According to the National Institute on Drug Abuse, people can continue to experience flashbacks anywhere from weeks to years after using the hallucinogen. Another 2024 review suggests that psilocybin may have short-term and long-term antidepressant effects. Adults who took psilocybin experienced a clinically significant reduction in depressive symptoms compared with adults who took a placebo. Research in the review also suggests psilocybin may help to treat depression and anxiety due to end stage cancer.
Studies have demonstrated that psilocybin significantly impairs subjects’ ability to gauge time psilocybe semilanceata habitat intervals longer than 2.5 seconds, impairs their ability to synchronize to inter-beat intervals longer than 2 seconds, and reduces their preferred tapping rate. Psilocybin produces a variety of psychological, perceptual, interpersonal, and physical effects. Psilocin is about 1.4 times as potent as psilocybin because of the two compounds’ difference in molecular weight. It is primarily taken orally, but other routes of administration, such as intravenous injection, are sometimes employed by licensed medical researchers using pharmaceutical-grade psilocybin powder designed for injection.
Psychiatric and other disorders
The maximal levels of psilocin have been found to range from 8.2 ng/mL to 37.6 ng/mL across a dose range of 14 to 42 mg. The mean time to peak levels for psilocin is 1.05 to 3.71 hours in different studies, with most around 2 hours and the upper limit of 3.71 hours being an outlier. After oral administration, psilocybin is detectable in the blood circulation within 20 to 40 minutes, and psilocin is detectable after 30 minutes. Long-term repeated use of psilocybin may result in risk of cardiac valvulopathy and other complications by activating serotonin 5-HT2B receptors. Some of psilocybin’s behavioral and potential therapeutic effects may be mediated by changes to the gut microbiome. These effects are partially but not fully dependent on its activation of the serotonin 5-HT2A and/or 5-HT2C receptors.
A 2020 analysis suggests that higher doses of psilocybin may increase the risk of negative experiences. In the wild, people may mistake mushrooms containing psilocybin for other mushrooms that are poisonous. Eating mushrooms that contain psilocybin can have a variety of effects, ranging from euphoria to hallucinations.
Recent legislative developments and potential changes
Conversely, areas of the brain involved in the ToMN showed increased activity and functional activation in response to psychedelics. In studies done with single use psilocybin, areas of the DMN showed decreased functional connectivity (communication between areas of the brain). Psychedelics, including psilocybin, have been shown to affect different clusters of brain regions known as the “theory of mind network” (ToMN) and the default mode network (DMN). Further studies demonstrate that supportive settings significantly reduce the likelihood of adverse reactions, including panic, paranoia, or psychological distress.
- Guzmán suggests this is a vestige of Spanish colonial influence from several hundred years earlier, when mushroom use was persecuted by the Catholic Church.
- Selective serotonin 5-HT2A receptor antagonists like volinanserin block the head-twitch response (HTR), a behavioral proxy of psychedelic-like effects, induced by psilocybin in rodents, and the HTR is similarly absent in serotonin 5-HT2A receptor knockout mice.
- The psilocybin molecule is indirectly responsible for the hallucinogenic properties of the Psilocybe.
- In many countries, including Russia, India, and South Africa, psilocybin is illegal.
- These may take the form of a visual flashback, a traumatic recall of an intensely upsetting experience.
What impacts effects?
Psilocybin mushrooms, as well as other “soft drugs” which are stronger than cannabis but not synthetic, are legally available through smart shops in the Netherlands. This is because only the psilocybin and psilocin compounds are considered Schedule I drugs and there is no presence of these compounds in the spores themselves, only in the fruiting body of the cultivated spores. The purified chemicals psilocybin and psilocin are listed as Schedule II drugs under the United Nations 1971 Convention on Psychotropic Substances.
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There is a significant relationship between psilocybin’s hallucinogenic effects and serotonin 5-HT2A receptor occupancy in humans. Selective serotonin 5-HT2A receptor antagonists like volinanserin block the head-twitch response (HTR), a behavioral proxy of psychedelic-like effects, induced by psilocybin in rodents, and the HTR is similarly absent in serotonin 5-HT2A receptor knockout mice. Psilocybin’s and psilocin’s psychedelic effects are mediated specifically by agonism of the serotonin 5-HT2A receptor. Benzodiazepines might interfere with the therapeutic effects of psychedelics like psilocybin, such as sustained antidepressant effects. This strategy’s safety is not entirely clear and might have risks, but benzodiazepines have been used to manage psychedelics’ adverse psychological effects in clinical studies and in Emergency Rooms.
Relatedly, psilocybin has been found not to enhance but rather to inhibit hippocampal neurogenesis in rodents. It has been found to promote neuroplasticity in the brain in a rapid, robust, and sustained manner with a single dose. Psilocybin produces profoundly decreased locomotor and investigatory behavior in rodents, and this appears to be dependent on serotonin 5-HT1A receptor activation but not on activation of the serotonin 5-HT2A or 5-HT2C receptors. In addition, region-dependent alterations in brain glutamate levels may be related to the experience of ego dissolution.
