Question:

How do people react while tripping on Acid?

Answer:

The effects of LSD strongly depend on the mental state of the user and the circumstances in which the drug is used. Therefore, the same dose can produce good and bad trips in the same person, depending on the circumstances in which the drug is used.

More Info:

Trip sitter is a term used by recreational or spiritual drug users to describe a person who remains sober to ensure the safety of the drug user while he or she is under the influence of a drug; they are especially common with first-time experiences or when using psychedelics, dissociatives and deliriants. This practice can be qualified as a means of harm reduction. Also called a Psychedelic Guide or Guide, this latter term is more often used to describe someone who takes an active role in guiding a drug user's experiences as opposed to a sitter who merely remains present, ready to discourage bad trips and handle emergencies but not otherwise getting involved. Guides are more common amongst spiritual users of entheogens. [1] [2] Psychedelic guides were strongly encouraged by Timothy Leary and the other authors of The Psychedelic Experience: A Manual Based on the Tibetan Book of the Dead.[7] Trip sitters are also mentioned in the Responsible Drug User's Oath. Some sources recommend a sitter be present when certain drugs are used, regardless of the user's experience or comfort with the substance; for example, a sitter may be necessary for users of Salvia divinorum because the drug can sometimes cause both disorientation and a desire to move about before the effects have worn off. [3] Obviously, while the presence of a trip sitter or guide may make a drug user feel safer, it is no guarantee that a bad trip will not occur, or that the drug user will remain free of physical or mental harm. In some cases, a trip sitter may be a medical professional, such as the nurses used in psychedelic research or a therapist who performs psychedelic psychotherapy.[4] [5] Sometimes, a tripper will ask another, more experienced user to sit for them. However, the most common trip sitter is a friend or family member whom the drug user trusts. [1] Although an ideal sitter is one who is both personally experienced with the substance being used, as well as one trained to deal with any potential psychological or medical crisis that may arise, arguably the most important qualities may be the willingness to help, the responsibility needed to stay sober enough to be fully present, and the ability to be relaxed, accepting, and not interfere with the experience beyond the wishes of the user. A sitter should be willing to research the substance in question, and understand when to call for professional medical assistance.[1] [6] [7] Especially when using a short-acting substance such as smoked DMT or Salvia divinorum, it may be possible for two people to take turns, with one being the sitter while the other takes the psychedelic. A responsible trip sitter assists a drug user before, during, and after their experience; it is their responsibility to help the user by making sure they drink enough water, assisting them in moving around when needed, and generally doing whatever necessary to ensure their comfort throughout the trip.[1] [2] The responsible trip sitter will thoroughly research the substance which will be ingested (as well as the users) in order to answer all potential questions the user may have, and to prepare for any potential crisis situations it may cause. The sitter will discuss this research in detail with the user; it is also considered important to talk to the user about any ground rules for the session, how to handle any emergencies that may arise, and what, if any, guidance will be wanted during the trip.[1] [2] A trip sitter will also frequently help a drug user create a healthy set and setting for the experience. They do this by making sure the user's surroundings are comfortable and orderly, adjusting lighting, temperature, and music (if any) to suit the desired tone of the trip, and overall doing whatever they can to maximize the user's openness to the experience and minimize their fear.[1] [2] [7] A sitter typically remains present for the entire experience. In some cases, they may actively guide the experience of the user by adjusting their environment or through guided meditation or visualization. In other cases, they stay uninvolved except when the user has questions, fears, or needs for which the sitter can provide (such as making sure the user drinks enough water). Assistance in facing fears may be especially necessary if the experience turns into a bad trip. [1] [2] [4] [5] [7] In order to maintain the immediate well-being of the drug user, it is important for the sitter to know what situations he/she can or cannot handle on his/her own, and when to call for professional medical assistance. [6] Although the sitter may be called upon to intervene during a difficult situation, bad trip, or medical crisis, the mere presence of a caring sitter is often enough to keep a user comfortable and even enable deeper exploration of the drug's effects. [1] The experience of being present during an especially powerful experience, such as when the user reaches new insight into themselves or their beliefs about the nature of the universe, is reportedly quite rewarding. [7] A sitter may help the drug user to integrate or understand their experiences when the experience is complete. Just as they did before, and during the trip, they may reassure the user about any fears or worries that have occurred. This discussion may take place immediately after the drug's effects have worn off, or they may wait until a later date. [1] [2]
InChI=1S/C20H25N3O/c1-4-23(5-2)20(24)14-9-16-15-7-6-8-17-19(15)13(11-21-17)10-18(16)22(3)12-14/h6-9,11,14,18,21H,4-5,10,12H2,1-3H3/t14-,18-/m1/s1Yes 
Key:VAYOSLLFUXYJDT-RDTXWAMCSA-NYes  Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide (INN) and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synesthesia, an altered sense of time and spiritual experiences, as well as for its key role in 1960s counterculture. It is used mainly as an entheogen, recreational drug, and as an agent in psychedelic therapy. LSD is non-addictive, is not known to cause brain damage, and has extremely low toxicity relative to dose. However, adverse psychiatric reactions such as anxiety, paranoia, and delusions are possible. LSD was first synthesized by Albert Hofmann in 1938 from ergotamine, a chemical derived by Arthur Stoll from ergot, a grain fungus that typically grows on rye. The short form "LSD" comes from its early code name LSD-25, which is an abbreviation for the German "Lysergsäure-diethylamid" followed by a sequential number. LSD is sensitive to oxygen, ultraviolet light, and chlorine, especially in solution, though its potency may last for years if it is stored away from light and moisture at low temperature. In pure form it is a colorless, odorless, tasteless solid. LSD is typically delivered orally, usually on a substrate such as absorbent blotter paper, a sugar cube, or gelatin. In its liquid form, it can also be administered by intramuscular or intravenous injection. LSD is very potent, with 20–30 µg (micrograms) being the threshold dose. New clinical LSD experiments in humans started in 2009 for the first time in 40 years.][ Introduced by Sandoz Laboratories, with trade-name Delysid, as a drug with various psychiatric uses in 1947, LSD quickly became a therapeutic agent that appeared to show great promise. In the 1950s, officials at the U.S. Central Intelligence Agency (CIA) thought the drug might be applicable to mind control and chemical warfare; the agency's MKULTRA research program propagated the drug among young servicemen and students. The subsequent recreational use of the drug by youth culture in the Western world during the 1960s led to a political firestorm that resulted in its prohibition. Currently, a number of organizations—including the Beckley Foundation, MAPS, Heffter Research Institute and the Albert Hofmann Foundation—exist to fund, encourage and coordinate research into the medicinal and spiritual uses of LSD and related psychedelics. LSD can cause pupil dilation, reduced or increased appetite, and wakefulness. Other physical reactions to LSD are highly variable and nonspecific, some of which may be secondary to the psychological effects of LSD. Among the reported symptoms are numbness, weakness, nausea, hypothermia or hyperthermia, elevated blood sugar, goose bumps, heart rate increase, jaw clenching, perspiration, saliva production, mucus production, sleeplessness, hyperreflexia, and tremors. Some users, including Albert Hofmann, report a strong metallic taste for the duration of the effects. LSD is not considered addictive by the medical community. Rapid tolerance build-up prevents regular use,][ and cross-tolerance has been demonstrated between LSD, mescaline and psilocybin. This tolerance diminishes after a few days after cessation of use and is probably caused by downregulation of receptors2A5-HT in the brain. LSD's psychological effects (colloquially called a "trip") vary greatly from person to person, depending on factors such as previous experiences, state of mind and environment, as well as dose strength. They also vary from one trip to another, and even as time passes during a single trip. An LSD trip can have long-term psychoemotional effects; some users cite the LSD experience as causing significant changes in their personality and life perspective][. Widely different effects emerge based on what Timothy Leary called set and setting; the "set" being the general mindset of the user, and the "setting" being the physical and social environment in which the drug's effects are experienced. Some psychological effects may include an experience of radiant colors, objects and surfaces appearing to ripple or "breathe", colored patterns behind the closed eyelids (eidetic imagery), an altered sense of time (time seems to be stretching, repeating itself, changing speed or stopping), crawling geometric patterns overlaying walls and other objects, morphing objects, a sense that one's thoughts are spiraling into themselves, loss of a sense of identity or the ego (known as "ego death"), and other powerful psycho-physical reactions. Many users experience a dissolution between themselves and the "outside world". This unitive quality may play a role in the spiritual and religious aspects of LSD. The drug sometimes leads to disintegration or restructuring of the user's historical personality and creates a mental state that some users report allows them to have more choice regarding the nature of their own personality. If the user is in a hostile or otherwise unsettling environment, or is not mentally prepared for the powerful distortions in perception and thought that the drug causes, effects are more likely to be unpleasant than if he or she is in a comfortable environment and has a relaxed, balanced and open mindset. LSD causes an altered sensory experience of senses, emotions, memories, time, and awareness for 6 to 14 hours, depending on dosage and tolerance. Generally beginning within thirty to ninety minutes after ingestion, the user may experience anything from subtle changes in perception to overwhelming cognitive shifts. Changes in auditory and visual perception are typical. Visual effects include the illusion of movement of static surfaces ("walls breathing"), after image-like trails of moving objects ("tracers"), the appearance of moving colored geometric patterns (especially with closed eyes), an intensification of colors and brightness ("sparkling"), new textures on objects, blurred vision, and shape suggestibility. Users commonly report that the inanimate world appears to animate in an unexplainable way; for instance, objects that are static in three dimensions can seem to be moving relative to one or more additional spatial dimensions. Many of the