical usage by various human cultures predates recorded history. Introduced to the Western world in the 1950s, they garnered significant attention, particularly during the counterculture movement of the 1960s alongside LSD. However, societal backlash led to their prohibition in 1970.

Contemporary Usage and Research

Despite prohibition, psilocybin mushrooms remain one of the most widely used psychedelic substances, partly due to their ease of personal cultivation and harvesting. In recent years, they have regained attention within the context of the "psychedelic renaissance," undergoing investigation for their potential therapeutic benefits in treating conditions such as anxiety, depression, addiction, and other mental disorders.

Effects and Characteristics

Psilocybin mushrooms induce a range of subjective effects, including visual geometry, hallucinations, time distortion, enhanced introspection, conceptual thinking, euphoria, and ego loss. The intensity and duration of these effects can vary significantly depending on factors such as species and batch, complicating standardized dosing guidelines. Users often describe experiences as entheogenic, mystical, or transpersonal, fostering self-reflection and personal growth.

Contrasting Qualities

In contrast to other psychedelics like LSD, mescaline, and 2C-B, which may be characterized as stimulating and cerebral, psilocybin mushrooms are often described as having an earthy, subliminal, or dream-like quality. They also tend to produce more emotion enhancement, time distortion, and ego loss, along with increased nausea, confusion, and sedation.

Safety Considerations

While psilocybin mushrooms have low abuse potential and are not physiologically toxic or addictive, users should be aware of potential adverse psychological reactions, including severe anxiety, paranoia, delusions, and psychosis, especially among individuals predisposed to mental disorders. Harm reduction practices are highly recommended for those considering the use of this substance.

History and Culture

Ancient Usage and Rituals

Evidence suggests that psychoactive mushrooms have been integral to human religious ceremonies for millennia. In Mesoamerica, their ritualistic consumption dates back at least 3000 years. Murals discovered in the Sahara desert depict horned beings with mushroom-like objects, dating as far back as 9000 to 7000 BCE. Similarly, 6000-year-old pictographs near Villar del Humo in Spain depict mushrooms identified as Psilocybe hispanica, a local hallucinogenic species. Archaeological artifacts from Mexico indicate ritualistic use among Mayan and Aztec cultures, with the mushrooms referred to as "teonanácatl," meaning "God's flesh" in the Aztec language, Nahuatl.

Encounter with the West

Spanish explorers encountering the New World in the 16th century documented the ceremonial use of mushrooms among indigenous populations. However, Spanish colonization suppressed traditional practices, including mushroom rituals, for centuries. It wasn't until the 20th century that Western interest in psychedelic mushrooms rekindled.

Wasson's Discovery

In the mid-20th century, R. Gordon Wasson, an amateur ethnomycologist, studied the ritualistic use of psychoactive mushrooms in Mexico. In 1957, his experiences were detailed in "Seeking the Magic Mushroom," published in Life magazine. Collaborating with French mycologist Roger Heim, they identified several mushroom species, including Psilocybe, as sources of hallucinogenic compounds. Samples were sent to Albert Hofmann, known for synthesizing LSD, who isolated psilocybin, the primary psychoactive component.

Academic Exploration and Controversy

Psilocybin gained academic attention in the early 1960s, notably through the Harvard Psilocybin Project led by Timothy Leary, Ralph Metzner, and Richard Alpert. While initial studies showed promise, advocating for widespread psychedelic use led to Leary's dismissal from Harvard and increasing legal restrictions on psychedelics.

Legal Restrictions and Cultural Shifts

In response to growing concerns about psychedelic misuse, laws prohibiting hallucinogenic substances were enacted in the United States in 1966, followed by stricter regulations and categorization as Schedule I drugs in 1970. Despite these restrictions, interest in psychedelics persisted, leading to the release of influential books like "Psilocybin Magic Mushroom Grower's Guide" by Terence McKenna in 1976 and "Psilocybe Mushrooms & Their Allies" by Paul Stamets in 1978.

Contemporary Research and Resurgence

In the 1990s, psychedelic research experienced a resurgence, particularly in Europe, driven by advancements in neuroscience and brain imaging technology. Recent studies in the United States have further propelled psilocybin into the mainstream, attracting attention from both scientific and popular communities.

Common Names and Modern Research

Common Names

Psilocybin mushrooms are known by various names, including psychedelic mushrooms, magic mushrooms, shrooms, magic truffles, and boomers. The combination of psilocybin with MDMA is termed "hippie-flipping."

