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Psilocybin

Psilocybin is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from approximately a dozen other genera. 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 lysergic acid diethylamide (LSD), mescaline, and dimethyltryptamine (DMT). In general, the effects include euphoria, visual and mental hallucinations, changes in perception, distorted sense of time, and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks.

Imagery found on cave paintings and rock art of modern-day Spain and Algeria 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 the sixteenth century. In 1958, the Swiss chemist Albert Hofmann isolated psilocybin and psilocin from the mushroom Psilocybe mexicana. Hofmann's employer Sandoz marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic therapy. Although the increasingly restrictive drug laws of the 1960s and the 1970s curbed scientific research into the effects of psilocybin and other hallucinogens, its popularity as an entheogen (spirituality-enhancing agent) grew in the next decade, owing largely to the increased availability of information on how to cultivate psilocybin mushrooms.

The intensity and duration of the effects of psilocybin are variable, depending on species or cultivar of mushrooms, dosage, individual physiology, and set and setting, as was 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 the brain. The mind-altering effects of psilocybin typically last from two to six hours, although to individuals under the influence of psilocybin, the effects 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.

Early

There is evidence to suggest that psychoactive mushrooms have been used by humans in religious ceremonies for thousands of years. 6,000-year-old pictographs discovered near 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.

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.

Archaeological artifacts from Mexico, as well as the so-called Mayan "mushroom stones" of Guatemala have also been interpreted by some scholars as evidence for ritual and ceremonial use of psychoactive mushrooms in the Mayan and Aztec cultures of Mesoamerica. In Nahuatl, 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. Following the arrival of Spanish explorers to the New World in the sixteenth 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 the Indies of New Spain (published c. 1581), mushrooms were eaten in festivities conducted on the occasion of the accession to the throne of Aztec emperor Moctezuma II 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 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.

Although dozens of species of psychedelic mushrooms are found in Europe, there is little documented usage of these species in Old World history besides the use of Amanita muscaria among Siberian peoples. The few existing historical accounts about psilocybin mushrooms typically lack sufficient information to allow species identification, and usually refer to the nature of 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 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.

Modern
American banker and amateur ethnomycologist R. Gordon Wasson and his wife Valentina P. Wasson, 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 that he experienced during these rituals in "Seeking the Magic Mushroom", an article published in the popular 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 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 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 would affect psychoactivity. This research led to the development of ethocybin and CZ-74. Because the physiological effects of these compounds last only about three and a half hours (about half as long as psilocybin), they proved more manageable than the latter 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 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. According to a 2008 review of safety guidelines in human hallucinogenic research, however, Leary 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 the increase in unauthorized use of psychedelic drugs by the general public, psilocybin and other hallucinogenic drugs suffered negative press and faced increasingly restrictive laws. In the United States, laws were 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 and all purposes, including scientific research. United States politicians' agenda against LSD usage had swept psilocybin along with it into 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, globally, 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"), Hofmann described 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 a wide dissemination of information on the topic, which included works such as those by author Carlos Castaneda, and several books that taught the technique of growing psilocybin mushrooms. One of the most popular of this latter group 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, entitled Psilocybin: Magic Mushroom Grower's Guide. 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 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 a lack of clarity about laws concerning psilocybin mushrooms, specifically in the form of sclerotia (also known as "truffles"), European retailers in the late 1990s and early 2000s commercialized and marketed them in smartshops in the Netherlands and the UK, and online. Several websites emerged that have contributed to the accessibility of information on the mushrooms' description, use, effects and the exchange of mushroom experiences among users. Since 2001, six EU countries have tightened their legislation on psilocybin mushrooms in response to concerns about their prevalence and increasing usage. In 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 the United States have attracted attention from the popular press and brought psilocybin back into the limelight.

Reported effects

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 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 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 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 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 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 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 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 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.

Physical effects
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 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.

Psychiatric effects and perceptual disturbances
Psilocybin 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 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 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 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."

Theory of mind network and default mode network
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). 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 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 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.

Group perceptions
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 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 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.

Adverse effects
Most of 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 is recommended that pregnant women avoid its usage.

Toxicity
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 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 (LD50) when administered orally is 280 milligrams per kilogram (mg/kg), approximately one and a half times that of caffeine. When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5 mg/kg. Psilocybin comprises approximately 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kg of dried mushrooms, or 17 kg of fresh mushrooms, would be required for a 60 kg person to reach the 280 mg/kg LD50 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 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—, 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.

Psychiatric
Panic reactions can occur after consumption of psilocybin-containing mushrooms, especially if 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 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 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 and dependence
Tolerance to psilocybin builds and dissipates quickly; ingesting psilocybin more than about once 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 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, 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.

Cultural significance and "mystical" experiences
Psilocybin mushrooms have been and continue to be used in indigenous New World cultures in religious, divinatory, or spiritual contexts. Reflecting 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 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 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 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 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 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 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, 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 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 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 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 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 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 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.'"

Available forms
Although psilocybin may be prepared synthetically, outside of 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.

Physical properties
Psilocybin is a naturally-occurring substituted tryptamine that features an indole ring linked to an aminoethyl substituent. It 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 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 an ammonia-like taste. Its pKa values are estimated to be 1.3 and 6.5 for 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.

Laboratory synthesis
Albert Hofmann et al. were the first team to synthesize psilocybin in 1958. Since that time, various chemists have improved 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 the kilogram scale while employing less expensive reagents), publishing their results in 2020.

Biosynthesis

Isotopic labeling experiments from the 1960s suggested that the biosynthesis of psilocybin was a four-step process:
 * 1) decarboxylation of tryptophan to tryptamine
 * N,N-dimethylation of tryptamine at the N9 position to dimethyltryptamine
 * 1) 4-hydroxylation of dimethyltryptamine to psilocin
 * 2) O-phosphorylation of psilocin to psilocybin

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 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.

Pharmacodynamics

Psilocybin 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-HT2A receptors and low affinity to 5-HT1 receptors, including 5-HT1A and 5-HT1D; effects are also mediated via 5-HT2C receptors. The psychotomimetic (mimicking the mind distortion present in psychosis) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2A antagonist drug ketanserin. Various lines of evidence have shown that interactions with non-5-HT2 receptors also contribute to the subjective and behavioral effects of the drug. For example, psilocin indirectly increases the concentration of the neurotransmitter dopamine in 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 receptor D2, unlike another common 5-HT receptor agonist, lysergic acid diethylamide (LSD). Psilocin antagonizes H1 receptors with moderate affinity, compared to LSD which has a lower affinity. Serotonin receptors are located in numerous parts of 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.