basic visual effects resemble the phosphenes seen after applying pressure to the eye and have also been studied under the name "form constants". The auditory effects of LSD may include echo-like distortions of sounds, changes in ability to discern concurrent auditory stimuli, and a general intensification of the experience of music. Higher doses often cause intense and fundamental distortions of sensory perception such as synaesthesia, the experience of additional spatial or temporal dimensions, and temporary dissociation. LSD has been used in psychiatry for its perceived therapeutic value, in the treatment of alcoholism, pain and cluster headache relief, for spiritual purposes, and to enhance creativity. However, government organizations like the United States Drug Enforcement Administration maintain that LSD "produces no aphrodisiac effects, does not increase creativity, has no lasting positive effect in treating alcoholics or criminals, does not produce a 'model psychosis', and does not generate immediate personality change." In the 1950s and 1960s LSD was used in psychiatry to enhance psychotherapy. Some psychiatrists believed LSD was especially useful at helping patients to "unblock" repressed subconscious material through other psychotherapeutic methods, and also for treating alcoholism. One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender," presumably by forcing the user to face issues and problems in that individual's psyche. In December 1968, a survey was made of all 74 UK doctors who had used LSD in humans; 73 replied, 1 had moved overseas and was unavailable. The majority of UK doctors with clinical experience with LSD felt that LSD was effective and had acceptable safety: From 2008–2011 there has been ongoing research in Switzerland into using LSD to alleviate anxiety for terminally ill cancer patients coping with their impending deaths. Preliminary results from the study are promising, and no negative effects have been reported. Some studies in the 1960s that used LSD to treat alcoholism reduced levels of alcohol misuse in almost 60% of those treated, an effect which lasted six months but disappeared after a year. A 1998 review was inconclusive. However, a 2012 meta-analysis of six randomized controlled trials found evidence that a single dose of LSD in conjunction with various alcoholism treatment programs was associated with a decrease in alcohol abuse, lasting for several months. LSD was studied in the 1960s by Eric Kast as an analgesic for serious and chronic pain caused by cancer or other major trauma. Even at low (sub-psychedelic) dosages, it was found to be at least as effective as traditional opiates, while being much longer lasting in pain reduction (lasting as long as a week after peak effects had subsided). Kast attributed this effect to a decrease in anxiety; that is to say that patients were not experiencing less pain, but rather were less distressed by the pain they experienced. This reported effect is being tested (though not using LSD) in an ongoing (as of 2006) study of the effects of psilocybin on anxiety in terminal cancer patients. LSD has been used as a treatment for cluster headaches, an uncommon but extremely painful disorder. Researcher Peter Goadsby describes the headaches as "worse than natural childbirth or even amputation without anesthetic." Although the phenomenon has not been formally investigated, case reports indicate that LSD and psilocybin can reduce cluster pain and also interrupt the cluster-headache cycle, preventing future headaches from occurring. Currently existing treatments include various ergolines, among other chemicals, so LSD's efficacy may not be surprising. A dose-response study testing the effectiveness of both LSD and psilocybin was planned at McLean Hospital, although the current status of this project is unclear. A 2006 study by McLean researchers interviewed 53 cluster-headache sufferers who treated themselves with either LSD or psilocybin, finding that a majority of the users of either drug reported beneficial effects. Unlike use of LSD or MDMA in psychotherapy, this research involves non-psychological effects and often sub-psychedelic dosages. LSD is considered an entheogen because it can catalyze intense spiritual experiences, during which users may feel they have come into contact with a greater spiritual or cosmic order. Users claim to experience lucid sensations where they have "out of body" experiences. Some users report insights into the way the mind works, and some experience permanent shifts in their life perspective. LSD also allows users to view their life from an introspective point of view. Some users report using introspection to resolve unresolved or negative feelings towards an individual or incident that occurred in the past. Some users consider LSD a religious sacrament, or a powerful tool for access to the divine. Stanislav Grof has written that religious and mystical experiences observed during LSD sessions appear to be phenomenologically indistinguishable from similar descriptions in the sacred scriptures of the great religions of the world and the secret mystical texts of ancient civilizations. In the 1950s and 1960s, psychiatrists like Oscar Janiger explored the potential effect of LSD on creativity. Experimental studies attempted to measure the effect of LSD on creative activity and aesthetic appreciation. Seventy professional artists were asked to draw two pictures of a Hopi Indian kachina doll, one before ingesting LSD and one after. There have been no documented human deaths from an LSD overdose. It is physiologically well tolerated and there is no evidence for long-lasting physiological effects on the brain or other parts of the human organism. LSD may temporarily impair the ability to make sensible judgments and understand common dangers, thus making the user more susceptible to accidents and personal injury. It may cause temporary confusion, difficulty with abstract thinking, or signs of impaired memory and attention span. There is some indication that LSD may trigger a dissociative fugue state in individuals who are taking certain classes of antidepressants such as lithium salts and tricyclics. In such a state, the user has an impulse to wander, and may not be aware of his or her actions, which can lead to physical injury. Anonymous anecdotal reports have attributed seizures and one death to the combination of LSD with lithium. SSRIs noticeably reduce LSD's subjective effects. MAOIs are also reported to reduce the effects of LSD. LSD may trigger panic attacks or feelings of extreme anxiety, colloquially referred to as a "bad trip". No real prolonged effects have been proven; however, people with such conditions as schizophrenia and depression can worsen with LSD. While publicly available documents indicate that the CIA and Department Of Defense have discontinued research into the use of LSD as a means of mind control, research from the 1960s suggests there exists evidence that both mentally ill and healthy people are more suggestible while under its influence. There are some cases of LSD inducing a psychosis in people who appeared to be healthy before taking LSD. In most cases, the psychosis-like reaction is of short duration, but in other cases it may be chronic. It is difficult to determine whether LSD itself induces these reactions or if it triggers latent conditions that would have manifested themselves otherwise. The similarities of time course and outcomes between putatively LSD-precipitated and other psychoses suggest that the two types of syndromes are not different and that LSD may have been a nonspecific trigger.][ Estimates of the prevalence of LSD-induced prolonged psychosis lasting over 48 hours have been made by surveying researchers and therapists who had administered LSD: However, in neither survey study was it possible to compare the rate of lasting psychosis in these volunteers and patients receiving LSD with the rate of psychosis found in other groups of research volunteers or in other methods of psychiatric treatment (for example, those receiving placebo). Cohen (1960) noted: "Flashbacks" are a reported psychological phenomenon in which an individual experiences an episode of some of LSD's subjective effects long after the drug has worn off, usually in the days after typical doses. In some rarer cases, flashbacks have lasted longer, but are generally short-lived and mild compared to the actual LSD "trip". Flashbacks can incorporate both positive and negative aspects of LSD trips, and are typically elicited by triggers such as alcohol or cannabis use, stress, caffeine, or sleepiness. Flashbacks have proven difficult to study and are no longer officially recognized as a psychiatric syndrome. However, colloquial usage of the term persists and usually refers to any drug-free experience reminiscent of psychedelic drug effects, with the typical connotation that the episodes are of short duration. No definitive explanation is currently available for these experiences. Any attempt at explanation must reflect several observations: first, over 70 percent of LSD users claim never to have "flashed back"; second, the phenomenon does appear linked with LSD use, though a causal connection has not been established; and third, a higher proportion of psychiatric patients report flashbacks than other users. Several studies have tried to determine how likely a user of LSD, not suffering from known psychiatric conditions, is to experience flashbacks. The larger studies include Blumenfeld's in 1971 and Naditch and Fenwick's in 1977, which arrived at figures of 20% and 28%, respectively. Although flashbacks themselves are not recognized as a medical syndrome, there is a recognized syndrome called Hallucinogen Persisting Perception Disorder (HPPD) in which LSD-like visual changes are not temporary and brief, as they are in flashbacks, but instead are persistent, and cause clinically significant impairment or distress. The syndrome is a DSM-IV diagnosis. Several scientific journal articles have described the disorder. HPPD differs from flashbacks in that it is persistent and apparently entirely visual (although mood and anxiety disorders are sometimes diagnosed in the same individuals). A recent review suggests that HPPD (as defined in the DSM-IV) is rare and affects only a distinctly vulnerable subpopulation of users. However, it is possible that the prevalence of HPPD is underestimated because most of the diagnoses are applied to people who are willing to admit to their health care practitioner that they have previously used psychotropics, and presumably many people are reluctant to admit this. There is no consensus regarding the nature and causes of HPPD (or flashbacks). A study of 44 HPPD subjects who had previously ingested LSD showed EEG abnormalities. Given that some symptoms have environmental triggers, it may represent a failure to adjust visual processing to changing environmental conditions. There are no explanations for why only some individuals develop HPPD. Explanations in terms of LSD physically remaining in the body for months or years after consumption have been discounted by experimental evidence. Some say HPPD is a manifestation of post-traumatic stress disorder, not related to the direct action of LSD on brain chemistry, and varies according to the susceptibility of the individual to the disorder. Many emotionally intense experiences can lead to flashbacks when a person is reminded acutely of the original experience. However, not all published case reports of HPPD appear to describe an anxious hyper-vigilant state reminiscent of post-traumatic stress disorder. Instead, some cases appear to involve only visual symptoms. Early pharmacological testing by Sandoz in laboratory animals showed that LSD can stimulate uterine contractions, with efficacy comparable to ergobasine, the active uterotonic component of the ergot fungus. (Hofmann's work on ergot derivatives also produced a