Psilocybin

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Psilocybin

Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in more than 200 species of mushrooms, with hallucinogenic and serotonergic effects. Effects include euphoria, changes in perception, a distorted sense of time, and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks. Psilocybin is a prodrug of psilocin. That is, the compound itself is biologically inactive but quickly converted by the body to psilocin. Psilocybin is transformed into psilocin by dephosphorylation mediated via phosphatase enzymes. Psilocin is chemically related to the neurotransmitter serotonin and acts as a non-selective agonist of the serotonin receptors. Activation of one serotonin receptor, the serotonin 5-HT2A receptor, is specifically responsible for the hallucinogenic effects of psilocin and other serotonergic psychedelics. Psilocybin is usually taken orally. By this route, its onset is about 20 to 50 minutes, peak effects occur in about 1 to 2 hours, and its duration is about 4 to 6 hours. Psilocybin mushrooms were used ritualistically in pre-Columbian Mexico, but claims of their widespread ancient use are largely exaggerated and shaped by modern idealization and ideology. In 1958, the Swiss chemist Albert Hofmann isolated psilocybin and psilocin from the mushroom Psilocybe mexicana. His employer, Sandoz, marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic therapy. Increasingly restrictive drug laws of the 1960s and the 1970s curbed scientific research into the effects of psilocybin and other hallucinogens, but its popularity as an entheogen grew in the next decade, owing largely to the increased availability of information on how to cultivate psilocybin mushrooms. Possession of psilocybin-containing mushrooms has been outlawed in most countries, and psilocybin has been classified as a Schedule I controlled substance under the 1971 United Nations Convention on Psychotropic Substances. Psilocybin is being studied as a possible medicine in the treatment of psychiatric disorders such as depression, substance use disorders, obsessive–compulsive disorder, and other conditions such as cluster headaches. Psilocybin was approved for treatment-resistant depression in Australia in 2023. It is in late-stage clinical trials in the United States for treatment-resistant depression. A decision on approval of psilocybin for this indication is expected by the end of 2026. Especially at higher doses and combined with psychological support, single doses of psilocybin can produce rapid and long-lasting antidepressant effects that generally outperform placebo, though they show only modest advantages over conventional continuous antidepressants like selective serotonin reuptake inhibitor (SSRIs); the quality of evidence is generally low and trial bias is common.

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• Psilocybin - an overview | ScienceDirect Topics

  Psilocybin (sometimes referred to informally as “shrooms” or “magic mushrooms”) is the primary active constituent present in a variety of mushroom species, most notably those from the genus Psilocybe. Albert Hoffman first isolated psilocybin from mushrooms in 1957, and first synthesized psilocybin in 1958 (Passie, Seifert, Schneider, & Emrich, 2002). Psilocybin when ingested is metabolized into an active metabolite psilocin, which is an agonist at the 5-HT2AR among other serotonergic sites (Nichols, 2016). Anthropological evidence suggests that psilocybin has been used by various indigenous people for religious and healing ceremonies for centuries (Stamets, 1996; Wasson, 1980). Modern research with psilocybin began soon after cultural anthropologist Wasson (1957) provided one of the first [...] Psilocybin is a tryptamine alkaloid found naturally in several species of mushrooms of the genus Psilocybe. Psilocybin has four metabolites including the primary ‘active’ metabolite psilocin. Both psilocybin and psilocin have remarkable structural similarity to the indoleamine neurotransmitter 5-HT, a feature that is shared with other ‘classic’ or serotonergic psychedelics, including dimethyltryptamine (DMT, the psychoactive compound in ayahuasca) and the synthetic compound lysergic acid diethylamide (LSD). Following oral ingestion in humans, psilocybin is rapidly converted to psilocin before entering the systemic circulation. Conversion of psilocybin to psilocin occurs via dephosphorylation, which is promoted by the acidic environment of the stomach and through enzymatic alkaline [...] Psilocybin is one of two hallucinogenic compounds obtained from Teonanácatl, the sacred mushroom of Mexico, the other being psilocin. Although native Americans in Central and South America consumed psilocybe mushrooms for thousands of years, the first European record of their use was by a Spanish priest in the 16th century who recorded their use by the Aztec Indians. In 1957, Wasson published his own experience with the mushroom. This was soon followed by the isolation and recreational use of psilocybin, which was designated as a controlled substance in the United States in 1968. In the UK, psilocybin is present in the indigenous mushroom Psilocybe semilanceata (magic mushroom; liberty cap). Other mushroom species, such as Stropharia cubensis and Conocybe spp, also contain psilocybin.

• Psilocybin (Magic Mushrooms) | National Institute on Drug Abuse - NIH

  ## What is psilocybin? Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) comes from certain types of mushrooms found on nearly every continent.1 The mushrooms, which are also known as shrooms or magic mushrooms, are typically consumed dried or powdered. Psilocybin is part of a group of drugs called psychedelics—or hallucinogens—that have the potential to change a person’s sense of reality, leading them to see, hear, and feel things that are not happening in real life, or to experience reality in a different way.2 [...] Psilocin activity at the 5HT2a receptor affects how the brain works and how different brain regions communicate with each other. These altered patterns of brain activity contribute to a person’s profound change in consciousness. Some regions increase in activity and connectedness while others decrease.4 Studies suggest that psilocybin can temporarily disrupt communication among regions of the brain known as the default mode network, which is most active when we self-reflect.4,8 Reducing a person’s focus on their self may lead to a greater feeling of openness and increased connectedness to the world.4 ## What are the effects of psilocybin? [...] ## How does psilocybin work in the brain? When a person takes psilocybin, their body converts it to another substance, psilocin.1 Psilocin attaches to and activates receptors, or binding sites, for the brain chemical serotonin, primarily the serotonin 5-hydroxytryptamine 2A (5HT2a) receptor. Researchers think this action is responsible for much of a person’s subjective experience when they take the mushrooms.4

