LSD

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For other uses, see LSD (disambiguation).
LSD
Chemical name D-Lysergic acid diethylamide
or:
(6aR,9R)-N,N-diethyl-7-methyl-
4,6,6a,7,8,9-hexahydroindolo
[4,3-fg]quinoline-9-carboxamide
Chemical formula C20H25N3O
Molecular mass 323.43 g/mol
Melting point 80–85 °C
CAS number 50-37-3
SMILES O=[C@@](N(CC)CC)[C@H]
1CN(C)[C@](C2=C1)([H])
CC3=CNC4=C3C2=CC=C4
Image:Lsd-structure.png

D-lysergic acid diethylamide, commonly called acid, LSD, or LSD-25, is a powerful semisynthetic psychedelic drug colloquially measured in "hits" or "tabs". An average single dose of LSD during the 1960s was between 100 and 150 micrograms, a tiny amount roughly equal to one-tenth the weight of a grain of sand. Today, a typical single dose of LSD is as low as 25–50 micrograms. Threshold effects can be felt with as little as 20 micrograms. The effects of LSD can vary greatly, depending on factors such as previous experiences, state of mind and environment, as well as dose strength. Generally, LSD causes expansion and altered experience of senses, emotions, memories, and awareness for 8 to 14 hours. In addition, LSD usually produces visual effects such as moving geometric patterns, "trails" behind moving objects, and brilliant colors. LSD does not produce hallucinations in the strict sense but instead illusions and vivid daydream-like fantasies, in which ordinary objects and experiences can take on entirely different appearances or meanings. At higher concentrations it can cause synaesthesia. The drug sometimes spurs long-term or even permanent changes in a user's personality and life perspective.

LSD is synthesized from lysergic acid derived from ergot, a grain fungus that typically grows on rye. LSD is sensitive to oxygen, ultraviolet light, and chlorine, especially in solution (though its potency may last years if the substance is stored away from light and moisture at low temperature). In pure form it is colorless, odorless, and mildly bitter. LSD is typically delivered orally, usually on a substrate such as absorbent blotter paper, a sugar cube, or gelatin.

Introduced by Sandoz Laboratories as a drug with various psychiatric uses, LSD quickly became a therapeutic agent that appeared to show great promise. However, the extra-medical use of the drug in Western society in the middle years of the twentieth century led to a political firestorm and government insider panic that resulted in the banning of the substance for medical as well as recreational and spiritual uses. Despite this, it is still considered a promising drug in some intellectual circles.

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Origins and early history

Template:Main Image:LSD blotter paper.jpg "LSD" is an initialism formed from the German chemical name of the compound, Lysergsäure-diethylamid. It was first synthesized in 1938 by Swiss chemist Dr. Albert Hofmann at the Sandoz Laboratories in Basel as part of a large research program searching for medically useful ergot alkaloid derivatives. Its psychedelic properties were unknown until 5 years later, when Hofmann, acting on a hunch, returned to work on the chemical. He attributed the discovery of the compound's psychoactive effects to the accidental absorption of a tiny amount through his skin on April 16, which led to him testing a larger amount on himself for psychoactivity. <ref name="problem-child">Hofmann, Albert. LSD – My Problem Child (McGraw-Hill, 1980). ISBN 0-07-029325-2. Available online here or here.</ref>

Until 1966, LSD and psilocybin were provided by Sandoz Laboratories free of charge to interested scientists. The use of these compounds by psychiatrists to gain a better subjective understanding of the schizophrenic experience was an accepted practice. Many clinical trials were conducted on the potential use of LSD in psychedelic psychotherapy, generally with very positive results.

Cold War era intelligence services were keenly interested in the possibilities of using LSD for interrogation and mind control, and also for large-scale social engineering. The CIA conducted extensive research on LSD, which was mostly destroyed. <ref>ACHRE Report, chapter 3: "Supreme Court Dissents Invoke the Nuremberg Code: CIA and DOD Human Subjects Research Scandals".</ref> Project MKULTRA (also known as MK-ULTRA) was the code name for a CIA mind-control research program begun in the 1950s and continued until the late 1960s. There is much published evidence that the project involved not only the use of drugs to manipulate persons, but also the use of electronic signals to alter brain functioning; for details, see the MKULTRA article proper.

