Activation of one serotonin receptor, the serotonin 5-HT2A receptor, is specifically responsible for the hallucinogenic effects of psilocin and other serotonergic psychedelics. Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT),a is a naturally occurring tryptamine alkaloid and investigational drug found in more than 200 species of mushrooms, with hallucinogenic and serotonergic effects. In the 21st century, psilocybin mushrooms have been tested as a treatment for chronic mental disorders such as anxiety, depression, addiction, and post-traumatic stress disorder (PTSD). Many psilocybin mushrooms have a long history of traditional use and are popular as recreational drugs. Often called “magic mushrooms,” psilocybin mushrooms produce two primary psychoactive compounds, psilocybin and psilocin, which are responsible for their mind-altering effects. Regular use may also cause people to become tolerant to the effects of psilocybin, and cross-tolerance occurs with other drugs, including LSD and mescaline.
The onset of action of psilocybin taken orally is 0.5 to 0.8 hours (30–50 minutes) on average, with a range of 0.1 to 1.5 hours (5–90 minutes). Even after 14 months, those who reported mystical experiences scored on average 4 percentage points higher on the personality trait of Openness/Intellect; personality traits are normally stable across the lifespan for adults. About two-thirds said the experience increased their sense of well-being or life satisfaction. Almost a third of the subjects reported that the experience was the single most meaningful or spiritually significant event of their lives, and over two-thirds reported it was among their five most spiritually significant events. These negative effects were reported to be easily managed by the researchers and did not have a lasting negative effect on the subject’s sense of well-being. Two months after taking psilocybin, 79% of the participants reported moderately to greatly increased life satisfaction and sense of well-being.
Adverse effects
- 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.
- Repeated dosing of psilocybin is being explored for maximization and maintenance of depressive symptom improvement, with preliminary effectiveness observed.
- The effects of food on the pharmacokinetics of psilocybin have not been reported and are unknown, but no clear sign of food effects has been observed in preliminary analyses.
- Generally, the nonmedical use of psilocybin refers to mushrooms containing psilocybin; synthetic production of psilocybin is complicated and expensive.
- The EC50Tooltip half-maximal effective concentration for occupancy of the serotonin 5-HT2A receptor by psilocin in terms of circulating levels has been found to be 1.97 ng/mL.
Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. In 2018, the Food and Drug Administration designated psilocybin as a ‘breakthrough therapy,’ allowing research and studies into its treatment potential.
Psilocybin as a treatment for depression
A second Phase III trial by Compass Pathways involving multiple different doses of psilocybin is also underway, with results expected next year. In the previously described dose-ranging Phase II trial of psilocybin for depression, the time to median depressive event after administration of psilocybin was 92 to 189 days for 25 mg, 43 to 83 days for 10 mg, and 21 to 62 days for 1 mg, depending on the analysis. A 2025 network meta-analysis of RCTs of psilocybin for depression found that it did not significantly improve depression scores relative to placebo on day 2 post-dose but did improve them day 8 and day 15 post-dose. Preliminary meta-analyses suggest that improvements in depressive symptoms with psilocybin are dose-dependent and that higher doses may result in greater improvements than lower doses. It has been proposed that psychedelics like psilocybin may in fact act as active “super placebos” when used for therapeutic purposes.
Decriminalization vs. Legalization
No dose adjustment of psilocin is thought to be required as psilocin is inactivated mainly via metabolism as opposed to renal elimination. The elimination half-life of psilocybin, as psilocin, is 2.1 to 4.7 hours on average (range 1.2–18.6 hours) orally and 1.2 hours (range 1.8–4.5 hours) intravenously. CYP2D6 metabolizer phenotypes do not modify psilocin exposure in humans, suggesting that CYP2D6 is not critically involved in psilocin metabolism and is unlikely to result in interindividual differences in psilocin kinetics or effects.
Is psilocybin safe?
