Lysergic acid diethylamide

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Lysergic acid diethylamide (LSD)
INN: Lysergide
Lysergsaurediethylamid (LSD).svg
LSD-from-xtal-and-Spartan-PM3-3D-balls-web.png
Clinical data
Pronunciation/daɪ eθəl ˈæmaɪd/, /æmɪd/, or /eɪmaɪd/ [1] [2] [3]
Other namesLSD, LSD-25, LAD, Acid, Delysid, others
AHFS/Drugs.com Reference
Dependence
liability
Low [4]
Addiction
liability
None [5]
Routes of
administration
By mouth, under the tongue
Drug class Hallucinogen (psychedelic)
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Bioavailability 71% [6]
Protein binding Unknown [7]
Metabolism Liver (CYP450) [6]
Metabolites 2-Oxo-3-hydroxy-LSD [6]
Onset of action 30–40 minutes [8]
Elimination half-life 3.6 hours [6] [9]
Duration of action 8–20 hours [10]
Excretion Kidneys [6] [9]
Identifiers
  • (6aR,9R)-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.031 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H25N3O
Molar mass 323.440 g·mol−1
3D model (JSmol)
Melting point 80 to 85 °C (176 to 185 °F)
Solubility in water 7.034 [11]  mg/mL (20 °C)
  • CCN(CC)C(=O)[C@H]1CN([C@@H]2Cc3c[nH]c4c3c(ccc4)C2=C1)C
  • InChI=1S/C20H25N3O/c1-4-23(5-2)20(24)14-9-16-15-7-6-8-17-19(15)13(11-21-17)10-18(16)22(3)12-14/h6-9,11,14,18,21H,4-5,10,12H2,1-3H3/t14-,18-/m1/s1 Yes check.svgY
  • Key:VAYOSLLFUXYJDT-RDTXWAMCSA-N Yes check.svgY
   (verify)

Lysergic acid diethylamide (LSD), [lower-alpha 1] also known colloquially as acid, is a potent psychedelic drug. [12] Effects typically include intensified thoughts, emotions, and sensory perception. [13] At sufficiently high dosages LSD manifests primarily mental, visual, as well as auditory, hallucinations. [14] [15] Dilated pupils, increased blood pressure, and increased body temperature are typical. [16] Effects typically begin within half an hour and can last for up to 20 hours. [16] [17] LSD is also capable of causing mystical experiences and ego dissolution. [18] [15] It is used mainly as a recreational drug or for spiritual reasons. [16] [19] LSD is both the prototypical psychedelic and one of the "classical" psychedelics, being the psychedelics with the greatest scientific and cultural significance. [12] LSD is typically either swallowed or held under the tongue. [13] It is most often sold on blotter paper and less commonly as tablets, in a watery solution or in gelatin squares called panes. [16]

Contents

LSD is considered to be non-addictive with low potential for abuse. [20] [21] Frequent use rapidly builds tolerance, requiring exponentially larger doses to feel an effect. Adverse psychological reactions are possible, such as anxiety, paranoia, and delusions. [7] LSD is active in small amounts relative to other psychoactive compounds with doses measured in micrograms. [22] It is possible for LSD to induce either intermittent or chronic visual hallucinations, in spite of no further use. Common effects include visual snow and palinopsia. In cases where this causes distress or impairment it is diagnosed as hallucinogen persisting perception disorder (HPPD). [23] [24] While overdose from LSD is unknown, LSD can cause injury and death as a result of accidents stemming from psychological impairment. [16] [12] The effects of LSD are thought to stem primarily from it being an agonist at the 5-HT2A (serotonin) receptor, and while exactly how LSD exerts its effects by agonism at this receptor is still not fully known, corresponding increased glutamatergic neurotransmission and reduced default mode network activity are thought to be key mechanisms of action. [21] [7] [12] [25] [26] In addition to serotonin, LSD also binds to dopamine D1 and D2 receptors, which is why LSD tends to be more stimulating than compounds such as psilocybin. [27] [28] In pure form, LSD is clear or white in color, has no smell, and is crystalline. [13] It breaks down with exposure to ultraviolet light. [16]

LSD was first synthesized by Swiss chemist Albert Hofmann in 1938 from lysergic acid, a chemical derived from the hydrolysis of ergotamine, an alkaloid found in ergot, a fungus that infects grain. [16] [23] LSD was the 25th of various lysergamides Hofmann synthesized from lysergic acid while trying to develop a new analeptic, hence the alternate name LSD-25. Hofmann discovered its effects in humans in 1943, after unintentionally ingesting an unknown amount, possibly absorbing it through his skin. [29] [30] [31] LSD was subject to exceptional interest within the field of psychiatry in the 1950s and early 1960s, with Sandoz distributing LSD to researchers under the trademark name Delysid in an attempt to find a marketable use for it. [30]

LSD-assisted psychotherapy was used in the 1950s and early 1960s by psychiatrists such as Humphry Osmond, who pioneered the application of LSD to the treatment of alcoholism, with promising results. [32] [30] [33] [34] Osmond coined the term "psychedelic" (lit. mind manifesting) as a term for LSD and related hallucinogens, superseding the previously held "psychotomimetic" model in which LSD was believed to mimic schizophrenia. In contrast to schizophrenia, LSD induces transcendental experiences with lasting psychological benefit. [12] [30] During this time, the Central Intelligence Agency (CIA) began using LSD in the research project Project MKUltra, which used psychoactive substances to aid interrogation. The CIA administered LSD to unwitting test subjects in order to observe how they would react, and the most well-known example of this is Operation Midnight Climax. [30] LSD was one of several psychoactive substances evaluated by the U.S. Army Chemical Corps as possible non-lethal incapacitants in the Edgewood Arsenal human experiments. [30]

In the 1960s, LSD and other psychedelics were adopted by, and became synonymous with, the counterculture movement due to their perceived ability to expand consciousness. This resulted in LSD being viewed as a cultural threat to American values and the Vietnam war effort, and it was designated as a Schedule I (illegal for medical as well as recreational use) substance in 1968. [35] It was listed as a Schedule 1 controlled substance by the United Nations in 1971 and currently has no approved medical uses. [16] As of 2017, about 10% of people in the United States have used LSD at some point in their lives, while 0.7% have used it in the last year. [36] It was most popular in the 1960s to 1980s. [16] The use of LSD among US adults increased 56.4% from 2015 to 2018. [37]

Uses

Recreational

LSD is commonly used as a recreational drug in the company of friends, in large crowds, or by oneself. [38]

