181-529: Psilocybin , also known as 4-phosphoryloxy- N , N -dimethyltryptamine ( 4-PO-DMT ), and formerly sold under the brand name Indocybin , is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi . Psilocybin is itself biologically inactive but is quickly converted by the body to psilocin , which has mind-altering effects similar, in some aspects, to those of other classical psychedelics . Effects include euphoria , visual and mental hallucinations , changes in perception ,
362-419: A psychotherapeutic setting reveal that psychedelic drugs may assist with treating depression , alcohol addiction , and nicotine addiction . Although further research is needed, existing results suggest that psychedelics could be effective treatments for certain forms of psychopathology. A 2022 survey found that 28% of Americans had used a psychedelic at some point in their life. The term psychedelic
543-470: A "foolish mushroom" in his 1640 herbal Theatricum Botanicum . The first reliably documented report of intoxication with Psilocybe semilanceata —Europe's most common and widespread psychedelic mushroom—involved a British family in 1799, who prepared a meal with mushrooms they had picked in London's Green Park . American banker and amateur ethnomycologist R. Gordon Wasson and his wife, Valentina P. Wasson ,
724-623: 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 . Psilocybin mushrooms were ranked as the illicit drug with the lowest harm, corroborating conclusions reached earlier by expert groups in the United Kingdom. Psilocybin mushrooms have been and continue to be used in Indigenous American cultures in religious, divinatory , or spiritual contexts. Reflecting
905-464: A 25-year followup to the experiment, all of the subjects given psilocybin described their experience as having elements of "a genuine mystical nature and characterized it as one of the high points of their spiritual life". Psychedelic researcher Rick Doblin considered the study partially flawed due to incorrect implementation of the double-blind procedure, and several imprecise questions in the mystical experience questionnaire. Nevertheless, he said that
1086-415: A 60-kilogram (130 lb) person to reach the 280 mg/kg LD 50 value of rats. Based on the results of animal studies, the lethal dose of psilocybin has been extrapolated to be 6 grams, 1000 times greater than the effective dose of 6 milligrams. The Registry of Toxic Effects of Chemical Substances assigns psilocybin a relatively high therapeutic index of 641 (higher values correspond to
1267-513: A bad trip will occur, one's mood, surroundings, sleep, hydration , social setting, and other factors can be controlled (colloquially referred to as " set and setting ") to minimize the risk of a bad trip. The concept of "set and setting" also generally appears to be more applicable to psychedelics than to other types of hallucinogens such as deliriants, hypnotics and dissociative anesthetics. Classic psychedelics are considered to be those found in nature like psilocybin, DMT, mescaline, and LSD which
1448-530: 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, and has rarely been documented—as of 2011, only two cases attributed to overdosing on hallucinogenic mushrooms (without concurrent use of other drugs) have been reported in the scientific literature and may involve other factors aside from psilocybin. Panic reactions can occur after consumption of psilocybin-containing mushrooms, especially if
1629-405: 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. Psychedelic Psychedelic film Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and
1810-541: A causal relationship between psilocybin and the onset of psychosis has not been established as of 2011, researchers have called for investigation of the relationship. Many of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context. A population study on associations between psychedelic use and mental illness published in 2013 found no evidence that psychedelic use
1991-525: A continent in that southern part; full of animals and more populous than our Europe, or Asia, or Africa, and even more temperate and pleasant than any other region known to us. Vespucci's letter was a publishing sensation in Europe that was immediately and repeatedly reprinted in several other countries. Peter Martyr, who had been writing and circulating private letters commenting on Columbus's discoveries since 1493, often shares credit with Vespucci for designating
SECTION 10
#17328545677312172-452: A distorted sense of time , and perceived spiritual experiences . It can also cause adverse reactions such as nausea and panic attacks . Imagery in cave paintings and rock art of modern-day Algeria and Spain suggests that human use of psilocybin mushrooms predates recorded history. In Mesoamerica , the mushrooms had long been consumed in spiritual and divinatory ceremonies before Spanish chroniclers first documented their use in
2353-400: A greater appreciation for life, reduced anxiety, a sense of spiritual enlightenment, and a sense of belonging or interconnectedness with the universe. Negative experiences, colloquially known as "bad trips," evoke an array of dark emotions, such as irrational fear, anxiety, panic, paranoia, dread, distrustfulness, hopelessness, and even suicidal ideation. While it is impossible to predict when
2534-399: A half hours (about half as long as psilocybin's), they proved more manageable for use in psycholytic therapy . Sandoz also marketed and sold pure psilocybin under the name Indocybin to clinicians and researchers worldwide. There were no reports of serious complications when psilocybin was used in this way. In the early 1960s, Harvard University became a testing ground for psilocybin through
2715-444: A high dose reported feelings of significant fear and 17% experienced transient paranoia . In studies at Johns Hopkins , among those given a moderate dose (but still enough to "give a high probability of a profound and beneficial experience"), negative experiences were rare, whereas one-third of those given a high dose experienced anxiety or paranoia. Low doses can induce hallucinatory effects. Closed-eye hallucinations may occur, where
2896-445: A high enough dose. Luis Luna describes psychedelic experiences as having a distinctly gnosis -like quality, and says that they offer "learning experiences that elevate consciousness and can make a profound contribution to personal development ." Czech psychiatrist Stanislav Grof studied the effects of psychedelics like LSD early in his career and said of the experience, that it commonly includes "complex revelatory insights into
3077-571: A large open ocean between China on the east side of the map, and the inchoate largely water-surrounded North American and South American discoveries on the western side of map. Out of uncertainty, they depicted a finger of the Asian land mass stretching across the top to the eastern edge of the map, suggesting it carried over into the western hemisphere. E.g. the Cantino Planisphere denotes Greenland as "Punta d'Asia"—"edge of Asia". Some maps, e.g.,
3258-448: A later review by Jos ten Berge (1999), who concluded that dosage, set, and setting were fundamental factors in determining the outcome of experiments that tested the effects of psychedelic drugs on artists' creativity. After ingesting psilocybin, the user may experience a wide range of emotional effects which can include: feelings of disorientation, lethargy, giddiness, euphoria , joy, and depression . In one study, 31% of volunteers given
3439-474: A lower prevalence of use at 7.6%. Notably, less than 1% of U.S. adults reported using any psychedelic drugs within the past month. Psychedelic microdosing is the practice of using sub-threshold doses ( microdoses ) of psychedelics in an attempt to improve creativity, boost physical energy level, emotional balance, increase performance on problems-solving tasks and to treat anxiety, depression and addiction. The practice of microdosing has become more widespread in
3620-783: A non-supportive environment (see: set and setting ). Ingesting psilocybin in combination with other drugs, including alcohol , can also increase the likelihood of a bad trip. Other than the duration of the experience, the effects of psilocybin are similar to comparable dosages of lysergic acid diethylamide (LSD) or mescaline. However, in the Psychedelics Encyclopedia , author Peter Stafford noted, "The psilocybin experience seems to be warmer, not as forceful and less isolating. It tends to build connections between people, who are generally much more in communication than when they use LSD." Psychedelics, including psilocybin, have been shown to affect different clusters of brain regions known as
3801-428: A perceived "expansion of consciousness". Also referred to as classic hallucinogens or serotonergic hallucinogens , the term psychedelic is sometimes used more broadly to include various types of hallucinogens, such as those which are atypical or adjacent to psychedelia like salvia and MDMA , respectively. Classic psychedelics generally cause specific psychological, visual, and auditory changes, and oftentimes
SECTION 20
#17328545677313982-613: A physician, studied the ritual use of psychoactive mushrooms by the native population in the Mazatec village Huautla de Jiménez , Mexico. In 1957, Wasson described the psychedelic visions he experienced during these rituals in " Seeking the Magic Mushroom ", an article published in the American weekly Life magazine. Later the same year they were accompanied on a follow-up expedition by French mycologist Roger Heim , who identified several of
4163-562: A preference for evoking serotonin and dopamine release over norepinephrine (epinephrine) release. Psychedelic tryptamines found in nature include psilocin, DMT , 5-MeO-DMT, and tryptamines that have been synthesized in the laboratory include 4-HO-MET , 4-HO-MiPT , and 5-MeO-DALT . Phenethylamine is also a trace amine but to a lesser extent acts as a neurotransmitter in the human central nervous system (CNS). Phenethylamine instead regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1), which plays
4344-578: A psychedelic. A June 2024 report by the RAND Corporation suggests psilocybin mushrooms may be the most prevalent psychedelic drug among adults in the United States. The RAND national survey indicated that 3.1% of U.S. adults reported using psilocybin in the past year. Roughly 12% of respondents acknowledged lifetime use of psilocybin, while a similar percentage reported having used LSD at some point in their lives. MDMA , also known as ecstasy, showed