Pharmacokinetics

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 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 to produce several metabolites that can circulate in the blood plasma, including 4-hydroxyindole-3-acetaldehyde, 4-hydroxytryptophol, and 4-hydroxyindole-3-acetic acid. 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 glucuronated by 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. Within 24 hours, about 65% of 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 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.

Monoamine oxidase inhibitors (MAOI) have been known to prolong and enhance the effects of DMT and one study assumed that the effect on psilocybin would be similar since it is a structural analogue of DMT. Alcohol consumption may enhance the effects of psilocybin, because acetaldehyde, one of the primary breakdown metabolites of consumed alcohol, reacts with biogenic amines present in the body to produce MAOIs related to tetrahydroisoquinoline and β-carboline. Tobacco smokers may also experience more powerful effects with psilocybin, because tobacco smoke exposure decreases the activity of MAO in the brain and peripheral organs.

Analytical methods
Several relatively simple chemical tests—commercially available as reagent testing kits—can be used to assess the presence of psilocybin in extracts prepared from mushrooms. The drug reacts in the Marquis test to produce a yellow color, and a green color in the Mandelin reagent. Neither of these tests, however, is specific for psilocybin; for example, the Marquis test will react with many classes of controlled drugs, such as those containing primary amino groups and unsubstituted benzene rings, including amphetamine and methamphetamine. Ehrlich's reagent and DMACA reagent are used as chemical sprays to detect the drug after thin layer chromatography. Many modern techniques of analytical chemistry have been used to quantify psilocybin levels in mushroom samples. Although the earliest methods commonly used gas chromatography, the high temperature required to vaporize the psilocybin sample prior to analysis causes it to spontaneously lose its phosphoryl group and become psilocin—making it difficult to chemically discriminate between the two drugs. In forensic toxicology, techniques involving gas chromatography coupled to mass spectrometry (GC–MS) are the most widely used due to their high sensitivity and ability to separate compounds in complex biological mixtures. These techniques include ion mobility spectrometry, capillary zone electrophoresis, ultraviolet spectroscopy, and infrared spectroscopy. High-performance liquid chromatography (HPLC) is used with ultraviolet, fluorescence, electrochemical, and electrospray mass spectrometric detection methods.

Various chromatographic methods have been developed to detect psilocin in body fluids: the rapid emergency drug identification system (REMEDi HS), a drug screening method based on HPLC; HPLC with electrochemical detection; GC–MS;  and liquid chromatography coupled to mass spectrometry. Although the determination of psilocin levels in urine can be performed without sample clean-up (i.e., removing potential contaminants that make it difficult to accurately assess concentration), the analysis in plasma or serum requires a preliminary extraction, followed by derivatization of the extracts in the case of GC–MS. A specific immunoassay has also been developed to detect psilocin in whole blood samples. A 2009 publication reported using HPLC to quickly separate forensically important illicit drugs including psilocybin and psilocin, which were identifiable within about half a minute of analysis time. These analytical techniques to determine psilocybin concentrations in body fluids are, however, not routinely available, and not typically used in clinical settings.

Natural occurrence
Psilocybin is present in varying concentrations in over 200 species of Basidiomycota mushrooms. In a 2000 review on the worldwide distribution of hallucinogenic mushrooms, Gastón Guzmán and colleagues considered these to be distributed amongst the following genera: Psilocybe (116 species), Gymnopilus (14), Panaeolus (13), Copelandia (12), Hypholoma (6), Pluteus (6), Inocybe (6), Conocybe (4), Panaeolina (4), Gerronema (2), and Galerina (1 species). Guzmán increased his estimate of the number of psilocybin-containing Psilocybe to 144 species in a 2005 review. The majority of these are found in Mexico (53 species), with the remainder distributed in the United States and Canada (22), Europe (16), Asia (15), Africa (4), and Australia and associated islands (19). The diversity of psilocybin mushrooms is reported to have been increased by horizontal transfer of the psilocybin gene cluster between unrelated mushroom species. In general, psilocybin-containing species are dark-spored, gilled mushrooms that grow in meadows and woods of the subtropics and tropics, usually in soils rich in humus and plant debris. Psilocybin mushrooms occur on all continents, but the majority of species are found in subtropical humid forests. Psilocybe species commonly found in the tropics include P. cubensis and P. subcubensis. P. semilanceata—considered by Guzmán to be the world's most widely distributed psilocybin mushroom —is found in Europe, North America, Asia, South America, Australia and New Zealand, but is entirely absent from Mexico. Although the presence or absence of psilocybin is not of much use as a chemotaxonomical marker at the familial level or higher, it is used to classify taxa of lower taxonomic groups.

Both the caps and the stems contain psychoactive compounds, although the caps consistently contain more. The spores of these mushrooms do not contain psilocybin or psilocin. The total potency varies greatly between species and even between specimens of a species collected or grown from the same strain. Because most psilocybin biosynthesis occurs early in the formation of fruit bodies or sclerotia, younger, smaller mushrooms tend to have a higher concentration of the drug than larger, mature mushrooms. In general, the psilocybin content of mushrooms is quite variable (ranging from almost nothing to 2.5% of the dry weight) and depends on species, strain, growth and drying conditions, and mushroom size. Cultivated mushrooms have less variability in psilocybin content than wild mushrooms. The drug is more stable in dried than fresh mushrooms; dried mushrooms retain their potency for months or even years, while mushrooms stored fresh for four weeks contain only traces of the original psilocybin.

The psilocybin contents of dried herbarium specimens of Psilocybe semilanceata in one study were shown to decrease with the increasing age of the sample: collections dated 11, 33, or 118 years old contained 0.84%, 0.67%, and 0.014% (all dry weight), respectively. Mature mycelia contain some psilocybin, while young mycelia (recently germinated from spores) lack appreciable amounts. Many species of mushrooms containing psilocybin also contain lesser amounts of the analog compounds baeocystin and norbaeocystin, chemicals thought to be biogenic precursors. Although most species of psilocybin-containing mushrooms bruise blue when handled or damaged due to the oxidization of phenolic compounds, this reaction is not a definitive method of identification or determining a mushroom's potency.