Spiritual

LSD can catalyze intense spiritual experiences and is thus considered an entheogen. Some users have reported out of body experiences. In 1966, Timothy Leary established the League for Spiritual Discovery with LSD as its sacrament. [39] [40] 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. [41]

Medical

LSD currently has no approved uses in medicine. [42] [43] A meta analysis concluded that a single dose was effective at reducing alcohol consumption in alcoholism. [34] LSD has also been studied in depression, anxiety, [44] [45] and drug dependence, with positive preliminary results. [46] [47]

Effects

Some symptoms reported for LSD Possible physical effects of lysergic acid diethylamide (LSD).svg
Some symptoms reported for LSD

LSD is exceptionally potent, with as little as 20 μg capable of producing a noticeable effect. [16]

Patient with Mydriasis due to usage of LSD Mydriasis due to LSD usage.jpg
Patient with Mydriasis due to usage of LSD

Physical

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. [16]

Psychological

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 can last up to 20 hours in high doses. Users may also experience an "afterglow" of improved mood or perceived mental state for days or even weeks after ingestion in some experiences. [50] 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. [51] [52] Negative experiences, colloquially known as "bad trips," evoke an array of dark emotions, such as irrational fear, anxiety, panic, paranoia, dread, distrustfulness, hopelessness, and even suicidal ideation. [53] 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 (colloquially referred to as "set and setting") to minimize the risk of a bad trip. [54] [55]

Sensory

LSD causes an animated sensory experience of senses, emotions, memories, time, and awareness for 6 to 20 hours, depending on dosage and tolerance. [17] 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 also typical. [56] [57]

Some sensory effects may include an experience of radiant or more vibrant colors, objects and surfaces appearing to ripple, "breathe," or otherwise move, spinning fractals superimposed on one's vision, colored patterns behind closed eyelids, an altered sense of time, geometric patterns emerging on walls and other textured objects, and morphing objects. [56] Some users also report a strong metallic taste for the duration of the effects. [58] Food's texture or taste may be different, and users may also have an aversion to foods that they would normally enjoy. Similar effects have also been found in rats. [59]

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. [60] Many of the basic visual effects resemble the phosphenes seen after applying pressure to the eye and have also been studied as form constants. Sometimes these effects and patterns can be changed when concentrated on, or can change based on thoughts, emotions or music. [61] 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.

Adverse effects

Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. LSD was ranked 14th in dependence, 15th in physical harm, and 13th in social harm. Rational harm assessment of drugs radar plot.svg
Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. LSD was ranked 14th in dependence, 15th in physical harm, and 13th in social harm.

Out of the 20 drugs ranked in order of individual and societal harm by David Nutt, LSD was third to last, or approximately 1/10th as harmful as alcohol. The most significant adverse effect of LSD was impairment of mental functioning while intoxicated. [63]

Mental disorders

LSD may trigger panic attacks or feelings of extreme anxiety, known colloquially as a "bad trip". Although population studies have not found an increased incidence of mental illness in psychedelic drug users overall, with psychedelic users actually having lower rates of depression and substance abuse than the control group, [64] [65] there is evidence that people with severe mental illnesses like schizophrenia have a higher likelihood of experiencing adverse effects from taking LSD. [66]

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, [67] research from the 1960s suggests that both mentally ill and healthy people are more suggestible while under its influence. [68] [69] [70]

Flashbacks

"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 days or months after hallucinogen use. [71] [72] Individuals with hallucinogen persisting perception disorder experience intermittent or chronic flashbacks that cause distress or impairment in life and work. [24]

The etiology of the "flashback" phenomenon appears to be varied. Some researchers such as Krebs and Johansen (2015 [73] ) attribute at least some of the cases to be related to somatic symptom disorder, when people fixate on normal somatic experiences and perceptions that they weren't aware of before consuming the drug. Other researchers relate it to an associative reaction to a contextual cue akin to what people that have faced trauma or strongly emotional experiences face when receiving a triggering stimulus (Holland and Passie 2011 [74] ). There is no consensus on what are the risk factors but some researchers theorize that pre-existing psychopathologies may be a significant contributor (Abraham and Duffy 1996 [75] )

The prevalence of HPPD is difficult to estimate but appears to be very rare (Halpern et al 2016 [76] ), with estimates ranging from 1 in 20 users for the transitory and less serious type 1 HPPD, to 1 in 50,000 users for the more concerning type 2 HPPD. [77]

Contrary to rumors circulating the internet that LSD is stored in the spinal cord or other parts of your body long-term, [78] the pharmacological evidence (Passie et all 2008 [79] ) shows LSD has a short half-life of 175 minutes, undergoing enzymatic metabolism into more polar and therefore water-soluble compounds such as 2-oxo-3-hydroxy-LSD that are eliminated through the urine. No evidence of long term storage of LSD in the body exists.

Cancer and pregnancy

The mutagenic potential of LSD is unclear. Overall, the evidence seems to point to limited or no effect at commonly used doses. [80] Studies showed no evidence of teratogenic or mutagenic effects. [7] [81]

Addiction and tolerance

Tolerance to LSD builds up with consistent use [82] and cross-tolerance has been demonstrated between LSD, mescaline, [83] and psilocybin. [84] Researchers believe that tolerance returns to baseline after two weeks of not using psychedelics. [85]

The NIH states that LSD is addictive, [23] while most other sources state it is not. [20] [86] 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. [20] There are no recorded successful attempts to train animals to self-administer LSD in laboratory settings. [21]

Overdose

A report in 2008 stated that, though there was no "comprehensive review since the 1950s" and "almost no legal clinical research" since the 1970s, there had been "no documented human deaths from an LSD overdose". Eight individuals who accidentally consumed very high amounts by mistaking LSD for cocaine developed comatose states, hyperthermia, vomiting, gastric bleeding, and respiratory problems—all survived, however, with hospital treatment and without residual effects. [7] According to more recent reports, several behavioral-related fatalities and suicides have occurred due to LSD. [87] [88] 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 not recommended because they may have adverse effects. LSD is rapidly absorbed, so activated charcoal and emptying of the stomach is 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. [89]

Massive doses "should be treated with supportive care, including respiratory support and endotracheal intubation if needed. Hypertension [high blood pressure], tachycardia [rapid heart-beat], and hyperthermia should be treated symptomatically. Hypotension [low blood pressure] should be treated initially with fluids and subsequently with pressors if required." "Intravenous administration of anticoagulants, vasodilators, and sympatholytics may be useful" when treating ergotism. [89]