modified form of ergobasine which became a widely accepted medication used in obstetrics, under the trade name Methergine.) Therefore, LSD use by pregnant women could be dangerous and is contraindicated. However, the relevance of these animal studies to humans is unclear, and a 2008 medical reference guide to drugs in pregnancy and lactation stated, "It appears unlikely that pure LSD administered in a controlled condition is an abortifacient." Beginning in 1967, studies raised concerns that LSD might produce genetic damage or developmental abnormalities in fetuses. However, these initial reports were based on in vitro studies or were poorly controlled and have not been substantiated. In studies of chromosomal changes in human users and in monkeys, the balance of evidence suggests no increase in chromosomal damage. For example, white blood cells of people who had been given LSD in a clinical setting were examined for visible chromosomal abnormalities; overall, there appeared to be no lasting changes. Several studies have been conducted using illicit LSD users and provide a less clear picture. Interpretation of these data is generally complicated by factors such as the unknown chemical composition of street LSD, concurrent use of other psychoactive drugs, and diseases such as hepatitis in the sampled populations. It seems possible the small number of genetic abnormalities reported in users of street LSD is either coincidental or related to factors other than a toxic effect of pure LSD. A 2008 medical review concluded, "The available data suggest that pure LSD does not cause chromosomal abnormalities, spontaneous abortions, or congenital malformations. In 1969 Moseley (now Gottschalk) working at the University of California, Riverside, under Edward Crellin Pauling, using e. coli ligase mutant strain obtained results indicating no breakage and that therapeutically high doses actually reduced breakage." Reassurance in a calm, safe environment is beneficial. Agitation can be safely addressed with benzodiazepines such as Valium, but neuroleptics such as Haldol should be avoided because they may cause hallucinations or paranoid delusions. LSD is rapidly absorbed, so activated charcoal and emptying of the stomach may be of little benefit in the emergency department. Sedation or physical restraint is rarely required, and excessive restraint may cause complications such as hyperthermia (over-heating) or rhabdomyolysis. Massive doses require supportive care, which may include endotracheal intubation or respiratory support. High blood pressure, tachycardia (rapid heart-beat) and hyperthermia, if present, should be treated symptomatically. Treat low blood pressure initially with fluids and then with pressors if necessary. Intravenous administration of anticoagulants, vasodilators, and sympatholytics may be useful with massive doses. Balloon percutaneous transluminal angioplasty has been employed in some severe cases. LSD is a chiral compound with two stereocenters at the carbon atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)-D-LSD, has the absolute configuration (5R,8R). The C-5 isomers of lysergamides do not exist in nature and are not formed during the synthesis from D-lysergic acid. Retrosynthetically, the C-5 stereocenter could be analysed as having the same configuration of the alpha carbon of the naturally occurring amino acid L-tryptophan, the precursor to all biosynthetic ergoline compounds. However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of bases, as the alpha proton is acidic and can be deprotonated and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated by chromatography and can be isomerized to LSD. A totally pure salt of LSD will emit small flashes of white light when shaken in the dark. LSD is strongly fluorescent and will glow bluish-white under UV light. LSD is an ergoline derivative. It is commonly synthesised by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride and peptide coupling reagents. Lysergic acid is made by alkaline hydrolysis of lysergamides like ergotamine, a substance usually derived from the ergot fungus on agar plate, or theoretically possible, but impractical and uncommon from ergine (lysergic acid amide, LSA) extracted from morning glory seeds. "LSD," writes the chemist Alexander Shulgin, "is an unusually fragile molecule." It is stable for indefinite time if stored as a solid salt or dissolved in water, at low temperature and protected from air and light exposure. LSD has two labile protons at the tertiary stereogenic C5 and C8 positions, rendering these centres prone to epimerisation. The C8 proton is more labile due to the electron-withdrawing carboxamide attachment, but removal of the chiral proton at the C5 position (which was once also an alpha proton of the parent molecule tryptophan) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with the indole ring.][ LSD also has enamine-type reactivity because of the electron-donating effects of the indole ring. Because of this, chlorine destroys LSD molecules on contact; even though chlorinated tap water contains only a slight amount of chlorine, the small quantity of compound typical to an LSD solution will likely be eliminated when dissolved in tap water. The double bond between the 8-position and the aromatic ring, being conjugated with the indole ring, is susceptible to nucleophilic attacks by water or alcohol, especially in the presence of light. LSD often converts to "lumi-LSD", which is inactive in human beings. A controlled study was undertaken to determine the stability of LSD in pooled urine samples. The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. These studies demonstrated no significant loss in LSD concentration at 25°C for up to four weeks. After four weeks of incubation, a 30% loss in LSD concentration at 37°C and up to a 40% at 45°C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. It was also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of EDTA. A single dose of LSD may be between 100 and 500 micrograms—an amount roughly equal to one-tenth the mass of a grain of sand. Threshold effects can be felt with as little as 25 micrograms of LSD. Dosages of LSD are measured in micrograms (µg), or millionths of a gram. By comparison, dosages of most drugs, both recreational and medicinal, are measured in milligrams (mg), or thousandths of a gram. For example, an active dose of mescaline, roughly 0.2 to 0.5g, has effects comparable to 100 µg or less of LSD. In the mid-1960s, the most important black market LSD manufacturer (Owsley Stanley) distributed acid at a standard concentration of 270 µg. While street samples of the 1970s contained 30 to 300 µg. By the 1980s, the amount had reduced to between 100 and 125 µg, lowering more in the 1990s to the 20–80 µg range, and even more in the 2000s (decade). Estimates for the median lethal dose (LD50) of LSD range from 200 µg/kg to more than 1 mg/kg of human body mass, though most sources report that there are no known human cases of such an overdose. Other sources note one report of a suspected fatal overdose of LSD occurring in November 1975 in Kentucky in which there were indications that ~1/3 of a gram (320 mg or 320,000 µg) had been injected intravenously. (This is a very extraordinary amount, equivalent to over 3,000 times the average LSD dosage of ~100 µg). Experiments with LSD have also been done on animals; in 1962, an elephant named Tusko died shortly after being injected with 297 mg, but whether the LSD was the cause of his death is controversial (due, in part, to a plethora of other chemical substances administered simultaneously). LSD's effects normally last from 6–12 hours depending on dosage, tolerance, body weight and age. The Sandoz prospectus for "Delysid" warned: "intermittent disturbances of affect may occasionally persist for several days." Contrary to early reports and common belief, LSD effects do not last longer than the amount of time significant levels of the drug are present in the blood. Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175 minutes. However, using more accurate techniques, Papac and Foltz (1990) reported that 1 µg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1 hours, with a peak plasma concentration of 5 ng/mL at 3 hours post-dose. LSD may be quantified in urine as part of a drug abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Both the parent drug and its major metabolite are unstable in biofluids when exposed to light, heat or alkaline conditions and therefore specimens are protected from light, stored at the lowest possible temperature and analyzed quickly to minimize losses. LSD affects a large number of the G protein-coupled receptors, including all dopamine receptor subtypes, and all adrenoreceptor subtypes, as well as many others. Most serotonergic psychedelics are not dopaminergic. LSD's agonism of D2 receptors contributes to its psychoactive effects. LSD binds to most serotonin receptor subtypes except for 35-HT and 45-HT. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM. In humans, recreational doses of LSD can affect 1A5-HT (Ki=1.1nM), 2A5-HT (Ki=2.9nM), 2B5-HT (Ki=4.9nM), 2C5-HT (Ki=23nM), 5A5-HT (Ki=9nM [in cloned rat tissues]), and receptors65-HT (Ki=2.3nM). receptors5B5-HT, which are not present in humans, also have a high affinity for LSD. The psychedelic effects of LSD are attributed to its strong partial agonist effects at 5-HT2A receptors as specific 5-HT2A agonists are psychedelics and largely 5-HT2A specific antagonists block the psychedelic activity of LSD. LSD exhibits functional selectivity at the 5-HT2A and 5HT2C receptors in that it activates the signal transduction enzyme phospholipase A2 instead of activating the enzyme phospholipase C as the endogenous ligand serotonin does. Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex and therefore excitation in this area, specifically in layers IV and V. LSD, like many other drugs, has been shown to activate DARPP-32-related pathways. "... affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away." LSD was first synthesized on November 16, 1938 by Swiss chemist Albert Hofmann at the Sandoz Laboratories in Basel, Switzerland as part of a large research program searching for medically useful ergot alkaloid derivatives. LSD's psychedelic properties were discovered 5 years later when Hofmann himself accidentally ingested an unknown quantity of the chemical. The first intentional ingestion of LSD occurred on April 19, 1943, when Hofmann ingested 250 µg of LSD. He said this would be a threshold dose based on the dosages of other ergot alkaloids. Hofmann found the effects to be much stronger than he anticipated. Sandoz Laboratories introduced LSD as a psychiatric drug in 1947. Beginning in the 1950s the US Central Intelligence Agency began a research program code named Project MKULTRA. Experiments included administering LSD to CIA employees, military personnel, doctors, other government agents, prostitutes, mentally ill patients, and members of the general public in order to study their reactions, usually without the subject's knowledge. The project was revealed in the US congressional Rockefeller Commission report in 1975. In 1963 the Sandoz patents expired on LSD. Also in 1963, the US Food and Drug Administration classified LSD as an Investigational New Drug, which meant new restrictions on medical and scientific use. Several figures, including Aldous Huxley, Timothy Leary, and Al Hubbard, began to advocate the consumption of LSD. LSD became central to the counterculture of the 1960s. On October 24, 1968, possession of LSD was made illegal in the United States. The last FDA approved study of LSD in patients ended in 1980, while a study in healthy volunteers was made in the late 1980s. Legally approved and regulated psychiatric use of LSD continued in Switzerland until 1993. Today, medical research is resuming around the world. An active dose of LSD is very minute, allowing a large number of