Neurogenesis and Psychoplastogen Properties

Recent research has uncovered intriguing properties of psilocybin. Studies suggest that low doses of psilocybin may promote neurogenesis in the hippocampus, while higher doses have the opposite effect. Additionally, psilocybin is classified as a psychoplastogen, capable of inducing rapid and sustained neuroplasticity, potentially offering therapeutic benefits in psychiatric disorders.

Chemistry

Psilocybin and Psilocin: Molecular Structures

Psilocybin, scientifically known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), serves as a prodrug that undergoes conversion into the active compound psilocin within the body through a dephosphorylation reaction mediated by alkaline phosphatase enzymes. Both psilocybin and psilocin belong to the class of organic tryptamine compounds. They exhibit chemical resemblance to the amino acid tryptophan and structural similarity to the neurotransmitter serotonin.

Structural Characteristics

Tryptamines share a foundational structure consisting of a bicyclic indole heterocycle linked at R3 to an amino group via an ethyl side chain. Psilocybin features substitution at R4 of its indole heterocycle with a phosphoryloxy (-PO) functional group. Additionally, it possesses two methyl groups CH3- bound to the terminal amine RN. This configuration renders psilocybin the 4-phosphoryloxy ring-substituted analog of DMT.

Physical Properties

In their pure forms, psilocybin and psilocin manifest as white crystalline powders. They exhibit susceptibility to degradation in light, particularly when in solution; however, their stability remains robust at low temperatures in the absence of light under an inert atmosphere.

Pharmacology

Mechanism of Action

Psilocybin functions as a prodrug, necessitating conversion into psilocin within the body to elicit its effects. Upon ingestion, alkaline phosphatase and nonspecific esterase enzymes in the intestinal mucosa catalyze the dephosphorylation of psilocybin into psilocin.

Receptor Activity

The psychedelic effects of psilocin are attributed to its agonistic activity on serotonin 5-HT2A/C and 5-HT1A receptors. While activation of 5-HT2A receptors is deemed essential for hallucinogenic effects, the precise involvement of other receptor subtypes remains less elucidated.

Neurotransmitter Systems

In contrast to LSD, psilocin exerts negligible influence on dopamine receptors and primarily impacts the noradrenergic system only at high doses.

Functional Imaging Studies

Functional magnetic resonance imaging (fMRI) studies have indicated that psilocybin possesses a modulating effect on specific brain regions, notably the Default Mode Network.

Dosage

Threshold

  • Psilocybin: 2.5 mg

Light

  • Psilocybin: 2.5 - 10 mg

Common

  • Psilocybin: 10 - 25 mg

Strong

  • Psilocybin: 25 - 50 mg

Heavy

  • Psilocybin: 50 mg and above

Subjective Effects

The headspace induced by psilocybin mushrooms is commonly described as deeply relaxing, profound, and stoning in nature compared to more stimulating psychedelics such as LSD or 2C-B. Additionally, they are perceived as less clear-headed than other commonly used tryptamines such as 4-AcO-DMT, DMT, and ayahuasca. This distinction may be attributed to the presence of other alkaloids like norbaeocystin.

Disclaimer: The effects detailed below reference the Subjective Effect Index (SEI), a collection of anecdotal user reports and personal analyses from contributors to PsychonautWiki. Therefore, they should be approached with a degree of skepticism.

It should also be noted that these effects may not occur predictably or reliably; however, higher doses are more likely to elicit the full spectrum of effects. Conversely, adverse effects become increasingly probable with higher doses and may include addiction, severe injury, or death.

Physical Effects

  • Sedation: Psilocybin mushrooms are often reported to induce relaxation, a stoning sensation, and mild sedation. This sedation is frequently accompanied by excessive yawning.
  • Spontaneous Bodily Sensations: Users commonly experience a "body high" characterized by a pleasurable, soft, and all-encompassing tingling sensation or glow that intensifies with onset and peaks. This sensation can evoke feelings of euphoria and tranquility or heaviness and immobility depending on the dose and setting.
  • Perception of Bodily Heaviness: Psilocybin experiences often entail a sense of bodily heaviness, particularly during the initial phase. This sensation discourages movement and is more pronounced with certain species like Psilocybe azurescens.
  • Tactile Enhancement: While less prominent than with LSD or 2C-B, psilocybin induces tactile enhancement, often described as primitive and accompanied by slight itchiness or tickling sensations on the skin.
  • Changes in Felt Bodily Form: Users may feel physically connected to or conjoined with objects, accompanied by a sense of warmth or unity, particularly around the peak of the experience.
  • Pain Relief: Psilocybin may reduce inflammation and alter sensory processing, resulting in pain relief, albeit less intense than with LSD. However, increased pain perception is also possible.
  • Nausea: Nausea can be minimized or avoided by consuming psilocybin mushrooms on an empty stomach. It's recommended to fast for 6 to 8 hours beforehand or have a light meal 3 to 4 hours prior if feeling fatigued.
  • Changes in Felt Gravity
  • Excessive Yawning
  • Watery Eyes
  • Frequent Urination
  • Muscle Contractions
  • Olfactory Hallucination
  • Pupil Dilation
  • Runny Nose
  • Increased Salivation
  • Brain Zaps: Rare but possible, especially for individuals susceptible to serotonin-releasing agents like MDMA.
  • Seizure: While rare, seizures may occur, particularly in predisposed individuals under physically demanding conditions.