• Psilocybin - Wikipedia

  Psilocybin is most commonly consumed in the form of psilocybin-containing mushrooms, such as _Psilocybe_ species like _Psilocybe cubensis_. It may also be prepared synthetically, but outside of research settings it is not typically used in this form. Regardless of form, psilocybin is usually taken orally. The psilocybin present in certain species of 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 intravenouslyinjected "Injection (medicine)")mushroom extracts, with serious medical complications such as systemicmycological infection and hospitalization.( Another form of psilocybin (as well as of related psychedelics like 4-AcO-DMT) is [...] Possession of psilocybin-containing mushrooms has been outlawed in most countries, and psilocybin has been classified as a Schedule I controlled substance under the 1971 United Nations Convention on Psychotropic Substances. Psilocybin is being studied as a possible medicine in the treatment of psychiatric disorders such as depression "Depression (mood)"), substance use disorders, obsessive–compulsive disorder, and other conditions such as cluster headaches.( Psilocybin was approved for treatment-resistant depression in Australia in 2023.( It is in late-stage clinical trials in the United States for treatment-resistant depression.( A decision on approval of psilocybin for this indication is expected by the end of 2026.( Especially at higher doses and combined with psychological support, [...] Psilocybin is dephosphorylated into its active formpsilocin in the body and hence is a prodrug.( Psilocybin is metabolized in the intestines, liver, kidneys, blood, and other tissues "Tissue (biology)") and bodily fluids.( There is significant first-pass metabolism of psilocybin and psilocin with oral administration.( No psilocybin has been detected in the blood in humans after oral administration, suggesting virtually complete dephosphorylation into psilocin with the first pass.( It is also said to be converted 90% to 97% into psilocin.( The competitivephosphatase inhibitor β-glycerolphosphate, which inhibits psilocybin dephosphorylation, greatly attenuates the behavioral effects of psilocybin in rodents.( Psilocybin undergoes dephosphorylation into psilocin via the acidic environment of

• Clinical potential of psilocybin as a treatment for mental health ...

  Psilocybin, a classic hallucinogen, is a chemical produced by more than 100 species of mushrooms worldwide. It has high affinity for several serotonin receptors, including 5-HT1A, 5-HT2A, and 5-HT2C, located in numerous areas of the brain, including the cerebral cortex and thalamus. With legislation introduced in 1992, more work is being done to further understand the implications of psilocybin use in a number of disease states. Certain mental health disease states and symptoms have been studied, including depressed mood, anxiety disorders, obsessive-compulsive disorder, alcohol use disorder, and tobacco use disorder. This article provides an in-depth review of the study design and results of psilocybin in each of these conditions and discusses the clinical potential for use. [...] Psilocybin, a classic tryptamine hallucinogen, has similar properties to lysergic acid diethylamide (LSD) and mescaline with a slightly different chemical structure. Cross-tolerance between the different hallucinogens has been demonstrated, and research shows a common mechanism of action through serotonergic (5-HT) pathways. Psilocybin is a strong agonist at 5-HT2A as well as a moderate agonist at 5-HT1A and 5-HT2C.3 5-HT2A receptors are located within the thalamus and cortex of the brain. Activation of 5-HT2A receptors in the thalamus, the area of the brain responsible for sensory input, appears to decrease thalamic activity, thus leading to sensory alterations commonly referred to as hallucinations.4,5 Hallucinogenic effects typically onset within the first 20 to 40 minutes of use then [...] Keywords: hallucinogen, psilocybin, tobacco, addiction, depression, anxiety, psychedelic, obsessive-compulsive disorder, alcohol ## Background Psilocybin was first isolated by Albert Hofmann in 1957 from the Central American mushroom Psilocybe mexicana. The first synthetic psilocybin product was created shortly thereafter in 1958 and continues to be widely used today, both recreationally and in spiritual or religious rituals.1 It has since been found in more than 100 mushroom species worldwide with varying potency. These mushrooms are both cultivated and found in the wild. Cultivated mushrooms tend to be more potent through selection of stronger mushroom strains with more active ingredient (up to 10 times that of some wild mushroom species).2

• Psilocybin and magic mushrooms: Effects and risks

  # Psilocybin (magic mushrooms): What it is, effects and risks Psilocybin is a hallucinogenic chemical in certain mushrooms known as magic mushrooms. Eating mushrooms that contain psilocybin can have a variety of effects, ranging from euphoria to hallucinations. Some people use psilocybin as a recreational drug. It can provide feelings of euphoria and sensory distortion that are common to hallucinogenic drugs, such as LSD. Psilocybin is a Schedule I substance, meaning that the Drug Enforcement Administration (DEA) believes it has a high potential for abuse and serves no legitimate medical purpose. Although current research does not consider psilocybin addictive, users may experience disturbing hallucinations, anxiety, and panic after taking the drug. ## What is psilocybin? [...] ## What is psilocybin? Psilocybin mushrooms growing in a cluster.-1 Psilocybin is a hallucinogen that people can ingest through certain types of mushrooms. ### How it works Psilocybin works by binding to and activating serotonin receptors in parts of the brain, such as the prefrontal cortex and amygdala. These parts of the brain affect mood, cognition, and perception. Hallucinogens also work in other regions of the brain that regulate arousal and panic responses. Psilocybin may cause visual or auditory hallucinations. It may also distort how some people who use the drug perceive objects and people in their environment.