Lysergic acid diethylamide

"LSD" redirects here. For other uses, see LSD (disambiguation).

Lysergic acid diethylamide (LSD)
INN: Lysergide

2D structural formula and 3D models of LSD
Systematic (IUPAC) name
(6aR,9R)-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo-[4,3-fg]quinoline-9-carboxamide
Clinical data
Pronunciation /daɪ eθəl ˈæmaɪd/, /æmɪd/, or /eɪmaɪd/)[1][2][3]
Pregnancy
category
  • US: C (Risk not ruled out)
Dependence
liability		 Low[4]
Addiction
liability		 None[5]
Routes of
administration		 Oral, sublingual, intravenous, ocular, intramuscular
Legal status
Legal status
Pharmacokinetic data
Metabolism Hepatic
Biological half-life 3–5 hours[6][7]
Excretion Renal
Identifiers
CAS Number 50-37-3 YesY
ATC code none
PubChem CID 5761
IUPHAR/BPS 17
DrugBank DB04829 YesY
ChemSpider 5558 YesY
UNII 8NA5SWF92O YesY
ChEBI CHEBI:6605 YesY
ChEMBL CHEMBL263881 YesY
Synonyms Acid, LSD, lysergide
Chemical data
Formula C20H25N3O
Molar mass 323.44 g·mol−1
Physical data
Melting point 80 to 85 °C (176 to 185 °F)
  (verify)

Lysergic acid diethylamide (LSD), also known as acid, is a psychedelic drug known for its psychological effects. This may include altered awareness of the surroundings, perceptions, and feelings as well as sensations and images that seem real though they are not.[8] It is used mainly as a recreational drug and for spiritual reasons. LSD is typically either swallowed or held under the tongue.[8] It is often sold on blotter paper, a sugar cube, or gelatin. LSD injected intravenously takes effect in approximately 30 minutes.

LSD is not addictive.[8][9] However, adverse psychiatric reactions such as anxiety, paranoia, and delusions are possible.[10] LSD is in the ergoline family. LSD is sensitive to oxygen, ultraviolet light, and chlorine,[11] though it may last for years if it is stored away from light and moisture at low temperature. In pure form it is odorless and clear or white in color.[8] As little as 20–30 micrograms can produce an effect.[12]

LSD was first made by Albert Hofmann in Switzerland in 1938 from ergotamine, a chemical from the fungus, ergot. The laboratory name for the compound was the acronym for the German "Lyserg-säure-diäthylamid", followed by a sequential number: LSD-25.[11][13] Hofmann discovered its psychedelic properties in 1943.[14] LSD was introduced as a commercial medication under the trade-name Delysid for various psychiatric uses in 1947.[15] In the 1950s, officials at the U.S. Central Intelligence Agency (CIA) thought the drug might be useful for mind control and chemical warfare; the agency's Project MKUltra research program gave the drug to young servicemen and students. The subsequent recreational use by youth culture in the Western world as part of 1960s counterculture resulted in its prohibition.[16]

Uses

Medical

As of 2016, there are no medical indications for LSD and it is not used in clinical medicine.

Recreational

Pink elephant blotters containing LSD

LSD is commonly used as a recreational drug.[17]

Spiritual

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 sometimes report out of body experiences. In 1966, Timothy Leary established the League for Spiritual Discovery with LSD as its sacrament.[18][19] 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.[20]

Effects

Notable physical effects of LSD and their locales of occurrence.

Physical

LSD can cause pupil dilation, reduced 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, hyperreflexia, and tremors.

Psychological

LSD's psychological effects (colloquially called a "trip") vary greatly between persons and places. 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.[21]

An LSD trip can have long-term psychological or emotional effects; some users report the LSD experience caused significant long term changes in their personality and life perspective.[22] Widely different effects emerge based on what Timothy Leary called set and setting;[23] 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 perceptual changes and a loss of a sense of identity or the ego (known as "ego death").[24][25] Many users experience a dissolution of the boundary between themselves and the "outside world".[26] 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.[27]

Sensory

Some sensory 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, and morphing objects.[26] Some users, including Albert Hofmann, report a strong metallic taste for the duration of the effects.[28]

LSD causes an animated sensory experience of senses, emotions, memories, time, and awareness for 6 to 14 hours, depending on dosage and tolerance. 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.[26][29] 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 inexplicable way; for instance, objects that are static in three dimensions can seem to be moving relative to one or more additional spatial dimensions.[30] 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.