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
Dissociation constant of various serotonin receptors
Receptor
Ki(nM)
5-HT1A
1.1
5-HT2A
2.9
5-HT2B
4.9
5-HT2C
23
5-HT5A
9
5-HT6
2.3 LSDaffinities.GIF
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
Dissociation constant of various serotonin receptors
ReceptorKi(nM)
5-HT1A 1.1
5-HT2A 2.9
5-HT2B 4.9
5-HT2C 23
5-HT5A 9
5-HT6 2.3

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. [28] [90]

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. [86] 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). [91] [92] Although not present in humans, 5-HT5B receptors found in rodents also have a high affinity for LSD. [93] The psychedelic effects of LSD are attributed to cross-activation of 5-HT2A receptor heteromers. [94] 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. [95]

Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex [86] and therefore excitation in this area, specifically in layers IV and V. [96] LSD, like many other drugs of recreational use, has been shown to activate DARPP-32-related pathways. [97] The drug enhances dopamine D2 receptor protomer recognition and signaling of D2–5-HT2A receptor complexes, [27] which may contribute to its psychotropic effects. [27] LSD has been shown to have low affinity for H1 receptors, displaying antihistamine effects. [98] [99] [100]

LSD is a biased agonist that induces a conformation in serotonin receptors that preferentially recruits β-arrestin over activating G proteins. [101] [102] LSD also has an exceptionally long residence time when bound to serotonin receptors lasting hours, consistent with the long lasting effects of LSD despite its relatively rapid clearance. [101] [102] A crystal structure of 5-HT2B bound to LSD reveals an extracellular loop that forms a lid over the diethylamide end of the binding cavity which explains the slow rate of LSD unbinding from serotonin receptors. [103] [104] [105] The related lysergamide lysergic acid amide (LSA) that lacks the diethylamide moiety is far less hallucinogenic in comparison. [105]

Pharmacokinetics

The effects of LSD normally last between 6 and 12 hours depending on dosage, tolerance, and age. [106] The Sandoz prospectus for "Delysid" warned: "intermittent disturbances of affect may occasionally persist for several days." [107] Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175 minutes (about 3 hours). [91] 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. [108]

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] Concentrations of LSD decreased following first-order kinetics with a half-life of 3.6±0.9 hours and a terminal half-life of 8.9±5.9 hours. [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]

Chemistry

The four possible stereoisomers of LSD. Only (+)-LSD is psychoactive. Lysergide stereoisomers structural formulae v.2.png
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,[ citation needed ] 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. [106] LSD is strongly fluorescent and will glow bluish-white under UV light.

Synthesis

LSD is an ergoline derivative. It is commonly synthesized by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride [109] and peptide coupling reagents. [100] 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. [110] Lysergic acid can also be produced synthetically, although these processes are not used in clandestine manufacture due to their low yields and high complexity. [111] [112]

Research

The precursor for LSD, lysergic acid, has been produced by GMO baker's yeast. [113]

Dosage

White on White blotters (WoW) for sublingual administration 10 strip.jpg
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. [114] [115] The practice of using sub-threshold doses is called microdosing. [116] 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 (0.0001 g) or less of LSD. [107]

In the mid-1960s, the most important black market LSD manufacturer (Owsley Stanley) distributed LSD at a standard concentration of 270 µg, [117] 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, [118] and even more in the 2000s (decade). [117] [119]

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." [106]

LSD has two labile protons at the tertiary stereogenic C5 and C8 positions, rendering these centers 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.[ citation needed ]

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. [106] 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 UV or other kinds of light. LSD often converts to "lumi-LSD," which is inactive in human beings. [106]

A controlled study was undertaken to determine the stability of LSD in pooled urine samples. [120] 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

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. [121]

Maximum plasma concentrations were found to be 1.4 and 1.5 hours after oral administration of 100µg and 200µg respectively with a plasma half-life of 2.6 hours (ranging from 2.2–3.4 hours among 40 human test subjects). [122]

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

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 [123]

LSD was first synthesized on November 16, 1938 [124] 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. The abbreviation "LSD" is from the German "Lysergsäurediethylamid". [125]

LSD's psychedelic properties were discovered 5 years later when Hofmann himself accidentally ingested an unknown quantity of the chemical. [126] The first intentional ingestion of LSD occurred on April 19, 1943, [127] 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. [128] Sandoz Laboratories introduced LSD as a psychiatric drug in 1947 and marketed LSD as a psychiatric panacea, hailing it "as a cure for everything from schizophrenia to criminal behavior, 'sexual perversions', and alcoholism." [129] Sandoz would send the drug for free to researchers investigating its effects. [29]

Albert Hofmann in 2006 Albert Hofmann.jpg
Albert Hofmann in 2006
'Effects of Lysergic Acid Diethylamide (LSD) on Troops Marching' – 16mm film produced by the United States military circa 1958

Beginning in the 1950s, the US Central Intelligence Agency (CIA) began a research program code named Project MKUltra. The CIA introduced LSD to the United States, purchasing the entire world's supply for $240,000 and propagating the LSD through CIA front organizations to American hospitals, clinics, prisons and research centers. [130] 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 on LSD expired [118] and the Czech company Spofa began to produce the substance. [29] Sandoz stopped the production and distribution in 1965. [29]

Several figures, including Aldous Huxley, Timothy Leary, and Al Hubbard, had begun to advocate the consumption of LSD. LSD became central to the counterculture of the 1960s. [131] 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, [132] [133] and according to L. R. Veysey they profoundly influenced the thinking of the new generation of youth. [134]

On October 24, 1968, possession of LSD was made illegal in the United States. [135] 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. [136]

In November 2020, Oregon became the first US state to decriminalize possession of small amounts of LSD after voters approved Ballot Measure 110. [137]

Society and culture

Counterculture

Psychedelic art attempts to capture the visions experienced on a psychedelic trip. Hell0 Darinzo.jpg
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. [138] 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. [139] [140] 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). [141]

In San Francisco's Haight-Ashbury neighborhood, brothers Ron and Jay Thelin opened the Psychedelic Shop in January 1966. [142] 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. [143]

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.