Visual Effects

  • Enhancements
    • Colour Enhancement: Psilocybin may intensify colours relative to other psychedelics.
    • Pattern Recognition Enhancement
    • Visual Acuity Enhancement: Prominent at lower doses but suppressed at higher doses.
  • Distortions
    • Drifting: Detailed, realistic, slow, and smooth motion.
    • Colour Shifting
    • Colour Tinting
    • Visual Haze
    • Diffraction
    • Tracers
    • After Images
    • Symmetrical Texture Repetition
    • Perspective Distortions
    • Depth Perception Distortions
    • Recursion
    • Environmental Orbism
    • Scenery Slicing
    • Geometry: The visual geometry of psilocybin mushrooms resembles that of 4-AcO-DMT, ayahuasca, and 2C-E more than LSD or 2C-B. It's intricate, abstract, organic, brightly lit, multicoloured, glossy, soft-edged, large, slow-moving, smooth, rounded, non-immersive, and consistent in intensity. At higher doses, it's more likely to result in Level 8B visual geometry.

Hallucinatory States

  • Machinescapes
  • Transformations
  • Internal Hallucination: Common in dark environments at higher doses, characterized by lucid believability, interactive style, and diverse thematic content.
  • External Hallucination: More prevalent in dark settings, similar to internal hallucination in nature and theme.

Cognitive Effects

Emotion Enhancement

  • Psilocybin mushrooms induce a more prominent, consistent, and profound enhancement of emotions compared to other traditional psychedelics like mescaline or LSD. This can lead to strong feelings of compassion, urgency, and sporadic moments of intense emotional significance, periodically affected by cycles of enhancement and suppression.

Empathy, Affection, and Sociability Enhancement

  • Unlike MDMA and other entactogens, the enhancement of empathy, affection, and sociability induced by psilocybin feels less forced and more natural. Sociability enhancement is particularly emotional and occurs less frequently.

Euthymia

  • Psilocybin, when combined with psychotherapy treatment, acutely manifests as euthymia, outperforming "gold standard" treatments for several mental health problems.

Language Suppression

  • Psilocybin may lead to a perceived inability or unwillingness to talk aloud despite coherent thoughts within one's internal narrative, especially among inexperienced users.

Analysis Enhancement

  • Users often experience consistent enhancement of analysis and introspection.

Enhancement and Suppression Cycles

  • Psilocybin induces waves of stimulated and profound thinking followed by waves of thought suppression and mental intoxication in a cyclic fashion, occurring every 20 to 60 minutes.

Feelings of Impending Doom

  • Experienced mainly during the come-up phase, feelings of impending doom typically subside once primary effects begin. A positive and informed mindset is crucial to managing this effect.

Cognitive Euphoria

  • Psilocybin may induce cognitive euphoria, autonomous voice communication, and suggestibility enhancement.

Conceptual Thinking

  • Psilocybin enhances conceptual thinking, thought connectivity, and thought organization.

Confusion

  • More commonly observed in inexperienced users, confusion occurs at a higher rate with psilocybin compared to other psychedelics like LSD or DMT.

Novelty Enhancement

  • Users may experience increased creativity, novelty enhancement, and delusion.

Déjà Vu

  • Psilocybin may induce feelings of déjà vu, increased music appreciation, and immersion enhancement.

Memory Effects

  • Psilocybin enhances memory while suppressing certain memories and may induce ego death and mindfulness.

Personality Effects

  • Users may experience personality regression, catharsis, rejuvenation, addiction suppression, and time distortion.

Auditory Effects

  • Psilocybin induces auditory enhancement, distortion, hallucination, and multi-sensory effects like synaesthesia.