doses to be synthesized from a comparatively small amount of raw material. Twenty five kilograms of precursor ergotamine tartrate can produce 5–6 kg of pure crystalline LSD; this corresponds to 100 million doses. Because the masses involved are so small, concealing and transporting illicit LSD is much easier than smuggling other illegal drugs like cocaine or cannabis. Manufacturing LSD requires laboratory equipment and experience in the field of organic chemistry. It takes two to three days to produce 30 to 100 grams of pure compound. It is believed that LSD is not usually produced in large quantities, but rather in a series of small batches. This technique minimizes the loss of precursor chemicals in case a step does not work as expected. LSD is produced in crystalline form and then mixed with excipients or redissolved for production in ingestible forms. Liquid solution is either distributed in small vials or, more commonly, sprayed onto or soaked into a distribution medium. Historically, LSD solutions were first sold on sugar cubes, but practical considerations forced a change to tablet form. Appearing in 1968 as an orange tablet measuring about 6 mm across, "Orange Sunshine" acid was the first largely available form of LSD after its possession was made illegal. Tim Scully, a prominent chemist, made some of it, but said that most "Sunshine" in the USA came by way of Ronald Stark, who imported approximately thirty-five million doses from Europe. Over a period of time, tablet dimensions, weight, shape and concentration of LSD evolved from large (4.5–8.1 mm diameter), heavyweight (≥150 mg), round, high concentration (90–350 µg/tab) dosage units to small (2.0–3.5 mm diameter) lightweight (as low as 4.7 mg/tab), variously shaped, lower concentration (12–85 µg/tab, average range 30–40 µg/tab) dosage units. LSD tablet shapes have included cylinders, cones, stars, spacecraft, and heart shapes. The smallest tablets became known as "Microdots". After tablets came "computer acid" or "blotter paper LSD", typically made by dipping a preprinted sheet of blotting paper into an LSD/water/alcohol solution. More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975. About the same time as blotter paper LSD came "Windowpane" (AKA "Clearlight"), which contained LSD inside a thin gelatin square a quarter of an inch (6 mm) across. LSD has been sold under a wide variety of often short-lived and regionally restricted street names including Acid, Trips, Uncle Sid, Blotter, Lucy, Alice and doses, as well as names that reflect the designs on the sheets of blotter paper. Authorities have encountered the drug in other forms—including powder or crystal, and capsule. LSD manufacturers and traffickers in the United States can be categorized into two groups: A few large-scale producers, and an equally limited number of small, clandestine chemists, consisting of independent producers who, operating on a comparatively limited scale, can be found throughout the country. As a group, independent producers are of less concern to the Drug Enforcement Administration than the larger groups, as their product reaches only local markets. Since 2005, law enforcement in the United States and elsewhere has seized several chemicals and combinations of chemicals in blotter paper which were sold as LSD mimics, including DOB, 2C-I, DOC, a mixture of DOC and DOI, and a mixture of DOC and DOB. Street users of LSD are often under the impression that blotter paper which is actively hallucinogenic can only be LSD because that is the only chemical with low enough doses to fit on a small square of blotter paper. While it is true that LSD requires lower doses than most other hallucinogens, blotter paper is capable of absorbing a much larger amount of material. The DEA performed a chromatographic analysis of blotter paper containing 2C-C which showed that the paper contained a much greater concentration of the active chemical than typical LSD doses, although the exact quantity was not determined. Blotter LSD mimics can have relatively small dose squares; a sample of blotter paper containing DOC seized by Concord, California police had dose markings approximately 6 mm apart. The United Nations Convention on Psychotropic Substances (adopted in 1971) requires its parties to prohibit LSD. Hence, it is illegal in all parties to the convention, which includes the United States, Australia, New Zealand, and most of Europe. However, enforcement of extant laws varies from country to country. Medical and scientific research with LSD in humans is permitted under the 1971 UN Convention. In Canada, LSD is a controlled substance under Schedule III of the Controlled Drugs and Substances Act. Every person who seeks to obtain the substance, without disclosing authorization to obtain such substances 30 days before obtaining another prescription from a practitioner, is guilty of an indictable offense and liable to imprisonment for a term not exceeding 3 years. Possession for purpose of trafficking is an indictable offense punishable by imprisonment for 10 years. In the United Kingdom, LSD is a Schedule 1 Class 'A' drug. This means it has no recognised legitimate uses and possession of the drug without a license is punishable with 7 years imprisonment and/or an unlimited fine, and trafficking is punishable with life imprisonment and an unlimited fine (see main article on drug punishments Misuse of Drugs Act 1971). In 2000, after consultation with members of the Royal College of Psychiatrists' Faculty of Substance Misuse, the UK Police Foundation issued the Runciman Report which recommended "the transfer of LSD from Class A to Class B". In November 2009, the UK Transform Drug Policy Foundation released in the House of Commons a guidebooks to the legal regulation of drugs, After the War on Drugs: Blueprint for Regulation, which details options for regulated distribution and sale of LSD and other psychedelics. LSD is Schedule I in the United States, according to the Controlled Substances Act of 1970. This means LSD is illegal to manufacture, buy, possess, process, or distribute without a DEA license. By classifying LSD as a Schedule I substance, the Drug Enforcement Administration holds that LSD meets the following three criteria: it is deemed to have a high potential for abuse; it has no legitimate medical use in treatment; and there is a lack of accepted safety for its use under medical supervision. There are no documented deaths from chemical toxicity; most LSD deaths are a result of behavioral toxicity. There can also be substantial discrepancies between the amount of chemical LSD that one possesses and the amount of possession with which one can be charged in the U.S. This is because LSD is almost always present in a medium (e.g. blotter or neutral liquid), and the amount that can be considered with respect to sentencing is the total mass of the drug and its medium. This discrepancy was the subject of 1995 United States Supreme Court case, Neal v. U.S. Lysergic acid and lysergic acid amide, LSD precursors, are both classified in Schedule III of the Controlled Substances Act. Ergotamine tartrate, a precursor to lysergic acid, is regulated under the Chemical Diversion and Trafficking Act. Some notable individuals have commented publicly on their experiences with LSD. Some of these comments date from the era when it was legally available in the US and Europe for non-medical uses, and others pertain to psychiatric treatment in the 1950s and 1960s. Still others describe experiences with illegal LSD, obtained for philosophic, artistic, therapeutic, spiritual, or recreational purposes. Documentaries
InChI=1S/C17H25N/c1-4-10-16(11-5-1)17(12-6-2-7-13-17)18-14-8-3-9-15-18/h1,4-5,10-11H,2-3,6-9,12-15H2Yes 
Key:JTJMJGYZQZDUJJ-UHFFFAOYSA-NYes  Phencyclidine (a complex clip of the chemical name 1-(1-phenylcyclohexyl)piperidine), commonly initialized as PCP and known colloquially as angel dust, KJ (kristal joint), illy, or wet, is a recreational dissociative drug. Formerly used as an anesthetic agent, PCP exhibits hallucinogenic effects. First synthesized in 1926, it was eventually patented in 1952 by the Parke-Davis pharmaceutical company and marketed under the brand name Sernyl. In chemical structure, PCP is an arylcyclohexylamine derivative, and, in pharmacology, it is a member of the family of dissociative anesthetics. PCP works primarily as an NMDA receptor antagonist, which blocks the activity of the NMDA receptor and, like most antiglutamatergic hallucinogens, is significantly more dangerous than other categories of hallucinogens. Other NMDA receptor antagonists include ketamine, tiletamine, dextromethorphan and nitrous oxide. As a recreational drug, PCP may be ingested, smoked, or inhaled. PCP is well known for its primary action on ionotropic glutamate receptors, such as the NMDA receptor in rats and in rat brain homogenate. As such, PCP is an NMDA receptor antagonist. NMDA receptors mediate excitation, however, studies have shown that PCP unexpectedly produces substantial cortical activation in humans and rodents. Research also indicates that PCP inhibits nicotinic acetylcholine (nACh) receptors. Analogues of PCP exhibit varying potency at nACh receptors][ and NMDA receptors. In some brain regions, these effects are believed to act synergistically by inhibiting excitatory activity.][ PCP, like ketamine, also acts as a receptor2D partial agonist in rat brain homogenate. This activity may be associated with some of the more psychotic features of PCP intoxication, which is evidenced by the successful use of D2 receptor antagonists (such as haloperidol) in the treatment of PCP psychosis. Studies on rats indicate that PCP indirectly interacts with endorphin and enkephalin receptors to produce analgesia. PCP may also work as a dopamine reuptake inhibitor. PCP is metabolized into PCHP, PPC and PCAA. When smoked, some of it is broken down by heat into 1-phenyl-1-cyclohexene (PC) and piperidine. More than 30 different analogues of PCP were reported as being used on the street during the 1970s and 1980s, mainly in the USA. The best known of these are rolicyclidine (PCPy or 1-(1-phenylcyclohexyl)pyrrolidine); eticyclidine (PCE or N-ethyl-1-phenylcyclohexylamine); and tenocyclidine (TCP or 1-(1-(2-thienyl)cyclohexyl)piperidine). These compounds were never widely used and did not seem to be as well accepted by users as PCP itself, however they were all added onto Schedule I of the Controlled Substance Act because of their putative similar effects.][ The generalized structural motif required for PCP-like activity is derived from structure-activity relationship studies of PCP analogues, and summarized below. All of these analogues would have somewhat similar effects to PCP itself, although, with a range of potencies and varying mixtures of anesthetic, dissociative and stimulant effects depending on the particular substituents used. In some countries such as the USA, Australia, and New Zealand, all of these compounds would be considered controlled substance analogues of PCP, and are hence illegal drugs, even though many of them have never been made or tested.][ Some studies found that, like other NMDA receptor antagonists, phencyclidine can cause a kind of brain damage called Olney's lesions in rats. Studies conducted on rats showed that high doses of the NMDA receptor antagonist dizocilpine caused reversible vacuoles to form in certain regions of the rats' brains. All studies of Olney's lesions have only been performed on non-human animals and may not apply to humans. Phencyclidine has also been shown to cause schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in the rat brain, which are detectable both in living rats and upon necropsy examination of brain tissue. It also induces symptoms in humans that mimic schizophrenia. PCP was first synthesized in 1926 and later tested after World War II as a surgical anesthetic. Because of its adverse side effects, such as hallucinations, mania, delirium, and