Music and art

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." [144]

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, [145] the Rolling Stones, [146] the Moody Blues, [147] the Small Faces, [148] Syd Barrett, [149] 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. [150] Electric guitars are used to create feedback, and are played through wah wah and fuzzbox effect pedals. [151] Elaborate studio effects are often used, such as backwards tapes, panning, phasing, long delay loops, and extreme reverb. [152] In the 1960s there was a use of primitive electronic instruments such as early synthesizers and the theremin. [153] [154] Later forms of electronic psychedelia also employed repetitive computer-generated beats. [155] 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. [156] [157] [158]

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. [159]

Australia

LSD is a Schedule 9 prohibited substance in Australia under the Poisons Standard (February 2017). [160] 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. [160]

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. [161]

Canada

In Canada, LSD is a controlled substance under Schedule III of the Controlled Drugs and Substances Act. [53] 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 offence and liable to imprisonment for a term not exceeding 3 years. Possession for purpose of trafficking is an indictable offence 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 recognized legitimate uses and possession of the drug without a licence 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." [162]

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. [163]

United States

LSD is Schedule I in the United States, according to the Controlled Substances Act of 1970. [164] 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. [165]

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. [166]

Lysergic acid and lysergic acid amide, LSD precursors, are both classified in Schedule III of the Controlled Substances Act. [167] Ergotamine tartrate, a precursor to lysergic acid, is regulated under the Chemical Diversion and Trafficking Act.

Personal possession of small amounts of drugs including LSD (40 units or less) was decriminalized in the U.S. state of Oregon on February 1, 2021. [168] This came as a result of the passing of 2020 Oregon Ballot Measure 110. The movement to decriminalize psychedelics in the United States includes LSD in the ongoing effort in California. In November 2020, California Senator Scott Wiener introduced a bill to decriminalize psychedelics such as psilocybin, ayahuasca, ibogaine, and LSD. In April 2021, the bill has been approved by the Senates Public Safety Committee and the Health Committee, in May 2021, it was cleared by the Senate Appropriations Committee and approved by the California Senate, and in June 2021, advanced by the Assembly Public Safety Committee. [169] In mid 2022, the bill was gutted by committee and limited to organizing a study. Wiener announced that he is planning to reintroduce the bill in 2023. [170]

Mexico

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. [171] Many[ vague ] 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. [172]

Czech Republic

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. [173]

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. [173]

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. [174]

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. [175]

Ecuador

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. [176] 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. [176] [177] [178] The "CONSEP established, at their latest general meeting, that the 0.020 milligrams of LSD shall be considered the maximum consumer amount. [179]

Economics

Price

The street price of a single dose of LSD can be anywhere from $2 to $50. [180] In Europe, as of 2011, the typical cost of a dose was between 4.50 and 25. [16]

Production

Glassware seized by the DEA LSDLabGlassware.jpg
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 around 50–60 million doses at 100 µg. Because the masses involved are so small, concealing and transporting illicit LSD is much easier than smuggling cocaine, cannabis, or other illegal drugs. [181]

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. [181] [ dead link ]

Forms
Five doses of LSD, often called a "five strip" 5 LSD blotters.png
Five doses of LSD, often called a "five strip"

LSD is produced in crystalline form and is 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. [182]

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." [183]

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. [182] [183] More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975. [183] 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. [182] 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. [51] [184] Authorities have encountered the drug in other forms—including powder or crystal, and capsule. [185]

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. [186] [187]

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. [188]

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. [189]

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. [144]

Mimics
LSD blotter acid mimic actually containing DOC Docpsychadelic.jpg
LSD blotter acid mimic actually containing DOC
Different blotters which could possibly be mimics Lysergic.JPG
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, [190] [191] a mixture of DOC and DOI, [192] 25I-NBOMe, [193] and a mixture of DOC and DOB. [194] Many mimics are toxic in comparatively small doses, or have extremely different safety profiles. Many 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. [195] 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. [196] Several deaths have been attributed to 25I-NBOMe. [197] [198] [199] [200]

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. [201] New clinical LSD experiments in humans started in 2009 for the first time in 35 years. [202] As it is illegal in many areas of the world, potential medical uses are difficult to study. [42]

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." [203] More recently, experimental uses of LSD have included the treatment of alcoholism, [204] pain and cluster headache relief, [7] and prospective studies on depression. [205] [206] There is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits. [207] [208] [209]

Psychedelic therapy

In the 1950s and 1960s LSD was used in psychiatry to enhance psychotherapy known as psychedelic therapy. Some psychiatrists, such as Ronald A. Sandison who pioneered its use at Powick Hospital in England, believed LSD was especially useful at helping patients to "unblock" repressed subconscious material through other psychotherapeutic methods, [210] and also for treating alcoholism. [211] [212] [213] One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender," [33] 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. [214] [215]

In recent years organizations like the Multidisciplinary Association for Psychedelic Studies have renewed clinical research of LSD. [216]

It has been proposed that LSD be studied for use in the therapeutic setting particularly in anxiety. [217] [218] [44] [45]

Other uses

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. [219] [220] [221] [52]

Since 2008 there has been ongoing research into using LSD to alleviate anxiety for terminally ill cancer patients coping with their impending deaths. [222] [223] [44]

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. [34]

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

Recently, researchers discovered that LSD is a potent psychoplastogen, a compound capable of promoting rapid and sustained neural plasticity that may have wide-ranging therapeutic benefit. [224] LSD has been shown to increase markers of neuroplasticity in human brain organoids and improve memory performance in human subjects. [225]

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. [226]

Notable individuals

Some notable individuals have commented publicly on their experiences with LSD. [227] [228] Some of these comments date from the era when it was legally available in the US and Europe for non-medical uses, and others pertain to psychiatric treatment in the 1950s and 1960s. Still others describe experiences with illegal LSD, obtained for philosophic, artistic, therapeutic, spiritual, or recreational purposes.

See also

Notes

  1. From the German name Lysergsäure-diethylamid

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25C-NBOMe is a psychedelic drug and derivative of the psychedelic phenethylamine 2C-C. 25C-NBOMe appeared on online vendor sites in 2010 but was not reported in the literature until 2011. It acts as a potent agonist of the 5HT2A receptor, and has been studied in its 11C radiolabelled form as a potential ligand for mapping the distribution of 5-HT2A receptors in the brain, using positron emission tomography (PET). Multiple deaths have occurred from usage of 25C-NBOMe due to the ease of accidental overdose. The long-term toxic effects of the drug have not been researched.