4525-666: A qualified professional with appropriate set and setting. However, he called for an "abundance of caution" because in the absence of these conditions a range of negative reactions is possible, including "fear, a prolonged sense of dread, or full panic." He notes that driving or even walking in public can be dangerous during a psychedelic experience because of impaired hand-eye coordination and fine motor control . In some cases, individuals taking psychedelics have performed dangerous or fatal acts because they believed they possessed superhuman powers. Psilocybin-induced states of mind share features with states experienced in psychosis , and while
4706-583: A qualitative, numerical scale. In the 1962 Marsh Chapel Experiment , which was run by Pahnke at the Harvard Divinity School under the supervision of Timothy Leary, almost all of the graduate degree divinity student volunteers who received psilocybin reported profound religious experiences. One of the participants was religious scholar Huston Smith , author of several textbooks on comparative religion ; he later described his experience as "the most powerful cosmic homecoming I have ever experienced." In
4887-429: A reaction accompanied by fear, other unpleasant feelings, and occasionally by dangerous behavior. In general, the phrase "bad trip" is used to describe a reaction that is characterized primarily by fear or other unpleasant emotions, not just a transitory experience of such feelings. A variety of factors may contribute to a psilocybin user experiencing a bad trip, including "tripping" during an emotional or physical low or in
5068-832: A regular meditation practice and an extensive spiritual practice support program. Although other researchers have described instances of psychedelic drug usage leading to new psychological understandings and personal insights, it is not known whether these experimental results can be generalized to larger populations. Common 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%) (inability to properly direct or limit motions). The temporary increases in blood pressure caused by
5249-466: A route which Dr. Leary abandoned in the early 1960s." The National Institute of Drug Abuse -funded study, published in 2006, has been praised by experts for the soundness of its experimental design. In the experiment, 36 volunteers without prior experience with hallucinogens were given psilocybin and methylphenidate (Ritalin) in separate sessions; the methylphenidate sessions served as a control and psychoactive placebo . The degree of mystical experience
5430-523: A rye grain substrate; San Antonio 1971) to the production of Psilocybe [Stropharia] cubensis . The new technique involved the use of ordinary kitchen implements, and for the first time the layperson was able to produce a potent entheogen in his own home, without access to sophisticated technology, equipment or chemical supplies." San Antonio's technique describes a method to grow the common edible mushroom Agaricus bisporus . Because of lack of clarity about laws concerning psilocybin mushrooms, specifically in
5611-570: A sense of contact with a "Transcendent Other"—reflecting a deeper understanding of our connectedness with nature. Psychedelic drugs can induce states of consciousness that have lasting personal meaning and spiritual significance in individuals who are religious or spiritually inclined; these states are called mystical experiences . Some scholars have proposed that many of the qualities of a drug-induced mystical experience are indistinguishable from mystical experiences achieved through non-drug techniques , such as meditation or holotropic breathwork . In
Psilocybin - Misplaced Pages Continue
5792-449: A significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. When VMAT2 is inhibited monoamine neurotransmitters such as dopamine cannot be released into the synapse via typical release mechanisms. Mescaline is a naturally occurring psychedelic protoalkaloid of
5973-478: A single high dosage of psilocybin can cause long-term changes in the personality of its users. About half of the study participants—described as healthy, "spiritually active", and many possessing postgraduate degrees —showed an increase in the personality dimension of openness (assessed using the Revised NEO Personality Inventory ), and this positive effect was still apparent over a year after
6154-419: A speech on his 100th birthday, the inventor of LSD, Albert Hofmann said of the drug: "It gave me an inner joy, an open mindedness , a gratefulness, open eyes and an internal sensitivity for the miracles of creation... I think that in human evolution it has never been as necessary to have this substance LSD. It is just a tool to turn us into what we are supposed to be." With certain psychedelics and experiences,
6335-442: A state of depersonalization disorder . Usage by those with schizophrenia can induce acute psychotic states requiring hospitalization. The similarity of psilocybin-induced symptoms to those of schizophrenia has made the drug a useful research tool in behavioral and neuroimaging studies of this psychotic disorder. In both cases, psychotic symptoms are thought to arise from a "deficient gating of sensory and cognitive information" in
6516-422: A strong to extreme "experience of fear" or dysphoria (i.e., a "bad trip") at some point during the psilocybin session (which was not reported by any subject during the methylphenidate session); about one-third of these (13% of the total) reported that this dysphoria dominated the entire session. These negative effects were reported to be easily managed by the researchers and did not have a lasting negative effect on
6697-415: 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. When asked in an interview about the similarity of his work with Leary's, Griffiths explained the difference: "We are conducting rigorous, systematic research with psilocybin under carefully monitored conditions,
6878-484: A substantially altered state of consciousness . They have had the largest influence on science and culture, and include mescaline , LSD , psilocybin , and DMT . Most psychedelic drugs fall into one of the three families of chemical compounds: tryptamines , phenethylamines , or lysergamides (LSD is considered both a tryptamine and lysergamide). They act via serotonin 2A receptor agonism . When compounds bind to serotonin 5-HT 2A receptors, they modulate
7059-519: A user may also experience an " afterglow " of improved mood or perceived mental state for days or even weeks after ingestion in some cases. In 1898, the English writer and intellectual Havelock Ellis reported a heightened perceptual sensitivity to "the more delicate phenomena of light and shade and color" for a prolonged period of time after his exposure to mescaline. Good trips are reportedly deeply pleasurable, and typically involve intense joy or euphoria,
7240-405: A very strong correlation between 5-HT 2A receptor affinity and human hallucinogenic potency . In addition, the intensity of hallucinogenic effects in humans is directly correlated with the level of serotonin 5-HT 2A receptor occupancy as measured with positron emission tomography (PET) imaging . Serotonin 5-HT 2A receptor blockade with drugs like the semi-selective ketanserin and
7421-426: A week can lead to diminished effects. Tolerance dissipates after a few days, so doses can be spaced several days apart to avoid the effect. A cross-tolerance can develop between psilocybin and the pharmacologically similar LSD, and between psilocybin and phenethylamines such as mescaline and DOM . Repeated use of psilocybin does not lead to physical dependence . A 2008 study concluded that, based on US data from
Psilocybin - Misplaced Pages Continue
7602-456: Is 163 ± 64 minutes when taken orally, or 74.1 ± 19.6 minutes when injected intravenously. Psilocybin 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 . Psilocin is broken down by the enzyme monoamine oxidase (MAO) to produce several metabolites that can circulate in
7783-545: Is 280 milligrams per kilogram (mg/kg), approximately one and a half times that of caffeine . The lethal dose of psilocybin when administered intravenously in mice is 285 mg/kg and in rats is 280 mg/kg. When administered intravenously in rabbits, psilocybin's LD 50 is approximately 12.5 mg/kg. Psilocybin comprises approximately 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms (3.7 lb) of dried mushrooms, or 17 kilograms (37 lb) of fresh mushrooms, would be required for
7964-551: Is a derivative and functional analogue of LSD and a homologue of ALD-52 . It modifies the LSD molecule by adding a propionyl group to the nitrogen atom of LSD's indole . Although several attempts have been made, starting in the 19th and 20th centuries, to define common phenomenological structures of the effects produced by classic psychedelics, a universally accepted taxonomy does not yet exist. At lower doses, features of psychedelic experiences include sensory alterations, such as
8145-539: Is a psychoplastogen , which refers to a compound capable of promoting rapid and sustained neuroplasticity. Psilocybin is rapidly dephosphorylated in the body to psilocin , which is an agonist for several serotonin receptors , which are also known as 5-hydroxytryptamine (5-HT) receptors. In rats, psilocin binds with high affinity to 5-HT 2A receptors and low affinity to 5-HT 1 receptors , including 5-HT 1A and 5-HT 1D ; effects are also mediated via 5-HT 2C receptors. The psychotomimetic (mimicking
8326-714: Is almost unanimously agreed that psychedelics produce their effect by acting as strong partial agonists at the 5-HT 2A receptors. How this produces the psychedelic experience is unclear, but it is likely that it acts by increasing excitation in the cortex, possibly by specifically facilitating input from the thalamus , the major relay for sensory information input to the cortex . Additionally, researchers discovered that many psychedelics are potent psychoplastogens , compounds capable of promoting rapid and sustained neural plasticity . Psychedelics are thought to mediate their hallucinogenic effects by activation of serotonin 5-HT 2A receptors. Serotonergic psychedelics, such as