disorientation, it was shelved until the 1950s. In 1953, it was patented by Parke-Davis and named Sernyl (referring to serenity), but was only used in humans for a few years because of side-effects. In 1967, it was given the trade name Sernylan and marketed as a veterinary anesthetic, but was again discontinued. Its side effects and long half-life in the human body made it unsuitable for medical applications. PCP began to emerge as a recreational drug in major cities in the United States in 1967. In 1978, People magazine and Mike Wallace of 60 Minutes called PCP the country's "number one" drug problem. Although recreational use of the drug had always been relatively low, it began declining significantly in the 1980s. In surveys, the number of high school students admitting to trying PCP at least once fell from 13% in 1979 to less than 3% in 1990. PCP comes in both powder and liquid forms (PCP base is dissolved most often in ether), but typically it is sprayed onto leafy material such as cannabis, mint, oregano, parsley, or ginger leaves, then smoked.][ PCP is a Schedule II substance in the United States, a Schedule I drug by the Controlled Drugs and Substances act in Canada, a List I drug of the Opium Law in the Netherlands and a Class A substance in the United Kingdom. In its pure (free base) form, PCP is a yellow oil (usually dissolved in petroleum, diethyl ether, or tetrahydrofuran). Upon treatment with hydrogen chloride gas, or isopropyl alcohol saturated with hydrochloric acid, this oil precipitates into white-tan crystals or powder (PCP hydrochloride). In this, the salt form, PCP can be insufflated, depending upon the purity. However, most PCP on the illicit market often contains a number of contaminants as a result of makeshift manufacturing, causing the color to range from tan to brown, and the consistency to range from powder to a gummy mass.][ These contaminants can range from unreacted piperidine and other precursors, to carcinogens like benzene and cyanide-like compounds such as PCC (piperidinocyclohexyl carbonitrile).][ The term "embalming fluid" is often used to refer to the liquid PCP in which a cigarette is dipped, to be ingested through smoking, commonly known as "boat" or "water." The name most likely originated from the somatic "numbing" effect and feelings of dissociation induced by PCP, and has led to the widespread and mistaken belief that the liquid is made up of or contains real embalming fluid. Occasionally, however, some users and dealers could have, believing this myth, used real embalming fluid mixed with, or in place of, PCP. Smoking PCP is known as "getting wet", and a cigarette or joint which has been dipped in PCP may be referred to on the street as a "fry stick," "sherm," "leak," "amp," "lovely," "KJ (an abbreviation for 'Killer Joint')," "toe tag", "dipper", "happy stick," or "wet stick." "Getting wet" may have once been a popular method of using PCP, especially in the western United States where it may have been sold for about $10 to $25 per cigarette.][ Behavioral effects can vary by dosage. Low doses produce a numbness in the extremities and intoxication, characterized by staggering, unsteady gait, slurred speech, bloodshot eyes, and loss of balance. Moderate doses (5–10 mg intranasal, or 0.01–0.02 mg/kg intramuscular or intravenous) will produce analgesia and anesthesia. High doses may lead to convulsions. Users frequently do not know how much of the drug they are taking due to the tendency of the drug to be made illegally in uncontrolled conditions. Psychological effects include severe changes in body image, loss of ego boundaries, paranoia and depersonalization. Hallucinations, euphoria, suicidal impulses and aggressive behavior are reported. The drug has been known to alter mood states in an unpredictable fashion, causing some individuals to become detached, and others to become animated. Intoxicated individuals may act in an unpredictable fashion, possibly driven by their delusions and hallucinations. PCP may induce feelings of strength, power, and invulnerability as well as a numbing effect on the mind. Occasionally, this leads to bizarre acts of violence, such as in the case of Big Lurch, a former rapper who allegedly murdered and cannibalized his roommate while under the influence of PCP. However, studies by the Drug Abuse Warning Network in the 1970s show that media reports of PCP-induced violence are greatly exaggerated and that incidents of violence were unusual and often (but not always) limited to individuals with reputations for aggression regardless of drug use. The reports in question often dealt with a supposed increase in strength imparted by the drug; this could partially be explained by the anaesthetic effects of the drug. The most commonly cited types of incidents included self-mutilation of various types, breaking handcuffs (a feat reportedly requiring about 10,000 lbs of force to break a stainless steel chain of typical diameter), inflicting remarkable property damage, and pulling one's own teeth.][ Included in the portfolio of behavioral disturbances are acts of self-injury including suicide, and attacks on others or destruction of property. The analgesic properties of the drug can cause users to feel less pain, and persist in violent or injurious acts as a result. Recreational doses of the drug can also induce a psychotic state that resembles schizophrenic episodes which can last for months at a time with toxic doses. Users generally report they feel detached from reality, or that one's consciousness seems somewhat disconnected from reality. Symptoms are summarized by the mnemonic device RED DANES: rage, erythema (redness of skin), dilated pupils, delusions, amnesia, nystagmus (oscillation of the eyeball when moving laterally), excitation, and skin dryness. Management of phencyclidine intoxication mostly consists of supportive care — controlling breathing, circulation, and body temperature — and, in the early stages, treating psychiatric symptoms. Benzodiazepines, such as lorazepam, are the drugs of choice to control agitation and seizures (when present). Typical antipsychotics such as phenothiazines and haloperidol have been used to control psychotic symptoms, but may produce many undesirable side effects — such as dystonia — and their use is therefore no longer preferred; phenothiazines are particularly risky, as they may lower the seizure threshold, worsen hyperthermia, and boost the anticholinergic effects of PCP. If an antipsychotic is given, intramuscular haloperidol has been recommended. Forced acid diuresis (with ammonium chloride or, more safely, ascorbic acid) may increase clearance of PCP from the body, and was somewhat controversially recommended in the past as a decontamination measure. However, it is now known that only around 10% of a dose of PCP is removed by the kidneys, which would make increased urinary clearance of little consequence; furthermore, urinary acidification is dangerous, as it may induce acidosis and worsen rhabdomyolysis (muscle breakdown), which is not an unusual manifestation of PCP toxicity. M: CNS anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug (N1A/2AB/C/3/4/7A/B/C/D) M: CNS anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug (N1A/2AB/C/3/4/7A/B/C/D)
[3-(2-Dimethylaminoethyl)-1H-indol-4-yl] dihydrogen phosphate CN(C)CCc1cnc2CC=CC(OP(O)(O)=O)=c12 CN(C)CCC1=CN=C2CC=CC(OP(O)(O)=O)=C12 InChI=1S/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17)Yes 
Key: QVDSEJDULKLHCG-UHFFFAOYSA-NYes  InChI=1/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17) Schedule III(CA) Class A(UK) Schedule I(US) 220–228 °C (428–442 °F) Psilocybin ( ) is a naturally occurring psychedelic compound produced by more than 200 species of mushrooms, collectively known as psilocybin mushrooms. The most potent are members of the genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from about a dozen other genera. As a prodrug, psilocybin is quickly converted by the body to psilocin, which has mind-altering effects similar to those of LSD, mescaline, and DMT. The effects generally include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences, and can include possible adverse reactions such as nausea and panic attacks. Imagery found on prehistoric murals and rock paintings of modern-day Spain and Algeria suggest that human usage of psilocybin mushrooms dates back thousands of years. In Mesoamerica, the mushrooms had long been consumed in spiritual and divinatory ceremonies before Spanish chroniclers first documented their use in the 16th century. In a 1957 Life magazine article, American banker and ethnomycologist described his experiences ingesting psilocybin-containing mushrooms during a traditional ceremony in Mexico, introducing the drug to popular culture. Shortly afterward, the Swiss chemist Albert Hofmann isolated the active principle psilocybin from the mushroom Psilocybe mexicana. Hofmann's employer Sandoz marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic psychotherapy. Although increasingly restrictive drug laws of the late 1960s curbed scientific research into the effects of psilocybin and other hallucinogens, its popularity as an entheogen (spirituality-enhancing agent) grew in the next decade, largely owing to the increased availability of information on how to cultivate psilocybin mushrooms. Some users of the drug consider it an entheogen and a tool to supplement practices for transcendence, including meditation and psychonautics. 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. Psilocybin has a low toxicity and a relatively low harm potential, and reports of lethal doses of the drug are rare. Several modern bioanalytical methods have been adapted to rapidly and accurately screen the levels of psilocybin in mushroom samples and body fluids. Since the 1990s, there has been a renewal of scientific research into the potential medical and psychological therapeutic benefits of psilocybin for treating conditions including obsessive-compulsive disorder, cluster headaches, and anxiety related to terminal cancer. Possession of psilocybin-containing mushrooms has been outlawed in most countries, and it has been classified as a scheduled drug by many national drug laws. There is evidence to suggest that psychoactive mushrooms have been used by humans in religious ceremonies for thousands of years. Murals dated 9000 to 7000 BCE found in the Sahara desert in southeast Algeria depict horned beings dressed as dancers, clothed in garb decorated with geometrical designs, and holding mushroom-like objects. Parallel lines extend from the mushroom shapes to the center of the dancers' heads. 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. Archaeological artifacts from Mexico, as well as the so-called Mayan "mushroom stones" of Guatemala have similarly been interpreted by some scholars as evidence for ritual and ceremonial usage of psychoactive mushrooms in the Mayan and Aztec cultures of Mesoamerica. In Nahuatl, the language of the Aztecs, the mushrooms were called teonanácatl, or "God's flesh". Following the arrival of Spanish explorers to the New World 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 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 usage in his 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 conquerors. Although several psychedelic mushrooms are found in Europe, there is little documented usage of these species in Old World history. 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. American banker and amateur ethnomycologist R. Gordon Wasson and his wife Valentina studied the ritual use of psychoactive mushrooms by the native population in the Mazatec village Huautla de Jiménez. 