Lysergic acid diethylamide

LSD is commonly used as a recreational drug in the company of friends, in large crowds, or by oneself.[26] The street price of a single dose of LSD can be anywhere from $2 to $50.[27]

LSD can catalyze intense spiritual experiences and is thus considered an entheogen. Some user have reported out of body experiences. In 1966, Timothy Leary established the League for Spiritual Discovery with LSD as its sacrament.[28][29] 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 texts of ancient civilizations.[30]

LSD currently has no approved uses in medicine.[31][32] A meta analysis concluded that a single dose was effective at reducing alcohol consumption in alcoholism.[33] LSD has also been studied in depression, anxiety, and drug dependence, with positive preliminary results.[34]

LSD can cause pupil dilation, reduced appetite, profuse sweating, 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 elevated body temperature, blood sugar, and heart rate, alongside goose bumps, jaw clenching, mouth dryness, and hyperreflexia. In negative experiences, numbness, weakness, nausea, and tremors have also been exhibited.[14]

The most common immediate psychological effects of LSD are visual hallucinations and illusions (colloquially known as "trips"), which vary depending on how much is used and how the dosage interacts with the brain. Trips usually start within 20–30 minutes of taking LSD orally (less if snorted or taken intravenously), peak three to four hours after ingestion, and last up to 20 hours. Good trips are reportedly deeply stimulating and pleasurable, and typically involve intense joy or euphoria, a greater appreciation for life, reduced anxiety, a sense of spiritual enlightenment, and a sense of belonging or interconnectedness with the universe.[37][38] Negative experiences, colloquially known as "bad trips," evoke an array of dark emotions, such as irrational fear, anxiety, panic, paranoia, dread, distrustfulness, hopelessness, intrusive thoughts of harming others, and even suicidal ideation.[39] While it is impossible to predict when a bad trip will occur, one's mood, surroundings, sleep, hydration, social setting, and other factors can be controlled to minimize the risk of a bad trip.[40][41]

LSD causes an animated sensory experience of senses, emotions, memories, time, and awareness for 6 to 20 hours, depending on dosage and tolerance.[15] Generally beginning within 30 to 90 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.[42][43]

Some sensory effects may include an experience of radiant colors, objects and surfaces appearing to ripple or "breathe," spinning fractals superimposed on one's vision, colored patterns behind the closed eyelids, an altered sense of time, geometric patterns emerging on walls and other textured objects, and morphing objects.[42] Some users report a strong metallic taste for the duration of the effects.[44]

Some report that the inanimate world appears to animate in an inexplicable way; for instance, objects that are static in three dimensions can seem to be moving relative to one or more additional spatial dimensions.[45] Many of the basic visual effects resemble the phosphenes seen after applying pressure to the eye and have also been studied as form constants. The auditory effects of LSD may include echo-like distortions of sounds, changes in ability to discern concurrent auditory and visual stimuli, and a general intensification of the experience of music. Higher doses often cause intense and fundamental distortions of sensory perception such as synesthesia, the experience of additional spatial or temporal dimensions, and temporary dissociation.

LSD may trigger panic attacks or feelings of extreme anxiety, known familiarly as a "bad trip." Review studies suggest that LSD likely plays a role in precipitating the onset of acute psychosis in previously healthy individuals with an increased likelihood in individuals who have a family history of schizophrenia.[7][48] There is evidence that people with severe mental illnesses like schizophrenia have a higher likelihood of experiencing adverse effects from taking LSD.[48]

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,[49] research from the 1960s suggests that both mentally ill and healthy people are more suggestible while under its influence.[50][51][52]

"Flashbacks" are a reported psychological phenomenon in which an individual experiences an episode of some of LSD's subjective effects after the drug has worn off, persisting for months or years after hallucinogen use.[53] Individuals with hallucinogen persisting perception disorder experience intermittent or chronic flashbacks that cause distress or impairment in life and work.[19]

The mutagenic potential of LSD is unclear. Overall, the evidence seems to point to limited or no effect at commonly used doses.[54] Studies showed no evidence of teratogenic or mutagenic effects.[7]

Tolerance to LSD builds up with consistent use[55] and cross-tolerance has been demonstrated between LSD, mescaline,[56] and psilocybin.[57] Researchers believe that tolerance returns to baseline after two weeks of being drug-free.[58]

The NIH states that LSD is addictive,[18] while most other sources state it is not.[17][59] A 2009 textbook states that it "rarely produce[s] compulsive use."[5] A 2006 review states it is readily abused but does not result in addiction.[17]