Adverse effects

In a 2011 survey of 292 clinical experts in Scotland, LSD ranked 4th lowest in personal harm and 6th lowest in social harm out of 19 common recreational drugs.[31]

Mental disorders

LSD may trigger panic attacks or feelings of extreme anxiety, colloquially referred to as a "bad trip". There is evidence that people with severe mental illnesses like schizophrenia have a higher likelihood of experiencing adverse effects from taking LSD (see psychosis for further details).[32] No real prolonged effects have been proven, although PTSD has been reported after some intensely distressful LSD experiences.

Historical data suggests that there has been the occasional incidence of long-term, albeit temporary LSD induced psychosis in people who appeared to be healthy prior to taking the drug.[33] Recent evidence disputes the suggestion that LSD use puts a person at risk for developing long lasting mental disorders. An analysis of information from the National Survey on Drug Use and Health showed that the use of psychedelic drugs such as LSD is associated with significantly reduced odds of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt.[34]

Suggestibility

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,[35] research from the 1960s suggests that both mentally ill and healthy people are more suggestible while under its influence.[36][37]

Flashbacks

Some individuals may experience "flashbacks" and a syndrome of long-term and occasionally distressing perceptual changes.[38][39]

"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".[40] Several studies have tried to determine the likelihood that a user of LSD, not suffering from known psychiatric conditions, will experience flashbacks. The larger studies include Blumenfeld's in 1971[40][41][42][43][44] and Naditch and Fenwick's in 1977,[45][46][47][48][49] which arrived at figures of 20%[41] and 28%,[45] respectively.[38][50][51]

Hallucinogen persisting perception disorder (HPPD) describes a post-LSD exposure syndrome 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.[52] 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 uncommon and affects a distinctly vulnerable subpopulation of users.[53][54]

Pregnancy

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.

The mutagenic potential of LSD is unclear. Overall, the evidence seems to point to limited or no effect at commonly used doses.[55]

Tolerance

Tolerance to LSD builds up over consistent use[56] and cross-tolerance has been demonstrated between LSD, mescaline[57] and psilocybin.[58] This tolerance is probably caused by downregulation of 5-HT2A receptors in the brain and diminishes a few days after cessation of use.

LSD is not addictive.[5][9][59] Experimental evidence has demonstrated that LSD use does not yield positive reinforcement in either human or animal subjects.[5][60][61]

Overdose

Reassurance in a calm, safe environment is beneficial. Agitation can be safely addressed with benzodiazepines such as lorazepam or diazepam. Neuroleptics such as haloperidol are recommended against because they may have adverse effects. LSD is rapidly absorbed, so activated charcoal and emptying of the stomach will be of little benefit, unless done within 30–60 minutes of ingesting an overdose of LSD. Sedation or physical restraint is rarely required, and excessive restraint may cause complications such as hyperthermia (over-heating) or rhabdomyolysis.[62]

Massive doses require supportive care, which may include endotracheal intubation or respiratory support.[62] Overdose has been recorded at 1,000 to 7,000μg per 100ml & 2.1 to 26 ng per ml in serum concentrations of the tartrate salt form. It is recommended that high blood pressure, tachycardia (rapid heart-beat), and hyperthermia, if present, are treated symptomatically, and that low blood pressure is treated initially with fluids and then with pressors if necessary. Intravenous administration of anticoagulants, vasodilators, and sympatholytics may be useful with massive doses.[62][63]

Pharmacology

Pharmacodynamics

Binding affinities of LSD for various receptors. The lower the dissociation constant (Ki), 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 Ki Database