The British government also indulged in LSD testing; in 1953 and 1954, scientists working for MI6 dosed servicemen in an effort to find a "truth drug". (In all probability, MI6 was motivated by rumors that the Soviet Union had developed brainwashing drugs.) The test subjects were not informed that they were being given LSD, and had in fact been told that they were participating in a medical project to find a cure for the common cold. One subject, aged 19 at the time, reported seeing "walls melting, cracks appearing in people's faces … eyes would run down cheeks, Salvador Dalí-type faces … a flower would turn into a slug". After keeping the trials secret for many years, MI6 agreed in 2006 to pay the former test subjects financial compensation. Like the CIA, MI6 decided that LSD was not a practical drug for brainwashing purposes. <ref>Rob Evans, "MI6 pays out over secret LSD mind control tests". The Guardian 24 February 2006.</ref>

LSD first became popular recreationally among a small group of mental health professionals such as psychiatrists and psychologists during the 1950s, as well as by socially prominent and politically powerful individuals such as Henry and Clare Boothe Luce to whom the early LSD researchers were connected socially.

Several mental health professionals involved in LSD research, most notably Harvard psychology professors Drs. Timothy Leary and Richard Alpert (later known as Ram Dass), became convinced of LSD's potential as a tool for spiritual growth. In 1961, Dr. Timothy Leary received grant money from the Harvard University to study the effects of LSD on test subjects. 3,500 doses were given to over 400 people. Of those tested, 90% said they would like to repeat the experience, 83% said they had "learned something or had insight," and 62% said it had changed their life for the better.

Their research became more esoteric and controversial, alleging links between the LSD experience and the state of enlightenment sought after in many mystical traditions. They were dismissed from the traditional academic psychology community, and as such cut off from legal scientific acquisition of the drug. The experiments lost their scientific pretense, and the pair evolved into countercultural spiritual gurus, encouraging people to question authority and challenge the status quo, a concept summarized in their catchprase, "Turn on, tune in, and drop out". Predictably, the drug was banned in the United States in 1967, with scientific therapeutic research as well as individual research also becoming prohibitively difficult. Many other countries, under pressure from the U.S., quickly followed suit.

Since 1967, underground recreational and therapeutic LSD use has continued in many countries, supported by a black market and popular demand for the drug. Legal, academic research experiments on the effects and mechanisms of LSD are also conducted on occasion, but rarely involve human subjects.

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Summary on LSD use

According to two researchers associated with the NIDA <ref>"LSD : Still With Us After All These Years" by Epidemiologist Leigh A. Henderson & NIDA Project Officer William J. Glass : A Review of "LSD : Still With Us After All These Years".</ref> in their 1994 review of the literature on LSD,

  • LSD use is relatively uncommon in comparison with use of alcohol, marijuana, or cocaine and misuse of prescription drugs. Long-term trends in LSD use show stability over the last fifteen years in both proportion (roughly 5% annually) and age (generally, 16-23) of users.
  • LSD is primarily used by suburban white males in their late teens and early 20s. A shift in use from the upper level of this band to the lower level could contribute to the perception that use has increased among young adolescents.
  • LSD is characterized by infrequent episodic use culminating in "maturing out" after two to four years.
  • Adverse health consequences of LSD are comparatively rare, with "bad trips" being the most common adverse reaction. Nonetheless, severe bad trips are one of the primary reasons youths discontinue LSD use.
  • Although some health consequences may be related to length of use, size of dose, and the interaction of other drugs, there is considerable uncertainty over why LSD adversely affects some individuals more severely than others.
  • Despite dire warnings, LSD use doesn't result in mental illness and does not damage genes or chromosomes.
  • Black market LSD remains generally unadulterated, although manufacturing by-products do appear. In the 1960s, doses were reported to have ranged from 200 to 1000 micrograms; in the 1970's, street samples ranged from 30 to 300 µg; in the mid-1980s, the average was about 100 to 125 µg; in the 1990s it is 20 to 80 µg. Lower doses generally mean fewer bad trips.
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Dosage

