Psilocybin is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. 

Psilocybin is itself biologically inactive.

Psilocybin is converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of lysergic acid diethylamide (LSD), mescaline, and dimethyltryptamine (DMT). 

Its  effects include euphoria, visual and mental hallucinations, changes in perception, distorted sense of time, and perceived spiritual experiences. 

It can also cause adverse reactions such as nausea and panic attacks.

Routes of administration Oral, intravenous

Metabolism Hepatic

Biological half-life Oral: 163±64 min

Intravenous: 74.1±19.6 min

Excretion Renal

Its effects of psilocybin are highly variable and depend on the mindset and environment.

After drug ingestion, a wide range of subjective effects may be experienced: feelings of disorientation, lethargy, giddiness, euphoria, joy, and depression. 

In one study, 31% of volunteers given a high dose reported feelings of significant fear and 17% experienced transient paranoia.

When given a moderate dose negative experiences are rare, whereas one-third of those given a high dose experience anxiety or paranoia.

Low doses can induce hallucinatory effects, with closed-eye hallucinations: affected individual sees multicolored geometric shapes and vivid imaginative sequences; synesthesia, such as tactile sensations when viewing colors.

At higher doses, the drug can lead to an increase in affective responses, the enhanced ability for introspection, regression to primitive/childlike thinking, and activation of vivid memories with pronounced emotional undertones, and open-eye visual hallucinations are common.

Even a single high dosage of psilocybin can cause long-term changes in the personality of its users. 

About half of the study participants showed an increase in the personality dimension of openness, and this positive effect was apparent more than a year after the psilocybin session. 

A study found that doses of 20 to 30mg/70kg psilocybin induced  mystical-type experiences and brought more lasting changes to traits including altruism, gratitude, forgiveness and feeling close to others when they were combined with a regular meditation practice and an extensive spiritual practice support program.

Common physical effects and responses include pupil dilation (93%); changes in heart rate (100%), including increases (56%), decreases (13%), and variable responses (31%); changes in blood pressure (84%), including hypotension (34%), hypertension (28%), and general instability (22%); changes in stretch reflex (86%), including increases (80%) and decreases (6%); nausea (44%); tremor (25%); and dysmetria (16%).

Nausea or vomiting is experienced by over a quarter of those who had used psilocybin mushrooms in the last year, although this effect is caused by the mushroom rather than psilocybin itself.

In one study, administration of gradually increasing dosages of psilocybin daily for 21 days had no measurable effect on electrolyte levels, blood sugar levels, or liver toxicity tests.

intrapartum antibiotics can cause perceptual distortions, that is linked to its influence on the activity of the prefrontal cortex.

It influences the subjective experience of the passage of time, and feels as if time is slowed down, that minutes appear to be hours or time stands still.

It significantly impairs subjects’ ability to gauge time intervals longer than 2.5 seconds.

Psilocybin affects the prefrontal cortex activity, and its role in time perception.

Some have a pleasant experience and experience a sense of connection to others, nature, and the universe.

In other  perceptions and emotions are often intensified. 

Users may have an unpleasant experiences accompanied by fear, or other unpleasant feelings, and occasionally by dangerous behavior. 

A bad trip is used to describe a reaction that is characterized primarily by fear or other unpleasant emotions, that are not just transitory.

Factors that contribute to a psilocybin user experiencing a bad trip, include emotional or physical lows or in a non-supportive environment.

Ingestion of other drugs, including alcohol.

Effects of psilocybin are similar to comparable dosages of lysergic acid diethylamide (LSD) or mescaline. 

The psilocybin experience seems to be warmer, less forceful, less isolating and tends to build connections between people, than LSD.

 In many societies that powerful mind-active substances such as psilocybin are regularly consumed ritually for therapeutic purposes or for transcending normal, everyday reality.

The mushrooms are revered as powerful spiritual sacraments that provide access to sacred worlds. 

Psychedelic drugs can induce states of consciousness that have lasting personal meaning and spiritual significance in individuals who are religious or spiritually inclined: mystical experiences. 

Negative effects are repoerted to easily managed and did not have a lasting negative effect on the subject’s sense of well-being.

60% of psilocybin users report that their use of psilocybin had a long-term positive impact on their sense of well-being.

Other experts describe this phenomenon as toxic delirium.

The psilocybin present in mushrooms can be ingested in several ways: by consuming fresh or dried fruit bodies, by preparing an herbal tea, or by combining with other foods to mask the bitter taste.

In rare cases people have injected mushroom extracts intravenously.

Most of the few fatal incidents reported in the literature that are associated with psychedelic mushroom usage involve the simultaneous use of other drugs, especially alcohol. 

The most common cause of hospital admissions resulting from psychedelic mushrooms  involves bad trips or panic reactions: extremely anxiousness, confusion, agitation or disorientation. 

Accidents, self-injury, or suicide attempts can result from serious cases of such psychotic episodes.

An increasing number of psilocybin mushroom overdoses are occurring, but the number of events requiring hospitalization remain low. and overdoses are generally mild and self-limiting. 

