Psilocybin produces profound anti-inflammatory effects mediated by serotonin 5-HT2A receptor activation in preclinical studies. Serotonin 5-HT2C receptor activation and downstream inhibition of the mesolimbic dopamine pathway may be involved in the limited addictive potential of serotonergic psychedelics like psilocybin. In humans, ketanserin blocked psilocybin’s hallucinogenic effects but not all of its cognitive and behavioral effects. In addition, the serotonin 5-HT1B receptor has been found to be required for psilocybin’s persisting antidepressant- and anxiolytic-like effects as well as acute hypolocomotion in animals. Psilocybin’s psychedelic effects can be blocked by serotonin 5-HT2A receptor antagonists like ketanserin and risperidone in humans. Psilocybin is a serotonergic psychedelic that acts as a prodrug of psilocin, the active form of the drug.
- However, it has been demonstrated that P. fuscofulva, a species which used to be known as P. atrobrunnea, belongs to the genus Psilocybe s.s., but does not contain psychotropic compounds.
- The relatively easy availability of hallucinogenic Psilocybe from wild and cultivated sources has made it among the most widely used of the hallucinogenic drugs.
- The competitive phosphatase inhibitor β-glycerolphosphate, which inhibits psilocybin dephosphorylation, greatly attenuates the behavioral effects of psilocybin in rodents.
- The men publicized the fungi’s consciousness-expanding properties, which are somewhat similar to synthetic drugs such as LSD.
- A growing body of research has suggested that psilocybin combined with psychotherapy may be helpful for depression in the short and medium term.
Health Conditions
Psilocybin is most commonly consumed in the form of psilocybin-containing mushrooms, such as Psilocybe species like Psilocybe cubensis. Psilocybin-containing mushrooms vary in their psilocybin and psilocin content, but are typically around 1% of the dried weight of the mushrooms (in terms of total or combined psilocybin and psilocin content). Especially at higher doses and combined with psychological support, psilocybin can produce rapid and sometimes lasting antidepressant effects that generally outperform placebo but show only modest advantages over conventional SSRIs; evidence quality is generally low and trial bias is common.
Factors such as mental health, setting, quantity, and expectations may affect the experience someone has after using psilocybin. Hallucinogenic drugs may cause unpredictable, potentially dangerous behavior, which can lead to injuries. The only way to eliminate the risk of a bad trip is by not taking magic mushrooms. People should visit an emergency room immediately if these symptoms occur after eating mushrooms. Some psilocybin users risk accidental poisoning from eating a poisonous mushroom by mistake.
Psilocybin works by binding to and activating serotonin receptors in parts of the brain, such as the prefrontal cortex and amygdala. By the early 1970s, a number of psychoactive Psilocybe species were described from temperate North America, Europe, and Asia and were widely collected. The popularization of entheogens by Wasson, Timothy Leary, and others has led to an explosion in the use of hallucinogenic Psilocybe throughout the world.
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This meta-analysis included both RCTs and prospective open-label studies, and calculated effect sizes by comparing to the placebo group or by using pre-treatment (baseline) values. One meta-analysis found that the highest assessed dose in clinical trials, 30 to 35 mg per 70 kg body weight, was the most effective, with an effect size (Hedges’ g) of 3.1 (relative to 1.3 overall), but based on only one study for that dosing subgroup. Psilocybin has been a subject of clinical research since the early 1960s, when the Harvard Psilocybin Project evaluated the potential value of psilocybin as a treatment for certain personality disorders. Government Accountability Office (GAO) notes that people may petition the DEA for exemptions to use psilocybin for religious purposes. Similarly, religious groups like America’s Uniao do Vegetal (UDV) use psychedelics in traditional ceremonies. Schedule I drugs are defined as drugs with a high potential for abuse or drugs that have no recognized medical uses.
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Low doses are 5 to 10 mg, an intermediate or “good effect” dose is 20 mg, and high or ego-dissolution doses are 30 to 40 mg. It is also under development for the treatment of depression and for various other indications elsewhere, such as the United States and Europe, but has not yet been approved in other countries (see below). It is in late-stage clinical trials in the United States for treatment-resistant depression. 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.
Global legal status of psilocybin mushrooms
A third meta-analysis found that half of psilocybin’s maximal antidepressant effect occurred with a dose of about 10 mg per 70 kg body weight, while 95% of the maximal effect occurred at a dose of about 41 mg per 70 kg body weight, and that higher doses might especially be better for treatment-resistant depression. Meta-analyses of psychedelics for depression and other psychiatric conditions have found that psilocybin has the greatest number of studies and the most evidence of benefit, relative to other psychedelics like ayahuasca and LSD. A June 2024 report by the RAND Corporation suggests the total number of use days for psychedelics is two orders of magnitude smaller than it is for cannabis, and unlike people who use cannabis and many other drugs, infrequent users of psychedelics account for most of the total days of use. In response to concerns about the increase in unauthorized use of psychedelic drugs by the general public, psilocybin and other hallucinogenic drugs were unfavorably covered in the press and faced increasingly restrictive laws. Dozens of species of psychedelic mushrooms are found in Europe, but there is little documented usage of them in Old World history besides the use of Amanita muscaria among Siberian peoples. The diversity of psilocybin mushrooms is reported to have been increased by horizontal transfer of the psilocybin gene cluster between unrelated mushroom species.
- failed verification Less frequently reported adverse effects include paranoia, confusion, prolonged derealization (disconnection from reality), and mania.
- About two-thirds said the experience increased their sense of well-being or life satisfaction.
- In general, psilocybin mushrooms are gilled and produce dark spores; they may closely resemble poisonous species.
- These effects are partially but not fully dependent on its activation of the serotonin 5-HT2A and/or 5-HT2C receptors.