<span class="mw-page-title-main">2-Bromo-LSD</span> Chemical compound

2-Bromo-LSD, also known as BOL-148, is a derivative of lysergic acid invented by Albert Hofmann, as part of the original research from which the closely related compound LSD was also derived. 2-Bromo-LSD was found to be inactive as a psychedelic and so was comparatively little researched for many years, although its similar behavior in the body made it useful for radiolabelling studies. It was found to bind to many of the same receptors as LSD, but acting as a neutral antagonist rather than an agonist. However its generally similar behavior to LSD in some respects has shown to be very useful in one specific area, the treatment of cluster headaches. These debilitating attacks have been known for some time to be amenable to treatment with certain hallucinogenic drugs such as LSD and psilocybin, but because of the illegal status of these drugs and the kind of mental changes they induce, research into their medical use has been slow and therapeutic application limited to very specific circumstances under strict supervision. It had been thought that this specific therapeutic action against cluster headaches was limited to hallucinogenic drugs of this type, and would always present a major barrier to their clinical use. However a serendipitous discovery found that 2-bromo-LSD is also able to produce this therapeutic effect, despite lacking the other effects of LSD. This has led to a resurgence of interest and research into 2-bromo-LSD and its possible medical uses. Some isolated incidents of hallucinogenic responses have been reported, but as with other non-hallucinogenic LSD analogues such as lisuride, this appears to be a rare side effect occurring only in individuals with an as yet unexplained susceptibility to this reaction. 2-Bromo-LSD reportedly attenuates the effects of LSD in humans.

Psychedelic microdosing is the practice of using sub-threshold doses (microdoses) of serotonergic psychedelic drugs in an attempt to improve creativity, boost physical energy level, promote emotional balance, increase performance on problems-solving tasks and to treat anxiety, depression and addiction. The practice of microdosing has become more widespread in the 21st century with more people claiming long-term benefits from the practice.

<span class="mw-page-title-main">1V-LSD</span> Chemical compound

1V-LSD or 1-valeryl-D-lysergic acid diethylamide is a psychotropic substance and a research chemical with psychedelic effects. 1V-LSD is an artificial derivative of natural lysergic acid, which occurs in ergot alkaloids, as well as being an analogue of LSD. 1V-LSD has been sold online until an amendment to the German NpSG was enforced in 2022 which controls 1P-LSD and now 1cP-LSD, 1V-LSD and several other lysergamides.