LSD is, by weight, one of the most potent drugs yet discovered. Both subjective reports and pharmacological methods such as receptor binding assays determine LSD to be, per mole, around 100 times more potent than psilocybin and psilocin and around 4,000 times more potent than mescaline. Dosages of LSD are measured in micrograms (µg), or millionths of a gram. By comparison, dosages of almost all other drugs, both recreational and medical, are measured in milligrams (mg), or thousandths of a gram.

The dosage level that will produce a threshold hallucinogenic effect in humans is generally considered to be 20–30 micrograms, with the drug's effects becoming markedly more evident at higher dosages<ref>Stoll, W.A. (1947). Ein neues, in sehr kleinen Mengen wirsames Phantastikum. Schweiz. Arch. Neur. 60,483.</ref><ref>Template:Cite journal</ref>. In the late 1990s, LSD obtained during drug law enforcement operations in the United States has usually ranged between 20 and 80 micrograms per dose. During the 1960s, dosages were commonly 300 micrograms or more. Dosages by frequent users can be as high as 1,200 micrograms, although such a high dosage may precipitate unpleasant physical and psychological reactions.

Estimates for the lethal dosage (LD50) of LSD range from 200 micrograms per kilogram to more than 1,000 micrograms per kilogram of human body-weight, 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 in which there were indications that ~1/3 of a gram (320 mg or 320,000 µg) had been injected intravenously, i.e., over 3,000 more typical oral doses of ~100 µg had been injected. <ref>Dose information from Erowid</ref>

LSD is not considered addictive, in that its users do not exhibit the medical community's commonly accepted definitions of addiction and physical dependence. Rapid tolerance build-up prevents regular use, and there is cross-tolerance shown between LSD, mescaline and psilocybin. This tolerance diminishes after a few days' abstention from use.

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Effects

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Physical

Physical reactions to LSD are highly variable and may include the following: uterine contractions, hyperthermia (body temperature increase), elevated blood sugar levels, dry-mouth, goose bumps, heart-rate increase, jaw clenching, nausea, perspiration, pupil-dilation, salivation, mucus production, sleeplessness and tremors. Cramps and muscle tension or soreness are also fairly commonly reported, but rather than being direct effects of LSD in the bloodstream, these symptoms are believed by some to be the result of awkward positions assumed by users experiencing fluctuations in their awareness of the passage of time and their own physical discomfort.

LSD was studied in the 1960s by Eric Kast as a painkiller for serious and chronic pain caused by cancer or other major trauma<ref>Template:Cite journal</ref>. Even at low (sub-psychedelic) dosages, it was found to be at least as effective as traditional opiates while being much longer lasting (pain reduction lasting as long as a week after peak effects had subsided). Kast attributed this effect to a decrease in anxiety. This reported effect is being tested (though not using LSD) in an ongoing (as of 2006) study of the effects of the hallucinogen psilocybin on anxiety in terminal cancer patients.

Furthermore, LSD has been illicitly 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." <ref>Dr. Goadsby is quoted in "Research into psilocybin and LSD as cluster headache treatment", and he makes an equivalent statement in an Health Report interview on Australian Radio National (9 August 1999).</ref> 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 ergotamines, among other chemicals, so LSD's efficacy may not be surprising. A dose-response study, testing the effectiveness of both LSD and psilocybin is, as of 2006, being planned at McLean Hospital. Unlike attempts to use LSD or MDMA in psychotherapy, this research involves non-psychological effects and often sub-psychedelic dosages; therefore, it is plausibly a way that a respected medical use of LSD will arise. <ref>Summarized from "Research into psilocybin and LSD as cluster headache treatment" and the Clusterbusters website.</ref>