Advocacy for tolerance
Despite being illegal in many typically Western countries, such as the UK, Australia and some US states, less conservative governments opt to nurture the legal use of psilocybin and other psychedelic drugs. In Amsterdam, Netherlands, authorities provide education and promotion on the safe use of psychedelic drugs, such as psilocybin, in an aim to reduce public harm. Similarly, religious groups like America's Uniao do Vegetal, UDV, use psychedelics in traditional ceremonies. A report from the U.S. Government Accountability Office (GAO) notes that people may petition the DEA for exemptions to use psilocybin for religious purposes.

From 1 July 2023, the Australian medicines regulator has permitted psychiatrists to prescribe psilocybin for the therapeutic treatment of post-traumatic stress disorder.

Advocates for legalization argue there is a lack of evidence of harm, and potential use in treating certain mental health conditions. Research is difficult to conduct because of the legal status of psychoactive substances. Advocates for legalization also promote the utility of "ego dissolution" and argue bans are cultural discrimination against traditional users.

Usage
A 2009 national survey of drug use by the US Department of Health and Human Services concluded that the number of first-time psilocybin mushroom users in the United States was roughly equivalent to the number of first-time users of cannabis. A June 2024 report by the RAND Corporation suggests the total number of use days for psychedelics is two orders of magnitude smaller than it is for cannabis, and unlike people who use cannabis and many other drugs, infrequent users of psychedelics account for most of the total days of use. The 2024 report by the RAND Corporation suggests psilocybin mushrooms may be the most prevalent psychedelic drug among adults in the United States.

In European countries, the lifetime prevalence estimates of psychedelic mushroom usage among young adults (15–34 years) range from 0.3% to 14.1%.

In modern Mexico, traditional ceremonial use survives among several indigenous groups, including the Nahuas, the Matlatzinca, the Totonacs, the Mazatecs, Mixes, Zapotecs, and the Chatino. Although hallucinogenic Psilocybe species are abundant in low-lying areas of Mexico, most ceremonial use takes places in mountainous areas of elevations greater than 1500 m. Guzmán suggests this is a vestige of Spanish colonial influence from several hundred years earlier, when mushroom use was persecuted by the Catholic Church.

Research
Psilocybin has been a subject of clinical research since the early 1960s, when the Harvard Psilocybin Project evaluated the potential value of psilocybin as a treatment for certain personality disorders. Beginning in the 2000s, psilocybin has been investigated for its possible role in the treatment of nicotine dependence, alcohol dependence, obsessive–compulsive disorder (OCD), cluster headache, cancer-related existential distress anxiety disorders, and certain mood disorders. In 2018, the United States Food and Drug Administration (FDA) granted breakthrough therapy designation for psilocybin-assisted therapy for treatment-resistant depression. A systematic review published in 2021 found that the use of psilocybin as a pharmaceutical substance was associated with reduced intensity of depression symptoms. The role of psilocybin as a possible psychoplastogen is also being examined.

title: Psilocybin


text:
Talk:Planck units

Planck Energy Intro
"Most Planck units are extremely small, as in the case of Planck length or Planck time, or extremely large, as in the case of Planck temperature or Planck density. For comparison, the Planck energy EP is approximately equal to the energy released in the combustion of the fuel in an automobile fuel tank (57.2 L at 34.2 MJ/L of chemical energy)."

The intro to the Planck Energy section starts with a little bit about Planck units are very small or very big. The second sentence then talks about how much energy the Planck energy is, but gives no indication of how that level relates to the first. It feels like something is missing. Maybe remove the first sentence altogether? LambdaKnight (talk) 17:55, 3 March 2023 (UTC)

 * I think it is a hang-over of trying to address the mysticism of Planck units. The mention of scale was only to show that not all Planck units are extreme, which (possibly inappropriately) supposes that the reader might need to have this pointed out.  I've trimmed out the part aimed at highlighting the scale contrast.  —Quondum 18:15, 3 March 2023 (UTC)

Team-B-Vital Improvement Drive
Hello all!

This article has been chosen as this fortnight's effort for WP:Discord's #team-b-vital channel, a collaborative effort to bring Vital articles up to a B class if possible, similar to WP:Articles for Improvement. This effort will run for up to a fortnight, ending early if the article is felt to be at B-class or impossible to further improve. Articles are chosen by a quick vote among interested chatters, with the goal of working together on interesting Vital articles that need improving.

Thank you!  Rema goxer  (talk) 20:18, 22 September 2023 (UTC)

Can you add the Planck units of charge?
Planck units has no unit of charge? You can use either $$k_e=1$$ or $$\epsilon_0=1$$ to calculate the Pronic unit of charge, also compare with Stoney units and Hartree atomic units and “Natural units (particle and atomic physics)” and “Quantum chromodynamics units”, all these units have the unit of charge, but instead none of them have the unit of temperature, so could you also add the unit of temperature of them (simply use $$k_B=1$$)?

Also, due to the article, the Planck’s original definition of the Planck unit uses $$h=1$$, but in fact $$\hbar=1$$ is more natural since angular frequency $$\omega$$ is more natural than frequency $$f$$, thus the modern definition uses $$\hbar=1$$, by this logic, $$4\pi G=\epsilon_0=1$$ is more natural since this will make the impedance of free space $$Z_0=1$$, but why the modern definition does not use it and instead use the original $$G=k_e=1$$? 36.233.219.197 (talk) 07:44, 25 December 2023 (UTC)

 * The article already discusses different ways of adding an electrostatic unit to the Planck system and the change from $$h$$ to $$\hbar$$. XOR'easter (talk) 20:00, 28 December 2023 (UTC)