8507-405: Is an inaccurate descriptor of the actual effects of these drugs. In the lay press, the term psychedelic is still the most popular and has held sway for nearly four decades. Most recently, there has been a movement in nonscientific circles to recognize the ability of these substances to provoke mystical experiences and evoke feelings of spiritual significance. Thus, the term entheogen , derived from
8688-416: Is derived from naturally occurring ergotamine, and non-classic psychedelics are considered to be newer analogs and derivatives of pharmacophore lysergamides, tryptamine, and phenethylamine structures like 2C-B . Many of these psychedelics cause remarkably similar effects, despite their different chemical structure. However, many users report that the three major families have subjectively different qualities in
8869-596: Is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits. Psychedelics have also been shown to have potent anti-inflammatory activity and therapeutic effects in animal models of inflammatory diseases including asthma, and cardiovascular disease and diabetes. Psychedelic culture includes manifestations such as psychedelic music , psychedelic art , psychedelic literature , psychedelic film , and psychedelic festivals . Examples of psychedelic music would be rock bands like
9050-448: Is evidence to suggest that psychoactive mushrooms have been used by humans in religious ceremonies for thousands of years. The Tassili Mushroom Figure was discovered in Tassili , Algeria , and is believed to depict psychedelic mushrooms and the transformation of the user under their influence. The paintings are said to date back to 9000-7000 BC. 6,000-year-old pictographs discovered near
9231-433: Is found in the central nervous system of mammals . It is hypothesized to play a role as a neuromodulator on classical monoamine neurotransmitters , such as dopamine , serotonin, norepinephrine and epinephrine . Tryptamine acts as a non-selective serotonin receptor agonist to activate serotonin receptors, and a serotonin–norepinephrine–dopamine releasing agent (SNDRA) to release more monoamine neurotransmitter, with
SECTION 50
#17328545677319412-402: Is induced by serotonergic psychedelics and is a behavioral proxy of psychedelic-like effects in animals. The HTR is invariably induced by serotonergic psychedelics, is blocked by selective serotonin 5-HT 2A receptor antagonists, and is abolished in serotonin 5-HT 2A receptor knockout mice . In addition, there is a strong correlation between hallucinogenic potency in humans and potency in
9593-510: Is known to strongly influence the subjective experience of the passage of time . Users often feel as if time is slowed down, resulting in the perception that "minutes appear to be hours" or "time is standing still". Studies have demonstrated that psilocybin significantly impairs subjects' ability to gauge time 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 . These results are consistent with
9774-470: Is now named South America, that same map famously labels simply " America ". Martin Waldseemüller 's map of 1516 retreats considerably from his earlier map and back to classical authority, with the Asian land mass merging into North America, which he now calls Terra de Cuba Asie partis , and quietly drops the "America" label from South America, calling it merely Terra incognita . The western coast of
9955-635: Is often described as a key feature of the psychedelic experience. Many psychedelic drugs are illegal to possess without lawful authorisation, exemption or license worldwide under the UN conventions , with occasional exceptions for religious use or research contexts. Despite these controls, recreational use of psychedelics is common. Legal barriers have made the scientific study of psychedelics more difficult. Research has been conducted, however, and studies show that psychedelics are physiologically safe and rarely lead to addiction. Studies conducted using psilocybin in
10136-712: Is overwhelming. The serotonin 5-HT 2A receptor activates several downstream signaling pathways . These include the G q , β-arrestin2 , and other pathways. Activation of both the G q and β-arrestin2 pathways have been implicated in mediating the hallucinogenic effects of serotonergic psychedelics. However, subsequently, activation of the G q pathway and not β-arrestin2 has been implicated. Interestingly, G q signaling appeared to mediate hallucinogenic-like effects, whereas β-arrestin2 mediated receptor downregulation and tachyphylaxis . The lack of psychedelic effects with non-hallucinogenic serotonin 5-HT 2A receptor agonists may be due to partial agonism of
10317-504: Is recommended that pregnant women avoid its usage. Psilocybin has low toxicity , indicating that it has low potential for inducing life-threatening events like breathing or heart problems. Research shows that health risks may develop with use of psilocybin. Nonetheless, hospitalizations from it are rare, and overdoses are generally mild and self-limiting. A review regarding the management of psychedelic overdoses suggested that psilocybin-related overdose management should prioritize managing
10498-411: Is sometimes used for a much broader range of drugs, including empathogen–entactogens , dissociatives , and atypical hallucinogens/psychoactives such as Amanita muscaria , Cannabis sativa , Nymphaea nouchali and Salvia divinorum . Thus, the term serotonergic psychedelic is sometimes used for the narrower class. It is important to check the definition of a given source. This article uses
10679-528: Is structurally related to serotonin , a monoamine neurotransmitter which is a derivative of the amino acid tryptophan . 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. Other related indole-containing psychedelic compounds include dimethyltryptamine , found in many plant species and in trace amounts in some mammals, and bufotenin , found in
10860-485: Is the proposed use of psychedelic drugs to treat mental disorders . As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions. The procedure for psychedelic therapy differs from that of therapies using conventional psychiatric medications . While conventional medications are usually taken without supervision at least once daily, in contemporary psychedelic therapy
11041-669: The Terra Australis that had been posited as a hypothetical southern continent. All of the New World countries use the Latin script as its official script. The Florentine explorer Amerigo Vespucci is usually credited for coming up with the term "New World" ( Mundus Novus ) for the Americas in his 1503 letter, giving it its popular cachet, although similar terms had been used and applied before him. The Venetian explorer Alvise Cadamosto used
SECTION 60
#173285456773111222-476: The Americas . The term arose in the early 16th century during Europe 's Age of Discovery , after Italian explorer Amerigo Vespucci published the Latin -language pamphlet Mundus Novus , presenting his conclusion that these lands (soon called America based on Amerigo's name ) constitute a new continent . This realization expanded the geographical horizon of earlier European geographers, who had thought that
11403-634: The Grateful Dead , Jefferson Airplane and The Beatles . Many psychedelic bands and elements of the psychedelic subculture originated in San Francisco during the mid to late 1960s. Many psychedelics are classified under Schedule I of the United Nations Convention on Psychotropic Substances of 1971 as drugs with the greatest potential to cause harm and no acceptable medical uses. In addition, many countries have analogue laws; for example, in
11584-595: The Gulf of Paria implied that a previously unknown continent must lie behind it. Columbus proposes that the South American landmass is not a "fourth" continent, but rather the terrestrial paradise of Biblical tradition, a land allegedly known, but undiscovered, by Christendom . In another letter to the nurse of Prince John, written 1500, Columbus refers to having reached a "new heavens and world" ("nuevo cielo é mundo") and that he had placed "another world" ("otro mundo") under
11765-661: The Rio Grande Valley in North America by native tribes as an entheogen . In the Andean region of South America, the San Pedro cactus ( Trichocereus macrogonus var. pachanoi , syn. Echinopsis pachanoi ) has a long history of use, possibly as a traditional medicine . Archaeological studies have found evidence of use going back two thousand years, to Moche culture, Nazca culture , and Chavín culture . Although authorities of
11946-629: The Roman Catholic church attempted to suppress its use after the Spanish conquest, this failed, as shown by the Christian element in the common name "San Pedro cactus" – Saint Peter cactus. The name has its origin in the belief that just as St Peter holds the keys to heaven, the effects of the cactus allow users "to reach heaven while still on earth." In 2022, the Peruvian Ministry of Culture declared
12127-548: The Schedule ;I category of illicit drugs. Such restrictions on the use of these drugs in human research made funding for such projects difficult to obtain, and scientists who worked with psychedelic drugs faced being "professionally marginalized". Although Hofmann tested these compounds on himself , he never advocated their legalization or medical use. In his 1979 book LSD—mein Sorgenkind ( LSD—My Problem Child ), he described
12308-558: The West Indies with what returning sailors told him of the East Indies . Vespucci wrote a preliminary letter to Lorenzo, while anchored at Bezeguiche, which he sent back with the Portuguese fleet, which expressed a certain puzzlement about his conversations. Vespucci ultimately was convinced while on his mapping expedition of eastern Brazil from 1501 to 1502. After returning from Brazil in
12489-596: The basal ganglia , and some psychotomimetic symptoms of psilocin are reduced by haloperidol , a non-selective dopamine receptor antagonist. Taken together, these suggest that there may be an indirect dopaminergic contribution to psilocin's psychotomimetic effects. Psilocybin and psilocin have no affinity for dopamine D 2 receptor , unlike another common 5-HT receptor agonist, lysergic acid diethylamide (LSD). Psilocin antagonizes histamine H 1 receptors with moderate affinity, compared to LSD which has lower affinity. Serotonin receptors are located in numerous parts of