Binding affinities of LSD for various receptors. The lower the dissociation constant (K_i), the more strongly LSD binds to that receptor (i.e. with higher affinity). The horizontal line represents an approximate value for human plasma concentrations of LSD, and hence, receptor affinities that are above the line are unlikely to be involved in LSD's effect. Data averaged from data from the K_i Database

Most serotonergic psychedelics are not significantly dopaminergic, and LSD is therefore atypical in this regard. The agonism of the D₂ receptor by LSD may contribute to its psychoactive effects in humans.[63][64]

LSD binds to most serotonin receptor subtypes except for the 5-HT₃ and 5-HT₄ receptors. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM.[59] In humans, recreational doses of LSD can affect 5-HT_1A (K_i=1.1nM), 5-HT_2A (K_i=2.9nM), 5-HT_2B (K_i=4.9nM), 5-HT_2C (K_i=23nM), 5-HT_5A (K_i=9nM [in cloned rat tissues]), and 5-HT₆ receptors (K_i=2.3nM).[65][66] Although not present in humans, 5-HT_5B receptors found in rodents also have a high affinity for LSD.[67] The psychedelic effects of LSD are attributed to cross-activation of 5-HT_2A receptor heteromers.[68] Many but not all 5-HT_2A agonists are psychedelics and 5-HT_2A antagonists block the psychedelic activity of LSD. LSD exhibits functional selectivity at the 5-HT_2A and 5HT_2C receptors in that it activates the signal transduction enzyme phospholipase A2 instead of activating the enzyme phospholipase C as the endogenous ligand serotonin does.[69]

Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex[59] and therefore excitation in this area, specifically in layers IV and V.[70] LSD, like many other drugs of recreational use, has been shown to activate DARPP-32-related pathways.[71] The drug enhances dopamine D₂ receptor protomer recognition and signaling of D₂–5-HT_2A receptor complexes,[72] which may contribute to its psychotic effects.[72] LSD has been shown to have low affinity for H1 receptors, displaying antihistamine effects.[73][74][75]

The crystal structure of LSD bound in its active state to a serotonin receptor, specifically the 5-HT_2B receptor, has been elucidated for the first time in 2017.[76][77][78] The LSD-bound 5-HT_2B receptor is regarded as an excellent model system for the 5-HT_2A receptor and the structure of the LSD-bound 5-HT_2B receptor was used in the study as a template to determine the structural features necessary for the activity of LSD at the 5-HT_2A receptor.[76][77][78] The diethylamide moiety of LSD was found to be a key component for its activity, which is in accordance with the fact that the related lysergamide lysergic acid amide (LSA) is far less hallucinogenic in comparison.[78] LSD was found to stay bound to both the 5-HT_2A and 5-HT_2B receptors for an exceptionally long amount of time, which may be responsible for its long duration of action in spite of its relatively short terminal half-life.[76][77][78] The extracellular loop 2 leucine 209 residue of the 5-HT_2B receptor forms a 'lid' over LSD that appears to trap it in the receptor, and this was implicated in the potency and functional selectivity of LSD and its very slow dissociation rate from the 5-HT₂ receptors.[76][77][78]

The effects of LSD normally last between 6 and 12 hours depending on dosage, tolerance, body weight, and age.[79] The Sandoz prospectus for "Delysid" warned: "intermittent disturbances of affect may occasionally persist for several days."[80] Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175 minutes (about 3 hours).[65] 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.[81]

The pharmacokinetics of LSD were not properly determined until 2015, which is not surprising for a drug with the kind of low-μg potency that LSD possesses.[9][6] In a sample of 16 healthy subjects, a single mid-range 200 μg oral dose of LSD was found to produce mean maximal concentrations of 4.5 ng/mL at a median of 1.5 hours (range 0.5–4 hours) post-administration.[9][6] After attainment of peak levels, concentrations of LSD decreased following first-order kinetics with a terminal half-life of 3.6 hours for up to 12 hours and then with slower elimination with a terminal half-life of 8.9 hours thereafter.[9][6] The effects of the dose of LSD given lasted for up to 12 hours and were closely correlated with the concentrations of LSD present in circulation over time, with no acute tolerance observed.[9][6] Only 1% of the drug was eliminated in urine unchanged whereas 13% was eliminated as the major metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) within 24 hours.[9][6] O-H-LSD is formed by cytochrome P450 enzymes, although the specific enzymes involved are unknown, and it does not appear to be known whether O-H-LSD is pharmacologically active or not.[9][6] The oral bioavailability of LSD was crudely estimated as approximately 71% using previous data on intravenous administration of LSD.[9][6] The sample was equally divided between male and female subjects and there were no significant sex differences observed in the pharmacokinetics of LSD.[9][6]