The suggestion was accepted by unanimous vote of the Nomenclature Committee for Fungi of the International Botanical Congress in 2010, meaning that P. semilanceata (a member of the bluing clade) now serves as the type species of the genus. In 2007, a paper by Redhead et al. proposed conserving the genus Psilocybe with Psilocybe semilanceata as its type species. The phylogenetic study by Matheny et al., placed the non-bluing Psilocybe and its close relatives in a basal position within the Strophariaceae, a sister taxon to a clade containing the other genera within that family. A 2006 molecular phylogenetic study of the Agaricales by Matheny and colleagues, further demonstrated the separation of the bluing and non-bluing clades of Psilocybe in a larger, strongly supported phylogenetic tree of the Agaricales.
Functional unblinding by their psychoactive effects and positive psychological expectancy effects (i.e., the placebo effect) are major limitations and sources of bias of clinical trials of psilocybin and other psychedelics for treatment of depression. However, psilocybin mushrooms have had numerous medicinal and religious uses in dozens of cultures throughout history and have a significantly lower potential for abuse than other Schedule I drugs. The RAND Corporation report suggests psilocybin mushrooms may be the most prevalent psychedelic drug among U.S. adults. The few existing accounts that mention psilocybin mushrooms typically lack sufficient information to allow species identification, focusing on their effects.
Are psilocybin mushroom spores legal?
The researchers suggest it may help to regulate the brain’s reward system in people with depression or suicidal ideation. According to a 2022 review, psilocybin may have therapeutic potential for treating depression. The effects of psilocybin are psilocybe semilanceata habitat generally similar to those of LSD. According to the National Survey on Drug Use and Health, 8.8 million Americans ages 12 and older used hallucinogens, including psilocybin, in 2023. Manufacturers can also crush dried mushrooms into a powder and prepare them in capsule form.
Abuse potential of psilocybin
This is because the Supreme Court of Florida does not believe that these mushrooms could “reasonably be found to be containers of the schedule I substance, psilocybin”. The relatively easy availability of hallucinogenic Psilocybe from wild and cultivated sources has made it among the most widely used of the hallucinogenic drugs. At present, hallucinogenic mushroom use has been reported among a number of groups spanning from central Mexico to Oaxaca, including groups of Nahua, Mixtecs, Mixe, Mazatecs, Zapotecs, and others. After the Spanish conquest of the Americas, the use of hallucinogenic plants and mushrooms, like other pre-Christian traditions, was forcibly suppressed and driven underground. Shamans, or curanderas would avidly ingest the “sacred mushrooms” for the extrasensory perceptual effects it gave them in order to better assess problems faced in their society.
Long-term effects
Taking certain additional psychoactive drugs may reduce or end the effects of hallucinogens by counteracting their effects on the brain. Magic mushrooms have a low risk of addiction, but research is ongoing, and people may risk poisoning from picking the wrong types of mushrooms. Adverse side effects are often mild or moderate and may resolve with time, but some people may require medical treatment.
- In addition, there is cross-tolerance with the hallucinogenic effects of other psychedelics such as LSD.
- A 2025 network meta-analysis of RCTs of psilocybin for depression found that it did not significantly improve depression scores relative to placebo on day 2 post-dose but did improve them day 8 and day 15 post-dose.
- Psychological distress is a potential adverse event after recreational use of psilocybin.
- In modern times, psilocybin use may be recreational at dance clubs or by people seeking a transcendent spiritual experience.
- The pharmacokinetics of administered psilocybin and psilocin in rodents, for instance in terms of psilocin tissue distribution kinetics, are described as very similar or identical, suggesting very rapid or near-immediate cleavage of psilocybin into psilocin.
No psilocybin has been detected in the blood in humans after oral administration, suggesting virtually complete dephosphorylation into psilocin with the first pass. There is significant first-pass metabolism of psilocybin and psilocin with oral administration. Psilocybin is dephosphorylated into its active form psilocin in the body and hence is a prodrug. Conversely, psilocin is lipophilic and readily crosses the blood–brain barrier to exert effects in the central nervous system. The effects of food on the pharmacokinetics of psilocybin have not been reported and are unknown, but no clear sign of food effects has been observed in preliminary analyses.