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Pharmacological

Image:LSDaffinities.GIF

LSD affects an enormous number of receptors, including all dopamine receptor subtypes, all adrenoreceptor subtypes as well as many others. LSD binds to most serotonin receptor subtypes except for 5-HT3 and 5-HT4. However, most of these receptors are affected at too low affinity to be activated by the brain concentration of approximate 10–20 nM. <ref name="nichols">Template:Cite journal</ref> Recreational doses of LSD can affect 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5 B and 5-HT6 The hallucinogenic effects of LSD are attributed to its strong partial agonist effects at 5-HT2A receptors as specific 5-HT2A agonist drugs are hallucinogenic and largely 5-HT2A specific antagonists block the hallucinogenic activity of LSD. <ref name="nichols"/> Exactly how this produces the drug's effects is unknown, but it is likely thought that it works by increasing glutamate release and hence excitation, in the cortex, specifically in layer IV and V<ref>BilZ0r. "The Neuropharmacology of Hallucinogens: a technical overview". Erowid, v3.1 (August 2005).</ref>

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Psychological

LSD's psychological effects (colloquially called a "trip") vary greatly from person to person, from one trip to another, and even as time passes during a single trip. Widely different effects emerge based on 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.

An LSD trip can have long lasting or even permanent neutral, negative, and positive psychoemotional effects. LSD experiences can range from indescribably ecstatic to extraordinarily difficult; many difficult experiences (or "bad trips") result from a panicked user feeling that he or she has been permanently severed from reality and his or her ego. 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.

Conversely, a pleasant, comfortable environment and a relaxed, balanced and open mindset will often result in a unique experience.

Many users experience a dissolution between themselves and the "outside world": cognitive differences between subject ("I") and object ("me", "you", "it") break down or seem absurd. <ref name="linton-langs">Linton, Harriet B. and Langs, Robert J. "Subjective Reactions to Lysergic Acid Diethylamide (LSD-25)". Arch. Gen. Psychiat. Vol. 6 (1962): 352–68.</ref> This unitive quality may play a role in the spiritual and religious aspects of LSD.

Some experts hypothesize that drugs such as LSD may be useful in psychotherapy, especially when the patient is unable to "unblock" repressed subconscious material through other psychetherapeutic methods<ref>Cohen, S. (1959). The therapeutic potential of LSD-25. A Pharmacologic Approach to the Study of the Mind, p251–258.</ref>, and also for treating alcholism. One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender,"<ref>Template:Cite journal</ref> presumably by forcing the user to face issues and problems in that individual's psyche. Many believe that, in contrast, other drugs (such as alcohol, heroin, and cocaine) are used to escape from reality. Studies in the 1950s that used LSD to treat alcoholism professed a 50% success rate<ref>Maclean, J.R.; Macdonald, D.C.; Ogden, F.; Wilby, E., "LSD-25 and mescaline as therapeutic adjuvants." In: Abramson, H., Ed., The Use of LSD in Psychotherapy and Alcoholism, Bobbs-Merrill: New York, 1967, pp. 407–426; Ditman, K.S.; Bailey, J.J., "Evaluating LSD as a psychotherapeutic agent," pp.74–80; Hoffer, A., "A program for the treatment of alcoholism: LSD, malvaria, and nicotinic acid," pp. 353–402.</ref>, higher than estimates near 10% for Alcoholics Anonymous<ref>Minogue, S. J. "Alcoholics Anonymous." The Medical Journal of Australia May 8 (1948):586–587.</ref>.

Some LSD studies were criticized for methodological flaws, and different groups had inconsistent results. Mangini's 1998 paper <ref>Template:Cite journal</ref> reviews this history and concludes that the efficacy of LSD in treating alcoholism remains an open question.

Many 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 60s. Still others describe experiences with illegal LSD, obtained for philosophic, artistic, therapeutic, spiritual, or recreational purposes.