 * Despite being a contributor to its inclusion, I am somewhat concerned about the undue weight given to the concept of a "Planck charge" in this article. We cite primary (arXiv) and tertiary (non-reliable online encyclopedia/textbook) sources, because reliable sources are simply not available on this.  I suspect that Planck failed to mention it because in the system of quantities of the time, charge was not considered to be an independent dimension, and thus a unit of charge was inherently implied as a derived unit.  However, we have nothing to substantiate this hunch, and so we cannot make any such claim.  It is not entirely clear to me how to reduce the weight without removing the mention of charge, since it is not even clear whether charge was implicitly included or not included.  —Quondum 21:54, 30 December 2023 (UTC)
 * It is a subject of rather niche interest, as evidenced by the sources about it being poor, obscure, and/or marginal. I have shortened the last paragraph of the introduction, because the article really doesn't say enough on the topic to justify giving it such prominent placement. WP:DUE and MOS:LEAD, etc. XOR'easter (talk) 22:35, 30 December 2023 (UTC)
 * That seems better. I also removed a somewhat stretched statement in the body.  What is left is still only weakly supported, but I do not think it would help to remove it.  —Quondum 23:16, 30 December 2023 (UTC)

What is Planck Temperature?
10^34 K seems rather hot 142.163.195.238 (talk) 19:20, 15 January 2024 (UTC)

The intro with "numerical value of 1"

 * Expressing one of these physical constants in terms of Planck units yields a numerical value of 1.

I think it would add a lot of understanding here to follow this sentence with "(For example, c = 1 Planck length / Planck time.)" D. F. Schmidt (talk) 15:52, 23 March 2024 (UTC)

Significance - "unit charge"
I don't understand this sentence:

the disparity of magnitude of force is a manifestation of the fact that the charge on the protons is approximately the unit charge but the mass of the protons is far less than the unit mass

because earlier in the article it says

Other tabulations add [...] a unit for electric charge, so that either the Coulomb constant or the vacuum permittivity is normalized to 1 and then gives the two possible derivations.

so what is meant by the "unit charge"? Is there even a unit charge in Planck Units? Neither 3.3e or 11.7e feels especially close to the charge of a proton, although I guess when you're comparing it to the unit mass, it is much closer...?

The fact that "unit charge" just links back to this article doesn't really help either... Timtjtim (talk) 22:32, 27 June 2024 (UTC)

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Talk:Planck units


text:
Shakespearean tragedy

Shakespearean tragedy is the designation given to most tragedies written by playwright William Shakespeare. Many of his history plays share the qualifiers of a Shakespearean tragedy, but because they are based on real figures throughout the history of England, they were classified as "histories" in the First Folio. The Roman tragedies—Julius Caesar, Antony and Cleopatra and Coriolanus—are also based on historical figures, but because their sources were foreign and ancient, they are almost always classified as tragedies rather than histories. Shakespeare's romances (tragicomic plays) were written late in his career and published originally as either tragedy or comedy. They share some elements of tragedy, insofar as they feature a high-status central character, but they end happily like Shakespearean comedies. Almost three centuries after Shakespeare's death, the scholar F. S. Boas also coined a fifth category, the "problem play," for plays that do not fit neatly into a single classification because of their subject matter, setting, or ending. Scholars continue to disagree on how to categorize some Shakespearean plays.

Chronology
Below is the list of Shakespeare's plays listed as tragedies in the First Folio, along with the date range in which each play is believed to have been written.

Influences and sources
The English Renaissance, when Shakespeare was writing, was fueled by a renewed interest in Roman and Greek classics and neighboring renaissance literature written years earlier in Italy, France, and Spain. Shakespeare wrote the majority of his tragedies under the rule of James I, and their darker contents may reflect the general mood of the country following the death of Elizabeth I, as well as James's theatrical preferences. Shakespeare, as was customary for other playwrights in his day, used history, other plays, and non-dramatic literature as sources for his plays. Additionally, tragedy was a new and exciting theatrical phenomenon in the late 16th century, rather than an established and self-evident dramatic form; because of this, Shakespeare and his contemporaries' plays did not necessary fit into a single genre. In Elizabethan England there was no copyright law or protections against plagiarism, so characters, plots, and even whole phrases of poetry were considered common property. The majority of Shakespeare's tragedies are based on historical figures, with the exception of Measure for Measure and Othello, which are based on narrative fictions by Giraldi Cintio. The historical basis for Shakespeare's Roman plays comes from The Lives of Noble Grecians and Romans by Plutarch, whereas the source of Shakespeare's Britain-based plays and Hamlet (based on the Danish Prince Amleth) derive from Holinshed's Chronicles. Furthermore, the French author Belleforest published The Hystorie of Hamblet, Prince of Denmarke in 1582, which includes specifics from how the prince pretended madness, to how the prince stabbed and killed the King's counsellor who was eavesdropping on Hamlet and his mother behind the arras in the Queen's chamber. The story of Lear appears in Geoffrey of Monmouth's Historia regium Britanniae c. 1135, and then in John Higgins' poem The Mirror for Magistrates in 1574, as well as appearing in Holinshed's Chronicles in 1587. Some events that happen in Shakespeare's King Lear were inspired by various episodes of Philip Sidney's Arcadia from 1590, while the nonsensical musings of Edgar's "poor Tom" heavily reference Samuel Harsnett's 1603 book, A Declaration of Egregious Popish Impostures.

Contemporary tragedy
Tragedies from these eras traced their philosophical essence back to the Senecan tragedy, grounded in nobles who have a tragic flaw or commit a grave error (hamartia) which leads to their reversal of fortune (peripeteia). (However, some critics have argued that the "pseudo-Aristotelian" concept of the tragic flaw does not apply to Shakespeare's tragic figures. ) Revenge tragedy was another increasingly popular genre in this age; Shakespeare's Hamlet is one example of this. Plays of this age were also decidedly secular, in contrast to the religious morality plays which, by this time, were outlawed by Elizabeth I. One marked difference between English renaissance tragedies and the classics that inspired them was the use and popularity of violence and murder on stage.

Select exemplary (non-Shakespearean) Elizabethan and Jacobean tragedies:
 * The Spanish Tragedy by Thomas Kyd
 * The Jew of Malta by Christopher Marlowe
 * Tamburlaine by Christopher Marlowe
 * Doctor Faustus by Christopher Marlowe
 * Antonio's Revenge by John Marston
 * The Revenger's Tragedy by Thomas Middleton
 * 'Tis Pity She's a Whore by John Ford

title: Shakespearean tragedy


text:
Fidelio

Fidelio, originally titled Leonore, oder Der Triumph der ehelichen Liebe (Leonore, or The Triumph of Marital Love), Op. 72, is the only opera by German composer Ludwig van Beethoven. The libretto was originally prepared by Joseph Sonnleithner from the French of Jean-Nicolas Bouilly. The opera premiered at Vienna's Theater an der Wien on 20 November 1805. The following year, Beethoven's friend Stephan von Breuning rewrote the libretto, shortening the work from three acts to two. After further work on the libretto by Georg Friedrich Treitschke, a final version was performed at the Kärntnertortheater on 23 May 1814. As these libretto revisions were going on, Beethoven was also revising some of the music. By convention, only the final version is called Fidelio, and the others are referred to as Leonore.