LSD is an ergoline derivative. It is commonly synthesized by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride[82] and peptide coupling reagents.[83] 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.[84] Lysergic acid can also be produced synthetically, eliminating the need for ergotamines.[85][86]

White on White blotters (WoW) for sublingual administration

A single dose of LSD may be between 40 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.[87][88] 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 0.5 g, has effects comparable to 100 µg or less of LSD.[80]

In the mid-1960s, the most important black market LSD manufacturer (Owsley Stanley) distributed acid at a standard concentration of 270 µg,[89] while street samples of the 1970s contained 30 to 300 µg. By the 1980s, the amount had reduced to between 100 and 125 µg, dropping more in the 1990s to the 20–80 µg range,[90] and even more in the 2000s (decade).[89][91]

"LSD," writes the chemist Alexander Shulgin, "is an unusually fragile molecule ... As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely."[79]

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.[79] 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.[79]

A controlled study was undertaken to determine the stability of LSD in pooled urine samples.[92] 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.

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.[93]

The apparent plasma half life of LSD is considered to be around 5.1 hours with peak plasma concentrations occurring 3 hours after administration.[94]

LSD can be detected using an Ehrlich's reagent and a Hofmann's reagent.

Psychedelic art attempts to capture the visions experienced on a psychedelic trip

By the mid-1960s, the youth countercultures in California, particularly in San Francisco, had adopted the use of hallucinogenic drugs, with the first major underground LSD factory established by Owsley Stanley.[110] From 1964, the Merry Pranksters, a loose group that developed around novelist Ken Kesey, sponsored the Acid Tests, a series of events primarily staged in or near San Francisco, involving the taking of LSD (supplied by Stanley), accompanied by light shows, film projection and discordant, improvised music known as the psychedelic symphony.[111][112] The Pranksters helped popularize LSD use, through their road trips across America in a psychedelically-decorated converted school bus, which involved distributing the drug and meeting with major figures of the beat movement, and through publications about their activities such as Tom Wolfe's The Electric Kool-Aid Acid Test (1968).[113]

In San Francisco's Haight-Ashbury neighborhood, brothers Ron and Jay Thelin opened the Psychedelic Shop in January 1966.[114] The Thelins opened the store to promote safe use of LSD, which was then still legal in California. The Psychedelic Shop helped to further popularize LSD in the Haight and to make the neighborhood the unofficial capital of the hippie counterculture in the United States. Ron Thelin was also involved in organizing the Love Pageant rally, a protest held in Golden Gate park to protest California's newly adopted ban on LSD in October 1966. At the rally, hundreds of attendees took acid in unison. Although the Psychedelic Shop closed after barely a year-and-a-half in business, its role in popularizing LSD was considerable.[115]

A similar and connected nexus of LSD use in the creative arts developed around the same time in London. A key figure in this phenomenon in the UK was British academic Michael Hollingshead, who first tried LSD in America in 1961 while he was the Executive Secretary for the Institute of British-American Cultural Exchange. After being given a large quantity of pure Sandoz LSD (which was still legal at the time) and experiencing his first "trip," Hollingshead contacted Aldous Huxley, who suggested that he get in touch with Harvard academic Timothy Leary, and over the next few years, in concert with Leary and Richard Alpert, Hollingshead played a major role in their famous LSD research at Millbrook before moving to New York City, where he conducted his own LSD experiments. In 1965 Hollingshead returned to the UK and founded the World Psychedelic Center in Chelsea, London.

In both music and art, the influence of LSD was soon being more widely seen and heard thanks to the bands that participated in the Acid Tests and related events, including the Grateful Dead, Jefferson Airplane and Big Brother and the Holding Company, and through the inventive poster and album art of San Francisco-based artists like Rick Griffin, Victor Moscoso, Bonnie MacLean, Stanley Mouse & Alton Kelley, and Wes Wilson, meant to evoke the visual experience of an LSD trip. LSD had a strong influence on the Grateful Dead and the culture of "Deadheads."[116]