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 multinational pharmaceutical company Sandoz (now Novartis). Hofmann, who had in 1938 created LSD, led a research group that isolated and identified the psychoactive compounds from Psilocybe mexicana. Hofmann was aided in the discovery process by his willingness to ingest mushroom extracts to help verify the presence of the active compounds. He and his colleagues later synthesized a number of compounds chemically related to the naturally occurring psilocybin, to see how structural changes would affect psychoactivity. The new molecules differed from psilocybin in the position of the phosphoryl or hydroxyl group at the top of the indole ring, and in the numbers of methyl groups (CH3) and other additional carbon chains. Two diethyl analogs (containing two ethyl groups in place of the two methyl groups) of psilocybin and psilocin were synthesized by Hofmann: 4-phosphoryloxy-N,N-diethyltryptamine, called CEY-19, and 4-hydroxy-N,N-diethyltryptamine, called CZ-74. Because their physiological effects last only about three and a half hours (about half as long as psilocybin), they proved more manageable in European clinics using "psycholytic therapy"—a form of psychotherapy involving the controlled use of psychedelic drugs. Sandoz marketed and sold pure psilocybin under the name Indocybin to physicians and clinicians 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 pharmaceutical. 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. Further backlash against LSD usage swept psilocybin along with it into the Schedule I category of illicit drugs in 1970. Subsequent 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". 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." Because of a lack of clarity about laws about psilocybin mushrooms, retailers in the late 1990s and early 2000s (decade) 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 description, use, effects and exchange of 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 thrust psilocybin back into the limelight. 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 Agrocybe, Galerina and Mycena (1 species each). 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 US and Canada (22), Europe (16), Asia (15), Africa (4), and Australia and associated islands (19). 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 the psychoactive compounds, although the caps contain consistently 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 1.5% 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.
Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine or 4-PO-DMT) is a prodrug that is converted into the pharmacologically active compound psilocin in the body by a dephosphorylation reaction. This chemical reaction takes place under strongly acidic conditions, or under physiological conditions in the body, through the action of enzymes called phosphatases. Psilocybin is a tryptamine compound with a chemical structure containing an indole ring linked to an ethylamine substituent. It is chemically related to the amino acid tryptophan, and is structurally similar to the neurotransmitter serotonin. 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 bufotenine, found in the skin of psychoactive toads. Biosynthetically, the biochemical transformation from tryptophan to psilocybin involves several enzyme reactions: decarboxylation, methylation at the N9 position, 4-hydroxylation, and O-phosphorylation. Isotopic labeling experiments suggest that tryptophan decarboxylation is the initial biosynthetic step and that O-phosphorylation is the final step. The precise sequence of the intermediate enzymatic steps is not known with certainty, and the biosynthetic pathway may differ between species. Psilocybin is a zwitterionic alkaloid that is soluble in water, methanol and aqueous ethanol, but insoluble in organic solvents like chloroform and petroleum ether. Exposure to light is detrimental to the stability of aqueous solutions of psilocybin, and will cause it to rapidly oxidize—an important consideration when using it as an analytical standard. Osamu Shirota and colleagues reported a method for the large-scale synthesis of psilocybin without chromatographic purification in 2003. Starting with 4-hydroxyindole, they generated psilocybin from psilocin in 85% yield, a marked improvement over yields reported from previous syntheses. Purified psilocybin is a white, needle-like crystalline powder with a melting point between 220–228 °C (428–442 °F), and a slightly ammonia-like taste. 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 test. 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. Psilocybin is rapidly dephosphorylated in the body to psilocin, which is a partial agonist for several serotonergic receptors. Psilocin has a high affinity for the 2A5-HT serotonin receptor in the brain, where it mimics the effects of serotonin (5-hydroxytryptamine, or 5-HT). Psilocin binds less tightly to other serotonergic receptors 1A5-HT, 1D5-HT, and 2C5-HT. 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 and motivation. The psychotomimetic (psychosis-mimicking) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2A antagonist drugs ketanserin and risperidone. Although the 5-HT2A receptor is responsible for most of the effects of psilocin, various lines of evidence have shown that interactions with non-5-HT2A 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. In contrast to LSD, which binds to all dopamine receptor subtypes, psilocybin and psilocin have no affinity for the dopamine receptors. The chemical structures of psilocybin and related analogs have been used in computational biology to help model the structure, function, and ligand-binding properties of the 5-HT2C G-protein-coupled receptor. The toxicity of psilocybin is low. 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 kilograms (3.7 lb) of dried mushrooms, or 17 kilograms (37 lb) of fresh mushrooms, would be required for a 60-kilogram (130 lb) 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 at recreational or medicinal levels, 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. Most of the comparatively few fatal incidents reported in the literature that are associated with psychedelic mushroom usage involve the simultaneous use of other drugs, especially alcohol. Probably the most common cause of hospital admissions resulting from magic mushroom usage involve "bad trips" or panic reactions, in which affected individuals become extremely anxious, confused, agitated, or disoriented. Accidents, self-injury, or suicide attempts can result from serious cases of acute psychotic episodes. 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". Similarly, 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. Magic mushrooms were ranked as the illicit drug with the lowest harm, corroborating conclusions reached earlier by expert groups in the United Kingdom. Although no studies have linked psilocybin with birth defects, it is recommended that pregnant women avoid its usage. 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 a tisane, or by combining with other foods to mask the bitter taste. In rare cases people have injected mushroom extracts intravenously. 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. A dosage of 4–10 mg, corresponding roughly to 50–300 micrograms per kilogram (µg/kg) of body weight, is required to induce psychedelic effects. A typical recreational dosage is 10–50 mg psilocybin, which is roughly equivalent to 10–50 grams of fresh mushrooms, or 1–5 grams of dried mushrooms. A small number of people are unusually sensitive to psilocybin, such that a normally threshold-level dose of about 2 mg can result in effects usually associated with medium or high doses. In contrast, there are some who require relatively high doses to experience noticeable effects. Individual brain chemistry and metabolism play a large role in determining a person's response to psilocybin. 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 toxic 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 about 100 times less potent than LSD on a weight per weight basis, and the physiological effects last about half as long. 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. Monoamine oxidase inhibitors (MAOI) have been known to prolong and enhance the effects of psilocybin. 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 can also experience more powerful effects with psilocybin, because tobacco smoke exposure decreases levels of MAO in the brain and peripheral organs. 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. Ninety-eight 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. Those placed in groups of more than eight individuals generally felt that the groups were less supportive, and their experiences were less pleasant. Conversely, smaller groups (fewer than six individuals) were seen as more supportive. Participants also reported having 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, a wide range of subjective effects may be experienced: feelings of disorientation, lethargy, giddiness, euphoria, joy, and depression. About a third of users report feelings of anxiety or paranoia. Low doses of the drug can induce hallucinatory effects. Closed-eye hallucinations may occur, in which the affected individual sees multicolored geometric shapes and vivid imaginative sequences. Some individuals report experiencing 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 apparent more than 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." 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 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 club goers in the UK found that nausea or vomiting was experienced by over a quarter of those who had used hallucinogenic 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 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 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 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." Panic reactions can occur after consumption of psilocybin-containing mushrooms, especially if the ingestion is accidental or otherwise unexpected. Reactions characterized by violence, aggression, homicidal and suicidal attempts, prolonged 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, 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. 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 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. Similarly, 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. In 2011, Griffiths and colleagues published the results of further studies designed to learn more about the optimum psilocybin doses needed for positive life-changing experiences, while minimizing the chance of negative reactions. In a 14-month followup, the researchers found that 94% of the volunteers rated their experiences with the drug as one of the top five most spiritually significant of their lives (44% said it was the single most significant). None of the 90 sessions that took place throughout the study were rated as decreasing well-being or life satisfaction. Moreover, 89% reported positive changes in their behaviors as a result of the experiences. The conditions of the experimental design included a single drug experience a month, on a couch, in a living-room-like setting, with eye shades and carefully chosen music (classical and world music). As an additional precaution to guide the experience, as with the 2006 study, the 2011 study included a "monitor" or "guide" whom the volunteers supposedly trusted. The monitors provided gentle reassurance when the volunteers experienced anxiety. The volunteers and monitors all remained blind to the exact dosages for the sake of the experiment. Psilocybin has been a subject of medical research since the 1960s, when Leary and Alpert ran the Harvard Psilocybin Project, in which they carried out a number of experiments to evaluate the therapeutic value of psilocybin in the treatment of personality disorders, or to augment psychological counseling. In the 2000s (decade), there was a renewal of research concerning the use of psychedelic drugs for potential clinical applications, such as to address anxiety disorders, major depression, and