Psilocybin related overdose management should prioritize managing adverse effects, such as anxiety and paranoia, rather than specific pharmacological interventions.

Its physiological toxicity is usually limited.

Based on the results of animal studies, the lethal dose of psilocybin has been suggested be 6 grams, 1000 times greater than the effective dose of 6 milligrams.

Psilocybin a relatively high therapeutic index of 641, with higher values corresponding  to a better safety profile: for comparison, the therapeutic indices of aspirin and nicotine are 199 and 21, respectively.

The lethal dose from psilocybin toxicity alone is unknown.

Panic reactions can occur after consumption of psilocybin-containing mushrooms.

Rarely violent behavior, suicidal thoughts, schizophrenia-like psychosis, and convulsions have been reported.

Almost a quarter of those who had used psilocybin mushrooms experience a panic attack.

Other adverse effects less frequently reported include paranoia, confusion, disconnection from reality, mania, and induced state of depersonalization, and acute psychosis.

Psychotic symptoms are thought to arise from the impaired gating of sensory and cognitive information in the brain, leading  to cognitive fragmentation and psychosis.

Flashbacks can occur long after having used psilocybin mushrooms. 

Hallucinogen persisting perception disorder (HPPD) is characterized by a continual presence of visual disturbances similar to those generated by psychedelic substances. 

Neither flashbacks nor HPPD are commonly associated with psilocybin usage.

Tolerance to psilocybin builds and dissipates quickly.

The ingestion of psilocybin more than about once a week can lead to diminished effects. 

Tolerance dissipates after a few days.

A cross-tolerance can develop between psilocybin and LSD, and between psilocybin and phenethylamines such as mescaline.

Repeated use of psilocybin does not lead to physical dependence.

Adolescent-onset usage of hallucinogenic drugs, including psilocybin, did not increase the risk of drug dependence in adulthood.

This was in contrast to adolescent usage of cannabis, cocaine, inhalants, anxiolytic medicines, and stimulants, all of which were associated with an excess risk of developing drug dependence.

The  relative harm of psilocybin mushrooms compared to a selection of 19 recreational drugs, including alcohol, cannabis, cocaine, ecstasy, heroin, and tobacco, is ranked as the illicit drug with the lowest harm.

Psilocybin is a naturally-occurring substituted tryptamine, which is a derivative of the amino acid tryptophan. 

Psilocybin is a white, crystalline solid.

The neurotransmitter serotonin is structurally similar to psilocybin.

Psilocybin is a psychoplastogen, which refers to a compound capable of promoting rapid and sustained neuroplasticity.

Psilocybin is rapidly dephosphorylated to psilocin, which is an agonist for several serotonin receptors, which are also known as 5-hydroxytryptamine (5-HT) receptors. 

Psilocin indirectly increases the concentration of the neurotransmitter dopamine in the basal ganglia.

Some psychotomimetic symptoms of psilocin are reduced by haloperidol, a non-selective dopamine receptor antagonist. 

There may be an indirect dopaminergic contribution to psilocin’s psychotomimetic effects.

Psilocybin is converted in the liver to the pharmacologically active psilocin, which is then either glucuronated to be excreted in the urine or further converted to various psilocin metabolites.

Psilocybin’s effects begin 10–40 minutes after ingestion, and last 2–6 hours depending on dose.

The half life of psilocybin is 163 ± 64 minutes when taken orally, or 74.1 ± 19.6 minutes when injected intravenously.

it is metabolized mostly in the liver, as it becomes converted to psilocin, it undergoes a first-pass effect, whereby its concentration is greatly reduced before it reaches the systemic circulation. 

About 50% of ingested psilocybin is estimated to be absorbed through the stomach and intestine. 

Within 24 hours, about 65% of the absorbed psilocybin is excreted into the urine, and a further 15–20% is excreted in the bile and feces. 

The drug is still detectable in the urine after 7 days.

Psychological effects occur with a blood plasma concentration of 4–6 μg/liter.

Psilocybin is approximately 1/100 the potency of LSD on a weight per weight basis, and the physiological effects last about half as long.

Alcohol consumption may enhance the effects of psilocybin, because acetaldehyde, one of the primary breakdown metabolites of consumed alcohol, reacts with biogenic amines present in the body to produce MAOIs.

Tobacco smokers may also experience more powerful effects, because tobacco smoke exposure decreases the activity of MAO in the brain and peripheral organs.

Several chemical tests commercially available as reagent testing kits—can be used to assess the presence of psilocybin in extracts prepared from mushrooms. 

Various chromatographic methods have been developed to detect psilocin in body fluids.

Younger, and smaller mushrooms tend to have a higher concentration of the drug than larger, mature mushrooms.

The psilocybin content of mushrooms is quite variable with a range from almost nothing to 2.5% of the dry weight.

Cultivated mushrooms have less variability in psilocybin content than wild mushrooms.

The drug is more stable in dried than fresh mushrooms, as dried mushrooms retain their potency for months or even years.

Mushrooms stored fresh for four weeks contain only traces of the original psilocybin.

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