Among the many famous people in the UK that Michael Hollingshead is reputed to have introduced to LSD are artist and Hipgnosis founder Storm Thorgerson, and musicians Donovan, Keith Richards, Paul McCartney, John Lennon, and George Harrison. Although establishment concern about the new drug led to it being declared an illegal drug by the Home Secretary in 1966, LSD was soon being used widely in the upper echelons of the British art and music scene, including members of the Beatles, the Rolling Stones, the Moody Blues, the Small Faces, Pink Floyd, Jimi Hendrix and others, and the products of these experiences were soon being both heard and seen by the public with singles like the Small Faces' "Itchycoo Park" and LPs like the Beatles' Sgt. Pepper's Lonely Hearts Club Band and Cream's Disraeli Gears, which featured music that showed the obvious influence of the musicians' recent psychedelic excursions, and which were packaged in elaborately-designed album covers that featured vividly-coloured psychedelic artwork by artists like Peter Blake, Martin Sharp, Hapshash and the Coloured Coat (Nigel Waymouth and Michael English) and art/music collective The Fool.

In the 1960s, musicians from psychedelic music and psychedelic rock bands began to refer (at first indirectly, and later explicitly) to the drug and attempted to recreate or reflect the experience of taking LSD in their music. A number of features are often included in psychedelic music. Exotic instrumentation, with a particular fondness for the sitar and tabla are common.[117] Electric guitars are used to create feedback, and are played through wah wah and fuzzbox effect pedals.[118] Elaborate studio effects are often used, such as backwards tapes, panning, phasing, long delay loops, and extreme reverb.[119] In the 1960s there was a use of primitive electronic instruments such as early synthesizers and the theremin.[120][121] Later forms of electronic psychedelia also employed repetitive computer-generated beats.[122] Songs allegedly referring to LSD include John Prine's "Illegal Smile" and the Beatles' song "Lucy in the Sky with Diamonds," although the authors of the latter song repeatedly denied this claim.[123][124][125]

In modern times, LSD has had a prominent influence on artists such as Keith Haring, electronic dance music, and the jam band Phish.

The United Nations Convention on Psychotropic Substances (adopted in 1971) requires the signing parties to prohibit LSD. Hence, it is illegal in all countries that were parties to the convention, including the United States, Australia, New Zealand, and most of Europe. However, enforcement of those laws varies from country to country. Medical and scientific research with LSD in humans is permitted under the 1971 UN Convention.[126]

LSD is a Schedule 9 prohibited substance in Australia under the Poisons Standard (February 2017).[127] A Schedule 9 substance is defined as a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[127]

In Western Australia section 9 of the Misuse of Drugs Act 1981 provides for summary trial before a magistrate for possession of less than 0.004g; section 11 provides rebuttable presumptions of intent to sell or supply if the quantity is 0.002g or more, or of possession for the purpose of trafficking if 0.01g.[128]

In Canada, LSD is a controlled substance under Schedule III of the Controlled Drugs and Substances Act.[39] 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 recognized 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."[129]

In November 2009, the UK Transform Drug Policy Foundation released in the House of Commons a guidebook 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.[130]

LSD is Schedule I in the United States, according to the Controlled Substances Act of 1970.[131] This means LSD is illegal to manufacture, buy, possess, process, or distribute without a license from the Drug Enforcement Administration (DEA). By classifying LSD as a Schedule I substance, the DEA 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.[132]

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 US. This is because LSD is almost always present in a medium (e.g. blotter or neutral liquid), and in some contexts, 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. United States, which determined that for finding minimum sentence lengths, the total medium weight is used, while for determining the severity of the offense, an estimation of the chemical mass is used.[133]

Lysergic acid and lysergic acid amide, LSD precursors, are both classified in Schedule III of the Controlled Substances Act.[134] Ergotamine tartrate, a precursor to lysergic acid, is regulated under the Chemical Diversion and Trafficking Act.

In April 2009, the Mexican Congress approved changes in the General Health Law that decriminalized the possession of illegal drugs for immediate consumption and personal use, allowing a person to possess a moderate amount of LSD. The only restriction is that people in possession of drugs should not be within a 300-meter radius of schools, police departments, or correctional facilities. Marijuana, along with cocaine, opium, heroin, and other drugs were also decriminalized; their possession is not considered a crime as long as the dose does not exceed the limit established in the General Health Law.[135] Many question this, as cocaine is as synthesised as heroin, and both are produced as extracts from plants. The law establishes very low amount thresholds and strictly defines personal dosage. For those arrested with more than the threshold allowed by the law this can result in heavy prison sentences, as they will be assumed to be small traffickers even if there are no other indications that the amount was meant for selling.[136]

In the Czech Republic, until 31 December 1998 only drug possession "for other person" (i.e. intent to sell) was criminal (apart from production, importation, exportation, offering or mediation, which was and remains criminal) while possession for personal use remained legal.[137]