12670-575: The defeat of the Aztecs , the Spanish forbade traditional religious practices and rituals that they considered "pagan idolatry", including ceremonial mushroom use. For the next four centuries, the Indians of Mesoamerica hid their use of entheogens from the Spanish authorities. Dozens of species of psychedelic mushrooms are found in Europe, but there is little documented usage of them in Old World history besides
12851-546: The glucuronosyltransferase enzymes UGT1A9 in the liver, and by UGT1A10 in the small intestine. Based on studies using animals , about 50% of ingested psilocybin is absorbed through the stomach and intestine. About 80% of psilocin is glucuronidated into psilocin- O -glucuronide and about 4% is demethylated and oxidatively deaminated via MAO into 4-HIAL. 4-HIAL is subsequently oxidized by aldehyde dehydrogenase (ALDH) into 4-HIAA or can be converted by alcohol dehydrogenase (ADH) into 4-HTOL. Within 24 hours, about 65% of
13032-471: The locus coeruleus , nucleus accumbens , and amygdala , and activation of the PFC by serotonergic psychedelics may thereby modulate these areas. In addition to the PFC, there is moderate to high expression of serotonin 5-HT 2A receptors in the primary visual cortex (V1) as well as expression of the serotonin 5-HT 2A receptor in other visual areas, and activation of these receptors may contribute to or mediate
13213-607: The medial prefrontal cortex (mPFC). Activation of serotonin 5-HT 2A receptors in this area results in marked excitatory and inhibitory effects as well as increased release of glutamate and GABA . Direct injection of serotonin 5-HT 2A receptor agonists into the mPFC produces the HTR. Drugs that suppress glutamatergic activity in the mPFC, including AMPA receptor antagonists, metabotropic glutamate mGlu 2 / 3 receptor agonists, μ-opioid receptor agonists, and adenosine A 1 receptor agonists, block or suppress many of
13394-556: The serotonin 5-HT 2A receptor but also of the serotonin 5-HT 2B receptor and other serotonin receptors . A potential risk of frequent repeated use of serotonergic psychedelics is cardiac fibrosis and valvulopathy caused by 5-HT 2B receptor activation. However, single high doses or widely spaced doses (e.g., months) are widely thought to be safe and concerns about cardiac toxicity apply more to chronic psychedelic microdosing or very frequent use (e.g., weekly). Selective 5-HT 2A receptor agonists that do not activate
13575-555: The substituted phenethylamine class. Amides of lysergic acid are collectively known as lysergamides , and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine receptors . The structure of lysergamides contains the structure of both tryptamines and phenethylamines. LSD (Lysergic Acid Diethylamide) is one of many lysergamides. A wide range of lysergamides have emerged in recent years, inspired by existing scientific literature. Others, have appeared from chemical research. 1P-LSD
13756-400: The tryptamines psilocin , DMT , and 5-MeO-DMT , the phenethylamines mescaline , DOM , and 2C-B , and ergolines and lysergamides like LSD , all act as agonists of the serotonin 5-HT 2A receptors. In addition, some psychedelics, such as phenethylamines like DOM and 2C-B, show high selectivity for the serotonin 5-HT 2 receptors over other serotonin receptors . There is
13937-462: The turkey were originally domesticated by pre-Columbian peoples in Mesoamerica . Agriculturalists in the Andean region of South America brought forth the cassava , peanut , potato , quinoa and domesticated animals like the alpaca , guinea pig and llama . Other New World crops include the sweetpotato , cashew , cocoa , rubber , sunflower , tobacco , and vanilla , and fruits like
14118-540: The "discoverer of the new globe" ("Colonus ille novi orbis repertor"). A year later, on 20 October 1494, Peter Martyr again refers to the marvels of the New Globe ("Novo Orbe") and the " Western Hemisphere " ("ab occidente hemisphero"). In Columbus's 1499 letter to the Catholic Monarchs of Spain, reporting the results of his third voyage, he relates how the massive waters of South America's Orinoco delta rushing into
14299-413: The "feel" of the experience, which are difficult to describe. Some compounds, such as 2C-B, have extremely tight "dose curves", meaning the difference in dose between a non-event and an overwhelming disconnection from reality can be very slight. There can also be very substantial differences between the drugs; for instance, 5-MeO-DMT rarely produces the visual effects typical of other psychedelics. Despite
14480-466: The "theory of mind network" (ToMN) and the default mode network (DMN). The ToMN involves making inferences and understanding social situations based on patterns whereas, the DMN relates more to introspection and one's sense of self. The DMN in particular is related to increased rumination and worsening self-image in patients with major depressive disorder (MDD). In studies done with single use psilocybin, areas of
14661-480: The 1506 Contarini–Rosselli map and the 1508 Johannes Ruysch map, bowing to Ptolemaic authority and Columbus's assertions, have the northern Asian landmass stretching well into the western hemisphere and merging with known North America, Labrador, Newfoundland, etc. These maps place the island of Japan near Cuba and leave the South American continent—Vespucci's "New World" proper—detached and floating below by itself. The Waldseemüller map of 1507, which accompanied
14842-540: The 16th century. 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 (spirituality-enhancing agent) grew in
15023-405: The 1960s, Walter Pahnke and colleagues systematically evaluated mystical experiences (which they called "mystical consciousness") by categorizing their common features. These categories, according to Pahnke, "describe the core of a universal psychological experience, free from culturally determined philosophical or theological interpretations", and allow researchers to assess mystical experiences on
15204-419: The 1990s, hallucinogens and their effects on human consciousness were again the subject of scientific study, particularly in Europe. Advances in neuropharmacology and neuropsychology and the availability of brain imaging techniques have provided impetus for using drugs like psilocybin to probe the "neural underpinnings of psychotic symptom formation including ego disorders and hallucinations". Recent studies in
15385-599: The 21st century with more people claiming long-term benefits from the practice. A 2022 study recognized signatures of psilocybin microdosing in natural language and concluded that low amount of psychedelics have potential for application, and ecological observation of microdosing schedules. While the method of action of psychedelics is not fully understood, they are known to show affinities for various 5-HT (serotonin) receptors in different ways and levels, and may be classified by their activity at different 5-HT sub-types, particularly 5-HT 1A , 5-HT 2A , and 5-HT 2C . It
15566-545: The 5-HT 2B receptor or other serotonin receptors, such as 25CN-NBOH , DMBMPP , and LPH-5 , have been developed and are being studied. Selective 5-HT 2A receptor agonists are expected to avoid the cardiac risks of 5-HT 2B receptor activation. Psychedelic substances which may have therapeutic uses include psilocybin, LSD, and mescaline. During the 1950s and 1960s, lack of informed consent in some scientific trials on psychedelics led to significant, long-lasting harm to some participants. Since then, research regarding
15747-419: The Americas as a new world. Peter Martyr used the term Orbe Novo , meaning "New Globe", in the title of his history of the discovery of the Americas, which began appearing in 1511. The Vespucci passage above applied the "New World" label to merely the continental landmass of South America . At the time, most of the continent of North America was not yet discovered, and Vespucci's comments did not eliminate
15928-577: The Americas remained unclear. That there must be a large ocean between Asia and the Americas was implied by the known existence of vast continuous sea along the coasts of East Asia . Given the size of the Earth as calculated by Eratosthenes this left a large space between Asia and the newly discovered lands. Even prior to Vespucci, several maps, e.g. the Cantino planisphere of 1502 and the Canerio map of 1504, placed
16109-445: The Americas until they were introduced by post-Columbian contact in the 1490s. Many common crops were originally domesticated in the Americas before they spread worldwide after Columbian contact, and are still often referred to as " New World crops ". Common beans ( phaseolus ), maize , and squash —the " three sisters "—as well as the avocado , tomato , and wide varieties of capsicum ( bell pepper , chili pepper , etc.), and
16290-761: The Americas, to distinguish them from their counterparts in the "Old World" (Europe, Africa and Asia)—e.g., New World monkeys , New World vultures , New World warblers . The label is also often used in agriculture. Asia, Africa, and Europe share a common agricultural history stemming from the Neolithic Revolution , and the same domesticated plants and animals spread through these three continents thousands of years ago, making them largely indistinct and useful to classify together as "Old World". Common Old World crops, e.g., barley , lentils , oats , peas , rye , wheat , and domesticated animals, e.g., cattle , chickens , goats , horses , pigs , sheep , did not exist in
16471-516: The Atlantic coast of North America in what is present-day Canada and the United States . The term "New World" is still commonly employed when discussing historic spaces, particularly the voyages of Christopher Columbus and the subsequent European colonization of the Americas . It has been framed as being problematic for applying a colonial perspective of discovery and not doing justice to either
16652-559: The DMN showed decreased functional connectivity (communication between areas of the brain). This provides functional insight into the work of psilocybin in increasing one's sense of connection to one's surroundings, as the areas of the brain involved in introspection decrease in functionality under the effects of the drug. Conversely, areas of the brain involved in the ToMN showed increased activity and functional activation in response to psychedelics. These results were not unique to psilocybin and there