The libretto tells how Leonore, disguised as a prison guard named "Fidelio", rescues her husband Florestan from death in a political prison. Bouilly's scenario fits Beethoven's aesthetic and political outlook: a story of personal sacrifice, heroism, and eventual triumph. With its underlying struggle for liberty and justice mirroring contemporary political movements in Europe, such topics are typical of Beethoven's "middle period". Notable moments in the opera include the "Prisoners' Chorus" (O welche Lust—"O what a joy"), an ode to freedom sung by a chorus of political prisoners, Florestan's vision of Leonore who comes as an angel to rescue him, and the scene in which the rescue finally takes place. The finale celebrates Leonore's bravery with alternating contributions of soloists and chorus.

Composition and 19th century performance history
Fidelio had a long and complicated history of composition. Portions of the score were originally written for an earlier, never-completed opera. Beethoven revised Fidelio three times; the work caused Beethoven so much vexation that he vowed never to compose another opera.

The distant origin of Fidelio dates from 1803, when the librettist and impresario Emanuel Schikaneder worked out a contract with Beethoven to write an opera. The contract included free lodging for Beethoven in the apartment complex that was part of Schikaneder's large suburban theater, the Theater an der Wien. Beethoven was to set a new libretto by Schikaneder, entitled Vestas Feuer; however, this libretto was not to Beethoven's liking. He spent about a month composing music for it, then abandoned it when the libretto for Fidelio came to his attention.

The time Beethoven spent on Vestas Feuer was not entirely wasted, as two important numbers from Fidelio, Pizarro's "'Ha! Welch' ein Augenblick!" and the duet "O namenlose Freude" for Leonore and Florestan, both originated as music for Vestas Feuer. Beethoven continued to live at the Theater an der Wien for some time after he had abandoned Vestas Feuer for Fidelio, and was eventually freed from his obligations to Schikaneder after the latter was fired from his post as theater director in 1804.

Fidelio itself, which Beethoven began in 1804 immediately after giving up on Vestas Feuer, was first performed in 1805 and was extensively revised by the composer for subsequent performances in 1806 and 1814. Although Beethoven used the title Leonore, oder Der Triumph der ehelichen Liebe ("Leonore, or The Triumph of Married Love"), the 1805 performances were billed as Fidelio at the theatre's insistence, to avoid confusion with Pierre Gaveaux's Léonore, ou L'amour conjugal (1798) and Ferdinando Paer's Leonora (1804), both of which were based on the same source material as Beethoven's opera (and in fact Beethoven is known to have owned a copy of Paer's score). Beethoven published the 1806 libretto and, in 1810, a vocal score under the title Leonore. The current convention is to use the name Leonore for both the 1805 (three-act) and 1806 (two-act) versions and Fidelio only for the final 1814 revision.

The first version, with a three-act German libretto adapted by Joseph Sonnleithner from the French of Jean-Nicolas Bouilly, premiered at the Theater an der Wien on 20 November 1805, with additional performances the following two nights. The success of these performances was hindered by the fact that Vienna was under French military occupation, and most of the audience were French military officers who had little interest in German opera.

After this premiere, Beethoven's friends suggested he revise and shorten the opera into just two acts, and he did so with the help of his close friend, Stephan von Breuning. The composer also wrote a new overture (now known as "Leonore No.3"; see below). In this form, the opera was first performed on 29 March and 10 April 1806, with greater success. Further performances were prevented by a disagreement between Beethoven and the theatre management.

In 1814, Beethoven revised his opera yet again, with additional work on the libretto by Georg Friedrich Treitschke. This version was first performed at the Kärntnertortheater on 23 May 1814, again under the title Fidelio. The 17-year-old Franz Schubert was in the audience, having sold his school books to obtain a ticket. The increasingly deaf Beethoven conducted the performance, "assisted" by Michael Umlauf, who later performed the same task for Beethoven at the premiere of the Ninth Symphony. The role of Pizarro was taken by Johann Michael Vogl, who later became known for his collaborations with Schubert. This version of the opera was a great success, and Fidelio has been part of the operatic repertory ever since.

Although critics have noted the similarity in plot with Gluck's opera Orfeo ed Euridice (1762) — another underground rescue mission in which the protagonist must control, or conceal, his emotions in order to retrieve his spouse — it is not known whether Beethoven or any of the librettists had this in mind while constructing the opera.

No other work of Beethoven's caused him so much frustration and disappointment. He found the difficulties posed by writing and producing an opera so disagreeable, he vowed never to compose another. In a letter to Treitschke he said, "I assure you, dear Treitschke, that this opera will win me a martyr's crown. You have by your co-operation saved what is best from the shipwreck. For all this I shall be eternally grateful to you."

The full score was not published until 1826, and all three versions are known as Beethoven's Opus 72.

The first performance outside Vienna took place in Prague on 21 November 1814, with a revival in Vienna on 3 November 1822. In its two-act version, the opera was staged in London on 18 May 1832 at the King's Theatre, and in New York on 9 September 1839 at the Park Theatre.

20th-century performance history

Fidelio was Arturo Toscanini's first complete opera performance given in the United States since 1915 and the first to be broadcast on radio, over the NBC network, in December 1944. Toscanini conducted the NBC Symphony Orchestra, featuring soloists Rose Bampton, Jan Peerce and Eleanor Steber, with the performance divided into two consecutive broadcasts. The recording of the opera was later issued by RCA Victor on LP and CD.

Fidelio was the first opera performed in Berlin after the end of World War II, with the Deutsche Oper staging it under the baton of Robert Heger at the only undamaged theatre, the Theater des Westens, in September 1945. At the time, Thomas Mann remarked: "What amount of apathy was needed [by musicians and audiences] to listen to Fidelio in Himmler's Germany without covering their faces and rushing out of the hall!"