What are the penalties for possessing psilocybin in states where it is illegal?
Examples of MAOIs that may potentiate psychedelics behaving as MAO-A substrates, such as psilocin, include phenelzine, tranylcypromine, isocarboxazid, and moclobemide, as well as harmala alkaloids like harmine and harmaline and chronic tobacco smoking. Combination of MAO-substrate psychedelics with monoamine oxidase inhibitors (MAOIs) can result in overdose and toxicity. The exact extent to which psilocin (and by extension psilocybin) is metabolized by MAO-A is not fully clear, but has ranged from 4% to 33% in different studies based on metabolite excretion. A clinical trial of psilocybin and midazolam coadministration found that midazolam clouded psilocybin’s effects and impaired memory of the experience. Benzodiazepines such as diazepam, alprazolam, clonazepam, and lorazepam, as well as alcohol, which act as GABAA receptor positive allosteric modulators, have been limitedly studied in combination with psilocybin and other psychedelics and are not known to directly interact with them. Serotonin 5-HT2A receptor antagonists that have been specifically shown in clinical studies to diminish or abolish psilocybin’s effects include ketanserin, risperidone, and chlorpromazine.
Is psilocybin safe?
In 1958, the Swiss chemist Albert Hofmann isolated psilocybin and psilocin from the mushroom Psilocybe mexicana. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Effects of varied doses of psilocybin on time interval reproduction in human subjects. Exploratory controlled study of the migraine-suppressing effects of psilocybin. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction.
The previous type species of the genus, Psilocybe montana (now Deconica montana), was in the non-bluing clade, but in 2010, the type species was changed to P. semilanceata, a member of the bluing clade. A 2002 study of the molecular phylogeny of the agarics indicated the genus Psilocybe as then defined was polyphyletic, falling into two distinct clades that are not directly related to each other.
Clinical trials, including both open-label trials and double-blind randomized controlled trials (RCTs), have found that single doses of psilocybin produce rapid and long-lasting antidepressant effects outperforming placebo in people with major depressive disorder and treatment-resistant depression. Likewise, a 2010 Dutch study ranked the relative harm of psilocybin mushrooms compared to a selection of 19 recreational drugs, including alcohol, cannabis, cocaine, ecstasy, heroin, and tobacco. At certain doses, psychedelic drugs, including psilocybin, can change peoples’ moods, thoughts, and perceptions. The lethal dose from psilocybin toxicity alone is unknown, and has rarely been documented—as of 2011update, only two cases attributed to overdosing on hallucinogenic mushrooms (without concurrent use of other drugs) have been reported in the scientific literature, and those may involve factors other than psilocybin.d In a 2024 meta-analysis of RCTs of psychedelics and escitalopram for treatment of depression, only “high-dose” psilocybin (≥20 mg) significantly outperformed escitalopram in improving depressive symptoms.
Medical and psychiatric aspects
However, the UN drug treaties do not apply to cultivation, preparation, or international transport of psilocybin mushrooms. In 1956, Roger Heim identified the hallucinogenic mushroom that the Wassons had brought back from Mexico as Psilocybe and in 1958, Albert Hofmann first reported psilocin and psilocybin as the active compound in these mushrooms. In June 2025, Compass Pathways, which is developing psilocybin for treatment-resistant depression, announced the results of a Phase III clinical trial of single-dose 25 mg psilocybin (COMP360) versus placebo. In Amsterdam, authorities provide education on and promote the safe use of psychedelic drugs, such as psilocybin, to reduce public harm.
In the United States, the Department of Veterans Affairs has been testing psilocybin and psilocin in an effort to reduce veterans’ mental health problems and suicide rates. Widespread recreational use of these mushrooms, however, prompted state and federal governments to strictly control them in many places. The men publicized the fungi’s consciousness-expanding properties, which are somewhat similar to synthetic drugs such as LSD.
It may also distort how some people who use the drug perceive objects and people in their environment. Only the truffle form of magic mushrooms (such as P. tampanensis) are currently legal, but these still contain the active ingredients and produce similar effect as the caps and stalks. There is some skepticism as to whether or not these “sacred mushrooms” were actually in the genus Psilocybe. By the 20th century, hallucinogenic psilocybe semilanceata habitat mushroom use was thought by non-Native Americans to have disappeared entirely. Hallucinogenic species of Psilocybe have a long history of use among the native peoples of Mesoamerica for religious communion, divination, and healing, from pre-Columbian times up to the present day. This is a plausible basis for the psychological effects of these hallucinogenic compounds.
This effect explains the euphoria experienced by ingestion of this “agonist.” Initially, hallucinogens were thought to blockade these serotonin neurotransmitters, but persistent research led to this agonist effect conclusion. To explain this effect, the psilocin molecule essentially mimics the serotonin molecule, binding to the 5-HT receptors and initiating the same response as the serotonin. The chemical structure of serotonin, a neurotransmitter, is similar to that of psilocin. Psilocybin is chemically far more stable than psilocin, the latter compound being largely lost when the mushroom is heated or dried. The degree of bluing in a Psilocybe fruit body roughly correlates with the concentration of psilocin in the mushroom.
It shows high affinity for most of the serotonin receptors, with the notable exception of the serotonin 5-HT3 receptor. Psilocin’s major metabolic pathway is glucuronidation by UDP-glucuronosyltransferase enzymes including UGT1A10 and UGT1A9. Psilocin, the active form of psilocybin, is a substrate of the monoamine oxidase (MAO) enzyme MAO-A. The Registry of Toxic Effects of Chemical Substances assigns psilocybin a relatively high therapeutic index of 641 (higher values correspond to a better safety profile); for comparison, the therapeutic indices of aspirin and nicotine are 199 and 21, respectively.