16833-567: The Department of Psychiatry and Behavioral Science at Johns Hopkins, responded as follows in a book review: "The unmentioned fact in The Harvard Psychedelic Club is that LSD, psilocybin, mescaline, and the like produce not a "higher consciousness" but rather a particular kind of "lower consciousness" known well to psychiatrists and neurologists—namely, ' toxic delirium .'" Although psilocybin may be prepared synthetically, outside of
17014-529: The Greek word entheos , which means "god within", was introduced by Ruck et al. and has seen increasing use. This term suggests that these substances reveal or allow a connection to the "divine within". Although it seems unlikely that this name will ever be accepted in formal scientific circles, its use has dramatically increased in the popular media and on internet sites. Indeed, in much of the counterculture that uses these substances, entheogen has replaced psychedelic as
17195-440: The HTR assay. Moreover, the HTR paradigm is one of the only animal tests that can distinguish between hallucinogenic serotonin 5-HT 2A receptor agonists and non-hallucinogenic serotonin 5-HT 2A receptor agonists, such as lisuride . In accordance with the preceding animal and human findings, it has been said that the evidence that the serotonin 5-HT 2A receptor mediates the hallucinogenic effects of serotonergic psychedelics
17376-483: The Indies "), and consequently came up with alternative names to refer to them. Only a few weeks after Columbus's return from his first voyage, Martyr wrote letters referring to Columbus's discovered lands as the "western antipodes" ("antipodibus occiduis", letter of 14 May 1493), the "new hemisphere of the earth" ("novo terrarum hemisphaerio", 13 September 1493). In a letter dated 1 November 1493, he refers to Columbus as
17557-520: The Indies of New Spain (published c. 1581), mushrooms were eaten in festivities conducted on the occasion of Aztec emperor Moctezuma II 's accession to the throne in 1502. The Franciscan friar Bernardino de Sahagún wrote of witnessing mushroom use in the Florentine Codex (published 1545–1590), and described how some merchants would celebrate upon returning from a successful business trip by consuming mushrooms to evoke revelatory visions. After
17738-520: The New World, including the Pacific Ocean , was discovered in 1513 by Vasco Núñez de Balboa , twenty years after Columbus' initial voyage. It was a few more years before the voyage of Ferdinand Magellan 's between 1519 and 1522 determined that the Pacific Ocean definitely formed a single large body of water that separates Asia from the Americas. Several years later, the Pacific Coast of North America
17919-497: The Spanish town of Villar del Humo illustrate several mushrooms that have been tentatively identified as Psilocybe hispanica , a hallucinogenic species native to the area. Some scholars have also interpreted archaeological artifacts from Mexico and the so-called Mayan "mushroom stones" of Guatemala as evidence of ritual and ceremonial use of psychoactive mushrooms in the Mayan and Aztec cultures of Mesoamerica . In Nahuatl ,
18100-400: The U.S. have attracted attention from the popular press and brought psilocybin back into the limelight. The effects of psilocybin are highly variable and depend on the mindset and environment in which the user has the experience: factors commonly referred to as set and setting . In the early 1960s, Timothy Leary and colleagues at Harvard University investigated the role of set and setting on
18281-729: The United States, the Federal Analogue Act of 1986 automatically forbids any drugs sharing similar chemical structures or chemical formulas to prohibited substances if sold for human consumption. In July 2022, though, under the United States Food and Drug Administration, the drug psilocybin was on track to be approved of as a treatment for depression, and MDMA as a treatment for post-traumatic stress disorder. U.S. states such as Oregon and Colorado have also instituted decriminalization and legalization measures for accessing psychedelics and states like New Hampshire are attempting to do
18462-610: The Western biomedical view; this is aided by the studies done by Leary. Within certain traditional societies, where the use of psilocybin is frequent for shamanic healing rituals, group collectives praise their guide, healer and shaman for helping alleviate their pains, aches and hurt. They do this through a group ritual practice where the group, or just the guide, ingests psilocybin to help extract any " toxic psychic residues or sorcerous implants " found in one's body. Group therapies using "classic" psychedelics are becoming more commonly used in
18643-464: The Western world in clinical practice. This is speculated to grow, provided the evidence remains indicative of their safety and efficacy. In social sense, the group is shaped by their experiences surrounding psilocybin and how they view the plant collectively. As mentioned in the anthropology article, the group partakes in a "journey" together, thus adding to the spiritual, social body where roles, hierarchies and gender are subjectively understood. Most of
18824-468: The absorbed psilocybin is excreted into the urine, and a further 15–20% is excreted in the bile and feces. Although most of the remaining drug is eliminated in this way within 8 hours, it is still detectable in the urine after 7 days. Clinical studies show that psilocin concentrations in the plasma of adults average about 8 μg/liter within 2 hours after ingestion of a single 15 mg oral psilocybin dose; psychological effects occur with
19005-527: The activity of key circuits in the brain involved with sensory perception and cognition. However, the exact nature of how psychedelics induce changes in perception and cognition via the 5-HT 2A receptor is still unknown. The psychedelic experience is often compared to non-ordinary forms of consciousness such as those experienced in meditation, mystical experiences , and near-death experiences , which also appear to be partially underpinned by altered default mode network activity. The phenomenon of ego death
19186-619: The affected individual sees multicolored geometric shapes and vivid imaginative sequences. Some individuals report synesthesia , such as tactile sensations when viewing colors. At higher doses, psilocybin can lead to "intensification of affective responses, enhanced ability for introspection, regression to primitive and childlike thinking, and activation of vivid memory traces with pronounced emotional undertones". Open-eye visual hallucinations are common, and may be very detailed, although rarely confused with reality. A 2011 prospective study by Roland R. Griffiths and colleagues suggests that
19367-413: The assessment of promising drug therapies for potential approval, to psilocybin therapy for treatment-resistant depression and major depressive disorder. Recreational use of psychedelics has been common since the psychedelic era of the mid-1960s and continues to play a role in various festivals and events, including Burning Man . A survey published in 2013 found that 13.4% of American adults had used
19548-431: 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. While many recent studies have concluded that psilocybin can cause mystical-type experiences having substantial and sustained personal meaning and spiritual significance, not all the medical community agree. Paul R. McHugh , formerly director of
19729-402: The blood plasma, including 4-hydroxyindole-3-acetaldehyde (4-HIAL), 4-hydroxyindole-3-acetic acid (4-HIAA), and 4-hydroxytryptophol (4-HTOL). Some psilocin is not broken down by enzymes and instead forms a glucuronide ; this is a biochemical mechanism animals use to eliminate substances by linking them with glucuronic acid , which can then be excreted in the urine. Psilocin is glucuronidated by
19910-549: The body of high-quality evidence on psychedelic therapy remains relatively small and more, larger studies are needed to reliably show the effectiveness and safety of psychedelic therapy's various forms and applications. On the basis of favorable early results, ongoing research is examining proposed psychedelic therapies for conditions including major depressive disorder , and anxiety and depression linked to terminal illness . The United States Food and Drug Administration has granted "breakthrough therapy" status, which expedites
20091-658: The brain that ultimately lead to "cognitive fragmentation and psychosis". Flashbacks (spontaneous recurrences of a previous psilocybin experience) 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, and correlations between HPPD and psychedelics are further obscured by polydrug use and other variables. Tolerance to psilocybin builds and dissipates quickly; ingesting psilocybin more than about once
20272-496: The brain, including the cerebral cortex , and are involved in a wide range of functions, including regulation of mood , motivation , body temperature , appetite and libido . Psilocybin induces region-dependent alterations in glutamate that may be associated with subjective experiences of ego dissolution . The effects of the drug begin 10–40 minutes after ingestion, and last 2–6 hours depending on dose, species, and individual metabolism. The half life of psilocybin
20453-456: The brain. Psilocybin's mind-altering effects typically last two to six hours, although to people under the influence of psilocybin, they may seem to last much longer, since the drug can distort the perception of time. 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 . There
20634-558: The case of iboga. Different countries and/or regions have come to be associated with traditional or spiritual use of particular psychedelics, such as the ancient and entheogenic use of psilocybe mushrooms by the native Mazatec people of Oaxaca , Mexico or the use of the ayahuasca brew in the Amazon basin , particularly in Peru for spiritual and physical healing as well as for religious festivals. Peyote has also been used for several thousand years in
20815-543: The chief of the navigation of Spain. Although the proceedings of the Toro-Burgos conferences are missing, it is almost certain that Vespucci articulated his recent 'New World' thesis to his fellow navigators there. During these conferences, Spanish officials seem to have accepted that the Antilles and the known stretch of Central America were not the Indies as they had hoped. Though Columbus still insisted they were. They set out