Not long after the end of World War II and the fall of Nazism, conductor Wilhelm Furtwängler remarked in Salzburg in 1948: [T]he conjugal love of Leonore appears, to the modern individual armed with realism and psychology, irremediably abstract and theoretical.... Now that political events in Germany have restored to the concepts of human dignity and liberty their original significance, this is the opera which, thanks to the music of Beethoven, gives us comfort and courage.... Certainly, Fidelio is not an opera in the sense we are used to, nor is Beethoven a musician for the theater, or a dramaturgist. He is quite a bit more, a whole musician, and beyond that, a saint and a visionary. That which disturbs us is not a material effect, nor the fact of the 'imprisonment'; any film could create the same effect. No, it is the music, it is Beethoven himself. It is this 'nostalgia of liberty' he feels, or better, makes us feel; this is what moves us to tears. His Fidelio has more of the Mass than of the Opera to it; the sentiments it expresses come from the sphere of the sacred, and preach a 'religion of humanity' which we never found so beautiful or necessary as we do today, after all we have lived through. Herein lies the singular power of this unique opera.... Independent of any historical consideration ... the flaming message of Fidelio touches deeply.

We realize that for us Europeans, as for all men, this music will always represent an appeal to our conscience.

On 5 November 1955, the Vienna State Opera was re-opened with Fidelio, conducted by Karl Böhm. This performance was the first live television broadcast by ORF at a time when there were about 800 television sets in Austria.

The first night of Fidelio at the Semperoper in Dresden on 7 October 1989 on the occasion of the 40th anniversary of the DDR (East Germany) coincided with violent demonstrations at the city's main train station. The applause after the "Prisoners' Chorus" interrupted the performance for considerable time, and the production by Christine Mielitz had the chorus appear in normal street clothes at the end, signifying their role as representatives of the audience. Four weeks later, on 9 November 1989, the fall of the Berlin Wall signalled the end of East Germany's regime.

Overtures
Beethoven struggled to produce an appropriate overture for Fidelio, and ultimately went through four versions. His first attempt, for the 1805 premiere, is believed to have been the overture now known as "Leonore No. 2" in C major. Beethoven then focused this version for the performances of 1806, creating "Leonore No. 3", also in C major. The latter is considered by many listeners as the greatest of the four overtures, but as an intensely dramatic, full-scale symphonic movement it had the effect of overwhelming the (rather light) initial scenes of the opera. Beethoven accordingly experimented with cutting it back somewhat, for a planned 1808 performance in Prague; this is believed to be the version now called "Leonore No. 1". Finally, for the 1814 revival Beethoven began anew, and with fresh musical material wrote what is now known as the Fidelio overture, in E major. As this somewhat lighter overture seems to work best of the four as a start to the opera, Beethoven's final intentions are generally respected in contemporary productions.

While some believe that Gustav Mahler introduced the practice of performing "Leonore No. 3" between the two scenes of the second act, something which was common until the middle of the twentieth century, David Cairns states that it goes back to the middle of the 19th century and was therefore prior to Mahler. In this location, it acts as a kind of musical reprise of the rescue scene that has just taken place.

Synopsis
Two years prior to the opening scene, the Spanish nobleman Florestan has exposed or attempted to expose certain crimes of a rival nobleman, Pizarro. In revenge, Pizarro has secretly imprisoned Florestan in the prison over which he is governor. Simultaneously, Pizarro has spread false rumors about Florestan's death.

The warden of the prison, Rocco, has a daughter, Marzelline, and an assistant, Jaquino, who is in love with Marzelline. The faithful wife of Florestan, Leonore, suspects that her husband is still alive. Disguised as a boy, under the alias "Fidelio", she gains employment working for Rocco. As the boy Fidelio, she earns the favor of her employer, Rocco, and also the affections of his daughter Marzelline, much to Jaquino's chagrin.

On orders, Rocco has been giving the imprisoned Florestan diminishing rations until he is nearly starved to death.

 * Place: A Spanish state prison, a few miles from Seville
 * Time: Late 17th century

Act 1
Jaquino and Marzelline are alone in Rocco's house. Jaquino asks Marzelline when she will agree to marry him, but she says that she will never marry him now that she has fallen in love with Fidelio, unaware that Fidelio is actually Leonore in disguise (Jetzt, Schätzchen, jetzt sind wir allein—"Now, darling, now we are alone"). Jaquino leaves, and Marzelline expresses her desire to become Fidelio's wife (O wär ich schon mit dir vereint—"If only I were already united with thee"). Rocco enters, looking for Fidelio, who then enters carrying a heavy load of newly repaired chains. Rocco compliments Fidelio, and misinterprets her modest reply as hidden attraction to his daughter. Marzelline, Fidelio, Rocco, and Jaquino sing a quartet about the love Marzelline has for Fidelio (Mir ist so wunderbar—"A wondrous feeling fills me", also known as the Canon Quartet).

Rocco tells Fidelio that as soon as the governor has left for Seville, Marzelline and Fidelio can be married. He tells them, however, that unless they have money, they will not be happy. (Hat man nicht auch Gold beineben—"If you don't have any money"). Fidelio demands to know why Rocco will not allow for help in the dungeons, especially as he always seems to return short of breath. Rocco says that there is a dungeon down there where he can never take Fidelio, which houses a man who has been wasting away for two years. Marzelline begs her father to keep Fidelio away from such a terrible sight, but Fidelio claims courage sufficient to cope with it. Rocco and Fidelio sing of courage (Gut, Söhnchen, gut—"All right, sonny, all right"), and Marzelline joins in their acclamations.

All but Rocco leave. A march is played as Pizarro enters with his guards. Rocco warns Pizarro that the minister plans a surprise visit tomorrow to investigate accusations of Pizarro's cruelty. Pizarro exclaims that he cannot let the minister discover the imprisoned Florestan, who has been thought dead. Instead, Pizarro will have Florestan murdered (Ha, welch ein Augenblick—"Hah! What a moment!"). As a signal, Pizarro orders that a trumpet be sounded at the minister's arrival. He offers Rocco money to kill Florestan, but Rocco refuses (Jetzt, Alter, jetzt hat es Eile!—"Now, old man, we must hurry!"). Pizarro says he will kill Florestan himself instead, and orders Rocco to dig a grave for him in the floor of the dungeon. Once the grave is ready, Rocco is to sound the alarm, upon which Pizarro will come into the dungeon and kill Florestan. Fidelio, hearing Pizarro's plot, is agitated, but hopes to rescue Florestan (Abscheulicher! Wo eilst du hin? and Komm, Hoffnung, lass den letzten Stern—"Monster! Where are you off to so fast?" and "Come, hope, let the last star").