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Sensory/perception

Generally beginning within thirty to ninety minutes after ingestion and continuing for the following six to twelve hours, the user may experience anything from subtle changes in perception to overwhelming cognitive shifts.

Changes in aural and visual perception are common, ranging from mild to profound. <ref name="linton-langs"/><ref>Template:Cite journal</ref> These sensory changes include basic "high-level" distortions such as the appearance of moving geometrical patterns, new textures on objects, blurred vision, image trailing, shape suggestibility and color variations. Users sometimes describe experiencing new, previously-unseen colors; sights and sounds may take on greater intensity or have more of an impact. Users commonly report that the inanimate world appears to animate in an unexplained way; that is, objects that are static in three dimensions can seem to be moving relative to one or more additional spatial dimensions. <ref>See, e.g., Gerald Oster's article "Moiré patterns and visual hallucinations". Psychedelic Rev. No. 7 (1966): 33–40.</ref>

Higher doses often bring about shifts at a lower cognitive level, causing intense and fundamental distortions of sensory perception such as synaesthesia, the experience of additional spatial or temporal dimensions, and temporary dissociation.

The sensory shifts caused by the drug can lead users to sit or lie in awkward positions for extended periods of time, resulting in muscle cramps and soreness that may mistakenly be attributed to the direct physical action of the drug.

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Spiritual

LSD is considered an entheogen because it often catalyzes intense spiritual experiences where users feel they have come into contact with a greater spiritual or cosmic order. It is common for users to believe that they have achieved insights into the way the mind works and some users experience permanent or long-lasting changes in their life perspective. Some users consider LSD a religious sacrament, or a powerful tool for access to the divine. Many books have been written comparing the LSD trip to the state of enlightenment of eastern philosophy.

Such experiences under the influence of LSD have been observed and documented by researchers such as Timothy Leary and Stanislav Grof. For example, Walter Pahnke conducted the Good Friday Marsh Chapel Experiment under Leary's supervision, performing a double blind experiment using volunteers who were students in religious graduate programs, e.g., divinity or theology. <ref>Video of the experiment can be viewed here.</ref> That study showed that hallucinogens could reliably be used to induce mystical religious states (at least in people with a spiritual predisposition).

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Acute duration

LSD's primary effects normally last from 6 to 12 hours. It is typical for users of LSD to be unable to sleep restfully (or at all, despite desperate attempts) until at least 12 hours have passed, and they do not feel completely "back to normal" until after getting one or two full nights of restful sleep, although they will exhibit no outward signs of impairment after the drug has worn off.

Contrary to early reports and common belief, LSD effects do not last longer than significant levels of the drug in the blood. Aghajanian and Bing <ref>Template:Cite journal</ref> found LSD had an elimination half-life of 175 min, while, more recently, Papac and Foltz <ref>Template:Cite journal</ref> reported that 1 µg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1 h with a peak plasma concentration of 1.9 ng/mL at 3 h post-dose. Notably, Aghajanian and Bing found that blood concentrations of LSD matched the time course of volunteers' difficulties with simple arithmetic problems.

Anecdotal reports indicate that administration of Thorazine or similar typical antipsychotic tranquilizers will not end an LSD trip, but rather will just immobilize and numb the patient. While it also may not end an LSD trip, the best chemical treatment for a "bad trip" is an anti-anxiety agent such as valium (diazepam) or other benzodiazepines. There have also been reports of Niacinamide being useful, a claim that has not been confirmed by multiple research groups using double-blind scientific methods and is therefore questionable.

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Physical dangers

Although LSD is generally considered nontoxic, it may temporarily impair the ability to make sensible judgments and understand common dangers, thus making the user susceptible to accidents and personal injury.

There is also 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. MAOIs and SSRIs are believed to interact more benignly, with a tendency to significantly reduce LSD's subjective effects.