20996-523: The comparatively few fatal incidents that are associated with psychedelic mushroom usage involve the simultaneous use of other drugs, especially alcohol . A common adverse effect resulting from psilocybin mushroom use involves "bad trips" or panic reactions , in which affected individuals become anxious, confused, agitated, or disoriented. Accidents, self-injury , or suicide attempts can result from serious cases of acute psychotic episodes . Although no studies have linked psilocybin with birth defects , it
21177-637: The context of finding out what is wrong with the individual, such as using psychedelic states to "identify" a disease and/or its cause, locate lost objects, and identify a victim or even perpetrator of sorcery . In some cultures and regions, even psychedelics themselves, such as ayahuasca and the psychedelic lichen of eastern Ecuador ( Dictyonema huaorani ) that supposedly contains both 5-MeO-DMT and psilocybin, have also been used by witches and sorcerers to conduct their malicious magic , similarly to nightshade deliriants like brugmansia and latua . Psychedelic therapy (or psychedelic-assisted therapy)
21358-492: The contrary perception of much of the public, psychedelic drugs are not addictive and are physiologically safe. As of 2016, there have been no known deaths due to overdose of LSD, psilocybin, or mescaline. Risks do exist during an unsupervised psychedelic experience, however; Ira Byock wrote in 2018 in the Journal of Palliative Medicine that psilocybin is safe when administered to a properly screened patient and supervised by
21539-526: The dominion of the Kings of Spain. The term "New World" ( Mundus Novus ) was coined in Spring 1503 by Amerigo Vespucci in a letter written to his friend and former patron Lorenzo di Pier Francesco de' Medici , which was published in Latin ) in 1503–04 under the title Mundus Novus . Vespucci's letter contains the first explicit articulation in print of the hypothesis that the lands discovered by European navigators to
21720-683: The drug can be a risk factor for users with pre-existing hypertension. These qualitative somatic effects caused by psilocybin have been corroborated by several early clinical studies. A 2005 magazine survey of clubgoers in the UK found that nausea or vomiting was 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 . Psilocybin
21901-530: The drug is administered in a single session (or sometimes up to three sessions) in a therapeutic context. The therapeutic team prepares the patient for the experience beforehand and helps them integrate insights from the drug experience afterwards. After ingesting the drug, the patient normally wears eyeshades and listens to music to facilitate focus on the psychedelic experience, with the therapeutic team interrupting only to provide reassurance if adverse effects such as anxiety or disorientation arise. As of 2022,
22082-580: The drug was novel. Group size, dosage, preparation, and expectancy were important determinants of the drug response. In general, those in groups of more than eight felt that the groups were less supportive, and their experiences less pleasant. Conversely, smaller groups (fewer than six) were seen as more supportive and reported more positive reactions to the drug in those groups. Leary and colleagues proposed that psilocybin heightens suggestibility, making an individual more receptive to interpersonal interactions and environmental stimuli. These findings were affirmed in
22263-476: The drug's role in affecting prefrontal cortex activity, and the role that the prefrontal cortex is known to play in time perception. However, the neurochemical basis of psilocybin's effects on the perception of time are not known with certainty. Users having a pleasant experience can feel a sense of connection to others, nature, and the universe; other perceptions and emotions are also often intensified. Users having an unpleasant experience (a " bad trip ") describe
22444-739: The effectiveness of psychedelic therapy has been conducted under strict ethical guidelines, with fully informed consent and a pre-screening to avoid people with psychosis taking part. Although the history behind these substances has hindered research into their potential medicinal value, scientists are now able to conduct studies and renew research that was halted in the 1970s. Some research has shown that these substances have helped people with such mental disorders as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), alcoholism, depression, and cluster headaches . It has long been known that psychedelics promote neurite growth and neuroplasticity and are potent psychoplastogens . There
22625-423: The effects of psilocybin. They administered the drug to 175 volunteers (from various backgrounds) in an environment intended to be similar to a comfortable living room. 98 of the subjects were given questionnaires to assess their experiences and the contribution of background and situational factors. Individuals who had experience with psilocybin prior to the study reported more pleasant experiences than those for whom
22806-702: The efforts of Timothy Leary and his associates Ralph Metzner and Richard Alpert (who later changed his name to Ram Dass ). Leary obtained synthesized psilocybin from Hofmann through Sandoz Pharmaceuticals. Some studies, such as the Concord Prison Experiment , suggested promising results using psilocybin in clinical psychiatry . But according to a 2008 review of safety guidelines in human hallucinogenic research, Leary's and Alpert's well-publicized termination from Harvard and later advocacy of hallucinogen use "further undermined an objective scientific approach to studying these compounds". In response to concerns about
22987-403: The experience increased their sense of well-being or life satisfaction. 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. Likewise, in a recent (2010) web-based questionnaire study designed to investigate user perceptions of
23168-422: The famous Cosmographiae Introductio volume, which includes reprints of Vespucci's letters, comes closest to modernity by placing a completely open sea, with no stretching land fingers, between Asia on the eastern side and the New World. It is represented two times in the same map in a different way: with and without a sea passage in the middle of what is now named Central America on the western side—which, on what
23349-574: The form of sclerotia (also known as "truffles"), in the late 1990s and early 2000s European retailers commercialized and marketed them in smartshops in the Netherlands, the UK, and online. Several websites emerged that contributed to the accessibility of information on the mushrooms' description, use, and effects, and users exchanged mushroom experiences. Since 2001, six EU countries have tightened their legislation on psilocybin mushrooms in response to concerns about their prevalence and increasing usage. In
23530-420: The historic or geographic complexity of the world. It is argued that both 'worlds' and the age of Western colonialism rather entered a new stage, as in the ' modern world '. In wine terminology , "New World" uses a particular definition. " New World wines " include not only North American and South American wines, but also those from South Africa , Australia , New Zealand , and all other locations outside
23711-447: The immediate adverse effects, such as anxiety and paranoia, rather than specific pharmacological interventions, as psilocybin's physiological toxicity tends to be rather limited. One analysis of people hospitalized from psilocybin poisoning found high urine concentrations of phenethylamine (PEA), indicating that PEA may contribute to the effects of psilocybin poisoning. In rats, the median lethal dose (LD 50 ) when administered orally
23892-671: 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. In the U.S., laws passed in 1966 that prohibited the production, trade, or ingestion of hallucinogenic drugs; Sandoz stopped producing LSD and psilocybin the same year. In 1970, Congress passed "The Federal Comprehensive Drug Abuse Prevention and Control Act" that made LSD, peyote, psilocybin, and other hallucinogens illegal to use for any purpose, including scientific research. United States politicians' agenda against LSD usage had swept psilocybin along with it into
24073-562: The ingestion is accidental or otherwise unexpected. Reactions characterized by violent behavior, suicidal thoughts, schizophrenia-like psychosis , and convulsions have been reported in the literature. A 2005 survey, conducted in the United Kingdom, found that almost a quarter of those who had used psilocybin mushrooms in the past year had experienced a panic attack. Other adverse effects, less frequently reported, include paranoia, confusion , prolonged derealization (disconnection from reality), and mania . Psilocybin usage can temporarily induce
24254-444: The intended meaning "mind manifesting" or alternatively "soul manifesting", and the implication that psychedelics can reveal unused potentials of the human mind. The term was loathed by American ethnobotanist Richard Schultes but championed by American psychologist Timothy Leary . Aldous Huxley had suggested his own coinage phanerothyme (Greek phaneroein - "to make manifest or visible" and Greek thymos "soul", thus "to reveal
24435-553: The intermediate steps has been shown to involve four enzymes (PsiD, PsiH, PsiK, and PsiM) in P. cubensis and P. cyanescens , although it is possible that the biosynthetic pathway differs between species. These enzymes are encoded in gene clusters in Psilocybe, Panaeolus, and Gymnopilus . Escherichia coli has been genetically modified to manufacture large amounts of psilocybin. Psilocybin can be produced de novo in GM yeast. Psilocybin
24616-418: The kilogram scale while employing less expensive reagents), publishing their results in 2020. Isotopic labeling experiments from the 1960s suggested that the biosynthesis of psilocybin was a four-step process: More recent research has demonstrated that—at least in P. cubensis — O -phosphorylation is in fact the third step, and that neither dimethyltryptamine nor psilocin are intermediates. The sequence of