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 significantly dopaminergic, and LSD is therefore rather unusual in this regard. LSD's agonism of D2 receptors contributes to its psychoactive effects.[64][65] 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 sufficiently activated by the brain concentration of approximately 10–20 nM.[59] In humans, recreational doses of LSD can affect 5-HT1A (Ki=1.1nM), 5-HT2A (Ki=2.9nM), 5-HT2B (Ki=4.9nM), 5-HT2C (Ki=23nM), 5-HT5A (Ki=9nM [in cloned rat tissues]), and 5-HT6 receptors (Ki=2.3nM).[6][66] 5-HT5B receptors, which are not present in humans, also have a high affinity for LSD.[67] The psychedelic effects of LSD are attributed to cross-activation of 5-HT2A receptor heteromers.[68] Many but not all 5-HT2A agonists are psychedelics and 5-HT2A 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.[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, has been shown to activate DARPP-32-related pathways.[71]

LSD enhances dopamine D2R protomer recognition and signaling of D2–5-HT2A receptor complexes. This mechanism may contribute to the psychotic actions of LSD.[72]

Pharmacokinetics

LSD's effects normally last from 6–12 hours depending on dosage, tolerance, body weight and age.[11] The Sandoz prospectus for "Delysid" warned: "intermittent disturbances of affect may occasionally persist for several days."[13] 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.[6] 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.[7]

Physical and chemical properties

The four possible stereoisomers of LSD. Only (+)-LSD is psychoactive.

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.

Pure salts of LSD are triboluminescent, emitting small flashes of white light when shaken in the dark.[11] LSD is strongly fluorescent and will glow bluish-white under UV light.

Synthesis

LSD is an ergoline derivative. It is commonly synthesised by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride[73] and peptide coupling reagents.[74] 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.[75] Lysergic acid can also be produced synthetically, eliminating the need for ergotamines.[76][77]

Dosage

White on White blotters (WoW)

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.[12][78] 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.[13]

In the mid-1960s, the most important black market LSD manufacturer (Owsley Stanley) distributed acid at a standard concentration of 270 µg,[79] 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,[80] and even more in the 2000s (decade).[79][81]

Reactivity and degradation

"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."[11]

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.[11] 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.[11]

A controlled study was undertaken to determine the stability of LSD in pooled urine samples.[82] 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.

Detection in body fluids

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.[83]

History

"... 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."

Albert Hofmann, on his first experience with LSD[84]

LSD was first synthesized on November 16, 1938[85] 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.[86] The first intentional ingestion of LSD occurred on April 19, 1943,[87] 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.[88] Sandoz Laboratories introduced LSD as a psychiatric drug in 1947.[89]

Albert Hofmann in 2006

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 subjects' knowledge. The project was revealed in the US congressional Rockefeller Commission report in 1975.

In 1963, the Sandoz patents expired on LSD.[80] 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.[90] In the early 1960s the use of LSD and other hallucinogens was advocated by new proponents of consciousness expansion such as Leary, Huxley, Alan Watts and Arthur Koestler,[91][92] and according to L. R. Veysey they profoundly influenced the thinking of the new generation of youth.[93]

On October 24, 1968, possession of LSD was made illegal in the United States.[94] 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.[95]

Society and culture

Counterculture, music and art

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.[96] 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.[97][98] 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).[99] In both music and art, the influence on 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.

Lysergic Acid Diethylamide, by Lambert P. Lambert and the Gorgettes, from the album Abbra Cadaver, 1967.

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 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. Among the many famous people in the UK that 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.[100] Electric guitars are used to create feedback, and are played through wah wah and fuzzbox effect pedals.[101] Elaborate studio effects are often used, such as backwards tapes, panning, phasing, long delay loops, and extreme reverb.[102] In the 1960s there was a use of primitive electronic instruments such as early synthesizers and the theremin.[103][104] Later forms of electronic psychedelia also employed repetitive computer-generated beats.[105] Songs referring to LSD include the Beatles' Lucy in the Sky with Diamonds. Psychedelic experiences were also reflected in psychedelic art, literature and film.[106]

Legal status

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.[107]

Australia

LSD is a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).[108] A Schedule 9 substance is 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.[108]

In Western Australia under the Misuse of Drugs Act 1981 0.004g of Lysergic Acid Diethylamide (LSD) is the amount required determining court of trial, 0.002g is considered intention to sell or supply and 0.01g is determined for purposes of drug trafficking.[109]

Canada

In Canada, LSD is a controlled substance under Schedule III of the Controlled Drugs and Substances Act.[110] 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.