various addictions. In 2008, the Johns Hopkins research team published guidelines for responsibly conducting medical research trials with psilocybin and other hallucinogens in humans. These included recommendations on how to screen potential study volunteers to exclude those with personal or family psychiatric histories that suggest a risk of adverse reactions to hallucinogens. A 2010 study on the short- and long-term subjective effects of psilocybin administration in clinical settings concluded that despite a small risk of acute reactions such as dysphoria, anxiety, or panic, "the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk"; the authors note, however, that the safety of the drug "cannot be generalized to situations in which psilocybin is used recreationally or administered under less controlled conditions." The first FDA-approved clinical study of psilocybin since 1970—led by Francisco Moreno at the University of Arizona and supported by the Multidisciplinary Association for Psychedelic Studies—studied the effects of psilocybin on nine patients with obsessive–compulsive disorder (OCD). The pilot study found that, when administered by trained professionals in a medical setting, the use of psilocybin was associated with substantial reductions in OCD symptoms in several of the patients. This effect may be caused by psilocybin's ability to reduce the levels of the 5-HT2A receptor, resulting in decreased responsiveness to serotonin. Psilocybin has additionally shown promise to ease the pain caused by cluster headaches, often considered not only the most painful of all types of headaches but "one of the worst pain syndromes known to mankind." In a 2006 study, half of cluster headache patients reported that psilocybin aborted the attacks, and most reported extended remission periods; similar results were reported for LSD. A 2011 review of alternative headache treatments concluded that, despite flaws in the study design, these results suggest that LSD and psilocybin may warrant further study for use in the prevention of cluster headaches—only subhallucinogenic doses of the drugs are required for effective treatment, and no other medications have been reported to stop a cluster headache cycle. Several modern studies have investigated the possibility that psilocybin can ease the psychological suffering associated with end-stage cancer. Preliminary results indicate that low doses of psilocybin can improve the mood and reduce the anxiety of patients with advanced cancer, and that the effects last from two weeks to six months. These results are comparable to those obtained from early studies that explored the use of LSD to improve the psychological well-being of terminally ill patients, but without the experimental rigor employed in modern clinical psychopharmacology research. 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 marijuana. 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 Nahuatls, the Matlazinca, 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 1,500 meters (4,900 ft). Guzmán suggests this is a vestige of Spanish colonial influence from several hundred years earlier, when mushroom use was persecuted by the Catholic Church. In the United States, psilocybin (and psilocin) were first subjected to federal regulation by the Drug Abuse Control Amendments of 1965, a product of a bill sponsored by Senator Thomas J. Dodd. The law—passed in July 1965 and effected on February 1, 1966—was an amendment to the federal Food, Drug and Cosmetic Act and was intended to regulate the unlicensed "possession, manufacture, or sale of depressant, stimulant and hallucinogenic drugs". The statutes themselves, however, did not list the "hallucinogenic drugs" that were being regulated. Instead, the term "hallucinogenic drugs" was meant to refer to those substances believed to have a "hallucinogenic effect on the central nervous system". Despite the seemingly strict provisions of the law, many people were exempt from prosecution. The statutes "permit[ted] … people to possess such drugs so long as they were for the personal use of the possessor, [for] a member of his household, or for administration to an animal". The federal law that specifically banned psilocybin and psilocin was enacted on October 24, 1968. The substances were said to have "a high potential for abuse", "no currently accepted medical use," and "a lack of accepted safety". On October 27, 1970, both psilocybin and psilocin became classified as Schedule I drugs and were simultaneously labeled "hallucinogens" under a section of the Comprehensive Drug Abuse Prevention and Control Act known as the Controlled Substances Act. Schedule I drugs are illicit drugs that are claimed to have no known therapeutic benefit. The United Nations Convention on Psychotropic Substances (adopted in 1971) requires its members to prohibit psilocybin, and parties to the treaty are required to restrict use of the drug to medical and scientific research under strictly controlled conditions. However, the mushrooms containing the drug were not specifically included in the convention, due largely to pressure from the Mexican government. Most national drug laws have been amended to reflect the terms of the convention; examples include the UK Misuse of Drugs Act 1971, the US Psychotropic Substances Act of 1978, the Canadian Controlled Drugs and Substances Act of 1996, and the Japanese Narcotics and Psychotropics Control Law of 2002. The possession and use of psilocybin is prohibited under almost all circumstances, and often carries severe legal penalties. Possession and use of psilocybin mushrooms, including the bluing species of Psilocybe, is therefore prohibited by extension. However, in many national, state, and provincial drug laws, there has been a great deal of ambiguity about the legal status of psilocybin mushrooms, as well as a strong element of selective enforcement in some places. Most US state courts have considered the mushroom a 'container' of the illicit drugs, and therefore illegal. A loophole further complicates the legal situation—the spores of psilocybin mushrooms do not contain the drugs, and are legal to possess in many areas. Jurisdictions that have specifically enacted or amended laws to criminalize the possession of psilocybin mushroom spores include Germany (since 1998), and California, Georgia, and Idaho in the United States. There is consequently an active underground economy involved in the sale of spores and cultivation materials, and an internet-based social network to support the illicit activity. After a long interruption in the use of psilocybin in research, there has been a general shift in attitudes regarding research with hallucinogenic agents. Many countries are revising their positions and have started to approve studies to test the physiological and therapeutic effects of hallucinogens.
Set and setting describes the context for psychoactive and particularly psychedelic drug experiences: one's mindset and the setting in which the user has the experience. This is especially relevant for psychedelic or hallucinogenic experiences. The term was coined by Timothy Leary, and became widely accepted by researchers in psychedelic psychotherapy.[1] 'Set' is the mental state a person brings to the experience, like thoughts, mood and expectations. 'Setting' is the physical and social environment. Social support networks have shown to be particularly important in the outcome of the psychedelic experience.[2] They are able to control or guide the course of the experience, both consciously and subconsciously. Stress, fear, or a disagreeable environment, may result in an unpleasant experience (bad trip). Conversely, a relaxed, curious person in a warm, comfortable and safe place is more likely to have a pleasant experience. In 1966, Timothy Leary conducted a series of experiments with dimethyltryptamine (DMT) with controlled set and setting. The aim was to see whether DMT, which had then been mostly thought of as a terror-inducing drug, could produce pleasant experiences under a supportive set and setting. It was found that it could.[3] Set and setting has also been investigated from a religious perspective.[4]
Responsible drug use is a harm reduction strategy based on a belief that illegal drug use can be responsible in terms of reduced or eliminated risk of negative impact on the lives of both the user and others. Some critics believe that all illegal recreational use is inherently irresponsible, due to the unpredictable, unregulated nature of the drugs and the risks of addiction, infection, and other side effects. Nevertheless, harm reduction advocates claim that the user can be responsible by employing the same general principles applicable to the use of alcohol: avoiding hazardous situations, excessive doses, and hazardous combinations of drugs; avoiding injection; and not using drugs at the same time as activities that may be unsafe without a sober state. Critics also point out that the unregulated nature of illegal drugs is due to lack of government regulation, and that if certain drugs were regulated by governments it would be easier to use them responsibly. Duncan and Gold argue that to use controlled and other drugs responsibly, a person must adhere to a list of principles. They argue that drug users must understand and educate themselves on the effects and legal status of the drug they are taking, measure accurate dosages and take other precautions to reduce the risk of overdose when taking drugs where an overdose is possible. If possible (rarely done), chemically test all drugs before use to determine their purity and strength. As well, they argue that drug users should avoid driving, operating heavy machinery, or otherwise situate themselves directly or indirectly responsible for the safety or care of another person while intoxicated. When taking hallucinogenic drugs, they suggest that a user have a trip sitter (or "copilot"). They also propose some ethical guidelines, such as; a person should never trick or persuade anyone to use a drug; a person should not allow drug use to overshadow other aspects of their life (i.e. financial and social responsibilities); a person should be morally conscious of the source of the drugs that a person is using. Duncan and Gold suggested that responsible drug use involves responsibility in three areas: situational responsibilities, health responsibilities, and safety-related responsibilities. Among situational responsibilities they included concerns over the possible situations in which drugs might be used legally. This includes the avoidance of hazardous situations; not using when alone; nor using due to coercion or when the use of drugs itself is the sole reason for use. Health responsibilities include: avoidance of excessive doses or hazardous combinations of drugs; awareness of possible health consequences of drug use; and not using a drug recreationally during periods of excessive stress. Safety-related responsibilities include: using the smallest dose necessary to achieve the desired effects; using only in relaxed settings with supportive companions; avoiding the use of drugs by injection; and not using drugs while performing complex tasks or those where the drug might impair one's ability to function safely. Responsible drug use is emphasized as a primary prevention technique in harm-reduction drug policies. Harm-reduction policies were popularized in the late 1980s although they began in the 1970s counter-culture where users were distributed cartoons explaining responsible drug use and consequences of irresponsible drug use. Some drugs are very addictive. Even moderate use may result in a strong physical need for an increased dosage. Drug use and users are often not considered socially acceptable; they are often marginalized socially and economically. Drug use may affect work performance; however, drug testing should not be necessary if this is so, as a user's work performance would