24797-627: The language of the Aztecs, the mushrooms were called teonanácatl —literally "divine mushroom": the agglutinative form of teō(tl) ("god", "sacred") and nanācatl ("mushroom") in Nahuatl. After Spanish explorers of the New World arrived in the 16th century, chroniclers reported the use of mushrooms by the natives for ceremonial and religious purposes. According to the Dominican friar Diego Durán in The History of
24978-487: The meaning of the word entheogen ("the god within"), the mushrooms are revered as powerful spiritual sacraments that provide access to sacred worlds. Typically used in small group community settings, they enhance group cohesion and reaffirm traditional values. Terence McKenna documented the worldwide practices of psilocybin mushroom usage as part of a cultural ethos relating to the Earth and mysteries of nature, and suggested that mushrooms enhanced self-awareness and
25159-459: The methods for the laboratory synthesis and purification of psilocybin. In particular, Shirota et al. reported a novel method in 2003 for the synthesis of psilocybin at the gram scale from 4-hydroxyindole that does not require chromatographic purification. Fricke et al. described an enzymatic pathway for the synthesis of psilocybin and psilocin, publishing their results in 2017. Sherwood et al. significantly improved upon Shirota's method (producing at
25340-409: The mind distortion present in psychosis) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT 2A antagonist drug ketanserin . Various lines of evidence have shown that interactions with non-5-HT 2 receptors also contribute to the subjective and behavioral effects of the drug. For example, psilocin indirectly increases the concentration of the neurotransmitter dopamine in
25521-631: The more common, narrower definition of psychedelic . A number of frequently mentioned or traditional psychedelics such as Ayahuasca (which contains DMT ), San Pedro , Peyote , and Peruvian torch (which all contain mescaline ), Psilocybe mushrooms (which contain psilocin / psilocybin ) and Tabernanthe iboga (which contains the unique psychedelic ibogaine ) all have a long and extensive history of spiritual , shamanic and traditional usage by indigenous peoples in various world regions, particularly in Latin America, but also Gabon , Africa in
25702-427: The most popular of the latter group, Psilocybin: Magic Mushroom Grower's Guide , was published in 1976 under the pseudonyms O. T. Oss and O. N. Oeric by Jeremy Bigwood, Dennis J. McKenna , K. Harrison McKenna, and Terence McKenna. Over 100,000 copies were sold by 1981. As ethnobiologist Jonathan Ott explains, "These authors adapted San Antonio's technique (for producing edible mushrooms by casing mycelial cultures on
25883-503: The mushrooms as Psilocybe species. Heim cultivated the mushrooms in France and sent samples for analysis to Albert Hofmann , a chemist employed by the Swiss pharmaceutical company Sandoz (now Novartis). Hofmann—who had synthesized lysergic acid diethylamide (LSD) in 1938—led a research group that isolated and identified the psychoactive alkaloids psilocybin and psilocin from Psilocybe mexicana , publishing their results in 1958. The team
26064-494: The name of choice and we may expect to see this trend continue. Robin Carhart-Harris and Guy Goodwin write that the term psychedelic is preferable to hallucinogen for describing classical psychedelics because of the term hallucinogen ' s "arguably misleading emphasis on these compounds' hallucinogenic properties." While the term psychedelic is most commonly used to refer only to serotonergic hallucinogens, it
26245-436: The nature of existence… typically accompanied by a sense of certainty that this knowledge is ultimately more relevant and 'real' than the perceptions and beliefs we share in everyday life." Traditionally, the standard model for the subjective phenomenological effects of psychedelics has typically been based on LSD, with anything that is considered "psychedelic" evidently being compared to it and its specific effects . During
26426-544: The neurochemical and behavioral effects of serotonergic psychedelics, including the HTR. Metabotropic glutamate mGlu 2 receptors are primarily expressed as presynaptic autoreceptors and may have inhibitory effects on glutamate release. Serotonergic psychedelics have been found to produce frontal cortex hyperactivity in humans in PET and single-photon emission computed tomography (SPECT) imaging studies. The PFC projects to many other cortical and subcortical brain areas, such as
26607-441: The new goal for Spanish explorers: find a sea passage or strait through the Americas, a path to Asia proper. The term New World was not universally accepted, entering English only relatively late, and has more recently been subject to criticism . While it became generally accepted after Amerigo Vespucci that Christopher Columbus ' discoveries were not Asia but a "New World", the geographic relationship between Europe and
26788-476: The next decade, owing largely to the increased availability of information on how to cultivate psilocybin mushrooms. The intensity and duration of psilocybin's effects vary, depending on species or cultivar of mushrooms, dosage, individual physiology, and set and setting , as shown in experiments led by Timothy Leary at Harvard University in the early 1960s. Once ingested, psilocybin is rapidly metabolized to psilocin, which then acts on serotonin receptors in
26969-588: The non-selective risperidone can abolish the hallucinogenic effects of psychedelics in humans. However, studies with more selective serotonin 5-HT 2A receptor antagonists, like pimavanserin , are still needed. In animals, potency for stimulus generalization to the psychedelic DOM in drug discrimination tests is strongly correlated with serotonin 5-HT 2A receptor affinity. Non-selective serotonin 5-HT 2A receptor antagonists, like ketanserin and pirenperone , and selective serotonin 5-HT 2A receptor antagonists, like volinanserin (MDL-100907), abolish
27150-400: The opinion of the ancients was, that the greater part of the world beyond the equinoctial line to the south was not land, but only sea, which they have called the Atlantic; and even if they have affirmed that any continent is there, they have given many reasons for denying it is inhabited. But this opinion is false, and entirely opposed to the truth. My last voyage has proved it, for I have found
27331-429: The period 2000–2002, adolescent-onset (defined here as ages 11–17) 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 clinical features associated with drug dependence". Likewise,
27512-457: The possibility that the islands of the Antilles discovered earlier by Christopher Columbus might still be the eastern edges of Asia, as Columbus continued to insist until his death in 1506. A 1504 globe , possibly created by Leonardo da Vinci , depicts the New World as only South America , excluding North America and Central America . A conference of navigators known as Junta de Navegantes
27693-406: The problematic use of these hallucinogens as inebriants. Despite the legal restrictions on psilocybin use, the 1970s witnessed the emergence of psilocybin as the "entheogen of choice". This was due in large part to wide dissemination of information on the topic, which included works such as those by Carlos Castaneda and several books that taught the technique of growing psilocybin mushrooms. One of
27874-497: The psilocybin session. According to the study authors, the finding is significant, because "no study has prospectively demonstrated personality change in healthy adults after an experimentally manipulated discrete event". A further study by Griffiths in 2017 found that doses of 20 to 30 mg/70 kg of psilocybin, inducing mystical-type experiences, brought more lasting changes to traits including altruism, gratitude, forgiveness and feeling close to others when they were combined with
28055-486: The research setting it is not typically used in this form. 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 injected mushroom extracts intravenously . Psilocybin is a naturally-occurring substituted tryptamine that features an indole ring linked to an aminoethyl substituent . It
28236-464: The same. J.D. Tuccille argues that increasing rates of use of psychedelics in defiance of the law are likely to result in more widespread legalization and decriminalization of access to the substances in the United States (as has happened with alcohol and cannabis ). Psychedelic Timeline by Tom Frame, Psychedelic Times New World The term " New World " is used to describe the majority of lands of Earth 's Western Hemisphere , particularly
28417-1002: The serotonin 5-HT 2A receptor with efficacy insufficient to produce psychedelic effects or may be due to biased agonism of the serotonin 5-HT 2A receptor. There appears to be a threshold level of G q activation (in terms of intrinsic activity , with E max Tooltip maximal efficacy >70%) required for production of hallucinogenic effects. Full agonists and partial agonists above this threshold are psychedelic 5-HT 2A receptor agonists, whereas partial agonists below this threshold, such as lisuride, 2-bromo-LSD , 6-fluoro-DET , 6-MeO-DMT , and Ariadne , are non-hallucinogenic 5-HT 2A receptor agonists. In addition, biased agonists that activate β-arrestin2 signaling but not G q signaling, such as ITI-1549 , IHCH-7086 , and 25N-N1-Nap , are non-hallucinogenic serotonin 5-HT 2A receptor agonists. The hallucinogenic effects of serotonergic psychedelics may be mediated in part or full by serotonin 5-HT 2A receptor activation in
28598-466: The skin of certain amphibians, especially the Colorado River toad . Psilocybin is a white, crystalline solid that is soluble in water, methanol and ethanol but insoluble in nonpolar organic solvents such as chloroform and petroleum ether . It has a melting point between 220 and 228 °C (428 and 442 °F), and an ammonia -like taste. Its pKa values are estimated to be 1.3 and 6.5 for
28779-427: The soul") to Osmond in 1956. Recently, the term entheogen (meaning "that which produces the divine within") has come into use to denote the use of psychedelic drugs, as well as various other types of psychoactive substances, in a religious, spiritual, and mystical context. In 2004, David E. Nichols wrote the following about the nomenclature used for psychedelic drugs: Many different names have been proposed over