United Kingdom

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".[111]

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.[112]

United States

LSD is Schedule I in the United States, according to the Controlled Substances Act of 1970.[113] 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.[114]

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.[115]

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.

Economics

Production

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.[116]

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.[116]

Forms
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.[117]

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".[118]

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.[117][118] More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975.[118] 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.[117] 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.[119][120] Authorities have encountered the drug in other forms—including powder or crystal, and capsule.[121]

Modern distribution

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.[122] As a group, independent producers are of less concern to the Drug Enforcement Administration than the larger groups because their product reaches only local markets.[123]

Mimics
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,[124][125] a mixture of DOC and DOI,[126] 25I-NBOMe,[127] and a mixture of DOC and DOB.[128] 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.[129] 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.[130] Several deaths have been attributed to 25I-NBOMe.[131][132][133][134]

Research

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.[135] New clinical LSD experiments in humans started in 2009 for the first time in 35 years.[136]

In 2001 the United States Drug Enforcement Administration stated 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."[137] More recently, experimental uses of LSD have included the treatment of alcoholism[138] and pain and cluster headache relief.[139] It has also been used for spiritual purposes, and for its putative effects in increasing creativity.[140]

Some hold that further research into the drug's potential as a treatment for addiction, among other things, is warranted.[141]

Psychedelic therapy

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,[142] and also for treating alcoholism.[143][144] One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender,"[145] 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.[146][147]

End-of-life anxiety

Since 2008 there has been ongoing research into using LSD to alleviate anxiety for terminally ill cancer patients coping with their impending deaths.[148][149]

Alcoholism treatment

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, but no effect was seen at one year. Adverse events included seizure, moderate confusion and agitation, nausea, vomiting, and acting in a bizarre fashion.[150]

Cluster headaches

LSD has been used as a treatment for cluster headaches with positive results in some small studies.[139][151]

Enhancing performance

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.[152][153][154][155]

See also

References

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Further reading

  • Marks, John. The Search for the Manchurian Candidate: The CIA and Mind Control (1979), ISBN 0-8129-0773-6
  • Hofmann, Albert. LSD My Problem Child: Reflections on Sacred Drugs, Mysticism and Science (1983) ISBN 978-0-9660019-8-3
  • Lee, Martin A. and Bruce Shlain. Acid Dreams: The Complete Social History of LSD: The CIA, the Sixties, and Beyond (1992) ISBN 978-0-8021-3062-4
  • Henderson, Leigh A. and William J. Glass. LSD: Still With Us After All These Years: Based on the National Institute of Drug Abuse Studies on the Resurgence of Contemporary LSD Use (1st edition 1994, 2nd edition 1998) ISBN 978-0-7879-4379-0
  • Stevens, Jay. Storming Heaven: LSD And The American Dream (1998) ISBN 978-0-8021-3587-2
  • Grof, Stanislav. LSD Psychotherapy. (April 10, 2001)
  • de Rios, Marlene Dobkin and Oscar Janiger. LSD, spirituality, and the creative process (2003, Inner Traditions) ISBN 978-0-89281-973-7 – "An exploration of how LSD influences imagination and the creative process. Based on the results of one of the longest clinical studies of LSD that took place between 1954 and 1962, before LSD was illegal. Includes personal reports, artwork, and poetry from the original sessions as testimony of the impact of LSD on the creative process."
  • Roberts, Andy. Albion Dreaming: A Popular History of LSD in Britain (2008), Marshall Cavendish, U.K, ISBN 1-905736-27-4
  • Bebergal, Peter, "Will Harvard drop acid again? Psychedelic research returns to Crimsonland", The Phoenix (Boston), June 2, 2008
  • Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A (2008). "The pharmacology of lysergic acid diethylamide: a review". CNS Neuroscience & Therapeutics 14 (4): 295–314. doi:10.1111/j.1755-5949.2008.00059.x. PMID 19040555. 
  • BBC News: Pont-Saint-Esprit poisoning: Did the CIA spread LSD? (2010)
  • Dale Bewan. Dropping Acid: A Beginner's Guide to the Responsible Use of LSD for Self-Discovery (1st edition 2013) ISBN 1492318191

External links

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