Transpersonal Effects

  • Psilocybin may enhance spirituality, existential self-realization, unity, and interconnectedness, akin to naturally occurring entheogenic tryptamines such as ayahuasca and ibogaine.

Combination Effects

Cannabis

  • Cannabis significantly amplifies the sensory and cognitive effects of psilocybin mushrooms. Caution is advised, especially for inexperienced users, as this combination can intensify anxiety, confusion, and delusion. Users are recommended to start with a fraction of their usual cannabis dose and consume it at a slower pace than usual.

Dissociatives

  • Dissociatives enhance the geometry, euphoria, dissociation, and hallucinatory effects of psilocybin mushrooms. However, combining them can result in more vivid visuals, intense internal hallucinations, confusion, nausea, delusions, and an increased risk of psychosis.

MDMA

  • MDMA enhances the visual, physical, and cognitive effects of psilocybin. Due to unpredictable synergy, it's advisable to start with lower dosages than one would take for either substance individually. The combination's toxicity is unknown, though there's evidence suggesting it may increase the neurotoxic effects of MDMA.

Alcohol

  • While not typically recommended due to potential dehydration, nausea, and physical fatigue at higher doses, low doses of alcohol can reduce anxiety during a psilocybin trip. It's advisable to wait until the "come down" phase to consume alcohol to avoid exacerbating nausea, especially within the first 2 - 3 hours of the experience.

Benzodiazepines

  • Benzodiazepines can reduce the intensity of cognitive, physical, and visual effects of a psilocybin trip, potentially mitigating a bad trip. However, caution is advised due to their high abuse potential and the risk of amnesia and reduced trip intensity.

Psychedelics

  • Combining psilocybin with other psychedelics intensifies and synergizes their physical, cognitive, and visual effects. Due to unpredictable synergy, combining psychedelics is generally not advised. If chosen, it's recommended to start with lower dosages than one would take for either substance individually.

Dosage and Preparation

Dosage

The potency of psilocybin mushrooms, measured by the total psilocybin and psilocin content, varies significantly between species and even within the same species. For instance, Psilocybe cubensis, one of the most commonly used species, contains 10–12 mg of psilocybin per gram of dried mushrooms.

Dosage Calculation

To determine the dosage of psilocybin, one can use the following mathematical formula: Desired psilocybin amount divided by the psilocybin strength of the strain. For instance, if aiming for a common dose of 15 mg psilocybin from cubensis with 1% psilocybin content:

15 mg / 1% = 15/0.01 = 1500 mg = 1.5 g

Psilocybe cubensis

Psilocybe cubensis, commonly known as cubes, is among the most frequently used species of psilocybin mushrooms. The recommended doses for oral consumption of dried cubensis mushrooms are typically:

  • Threshold: 0.25 - 0.5 g
  • Light: 0.5 - 1 g
  • Common: 1 - 2.5 g
  • Strong: 2.5 - 5 g
  • Heavy: 5 g or more

Preparation Methods

Various methods exist for preparing psilocybin mushrooms. Some common techniques include:

  • Brown rice flour psilocybin mushroom tek
  • Outdoor mushroom cultivation
  • Mushroom chocolates
  • Mushroom tea
  • Psilocybin mushroom lemon tek

Natural Occurrence

Psilocybin mushrooms are found in biological genera such as Copelandia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, Pluteus, and Psilocybe. The genus Psilocybe alone contains over 100 classified species.

Research

Antidepressant Effects

While further research is needed to establish the utility of psilocybin and other psychedelics in treating depression, preliminary studies have shown promising results:

  • A pilot study observed significantly decreased depression scores in terminal cancer patients six months after treatment with psilocybin.
  • An open-label study conducted in the UK in 2016 investigated the feasibility, safety, and efficacy of psilocybin in treating patients with unipolar treatment-resistant depression. Seven out of twelve patients met formal criteria for remission one week following psilocybin treatment, and five of those were still in remission at three months.

The mechanism behind these effects is not fully understood, but it is suggested that psilocin's deactivation of the medial prefrontal cortex (mPFC) may play a role, as the mPFC is known to be elevated in depression and normalized after effective treatment.

Toxicity and Harm Potential

Psilocybin mushrooms are generally well-tolerated physiologically, with an extremely low toxicity relative to dose. There is no evidence for long-lasting effects on the brain or other organs, and there are no documented deaths attributed to the direct effects of psilocybin mushrooms' toxicity.

However, their use can present serious hazards, such as impairing judgment and attention span, promoting erratic or dangerous behaviors, and causing intense negative experiences or psychotic episodes. In rare cases, lasting psychological trauma may occur if not properly managed or treated afterward.