28960-660: The spring of 1503, Vespucci authored the Mundus Novus letter in Lisbon and sent it to Lorenzo in Florence , with the famous opening paragraph: In passed days I wrote very fully to you of my return from new countries, which have been found and explored with the ships, at the cost and by the command of this Most Serene King of Portugal; and it is lawful to call it a new world, because none of these countries were known to our ancestors and to all who hear about them they will be entirely new. For
29141-574: The stimulus generalization of psychedelics in drug discrimination tests. Conversely, serotonin 5-HT 2B and 5-HT 2C receptor antagonists are ineffective. The potencies of serotonin 5-HT 2 receptor antagonists in blocking psychedelic substitution are strongly correlated with their serotonin 5-HT 2A receptor affinities. Highly selective serotonin 5-HT 2A receptor agonists have recently been developed and show stimulus generalization to psychedelics, whereas selective serotonin 5-HT 2C receptor agonists do not do so. The head-twitch response (HTR)
29322-615: The study cast "a considerable doubt on the assertion that mystical experiences catalyzed by drugs are in any way inferior to non-drug mystical experiences in both their immediate content and long-term effects". This sentiment was echoed by psychiatrist William A. Richards, who in a 2007 review stated "[psychedelic] mushroom use may constitute one technology for evoking revelatory experiences that are similar, if not identical, to those that occur through so-called spontaneous alterations of brain chemistry." A group of researchers from Johns Hopkins School of Medicine led by Roland Griffiths conducted
29503-464: The subject's sense of well-being. A follow-up study conducted 14 months after the original psilocybin session confirmed that participants continued to attribute deep personal meaning to the experience. Almost one-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 among their five most spiritually significant events. About two-thirds indicated that
29684-513: The term "un altro mondo" ("another world") to refer to sub-Saharan Africa , which he explored in 1455 and 1456 on behalf of the Portuguese. This was merely a literary flourish, not a suggestion of a new "fourth" part of the world. Cadamosto was aware that sub-Saharan Africa was part of the African continent. Peter Martyr d'Anghiera , an Italian chronicler at the service of Spain , doubted Christopher Columbus 's claims to have reached East Asia ("
29865-493: The traditional use of San Pedro cactus in northern Peru as cultural heritage . Although people of Western culture have tended to use psychedelics for either psychotherapeutic or recreational reasons, most indigenous cultures, particularly in South America, have seemingly tended to use psychedelics for more supernatural reasons such as divination . This can often be related to "healing" or health as well but typically in
30046-551: The traditional wine-growing regions of Europe, North Africa and the Near East . The usefulness of these terms for wines though have been questioned as arbitrary and too generalized. In a biological context, species can be divided into those in the Old World ( Palearctic , Afrotropic ) and those in the New World ( Nearctic , Neotropic ). Biological taxonomists often attach the "New World" label to groups of species found exclusively in
30227-490: The two successive phosphate hydroxy groups and 10.4 for the dimethylamine nitrogen, so it typically exists as a zwitterionic structure. There are two known crystalline polymorphs of psilocybin, as well as reported hydrated phases . Psilocybin rapidly oxidizes upon exposure to light—an important consideration when using it as an analytical standard . Albert Hofmann et al. were the first team to synthesize psilocybin in 1958. Since that time, various chemists have improved
30408-428: The use of Amanita muscaria among Siberian peoples. The few existing accounts that mention psilocybin mushrooms typically lack sufficient information to allow species identification, focusing on their effects. For example, Flemish botanist Carolus Clusius (1526–1609) described the bolond gomba ("crazy mushroom"), used in rural Hungary to prepare love potions. English botanist John Parkinson included details about
30589-491: The visual effects of serotonergic psychedelics. Serotonergic psychedelics also directly or indirectly modulate a variety of other brain areas. Although the hallucinogenic effects of serotonergic psychedelics are thought to be mediated by serotonin 5-HT 2A receptor activation, interactions with other receptors, such as the serotonin 5-HT 1A and 5-HT 2C receptors, may modulate and additionally contribute to their effects. Tryptamine , along with other trace amines ,
30770-862: The warping of surfaces, shape suggestibility, pareidolia and color variations. Users often report intense colors that they have not previously experienced, and repetitive geometric shapes or form constants are common as well. Higher doses often cause intense and fundamental alterations of sensory (notably visual ) perception, such as synesthesia or the experience of additional spatial or temporal dimensions. Tryptamines are well documented to cause classic psychedelic states, such as increased empathy , visual distortions (drifting, morphing, breathing, melting of various surfaces and objects), auditory hallucinations, ego dissolution or ego death with high enough dose, mystical, transpersonal and spiritual experiences, autonomous " entity " encounters, time distortion, closed eye hallucinations and complete detachment from reality with
30951-465: The watering stop at Bezeguiche in present-day Dakar , Senegal , as Vespucci was on his expedition to chart the coast of newly discovered Brazil and the ships of the Second Portuguese India armada , commanded by Pedro Álvares Cabral , were returning from India . Having already visited the Americas in prior years, Vespucci likely found it difficult to reconcile what he had already seen in
31132-485: The west were not the edges of Asia, as asserted by Christopher Columbus , but rather an entirely different continent that represented a "New World". According to Mundus Novus , Vespucci realized that he was in a "New World" on 17 August 1501 as he arrived in Brazil and compared the nature and people of the place with what Portuguese sailors told him about Asia . A chance meeting between two different expeditions occurred at
31313-482: The world only included Afro-Eurasian lands. Africa , Asia , and Europe became collectively called the " Old World " of the Eastern Hemisphere , while the Americas were then referred to as "the fourth part of the world", or the "New World". Antarctica and Oceania are considered neither Old World nor New World lands, since they were only discovered by Europeans much later. They were associated instead with
31494-422: The years for this drug class. The famous German toxicologist Louis Lewin used the name phantastica earlier in this century, and as we shall see later, such a descriptor is not so farfetched. The most popular names—hallucinogen, psychotomimetic, and psychedelic ("mind manifesting")—have often been used interchangeably. Hallucinogen is now, however, the most common designation in the scientific literature, although it
31675-424: Was aided in the discovery process by Hofmann's willingness to ingest mushroom extracts to help verify the presence of the active compounds. Next, Hofmann's team synthesized several structural analogs of these compounds to examine how these structural changes affect psychoactivity. This research led to the development of ethocybin and CZ-74 . Because these compounds' physiological effects last only about three and
31856-406: Was assembled by the Spanish monarchs at Toro in 1505 and continued at Burgos in 1508 to digest all existing information about the Indies, come to an agreement on what had been discovered, and set out the future goals of Spanish exploration. Amerigo Vespucci attended both conferences, and seems to have had an outsized influence on them—at Burgos, he ended up being appointed the first piloto mayor ,
32037-642: Was associated with increased prevalence of any mental illness. Using psychedelics poses certain risks of re-experiencing of the drug's effects, including flashbacks and hallucinogen persisting perception disorder (HPPD). These non-psychotic effects are poorly studied, but the permanent symptoms (also called "endless trip") are considered to be rare. Serotonin syndrome can be caused by combining psychedelics with other serotonergic drugs, including certain antidepressants, opioids, CNS stimulants (e.g. MDMA), 5-HT 1 agonists (e.g. triptans ), herbs and others. Serotonergic psychedelics are agonists not only of
32218-511: Was coined by the psychiatrist Humphrey Osmond during written correspondence with author Aldous Huxley (written in a rhyme: “To fathom Hell or soar angelic/Just take a pinch of psychedelic.” ) and presented to the New York Academy of Sciences by Osmond in 1957. It is irregularly derived from the Greek words ψυχή ( psychḗ , meaning 'mind, soul') and δηλείν ( dēleín , meaning 'to manifest'), with
32399-480: Was mapped. The discovery of the Bering Straits in the early 18th century, established that Asia and North America were not connected by land. But some European maps of the 16th century, including the 1533 Johannes Schöner globe , still continued to depict North America as connected by a land bridge to Asia. In 1524, the term "New World" was used by Giovanni da Verrazzano in a record of his voyage that year along
32580-418: Was measured using a questionnaire developed by Ralph W. Hood; 61% of subjects reported a "complete mystical experience" after their psilocybin session, while only 13% reported such an outcome after their experience with methylphenidate. Two months after taking psilocybin, 79% of the participants reported moderately to greatly increased life satisfaction and sense of well-being. About 36% of participants also had
32761-725: Was no significant difference in brain activation found in similar trials of mescaline and LSD. Information and studies into the DMN and ToMN are relatively sparse and their connections to other psychiatric illnesses and the use of psychedelics is still largely unknown. 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". Positive effects that psilocybin has on individuals can be observed by taking on an anthropological approach and moving away from
#730269