Most people in the study correctly guessed which therapy they had received, however, and it is not known if the effect from psilocybin lasted longer than 32 weeks. A 2022 study compared the effect of psychotherapy plus two psilocybin sessions to psychotherapy plus placebo in 93 people with moderate alcohol use disorder. Generally, the recreational use of psilocybin refers to mushrooms containing psilocybin; synthetic production of psilocybin is complicated and expensive. The U.S. Food and Drug Administration (FDA) granted “breakthrough therapy” designation to psilocybin-assisted psychotherapy for both major depressive disorder in 2019 and treatment-resistant depression in 2018. Generally, the nonmedical use of psilocybin refers to mushrooms containing psilocybin; synthetic production of psilocybin is complicated and expensive. Psilocybin can be consumed by eating fresh or dried psilocybin-containing mushrooms.
Norpsilocin (4-HO-NMT), formed from psilocin via demethylation mediated by the cytochrome P450 enzyme CYP2D6, is known to occur in mice in vivo and with human recombinant CYP2D6 in vitro but was not detected in humans in vivo. Approximately 80% of psilocin in blood plasma is in conjugated form, and conjugated psilocin levels are about fourfold higher than levels of free psilocin. Psilocybin’s glucuronidated metabolites include psilocin-O-glucuronide and 4-HIAA-O-glucuronide. Psilocybin undergoes dephosphorylation into psilocin via the acidic environment of the stomach or the actions of alkaline phosphatase (ALP) and non-specific esterases in tissues and fluids.
By this route, its onset is about 20 to 50 minutes, peak effects occur after about 1 to 2 hours, and its duration is about 4 to 6 hours. Psilocin is chemically related to the neurotransmitter serotonin and acts as a non-selective agonist of the serotonin receptors. Psilocybin is transformed into psilocin by dephosphorylation mediated via phosphatase enzymes. That is, the compound itself is biologically inactive but quickly converted by the body to psilocin. Effects include euphoria, changes in perception, a distorted sense of time (via brain desynchronization), and perceived spiritual experiences. WebMD does not provide medical advice, diagnosis or treatment.
Likewise, in a 2010 web-based questionnaire study designed to investigate user perceptions of the benefits and harms of hallucinogenic drug use, 60% of the 503 psilocybin users reported that their use of psilocybin had a long-term positive impact on their sense of well-being. A group of researchers from Johns Hopkins School of Medicine led by Roland Griffiths conducted a study to assess the immediate and long-term psychological effects of the psilocybin experience, using a modified version of the mystical experience questionnaire and a rigorous double-blind procedure. Psychedelic drugs can induce states of consciousness that have lasting personal meaning and spiritual significance in religious or spiritually inclined people; these states are called mystical experiences. Ingesting psilocybin in combination with other drugs, including alcohol, can also increase the likelihood of a bad trip. After ingesting psilocybin, the user may experience a wide range of emotional effects, which can include disorientation, lethargy, giddiness, euphoria, joy, and depression. Another form of psilocybin (as well as of related psychedelics like 4-AcO-DMT) is mushroom edibles such as chocolate bars and gummies, which may be purchased at psychedelic mushroom stores.
Since then, various chemists have improved the methods for laboratory synthesis and purification of psilocybin. There are two known crystalline polymorphs of psilocybin, as well as reported hydrated phases. Psilocybin is a member of the general class of tryptophan-based compounds that originally functioned as antioxidants in earlier life forms before assuming more complex functions in multicellular organisms, including humans. It is structurally related to serotonin, a monoamine neurotransmitter that is a derivative of the amino acid tryptophan.
However, some trials have not found psilocybin to significantly outperform placebo in the treatment of depression. The antidepressant effects of psilocybin with psychological support have been found to last at least 6 weeks following a single dose. In 2018, the United States Food and Drug Administration (FDA) granted breakthrough therapy designation for psilocybin-assisted therapy for treatment-resistant depression. From 1 July 2023, the Australian medicines regulator has permitted psychiatrists to prescribe psilocybin for the therapeutic treatment of treatment-resistant depression. Psilocybin and psilocin are listed as Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances. A 2009 national survey of drug use by the US Department of Health and Human Services concluded that the number of first-time psilocybin mushroom users in the United States was roughly equivalent to the number of first-time users of cannabis.