Psilocybe (/ˌsaɪloʊˈsaɪbi/ SY-loh-SY-bee) is a genus of gilled mushrooms, growing worldwide, in the family Hymenogastraceae. Repeated dosing of psilocybin is being explored for maximization and maintenance of depressive symptom improvement, with preliminary effectiveness observed. A 2025 meta-analysis found a moderate effect size advantage of psilocybin relative to placebo.
Serotonin 5-HT2A receptor antagonists such as atypical antipsychotics and certain antidepressants may block psilocybin’s hallucinogenic effects and hence may be considered contraindicated in this sense. Positive effects that psilocybin has on individuals can be observed by taking on an anthropological approach and moving away from the Western biomedical view; this is aided by the studies done by Leary. Through further anthropological studies regarding “personal insights” and the psychosocial effects of psilocybin, it can be seen in many traditional societies that powerful mind-active substances such as psilocybin are regularly “consumed ritually for therapeutic purposes or for transcending normal, everyday reality”.
Based on the results of animal studies and limited human case reports, the human lethal dose of psilocybin has been extrapolated to be 2,000 to 6,000 mg, which is around 1,000 times greater than its effective dose of 6 mg and 200 times the typical recreational dose of 10 to 30 mg. One analysis of people hospitalized for psilocybin poisoning found high urine concentrations of phenethylamine (PEA), suggesting that PEA might contribute to the effects of psilocybin poisoning. But single high doses or widely spaced doses (e.g., months apart) are thought to be safe, and concerns about cardiac toxicity apply more to chronic psychedelic microdosing or very frequent intermittent use (e.g., weekly). Psilocybin mushrooms were ranked as the illicit drug with the lowest harm, corroborating conclusions reached earlier by expert groups in the United Kingdom.
Serotonergic Drugs interacts with Psilocybin
However, according to Heim’s research in Mexico, he identified three species of Psilocybe that he believed were used in these native ceremonies. The Wassons did much to publicize their discovery, even publishing an article on their experiences in Life in 1957. Gordon Wasson became the first Westerners to actively participate in an indigenous mushroom ceremony.
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Hallucinogenic Psilocybe were known to the aboriginal Mexicans as teonanácatl (literally “divine mushroom”) and were reportedly served at the coronation of Moctezuma II in 1502. Woolley and Campbell conducted research to determine whether the depletion of the hormone serotonin had a direct effect on mental disorders and that hallucinations might be due to an excess of serotonin. This reaction is thought to be due to the oxidation of psilocybin after the outer surface of the fruit body has been breached.
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One study has suggested that psilocybin may be helpful for alcohol use disorder. An annual nationally representative survey on drug use and health reported that 9.68 percent of U.S. adults have used psilocybin at least once in their lifetime, based on data gathered between 2015 and 2018. For example, people who use psilocybin may report feeling strong emotions, seeing vibrant images, reliving vivid memories, or experiencing perceptual changes such as a sense of timelessness or a dissolving of the ego. The effects of taking psilocybin are hard to predict and can vary widely from person to person.
Meinhardt MW, Güngör C, Skorodumov I, Mertens LJ, Spanagel R. Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse. Effect of psilocybin on empathy and moral decision-making. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.
Psilocybin’s anti-inflammatory effects might be involved in its potential antidepressant benefits and might also have other therapeutic applications, such as treatment of asthma and neuroinflammation. Psilocin was also reported to act as a highly potent positive allosteric modulator of the tropomyosin receptor kinase B (TrkB), one of the receptors of brain-derived neurotrophic factor (BDNF), but subsequent studies failed to reproduce these findings and instead found no interaction of psilocin with TrkB. Unlike certain other psychedelics such as LSD, it appears to show little affinity for many other targets, such as dopamine receptors.
Neuroimaging features of psilocybin-induced toxic-metabolic encephalopathy in an adolescent. Pharmacokinetics and pharmacodynamics of oral psilocybin administration in healthy participants. Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Borowiak KS, Ciechanowski K, Waloszczyk P. Psilocybin mushroom (Psilocybe semilanceata) intoxication with myocardial infarction. Severe rhabdomyolysis, acute renal failure and posterior encephalopathy after ‘magic mushroom’ abuse.
- Effect of psilocybin on empathy and moral decision-making.
- Numerous drugs act as serotonin 5-HT2A receptor antagonists, including antidepressants like trazodone and mirtazapine, antipsychotics like quetiapine, olanzapine, and risperidone, and other agents like ketanserin, pimavanserin, cyproheptadine, and pizotifen.
- Psilocybe (/ˌsaɪloʊˈsaɪbi/ SY-loh-SY-bee) is a genus of gilled mushrooms, growing worldwide, in the family Hymenogastraceae.
The greatest species diversity seems to be in the neotropics, from Mesoamerica through Brazil and Chile. Ecologically, all species of Psilocybe are saprotrophs, growing on various kinds of decaying organic matter. Hallucinogenic species typically have a blue-staining reaction when the fruit body is bruised. 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.