Jaquino once again begs Marzelline to marry him, but she continues to refuse. Fidelio, hoping to discover Florestan, asks Rocco to let the poor prisoners roam in the garden and enjoy the beautiful weather. Marzelline similarly begs him, and Rocco agrees to distract Pizarro while the prisoners are set free. The prisoners, ecstatic at their temporary freedom, sing joyfully (O welche Lust—"O what a joy"), but remembering that they might be caught by the prison's governor Pizarro, are soon quiet.

After meeting with Pizarro, Rocco reenters and tells Fidelio that Pizarro will allow the marriage, and Fidelio will also be permitted to join Rocco on his rounds in the dungeon (Nun sprecht, wie ging's?—"Speak, how did it go?"). Rocco and Fidelio prepare to go to Florestan's cell, with the knowledge that he must be killed and buried within the hour. Fidelio is shaken; Rocco tries to discourage Fidelio from coming, but Fidelio insists. As they prepare to leave, Jaquino and Marzelline rush in and tell Rocco to run, as Pizarro has learned that the prisoners were allowed to roam, and is furious (Ach, Vater, Vater, eilt!—"O, father, father, hurry!").

Before they can leave, Pizarro enters and demands an explanation. Rocco, thinking quickly, answers that the prisoners were given a little freedom in honor of the Spanish king's name day, and quietly suggests that Pizarro should save his anger for the prisoner in the dungeon below. Pizarro tells him to hurry and dig the grave, and then announces that the prisoners will be locked up again. Rocco, Leonore, Jacquino, and Marzelline reluctantly usher the prisoners back to their cells. (Leb wohl, du warmes Sonnenlicht—"Farewell, you warm sunshine").

Act 2

Florestan is alone in his cell, deep inside the dungeons. He sings first of his trust in God, and then has a vision of his wife Leonore coming to save him (Gott! Welch Dunkel hier!—"God! What darkness here" and In des Lebens Frühlingstagen—"In the spring days of life"). Florestan collapses and falls asleep, while Rocco and Fidelio come to dig his grave. As they dig, Rocco urges Fidelio to hurry (Wie kalt ist es in diesem unterirdischen Gewölbe!—"How cold it is in this underground chamber" and Nur hurtig fort, nur frisch gegraben—"Come get to work and dig", the "Gravedigging Duet").

Florestan awakes and Fidelio recognizes him. When Florestan learns that the prison he is in belongs to Pizarro, he asks that a message be sent to his wife, Leonore, but Rocco says that it is impossible. Florestan begs for a drop to drink, and Rocco tells Fidelio to give him one. Florestan does not recognize Fidelio, his wife Leonore in disguise, but tells Fidelio that there will be reward for the good deed in Heaven (Euch werde Lohn in bessern Welten—"You shall be rewarded in better worlds"). Fidelio further begs Rocco to be allowed to give Florestan a crust of bread, and Rocco consents.

Rocco obeys his orders and sounds the alarm for Pizarro, who appears and asks if all is ready. Rocco says that it is, and instructs Fidelio to leave the dungeon, but Fidelio hides instead. Pizarro reveals his identity to Florestan, who accuses him of murder (Er sterbe! Doch er soll erst wissen—"Let him die! But first he should know"). As Pizarro brandishes a dagger, Fidelio leaps between him and Florestan and reveals her identity as Leonore, the wife of Florestan. Pizarro raises his dagger to kill her, but she pulls a gun and threatens to shoot him.

Just then, the trumpet is heard, announcing the arrival of the minister. Jaquino enters, followed by soldiers, to announce that the minister is waiting at the gate. Rocco tells the soldiers to escort Governor Pizarro upstairs. Florestan and Leonore sing to their victory as Pizarro declares that he will have revenge, while Rocco expresses his fear of what is to come (Es schlägt der Rache Stunde—"Revenge's bell tolls"). Together, Florestan and Leonore sing a love duet (O namenlose Freude!—"O unnamed joy!").

Here, the overture "Leonore No. 3" is sometimes played.

The prisoners and townsfolk sing to the day and hour of justice which has come (Heil sei dem Tag!—"Hail to the day!"). The minister, Don Fernando, announces that tyranny has ended. Rocco enters, with Leonore and Florestan, and he asks Don Fernando to help them (Wohlan, so helfet! Helft den Armen!—"So help! Help the poor ones!"). Rocco explains how Leonore disguised herself as Fidelio to save her husband. Previously in love with Fidelio, Marzelline is shocked. Rocco describes Pizarro's murder plot, and Pizarro is led away to prison. Florestan is released from his chains by Leonore, and the crowd sings the praises of Leonore, the loyal savior of her husband (Wer ein holdes Weib errungen—"Who has got a good wife").

Instrumentation
The orchestra consists of 1 piccolo, 2 flutes, 2 oboes, 2 clarinets, 2 bassoons, contrabassoon, 4 horns, 2 trumpets, 2 trombones, timpani, and strings. There is also an offstage trumpet.

Recordings

 * Fidelio discography

title: Fidelio


text:
Franche-Comté

Franche-Comté (, ; ; Frainc-Comtou: Fraintche-Comtè; Franche-Comtât; also Freigrafschaft; Franco Condado; all lit. 'Free County') is a cultural and historical region of eastern France. It is composed of the modern departments of Doubs, Jura, Haute-Saône and the Territoire de Belfort. In 2021, its population was 1,179,601.

From 1956 to 2015, the Franche-Comté was a French administrative region. Since 1 January 2016, it has been part of the new region Bourgogne-Franche-Comté.

The region is named after the Franche Comté de Bourgogne (Free County of Burgundy), definitively separated from the region of Burgundy proper in the fifteenth century. In 2016, these two-halves of the historic Kingdom of Burgundy were reunited, as the region of Bourgogne-Franche-Comté. It is also the 6th biggest region in France. The name "Franche-Comté" is feminine because the word "comté" in the past was generally feminine, although today it is masculine.