On 1 January 1999, an amendment of the Criminal Code, which was necessitated in order to align the Czech drug rules with the Single Convention on Narcotic Drugs, became effective, criminalizing possession of "amount larger than small" also for personal use (Art. 187a of the Criminal Code) while possession of small amounts for personal use became a misdemeanor.[137]

The judicial practice came to the conclusion that the "amount larger than small" must be five to ten times larger (depending on drug) than a usual single dose of an average consumer.[138]

Under the Regulation No. 467/2009 Coll, possession of less than 5 doses of LSD was to be considered smaller than large for the purposes of the Criminal Code and was to be treated as a misdemeanor subject to a fine equal to a parking ticket.[139]

According to the 2008 Constitution of Ecuador, in its Article 364, the Ecuadorian state does not see drug consumption as a crime but only as a health concern.[140] Since June 2013 the State drugs regulatory office CONSEP has published a table which establishes maximum quantities carried by persons so as to be considered in legal possession and that person as not a seller of drugs.[140][141][142] The "CONSEP established, at their latest general meeting, that the 0.020 milligrams of LSD shall be considered the maximum consumer amount.[143]

Glassware seized by the DEA

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 cocaine, cannabis, or other illegal drugs.[144]

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.[144]

Five doses of LSD, often called a "five strip"

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 these tablets, but said that most "Sunshine" in the USA came by way of Ronald Stark, who imported approximately thirty-five million doses from Europe.[145]

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 µg/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."[146]

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.[145][146] More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975.[146] 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.[145] 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.[37][147] Authorities have encountered the drug in other forms—including powder or crystal, and capsule.[148]

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.[149] As a group, independent producers are of less concern to the Drug Enforcement Administration than the large-scale groups because their product reaches only local markets.[150]

Many LSD dealers and chemists describe a religious or humanitarian purpose that motivates their illicit activity. Nicholas Schou's book Orange Sunshine: The Brotherhood of Eternal Love and Its Quest to Spread Peace, Love, and Acid to the World describes one such group, the Brotherhood of Eternal Love. The group was a major American LSD trafficking group in the late 1960s and early 1970s.[151]

In the second half of the 20th century, dealers and chemists loosely associated with the Grateful Dead like Owsley Stanley, Nicholas Sand, Karen Horning, Sarah Maltzer, "Dealer McDope," and Leonard Pickard played an essential role in distributing LSD.[116]

LSD blotter acid mimic actually containing DOC

Different blotters which could possibly be mimics

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,[152][153] a mixture of DOC and DOI,[154] 25I-NBOMe,[155] and a mixture of DOC and DOB.[156] 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.[157] 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.[158] Several deaths have been attributed to 25I-NBOMe.[159][160][161][162]

In the 1950s and 1960s LSD was used in psychiatry to enhance psychotherapy known as psychedelic therapy. Some psychiatrists believed LSD was especially useful at helping patients to "unblock" repressed subconscious material through other psychotherapeutic methods,[167] and also for treating alcoholism.[168][169][170] One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender,"[171] presumably by forcing the user to face issues and problems in that individual's psyche.

Two recent reviews concluded that conclusions drawn from most of these early trials are unreliable due to serious methodological flaws. These include the absence of adequate control groups, lack of followup, and vague criteria for therapeutic outcome. In many cases studies failed to convincingly demonstrate whether the drug or the therapeutic interaction was responsible for any beneficial effects.[172][173]

In recent years organizations like the Multidisciplinary Association for Psychedelic Studies have renewed clinical research of LSD.[174]

It has been proposed that LSD be studied for use in the therapeutic setting particularly in anxiety.[175]

In the 1950s and 1960s, some psychiatrists (e.g. 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.[176][177][178][38]

Since 2008 there has been ongoing research into using LSD to alleviate anxiety for terminally ill cancer patients coping with their impending deaths.[179][180]

A 2012 meta-analysis 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, but no effect was seen at one year. Adverse events included seizure, moderate confusion and agitation, nausea, vomiting, and acting in a bizarre fashion.[33]

LSD has been used as a treatment for cluster headaches with positive results in some small studies.[7]

LSD may have analgesic properties related to pain in terminally ill patients and phantom pain and may be useful for treating inflammatory diseases including rheumatoid arthritis.[181]

• Hofmann's Potion a documentary on the origins of LSD, 2002
• Power & Control LSD in The Sixties on YouTube, documentary film directed by Aron Ranen, 2006
• Inside LSD National Geographic Channel, 2009