As Albert Hofmann reports in LSD – My Problem Child, the early pharmacological testing Sandoz performed on the compound (before he ever discovered its psychoactive properties) indicated that LSD has a pronounced effect upon the mammalian uterus. Sandoz testing showed that LSD can stimulate uterine contractions with efficacy comparable to ergobasine, the active uterotonic component of the ergot fungus. (It is worth noting that 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.) LSD use by pregnant women is therefore contraindicated. <ref name="problem-child"/>

Initial studies in the 1960s and 70s 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 significant increase in chromosomal damage. For example, studies were conducted with people who had been given LSD in a clinical setting. <ref>Template:Cite journal</ref> White blood cells from these people 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 and concurrent use of other psychoactive drugs. It seems possible that the small number of congenital abnormalities reported in users of street LSD is either coincidental or related to factors other than a toxic effect of pure LSD.

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Flashbacks

There is also a commonly reported possibility of "flashbacks", a psychological phenomenon in which an individual experiences an episode of some of the subjective effects of LSD (this may be a positive or negative experience) long after the drug has been consumed and worn off — sometimes weeks, months or even years afterward.

Colloquial usage of the term 'flashbacks' refers to any experience reminiscent of LSD effects; these are commonly occasional brief experiences. However, psychiatry recognizes a disorder in which LSD-like effects are persistent and cause clinically-significant impairment or distress. This chronic flashback syndrome is called Hallucinogen Persisting Perception Disorder, a DSM-IV diagnosis. Several journal articles have described the disorder. <ref>See, for example, Template:Cite journal</ref>

Several studies have tried to determine how likely a "normal user" (that is a user not suffering from known psychiatric conditions) of LSD is to experience flashbacks. The larger studies include Blumenfeld's in 1971 <ref>Template:Cite journal</ref> and Naditch and Fenwick's in 1977 <ref>Template:Cite journal</ref>, which arrived at figures of 20% and 28%, respectively. A recent review suggests that chronic flashbacks, according to the DSM-IV definition, appears to be a rare disorder, that affect a distinctly vulnerable subpopulation of users. <ref>Template:Cite journal; Template:Cite journal [1]</ref> Differences in the estimated prevalence of flashbacks may partly depend on the multiple meanings of the term and the fact that hallucinogen persisting perception disorder can only be diagnosed in a person who admits to their health care practitioner that they have used hallucinogens.

Debate continues over the nature and causes of chronic flashbacks. Some say chronic flashbacks are a manifestation of post-traumatic stress disorder, not directly related to LSD's mechanism, and vary 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 chronic flashbacks appear to describe an anxious hyper-vigilant state reminiscent of post-traumatic stress disorder.

Several urban legends claim that intermittent flashbacks are the result of trace amounts of LSD or related chemicals being dislodged and released into the body after having been crystallized and stored in fat or spinal fluid cells. However, there is no evidence for this and scientific research suggests that it is not the case; LSD (which is water soluble) is metabolized in the liver, as with many other drugs, and its metabolites are excreted normally in the urine. <ref>LSD Myths from Erowid</ref>

An alternative theory regarding flashbacks postulates that it is a form of perceptual learning. People having unusual experiences while on LSD may be more likely to make similar interpretations of their sensory input in the future. This theory does not appear to explain why a subset of people develop hallucinogen persisting perception disorder and are unable to 'unlearn' their distressing perceptual patterns.

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Psychosis

There are some cases of LSD inducing or triggering a psychosis in people that were apparently healthy prior to taking LSD. This issue was reviewed extensively in a 1984 publication by Rick Strassman. <ref>Template:Cite journal</ref> In most cases, the psychosis-like reaction is of short duration, but in other cases it may be chronic. It is difficult to determine if LSD in itself induces these reactions or if it merely triggers latent conditions that would have manifested themselves otherwise. The similarities of time course and outcomes between putatively LSD-precipitated and other psychoses suggests that the two types of syndromes are not different and that LSD may have been a nonspecific trigger. Several studies have tried to estimate the prevalence of LSD-induced prolonged psychosis arriving at numbers of around 4 in 1,000 individuals (0.8 in 1,000 volunteers and 1.8 in 1,000 psychotherapy patients in Cohen 1960 <ref>Template:Cite journal</ref>; 9 per 1,000 psychotherapy patients in Melleson 1971 <ref>Template:Cite journal</ref>). But these rates are far lower than the lifetime prevalence for psychotic conditions: schizophrenia, to pick just one type of psychosis, has a lifetime prevalence of about 1% in populations that are not exposed to LSD. In itself, this suggests no causative link between LSD and chronic psychotic disorders.