References

  1. "Definition of "amide"". Collins English Dictionary. Archived from the original on April 2, 2015. Retrieved January 31, 2015.
  2. "American Heritage Dictionary Entry: amide". Ahdictionary.com. Archived from the original on April 2, 2015. Retrieved January 31, 2015.
  3. "amide – definition of amide in English from the Oxford Dictionary". Oxforddictionaries.com. Archived from the original on April 2, 2015. Retrieved January 31, 2015.
  4. Halpern JH, Suzuki J, Huertas PE, Passie T (June 7, 2014). "Hallucinogen Abuse and Dependence". In Price LH, Stolerman IP (eds.). Encyclopedia of Psychopharmacology A Springer Live Reference. Heidelberg, Germany: Springer-Verlag Berlin Heidelberg. pp. 1–5. doi:10.1007/978-3-642-27772-6_43-2. ISBN   978-3-642-27772-6. Hallucinogen abuse and dependence are known complications resulting from ... LSD and psilocybin. Users do not experience withdrawal symptoms, but the general criteria for substance abuse and dependence otherwise apply. Dependence is estimated in approximately 2 % of recent-onset users
  5. 1 2 Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2 ed.). New York: McGraw-Hill Medical. p. 375. ISBN   9780071481274. Several other classes of drugs are categorized as drugs of abuse but rarely produce compulsive use. These include psychedelic agents, such as lysergic acid diethylamide (LSD)
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 Dolder PC, Schmid Y, Haschke M, Rentsch KM, Liechti ME (June 2015). "Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans". The International Journal of Neuropsychopharmacology. 19 (1): pyv072. doi:10.1093/ijnp/pyv072. PMC   4772267 . PMID   26108222.
  7. 1 2 3 4 5 6 7 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. PMC   6494066 . PMID   19040555.
  8. Neinstein LS (2008). Adolescent Health Care: A Practical Guide. Lippincott Williams & Wilkins. p. 931. ISBN   9780781792561. Archived from the original on December 26, 2018. Retrieved January 27, 2017.
  9. 1 2 3 4 5 6 7 8 9 10 Mucke HA (July 2016). "From Psychiatry to Flower Power and Back Again: The Amazing Story of Lysergic Acid Diethylamide". Assay and Drug Development Technologies. 14 (5): 276–281. doi:10.1089/adt.2016.747. PMID   27392130.
  10. Kranzler HR, Ciraulo DA (April 2, 2007). Clinical Manual of Addiction Psychopharmacology. American Psychiatric Pub. p. 216. ISBN   9781585626632. Archived from the original on December 26, 2018. Retrieved January 27, 2017.
  11. "3,4-Methylenedioxymethamphetamine". pubchem.ncbi.nlm.nih.gov.
  12. 1 2 3 4 5 Nichols DE (April 2016). Barker EL (ed.). "Psychedelics". Pharmacological Reviews. 68 (2): 264–355. doi:10.1124/pr.115.011478. PMC   4813425 . PMID   26841800.
  13. 1 2 3 "What are hallucinogens?". National Institute of Drug Abuse. January 2016. Archived from the original on April 17, 2016. Retrieved April 24, 2016.
  14. Leptourgos P, Fortier-Davy M, Carhart-Harris R, Corlett PR, Dupuis D, Halberstadt AL, et al. (December 2020). "Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison". Schizophrenia Bulletin. 46 (6): 1396–1408. doi:10.1093/schbul/sbaa117. PMC   7707069 . PMID   32944778. Thalamocortical connectivity was found altered in psychedelic states. Specifically, LSD was found to selectively increase effective connectivity from the thalamus to certain DMN areas, while other connections are attenuated. Furthermore, increased thalamic connectivity with the right fusiform gyrus and the anterior insula correlated with visual and auditory hallucinations (AH), respectively.
  15. 1 2 Holze F, Vizeli P, Ley L, Müller F, Dolder P, Stocker M, et al. (February 2021). "Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects". Neuropsychopharmacology. 46 (3): 537–544. doi:10.1038/s41386-020-00883-6. PMC   8027607 . PMID   33059356.
  16. 1 2 3 4 5 6 7 8 9 10 11 12 "LSD profile (chemistry, effects, other names, synthesis, mode of use, pharmacology, medical use, control status)". EMCDDA. Archived from the original on April 28, 2021. Retrieved July 14, 2018.
  17. 1 2 Sloat S (January 27, 2017). "This is Why You Can't Escape an Hours-Long Acid Trip". Inverse. Archived from the original on June 11, 2021. Retrieved February 3, 2020.
  18. Liechti ME, Dolder PC, Schmid Y (May 2017). "Alterations of consciousness and mystical-type experiences after acute LSD in humans". Psychopharmacology. 234 (9–10): 1499–1510. doi:10.1007/s00213-016-4453-0. PMC   5420386 . PMID   27714429.
  19. Gershon L (July 19, 2016). "How LSD Went From Research to Religion". JSTOR Daily. Archived from the original on January 28, 2021. Retrieved July 14, 2018.
  20. 1 2 3 Lüscher C, Ungless MA (November 2006). "The mechanistic classification of addictive drugs". PLOS Medicine. 3 (11): e437. doi:10.1371/journal.pmed.0030437. PMC   1635740 . PMID   17105338.
  21. 1 2 3 Nichols DE (February 2004). "Hallucinogens". Pharmacology & Therapeutics. 101 (2): 131–181. doi:10.1016/j.pharmthera.2003.11.002. PMID   14761703.
  22. Appel JB, Whitehead WE, Freedman DX (July 1968). "Motivation and the behavioral effects of LSD". Psychonomic Science. 12 (7): 305–306. doi:10.3758/BF03331322. ISSN   0033-3131. S2CID   144527673.
  23. 1 2 3 "Commonly Abused Drugs Charts". National Institute on Drug Abuse. July 2, 2018. Archived from the original on March 1, 2020. Retrieved July 14, 2018.
  24. 1 2 Halpern JH, Lerner AG, Passie T (2018). A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 333–360. doi:10.1007/7854_2016_457. ISBN   978-3-662-55878-2. PMID   27822679.
  25. Girn M, Roseman L, Bernhardt B, Smallwood J, Carhart-Harris R, Spreng RN (May 3, 2020). "Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex". bioRxiv. doi:10.1101/2020.05.01.072314. S2CID   233346402.
  26. Carhart-Harris RL, Muthukumaraswamy S, Roseman L, Kaelen M, Droog W, Murphy K, et al. (April 2016). "Neural correlates of the LSD experience revealed by multimodal neuroimaging". Proceedings of the National Academy of Sciences of the United States of America. 113 (17): 4853–4858. Bibcode:2016PNAS..113.4853C. doi: 10.1073/pnas.1518377113 . PMC   4855588 . PMID   27071089.
  27. 1 2 3 Borroto-Escuela DO, Romero-Fernandez W, Narvaez M, Oflijan J, Agnati LF, Fuxe K (January 2014). "Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes". Biochemical and Biophysical Research Communications. 443 (1): 278–84. doi:10.1016/j.bbrc.2013.11.104. PMID   24309097.
  28. 1 2 Marona-Lewicka D, Thisted RA, Nichols DE (July 2005). "Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis". Psychopharmacology. 180 (3): 427–35. doi:10.1007/s00213-005-2183-9. PMID   15723230. S2CID   23565306.
  29. 1 2 3 4 Hofmann A (2009). LSD, my problem child: reflections on sacred drugs, mysticism, and science (Fourth ed.). Santa Cruz, CA: Multidisciplinary Association for Psychedelic Studies. ISBN   978-0-9798622-2-9. OCLC   610059315.