be observably deficient, and be grounds in itself for dismissal. In the case of discriminate use of amphetamines and similar drugs, work capacity actually increases, which in itself raises additional ethical considerations. Illegality causes supply problems, and artificially raises prices. The price of the drug soars far above the production and transportation costs. Purity and potency of many drugs is difficult to assess, as the drugs are illegal. Unscrupulous and unregulated middle men are drawn, by profit, into the industry of these valuable commodities. This directly affects the users ability to obtain and use the drugs safely. Drug dosage is problematic. Drug purity is problematic. Drug purchasing is problematic, forcing the user to take avoidable risks. Profit motivation rewards illegal sellers adding a cutting agent to drugs, diluting them; when a user, expecting a low dose, procures "uncut" drugs, an overdose can result. The morality of buying certain illegal drugs is also questioned given that the trade in cocaine, for instance, has been estimated to cause 20,000 deaths a year in Colombia alone. Increasing Western demand for cocaine causes several hundred thousand people to be displaced from their homes every year, indigenous people are enslaved to produce cocaine and people are killed by the land mines drug cartels place to protect their coca crops. However, the majority of deaths currently caused by the illegal drug trade can only take place in a situation in which the drugs are illegal. The illegality of drugs in itself may also cause social and economic consequences for those using them, and legal regulation of drug production and distribution could alleviate these and other dangers of illegal drug use. Harm reduction as applied to drug use began as a philosophy in the 1980s aiming to minimize HIV transmission between intravenous drug users. It also focused on condom usage to prevent the transmission of HIV through sexual contact. Harm reduction worked so effectively that researchers and community policy makers adapted the theory to other diseases to which drug users were susceptible, such as Hepatitis C. Harm reduction seeks to minimize the harms that can occur through the use of various drugs, whether legal (e.g. alcohol and nicotine), or illegal (e.g. heroin and cocaine). For example, people who inject illicit drugs can minimize harm to both themselves and members of the community through proper injecting technique, using new needles and syringes each time, and through proper disposal of all injecting equipment. Smoking a 700-mg. tobacco cigarette or cannabis joint (with the attendant heat shock, carbon monoxide, and combustion toxins) can be avoided by serving individual 25-mg. "single tokes" in a miniature pipe or using a vaporizer. Other harm reduction methods have been implemented with drugs such as crack cocaine. In some cities, peer health advocates (Weeks, 2006) have participated in passing out clean crack pipe mouthpiece tips to minimize the risk of Hepatitis A, B and C and HIV due to sharing pipes while lips and mouth contain open sores. Also, a study by Bonkovsky and Mehta reported that, just like shared needles, the sharing of straws used to "snort" cocaine can spread blood diseases such as Hepatitis C. The responsible user therefore minimizes the spread of blood-borne viruses such as hepatitis C and HIV in the wider community. The provision of supervised injection sites, also referred to as safe injection sites, operates under the premise of harm reduction by providing the injection drug user with a clean space and clean materials such as needles, sterile water, alcohol swabs, and other items used for safe injection. Vancouver, British Columbia opened a SiS called Insite in its poorest neighbourhood, the Downtown Eastside. Insite was opened in 2003 and has dramatically reduced many harms associated with injection drug use. The research arm of the site, run by The Centre of Excellence for HIV/AIDS has found that SiS leads to increases in people entering detox and addiction treatment without increasing drug-related crime. As well, it reduces the littering of drug paraphernalia (e.g., used needles) on the street and reduces the number of people injecting in public areas. The program is attracting the highest-risk users, which has led to less needle-sharing in the Downtown Eastside community, and in the 453 overdoses which occurred at the facility, health care staff have saved every person. In the Netherlands, where drug use is considered a social and health-related issue and not a law-related one, the government has opened clinics where drug users may consume their substances in a safe, clean environment. Users are given access to clean needles and other paraphernalia, monitored by health officials and are given the ability to seek help from drug addiction. Due to the project's initial success in reducing mortality ratios and viral spread amongst injection drug users, other projects have been started in Switzerland, Germany, Spain, Australia, Canada and Norway. France, Denmark and Portugal are also considering similar actions.][
Bad trip (drug-induced psychosis or psychedelic crisis) is a disturbing experience sometimes associated with use of a psychedelic drug such as LSD, Cannabinoids, Salvinorin A, DXM, mescaline, psilocybin, cannabis, DMT and sometimes even other drugs including alcohol and MDMA. The manifestations can range from feelings of vague anxiety and alienation to profoundly disturbing states of unrelieved terror, ultimate entrapment, or cosmic annihilation. Psychedelic specialists in the therapeutic community do not necessarily consider unpleasant experiences as threatening or negative, focusing instead on their potential to be highly beneficial to the user when properly resolved. They can be exacerbated by the inexperience or irresponsibility of the user or the lack of proper preparation and environment for the trip, and are reflective of unresolved psychological tensions triggered during the course of the experience. It is suggested that, at a minimum, such crises be managed by preventing the individual from harming oneself or others by whatever means necessary up to and including physical restraint, providing the patient with a safe and comfortable space, and supervising the intaker until all effects of the drug have completely worn off. A multitude of reactions can occur during a psychedelic crisis. Some users may experience a general sense of fear or an anxiety attack. A user may be overwhelmed with the disconnection many psychedelics cause, and fear that they are going insane or will never return to reality. This can cause the user to fall into a depressive mood. Other reactions include an amplification of nameless fears; that is, fears that are unfounded and are usually not encountered in normality. Users may exhibit actions suggesting harm to themselves or others around them. This harm could take the form of suicidal ideation, or full blown suicide attempts. Because of the magnification of emotions many psychedelics could possibly cause thoughts of death and intensely adverse reactions in some users. Users can believe that their death is imminent or that the very universe itself is collapsing. Rapidly accelerated aging of other people may be experienced, perpetuating the aforementioned fears to an even greater degree. Some users may experience disorientation. The normal views of time, space, and person can be substantially altered, causing fear. Some can worsen their condition by trying to fight the psychedelic experience after embarkment. There can be illusions of insects crawling over or into one's self, or of being in dirty places such as sewers. In rare cases, an apparent complete loss of control can be observed, and the behavior a person exhibits reflects a lack of normal understanding about navigation of a physical environment. This can cause accidental harm to themselves and others, including running into traffic, flailing around, or, as it may not necessarily involve physical movement, inducing a catatonic state, or causing seemingly random vocalizations, not limited to speech. This may be caused by a failure to recognize external stimuli for what it is. Stanislav Grof explains this feature: The effects of psychedelics vary widely from one individual to the next, and from one experience to the next. Sometimes individuals under the influence of such drugs do not understand that they have taken a drug and believe that they will never return to their ordinary, sober perception. In cases where the individual cannot be kept safe, hospitalization may be useful, though the value of this practice for individuals not mentally ill is disputed by proponents of investigative or recreational use of psychoactive compounds. Psychosis is exacerbated in individuals already suffering from this condition. Generally, a person experiencing a psychedelic crisis can be helped either to resolve the impasse, to bypass it, or, failing that, to terminate the experience. A person's thoughts before taking or while under the influence of the psychedelic, often greatly influence the trip. Helping someone through a bad trip can often be done by reminding them that they took a psychedelic drug, and giving them further reassurance. Let them know that the crisis they are in is caused by a combination of the psychedelic drug and the person's thoughts. Try to change their mood and make them realize that everything is okay, and they took this drug to have a good time. Remind them that the easiest way to get through this is to relax and enjoy themselves, and try to get their mind off of what was bothering them. A change of scenery can often help in addition to reassurance. You can bring them outside, or go for a walk, while talking about why they are having a bad trip. Medical treatment consists of supportive therapy and minimization of external stimuli. In some cases, sedation is used when necessary to control self-destructive behavior, or when hyperthermia occurs. Diazepam is the most frequently used sedative for such treatment, but other benzodiazepines such as lorazepam are also effective. Such sedatives will only decrease fear and anxiety, but will not subdue hallucinations. In severe cases, antipsychotics such as haloperidol can reduce or stop hallucinations. Haloperidol is effective against drug-induced psychosis caused by LSD and other tryptamines, amphetamines, ketamine and phencyclidine, According to Timothy Leary, a crisis can be a result of wrong set and setting. Leary advised that users of psychedelics be sure that they are comfortable before taking the drugs. Leary claimed that the frequency of difficult trips was highly exaggerated by anecdotes and fabrications in the popular press, and was actually about 1 in 1,000.][ Alternatively, psychiatrist R. D. Laing held that psychedelic crises and other such extreme experiences, drug-induced or not, were not necessarily artificial terrors to be suppressed but rather signs of internal conflict and opportunities for self-healing. The greater the pain and pathos of an experience, the greater the urgency to explore and resolve it, rather than attempt to cover it up or dismiss it.][ Likewise, Stanislav Grof suggested that painful and difficult experiences during a trip could be a result of the mind reliving experiences associated with birth, and that experiences of imprisonment, eschatological terror, or suffering far beyond anything imaginable in a normal state, if seen through to conclusion, often resolve into emotional, intellectual and spiritual breakthroughs. From this perspective, interrupting a bad trip, while initially seen as beneficial, can trap the tripper in unresolved psychological states. Grof also suggests that many cathartic experiences within psychedelic states, while not necessarily crises, may be the effects of consciousness entering a perinatal space.][
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