Lethal Dosage

The toxicity of psilocybin and psilocin is extremely low. Animal studies suggest a median lethal dose (LD50) of 280 milligrams per kilogram (mg/kg) of psilocybin when administered orally. Based on these results, the lethal dose of psilocybin for humans has been estimated to be 6 grams, significantly higher than the effective dose of 6 milligrams.

Psychosis and Mental Disorder Risk

Psilocybin mushrooms can exacerbate symptoms of various mental disorders and precipitate the early onset of schizophrenia in vulnerable individuals. Those with a personal or family history of mental disorders, particularly psychotic disorders like schizophrenia, should avoid using psilocybin mushrooms without consulting a qualified medical professional.

Dependence and Abuse Potential

Psilocybin mushrooms have low abuse and no physical dependence potential. There is no human clinical evidence of addiction, and withdrawal syndrome is virtually nonexistent. Tolerance to the effects of psilocybin builds almost immediately after ingestion and diminishes over time.

Hallucinogen-Persistence Perception Disorder (HPPD)

In rare cases, psilocybin mushrooms may trigger hallucinogen-persisting perception disorder (HPPD) in some individuals. The cause is unclear, but it is not believed to be related to the direct action on brain chemistry.

Dangerous Interactions

Mixing psilocybin mushrooms with certain substances can be dangerous and even life-threatening. It is essential to conduct independent research to ensure the safety of combining substances.

Legal Status

The legal status of psilocybin mushrooms varies widely across different countries and regions. In some places, such as the United States and many European countries, possession, sale, and cultivation of psilocybin mushrooms are illegal and classified as controlled substances. However, there are exceptions, such as Oregon and Colorado in the United States, where certain measures have been passed to decriminalize or legalize the therapeutic use of psilocybin mushrooms.

It is essential for individuals to research and understand the legal status of psilocybin mushrooms in their respective locations before possessing, using, or cultivating them.

Current Research

Ongoing research continues to explore the potential therapeutic benefits of psilocybin mushrooms, particularly in the treatment of mental health disorders such as depression, anxiety, and PTSD. Clinical trials and studies aim to further understand the mechanisms of action, optimal dosages, and long-term effects of psilocybin therapy.

Additionally, research efforts are focused on elucidating the safety profile and potential risks associated with psilocybin use, including the risk of adverse reactions, psychological distress, and long-term psychological consequences.

As scientific understanding of psilocybin mushrooms continues to evolve, it is hoped that evidence-based guidelines and regulations will be established to support safe and responsible use while maximizing the potential therapeutic benefits for individuals in need.

Frequently Asked Questions (FAQ)

Q: What is the dosage of psilocybin mushrooms?

A: The dosage of psilocybin mushrooms depends on various factors, including the potency of the mushroom species. Common dosage ranges from threshold doses of 0.25 - 0.5 grams to heavy doses of 5 grams or more.

Q: How can I calculate the dosage of psilocybin mushrooms?

A: To calculate the dosage, divide the desired amount of psilocybin by the psilocybin strength of the strain. For example, if you want to consume 15 mg of psilocybin from a strain with 1% psilocybin content, you would need to ingest approximately 1.5 grams of mushrooms.

Q: What are some common preparation methods for psilocybin mushrooms?

A: Common preparation methods include making mushroom tea, mushroom chocolates, and using the lemon tek method. These techniques aim to enhance the absorption and potency of psilocybin, providing different experiences for users.

Q: What is the legal status of psilocybin mushrooms?

A: The legal status of psilocybin mushrooms varies across different countries and regions. In some places, such as the United States and many European countries, possession, sale, and cultivation of psilocybin mushrooms are illegal and classified as controlled substances. However, there are exceptions, such as Oregon and Colorado in the United States, where certain measures have been passed to decriminalize or legalize the therapeutic use of psilocybin mushrooms.

Q: What is the current research status on psilocybin mushrooms?

A: Ongoing research aims to explore the therapeutic potential of psilocybin mushrooms in treating mental health disorders such as depression, anxiety, and PTSD. Clinical trials and studies are ongoing to understand the mechanisms of action, optimal dosages, and long-term effects of psilocybin therapy.

Q: Are psilocybin mushrooms safe to use?

A: Psilocybin mushrooms have been found to be physiologically well-tolerated with low toxicity relative to dose. However, their use can present serious hazards, including impairing judgment, inducing powerful delusions, and causing lasting psychological trauma if not properly managed. It is essential to use harm reduction practices and exercise caution when using psilocybin mushrooms.


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