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Chemistry

Image:LSD isomers.png

LSD is an example of an ergoline derivative. It is commonly produced from lysergic acid, which is made from ergotamine, a substance derived from the ergot fungus on rye, or from ergine (lysergic acid amide), a chemical found in morning glory and hawaiian baby woodrose seeds. It is theoretically possible to manufacture LSD from morning glory or hawaiian baby woodrose seeds although this is not economically feasible, and these seeds have never been found to be a successful starting material for LSD production. Lysergic acid can also be synthesized in the laboratory by relatively complex total syntheses.

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. However, LSD and iso-LSD, the two C-8 isomers, are rapidly interconverting in the presence of base. Non-psychoactive iso-LSD which has formed during the synthesis can be removed by chromatography and can be isomerized to LSD.

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Production

Image:LSDLabGlassware.jpg

Only a small amount of ergotamine tartrate is required to produce LSD in large batches. For example, 25 kilograms of ergotamine tartrate can produce 5 or 6 kilograms of pure LSD crystal that, under ideal circumstances, could be processed into 100 million dosage units, assuming a typical "hit" of 50 micrograms. This is more than enough to meet what is believed to be the entire annual U.S. demand for the drug. LSD manufacturers only need to create a small quantity of the substance, and thus they enjoy an ease of transport and concealment not available to traffickers of other illegal drugs (such as marijuana and cocaine). <ref name="DEA-pub">"LSD in the US – Manufacture", DEA Publications.</ref>

Manufacturing LSD requires laboratory equipment and experience in the field of organic chemistry. It takes two or three days to produce 30 to 100 grams of pure compound. It is believed that LSD usually is not produced in large quantities, but rather in a series of small batches. This technique minimizes the loss of precursor chemicals in case a synthesis step does not work as expected. <ref name="DEA-pub"/>

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Forms of LSD

Image:Ruby slippers image.jpg

LSD is produced in crystalline form and then mixed with excipients or diluted as a liquid for production in ingestible forms. Liquid solution is either distributed as-is in small vials or, more commonly, sprayed or soaked onto a distribution medium. Historically, LSD solutions were first sold on sugar cubes, but practical considerations forced a change to tablet form. Early pills or tabs were flattened on both ends and identified by color: "grey flat", "blue flat", and so forth. Next came "domes", which were rounded on one end, then "double domes" rounded on both ends, and finally small tablets known as "microdots". Later still, LSD began to be distributed in thin squares of gelatin ("window panes") and, most commonly, as blotter paper: sheets of paper impregnated with LSD and perforated into small squares of individual dosage units. The paper is then cut into small square pieces called "tabs" for distribution. Individual producers often print designs onto the paper serving to identify different makers, batches or strengths, and such "blotter art" often emphasizes psychedelic themes.

LSD is sold under more than 80 street names including Acid, 'Cid, Sid, Bart Simpsons, Barrels, Blotter, Doses, Heavenly blue, “L”, Liquid, Liquid A, Lucy in the sky with diamonds, Microdots, Mind detergent, Orange cubes, Orange micro, Owsley, Hits, Paper acid, Sacrament, Sandoz, Sugar, Sugar lumps, Sunshine, Tabs, Ticket, Trips, Twenty-five, Wedding bells, and Windowpane, as well as names that reflect the designs on the sheets of blotter paper. On occasion, authorities have encountered the drug in other forms — including powder or crystal, and capsule — and laced on other substances. More than 200 types of LSD tablets have been encountered since 1969 and more than 350 paper designs have been observed since 1975. Designs range from simple five-point stars in black and white to exotic artwork in full four-color print.