The principal cities are the capital Besançon, Belfort and Montbéliard. Other important cities are Dole (the capital before the region was conquered by Louis XIV in the late seventeenth century), Vesoul (capital of Haute-Saône), Arbois (the "wine capital" of the Jura), and Lons-le-Saunier (the capital of Jura).

History
The region has been inhabited since the Paleolithic age and was occupied by the Gauls. It was then heavily settled by Germanic peoples during the Germanic migrations, most notably the Burgundians, who settled in the region after the Gauls had vacated the area. Later, it was part of the territory of the Alemanni in the fifth century, then the Kingdom of Burgundy from 457 to 534. The Burgundians adopted Chalcedonian Christianity, Christianizing the region. In 534, it became part of the Frankish kingdom. In 561 it was included in the Merovingian Kingdom of Burgundy under Guntram, the third son of Clotaire I. In 613, Clotaire II reunited the Frankish Kingdom under his rule, and the region remained a part of the Kingdom of Burgundy under the later Merovingians and Carolingians.

County of Burgundy
The name Franche Comté de Bourgogne or Freigrafschaft Burgund in German (Free County of Burgundy) did not appear officially until 1366. It had been a territory of the County of Burgundy from 888, the province becoming subject to the Holy Roman Empire in 1034. It was definitively separated from the neighboring Duchy of Burgundy upon the latter's incorporation into the Kingdom of France in 1477. That year at the Battle of Nancy during the Burgundian Wars, the last duke, Charles the Bold, was killed in battle. Although the county, along with the Duchy, was seized by King Louis XI of France, in 1492 his son Charles VIII ceded it to Philip of Austria, the grandson and heir of Charles the Bold. When Philip's son, Emperor Charles V, inherited the Spanish throne in 1516, the Franche-Comté, along with the rest of the Burgundian lands (except Burgundy itself), passed to the Spanish.

Province of the Kingdom of France
Franche-Comté was captured by France in 1668, but returned to Spain under the Treaty of Aix-la-Chapelle. It was conquered a second time in 1674, and finally was ceded to France in the Treaty of Nijmegen (1678), leaving the Holy Roman Empire as a result. Enclaves such as Montbéliard remained outside French control.

The Franche-Comté was one of the last parts of France to have serfdom. In 1784, half of the population consisted of serfs, accounting for 400,000 out of the 1 million French serfs. Landowners took one-twelfth of the sale's price if a serf (mainmortable) wanted to sell up. Serfs were not forced to stay on the land, but the lord could claim droit de suite, whereby a peasant who died away from his holding left it to the lord, even if he had heirs. A runaway serf's land was forfeit after ten years. Louis XVI issued a decree banning these practices on 8 August 1779, but the Parlement of Besançon blocked this until 1787.

After 1790
The population of the region fell by a fifth from 1851 to 1946, reflecting low French natural growth and migration to more urbanized parts of the country. Most of the decline occurred in Haute-Saône and Jura, which remain among the country's more agriculture-dependent areas.

Environment
This region borders Switzerland and shares much of its architecture, cuisine, and culture with its neighbour. Between the Vosges range of mountains to the north and the Jura range to the south, the landscape consists of rolling cultivated fields, dense pine forest, and rampart-like mountains. Not so majestic as the Alps, the Jura mountains are more accessible and are France's first cross-country skiing area. It is also a superb place to hike, and there are some fine nature trails on the more gentle slopes. The Doubs and Loue valleys, with their timbered houses perched on stilts in the river, and the high valley of Ain, are popular visitor areas. The Région des Lacs is a land of gorges and waterfalls dotted with tiny villages, each with a domed belfry decorated with mosaic of tiles or slates or beaten from metal. The lakes are perfect for swimming in the warmer months. The summits of Haut Jura have wonderful views across Lac Léman (Lake Geneva) and toward the Alps.

Forty percent of the region's GDP is dependent on manufacturing activities, and most of its production is exported. Construction of automobiles and their parts is one of the most buoyant industries there. Forestry exploitation is steadily growing, and 38% of the agriculture is dairy and 17% cattle farming. The region has a large and lucrative cheese-making industry, with 40 million tonnes of cheese produced here each year, much of which is made by fruitières (traditional cheese dairies of Franche-Comté); for instance, Comté cheese comes from this region.

Geology

 * Vosges and Jura coal mining basins

Language
Among the regional languages of France, the term Franc-comtois refers to two dialects of two different languages. Franc-comtois is the name of the dialect of Langue d'Oïl spoken by people in the northern part of the region. The dialect of Arpitan has been spoken in its southern part since as early as the thirteenth century (the southern two-thirds of Jura and the southern third of Doubs). Both are recognized as languages of France.

People from Franche-Comté

 * Raymond Blanc, chef
 * Jean-Jacques Boissard, neo-Latin poet
 * Paul de Casteljau, mathematician
 * Gustave Courbet, painter
 * Frank Darabont, filmmaker
 * Charles Fourier, philosopher
 * Salah Gaham, concierge
 * Victor Hugo, poet, playwright, novelist, essayist, visual artist, statesman, human rights activist
 * Auguste and Louis Lumière, early filmmakers
 * Jean Mairet, dramatist
 * Jacques de Molay, last Grandmaster of the Knights Templar
 * Charles Nodier, author
 * Louis Pasteur, chemist and microbiologist
 * Antoine Perrenot de Granvelle, Burgundian statesman, leading minister of the Spanish Habsburgs
 * Nicolas Perrenot de Granvelle, minister of justice under Charles V, Holy Roman Emperor
 * Pierre-Joseph Proudhon philosopher, socialist
 * Jean Baptiste Alexandre Strolz
 * Jean-Baptiste-Antoine Suard, journalist
 * Hubert-Félix Thiéfaine, singer and songwriter
 * Louis Vuitton, designer
 * Arnaud Courlet de Vregille, painter

Typical regional products

 * Wine: Vin jaune, Arbois
 * Cheese: Cancoillotte, Bleu de Gex, Comté, Édel de Cléron, Metton, Morbier, Munster, Vacherin Mont d'Or
 * Sausages: Saucisse de Montbéliard, saucisse de Morteau, Gendarme

title: Franche-Comté