  30. 1 2 3 4 5 6 Lee MA, Shlain B (1992). Acid dreams: the complete social history of LSD: the CIA, the Sixties, and beyond. New York: Grove Weidenfeld. ISBN   0-8021-3062-3. OCLC   25281992.
  31. Ettinger RH (2017). Psychopharmacology. Psychology Press. p. 226. ISBN   978-1-351-97870-5. Archived from the original on September 27, 2021. Retrieved September 27, 2021.
  32. "Psychiatric Research with Hallucinogens". www.druglibrary.org. Archived from the original on July 26, 2021. Retrieved July 26, 2021.
  33. 1 2 Chwelos N, Blewett DB, Smith CM, Hoffer A (September 1959). "Use of d-lysergic acid diethylamide in the treatment of alcoholism". Quarterly Journal of Studies on Alcohol. 20 (3): 577–590. doi:10.15288/qjsa.1959.20.577. PMID   13810249.
  34. 1 2 3 Krebs TS, Johansen PØ (July 2012). "Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials". Journal of Psychopharmacology. 26 (7): 994–1002. doi:10.1177/0269881112439253. PMID   22406913. S2CID   10677273.
  35. United States Congress House Committee on Interstate and Foreign Commerce Subcommittee on Public Health and Welfare (1968). Increased Controls Over Hallucinogens and Other Dangerous Drugs: Hearings Before the Subcommittee on Public Health and Welfare of the Committee on Interstate and Foreign Commerce, House of Representatives, Ninetieth Congress, Second Session, on H.R. 14096, a Bill to Amend the Federal Food, Drug, and Cosmetic Act to Prescribe Penalties for the Possession of LSD and Other Hallucinogenic Drugs by Unauthorized Persons : H.R. 15355, a Bill to Amend the Federal Food, Drug, and Cosmetic Act by Increasing the Penalties for Illegal Manufacture and Traffic in Hallucinogenic Drugs (including LSD) and Other Depressant and Stimulant Drugs, Including Possession of Such Drugs for Sale Or Other Disposal to Another, and by Making it a Misdemeanor to Possess Any Such Drug for One's Own Use Except when Prescribed Or Furnished by a Licensed Practitioner, and for Other Purposes (and Similar Bills), February 19, 26, 276, and March 19, 1968. U.S. Government Printing Office. Archived from the original on July 13, 2020. Retrieved August 3, 2021.
  36. National Institute on Drug Abuse. "Hallucinogens". Archived from the original on June 3, 2020. Retrieved July 14, 2018.
  37. Yockey RA, Vidourek RA, King KA (July 2020). "Trends in LSD use among US adults: 2015-2018". Drug and Alcohol Dependence. 212: 108071. doi:10.1016/j.drugalcdep.2020.108071. PMID   32450479. S2CID   218893155.
  38. "DrugFacts: Hallucinogens – LSD, Peyote, Psilocybin, and PCP". National Institute on Drug Abuse. December 2014. Archived from the original on February 16, 2015. Retrieved February 17, 2015.
  39. Fahey D, Miller JS (eds.). Alcohol and Drugs in North America: A Historical Encyclopedia. p. 375. ISBN   978-1-59884-478-8.
  40. San Francisco Chronicle September 20, 1966 Page One
  41. Grof S, Grof JH (1979). Realms of the Human Unconscious (Observations from LSD Research). London: Souvenir Press (E & A) Ltd. pp. 13–14. ISBN   978-0-285-64882-1. Archived from the original on October 18, 2007. Retrieved November 18, 2007.
  42. 1 2 Nutt DJ, King LA, Nichols DE (August 2013). "Effects of Schedule I drug laws on neuroscience research and treatment innovation". Nature Reviews. Neuroscience. 14 (8): 577–85. doi:10.1038/nrn3530. PMID   23756634. S2CID   1956833.
  43. Campbell D (July 23, 2016). "Scientists study possible health benefits of LSD and ecstasy | Science". The Guardian. Archived from the original on July 23, 2016. Retrieved 2016-07-23.
  44. 1 2 3 Lustberg D (October 14, 2022). "Acid for Anxiety: Fast and Lasting Anxiolytic Effects of LSD". Psychedelic Science Review. Retrieved December 1, 2022.
  45. 1 2 Holze F, Gasser P, Müller F, Dolder PC, Liechti ME (September 2022). "Lysergic Acid Diethylamide-Assisted Therapy in Patients With Anxiety With and Without a Life-Threatening Illness: A Randomized, Double-Blind, Placebo-Controlled Phase II Study". Biological Psychiatry. 93 (3): 215–223. doi:10.1016/j.biopsych.2022.08.025. PMID   36266118. S2CID   252095586.
  46. Dos Santos RG, Osório FL, Crippa JA, Riba J, Zuardi AW, Hallak JE (June 2016). "Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years". Therapeutic Advances in Psychopharmacology. 6 (3): 193–213. doi:10.1177/2045125316638008. PMC   4910400 . PMID   27354908.
  47. "History of LSD Therapy". druglibrary.org. Retrieved November 7, 2022.
  48. "Hallucinogens – LSD, Peyote, Psilocybin, and PCP". NIDA InfoFacts. The National Institute on Drug Abuse (NIDA). June 2009. Archived from the original on November 21, 2009.
  49. Schiff PL (October 2006). "Ergot and its alkaloids". American Journal of Pharmaceutical Education. 70 (5): 98. doi:10.5688/aj700598. PMC   1637017 . PMID   17149427.
  50. Majić T, Schmidt TT, Gallinat J (March 2015). "Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences?". Journal of Psychopharmacology. 29 (3): 241–53. doi:10.1177/0269881114568040. PMID   25670401. S2CID   16483172.
  51. 1 2 Honig D. "Frequently Asked Questions". Erowid . Archived from the original on February 12, 2016.
  52. 1 2 McGlothlin W, Cohen S, McGlothlin MS (November 1967). "Long lasting effects of LSD on normals" (PDF). Archives of General Psychiatry. 17 (5): 521–32. doi:10.1001/archpsyc.1967.01730290009002. PMID   6054248. Archived from the original (PDF) on April 30, 2011.
  53. 1 2 Canadian government (1996). "Controlled Drugs and Substances Act". Justice Laws. Canadian Department of Justice. Archived from the original on December 15, 2013. Retrieved December 15, 2013.
  54. Rogge T (May 21, 2014), Substance use – LSD, MedlinePlus, U.S. National Library of Medicine, archived from the original on July 28, 2016, retrieved July 14, 2016
  55. CESAR (October 29, 2013), LSD, Center for Substance Abuse Research, University of Maryland, archived from the original on July 15, 2016, retrieved July 14, 2016
  56. 1 2 Linton HB, Langs RJ (1962). "Subjective Reactions to Lysergic Acid Diethylamide (LSD-25)" (PDF). Arch. Gen. Psychiatry. 6 (5): 352–68. doi:10.1001/archpsyc.1962.01710230020003. Archived (PDF) from the original on November 18, 2015.
  57. Katz MM, Waskow IE, Olsson J (February 1968). "Characterizing the psychological state produced by LSD". Journal of Abnormal Psychology. 73 (1): 1–14. CiteSeerX   10.1.1.409.4030 . doi:10.1037/h0020114. PMID   5639999.
  58. Hofmann A. "5. From Remedy to Inebriant". LSD: My Problem Child. Archived from the original on July 17, 2015. ... taste of metal on the palate.
  59. Parker LA (June 1996). "LSD produces place preference and flavor avoidance but does not produce flavor aversion in rats". Behavioral Neuroscience. 110 (3): 503–8. doi:10.1037/0735-7044.110.3.503. PMID   8888996.
  60. Oster G (1966). "Moiré patterns and visual hallucinations" (PDF). Psychedelic Review. 7: 33–40. Archived from the original (PDF) on October 16, 2015.