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Legal status

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 and most of Europe. However, enforcement of extant laws varies from country to country.

LSD is easy to conceal and smuggle. A tiny vial can contain thousands of doses. Not much money is made from retail-level sales of LSD, so the drug is typically not associated with the violent organized criminal organizations involved in cocaine and opiate smuggling.

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United States: Prior to 1970

Prior to 1967, LSD was available legally in the United States as an experimental psychiatric drug. (LSD "apostle" Al Hubbard actively promoted the drug between the 1950s and the 1970s and introduced thousands of people to it.) The US Federal Government classified it as a Schedule I drug according to the Controlled Substances Act of 1970. As such, 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. (LSD prohibition does not make an exception for religious use.) 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.

LSD has been manufactured illegally since the 1960s. Historically, LSD was distributed not for profit, but because those who made and distributed it truly believed that the psychedelic experience could do good for humanity, that it expanded the mind and could bring understanding and love. A limited number of chemists, probably fewer than a dozen, are believed to have manufactured nearly all of the illicit LSD available in the United States. The best known of these is undoubtedly Augustus Owsley Stanley III, usually known simply as Owsley. The former chemistry student set up a private LSD lab in the mid-Sixties in San Francisco and supplied the LSD consumed at the famous Acid Test parties held by Ken Kesey and his Merry Pranksters, and other major events such as the Gathering of the Tribes in San Francisco in January 1967. He also had close social connections to leading San Francisco bands the Grateful Dead, Jefferson Airplane and Big Brother and The Holding Company, regularly supplied them with his LSD and also worked as their live sound engineer and made many tapes of these groups in concert. Owsley's LSD activities — immortalized by Steely Dan in their song "Kid Charlemagne" — ended with his arrest at the end of 1967, but some other manufacturers probably operated continuously for 30 years or more.

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United States: 1970 to 2003

Image:LSDMissileSilo.jpg

American LSD usage declined in the 1970s and 1980s, then experienced a mild resurgence in popularity in the 1990s. Although there were many distribution channels during this decade, the U.S. DEA identified continued tours by the psychedelic rock band The Grateful Dead and the then-burgeoning rave scene as primary venues for LSD trafficking and consumption. American LSD usage fell sharply circa 2000. The decline is attributed to the arrest of two chemists, William Leonard Pickard, a Harvard-educated organic chemist, and Clyde Apperson.

Pickard was an alledged member of the Brotherhood of Eternal Love group that produced and sold LSD in California during the late 1960's and early 1970's. It is believed he had links to other "cooks" associated with this group- an original source of the drug back in the 1960's- and his arrest may have forced other operations to cease production, leading to the large decline in street availibility.

The DEA claims these two inviduals were responsible for the vast majority of LSD sold illegally in the United States and a significant amount of the LSD sold in Europe, and that they worked closely with organized traffickers. While this claim may have some bearing, it is not fully known the extent of Pickard's direct influence on the overall availibility in the United States. Some attest that "Pickard's Acid" was sold exclusively in Europe, and was not distributed through American music venues.

According to DEA reports, black market LSD availability dropped by 95% after the two were arrested in 2000. These arrests were a result of the largest LSD manufacturing raid in DEA history. <ref>Seper, Jerry. "Man sentenced to life in prison as dealer of LSD". The Washington Times 27 November 2003.</ref> Availibility has increased slightly as of summer 2005, but still remains limited. Template:Fact

In November of 2003, Pickard and Apperson were sentenced to two life sentences and two 30-year sentences, respectively, after being convicted in Federal Court of running a large scale LSD manufacturing operation out of several clandestine laboratories, including a former missile silo near Wamego, Kansas.

LSD manufacturers and traffickers can be categorized into two groups: A few large scale producers, such as the aforementioned Pickard and Apperson, 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 Agency than the larger groups, as their product reaches only local markets. Overall, LSD production in the United States is extremely limited, with very few individuals or groups capable of production.

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References

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See also

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Chemical

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Other

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External links

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