  61. Kaelen M, Roseman L, Kahan J, Santos-Ribeiro A, Orban C, Lorenz R, et al. (July 2016). "LSD modulates music-induced imagery via changes in parahippocampal connectivity". European Neuropsychopharmacology. 26 (7): 1099–109. doi:10.1016/j.euroneuro.2016.03.018. PMID   27084302. S2CID   24037275.
  62. Nutt D, King LA, Saulsbury W, Blakemore C (March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse". Lancet. 369 (9566): 1047–53. doi:10.1016/s0140-6736(07)60464-4. PMID   17382831. S2CID   5903121.
  63. Nutt DJ, King LA, Phillips LD (November 2010). "Drug harms in the UK: a multicriteria decision analysis". Lancet. 376 (9752): 1558–65. CiteSeerX   10.1.1.690.1283 . doi:10.1016/s0140-6736(10)61462-6. PMID   21036393. S2CID   5667719.
  64. Krebs TS, Johansen PØ (August 19, 2013). Lu L (ed.). "Psychedelics and mental health: a population study". PLOS ONE. 8 (8): e63972. Bibcode:2013PLoSO...863972K. doi: 10.1371/journal.pone.0063972 . PMC   3747247 . PMID   23976938.
  65. Johansen PØ, Krebs TS (March 2015). "Psychedelics not linked to mental health problems or suicidal behavior: a population study". Journal of Psychopharmacology. 29 (3): 270–9. doi:10.1177/0269881114568039. PMID   25744618. S2CID   2025731.
  66. Murray RM, Paparelli A, Morrison PD, Marconi A, Di Forti M (October 2013), "What can we learn about schizophrenia from studying the human model, drug-induced psychosis?", American Journal of Medical Genetics Part B, 162 (7, Special Issue: Identifying the Origins of Mental Illness: A Festschrift in Honor of Ming T. Tsuang): 661–670, doi:10.1002/ajmg.b.32177, PMID   24132898, S2CID   205326399
  67. Rockefeller IV JD (December 8, 1994). "Is Military Research Hazardous to Veterans Health? Lessons Spanning Half A Century, part F. HALLUCINOGENS". West Virginia: 103rd Congress, 2nd Session-S. Prt. 103-97; Staff Report prepared for the committee on veterans' affairs. Archived from the original on August 13, 2006. Retrieved December 13, 2018.
  68. Middlefell R (March 1967). "The effects of LSD on body sway suggestibility in a group of hospital patients" (PDF). The British Journal of Psychiatry. 113 (496): 277–80. doi:10.1192/bjp.113.496.277. PMID   6029626. S2CID   19439549. Archived from the original (PDF) on April 30, 2011.
  69. Sjoberg BM, Hollister LE (November 1965). "The effects of psychotomimetic drugs on primary suggestibility". Psychopharmacologia. 8 (4): 251–62. doi:10.1007/BF00407857. PMID   5885648. S2CID   15249061.
  70. "LSD, Suggestibility, and Personality Change". Psychology Today. Archived from the original on August 28, 2021. Retrieved May 13, 2020.
  71. Halpern JH, Pope HG (March 2003). "Hallucinogen persisting perception disorder: what do we know after 50 years?". Drug and Alcohol Dependence. 69 (2): 109–19. doi:10.1016/S0376-8716(02)00306-X. PMID   12609692.
  72. Müller F, Kraus E, Holze F, Becker A, Ley L, Schmid Y, et al. (January 2022). "Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants". Psychopharmacology. 239 (6): 1933–1943. doi:10.1007/s00213-022-06066-z. PMC   9166883 . PMID   35076721. S2CID   246276633.
  73. Johansen PØ, Krebs TS (March 2015). "Psychedelics not linked to mental health problems or suicidal behavior: a population study". Journal of Psychopharmacology. 29 (3): 270–279. doi:10.1177/0269881114568039. PMID   25744618. S2CID   2025731.
  74. Holland D, Passie T (2011) Flashback-Phaenomene als Nachwirkung von Halluzinogeneinnahme VWB-Verlag, Berlin
  75. Abraham HD, Duffy FH (October 1996). "Stable quantitative EEG difference in post-LSD visual disorder by split-half analysis: evidence for disinhibition". Psychiatry Research. 67 (3): 173–87. doi:10.1016/0925-4927(96)02833-8. PMID   8912957. S2CID   7587687.
  76. Halpern JH, Lerner AG, Passie T (2018). "A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD". Current Topics in Behavioral Neurosciences. 36: 333–360. doi:10.1007/7854_2016_457. ISBN   978-3-662-55878-2. PMID   27822679.
  77. Halpern JH, Lerner AG, Passie T (2018). "A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD". Current Topics in Behavioral Neurosciences. 36: 333–360. doi:10.1007/7854_2016_457. ISBN   978-3-662-55878-2. PMID   27822679.
  78. "Does LSD Stay in Your Spinal Cord Forever?". High Times. January 12, 2015.
  79. 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. PMC   6494066 . PMID   19040555.
  80. Li JH, Lin LF (November 1998). "Genetic toxicology of abused drugs: a brief review". Mutagenesis. 13 (6): 557–65. doi: 10.1093/mutage/13.6.557 . PMID   9862186.
  81. Ellwood, Beth (October 18, 2022). "Large national survey suggests that the use of psychedelics is not associated with lifetime cancer development". PsyPost. Retrieved December 19, 2022.
  82. Jonas S, Downer JD (October 1964). "Gross behavioural changes in monkeys following administration of LSD-25, and development of tolerance to LSD-25". Psychopharmacologia. 6 (4): 303–6. doi:10.1007/BF00413161. PMID   4953438. S2CID   11768927.
  83. Wolbach AB, Isbell H, Miner EJ (March 1962). "Cross tolerance between mescaline and LSD-25, with a comparison of the mescaline and LSD reactions". Psychopharmacologia. 3: 1–14. doi:10.1007/BF00413101. PMID   14007904. S2CID   23803624. Archived from the original on April 19, 2014. Retrieved December 1, 2007.
  84. Isbell H, Wolbach AB, Wikler A, Miner EJ (1961). "Cross tolerance between LSD and psilocybin". Psychopharmacologia. 2 (3): 147–59. doi:10.1007/BF00407974. PMID   13717955. S2CID   7746880. Archived from the original on March 15, 2016. Retrieved December 1, 2007.
  85. Schlemmer RF, Nawara C, Heinze WJ, Davis JM, Advokat C (March 1986). "Influence of environmental context on tolerance to LSD-induced behavior in primates". Biological Psychiatry. 21 (3): 314–7. doi:10.1016/0006-3223(86)90053-3. PMID   3947713. S2CID   35508993.
  86. 1 2 3 Nichols DE (February 2004). "Hallucinogens". Pharmacology & Therapeutics. 101 (2): 131–81. doi:10.1016/j.pharmthera.2003.11.002. PMID   14761703. Archived from the original on February 4, 2016. Retrieved January 23, 2006.
  87. "LSD – National Library of Medicine HSDB Database". toxnet.nlm.nih.gov. Archived from the original on March 22, 2018. Retrieved March 21, 2018.
  88. "LSD (Acid) Fatalities/Deaths". Erowid. Archived from the original on June 1, 2017.
  89. 1 2 LSD Toxicity Treatment & Management~treatment at eMedicine
  90. Nichols D (November 2012). "The End of a Chemistry Era ... Dave Nichols Closes Shop". Archived from the original on September 22, 2013. Retrieved September 24, 2013.
  91. 1 2 Aghajanian GK, Bing OH (1964). "Persistence of lysergic acid diethylamide in the plasma of human subjects" (PDF). Clinical Pharmacology and Therapeutics. 5 (5): 611–4. doi:10.1002/cpt196455611. PMID   14209776. S2CID   29438767. Archived from the original (PDF) on March 27, 2009.
  92. "PDSP database". Archived from the original on May 17, 2013. Retrieved June 28, 2013.
  93. Nelson DL (February 2004). "5-HT5 receptors". Current Drug Targets. CNS and Neurological Disorders. 3 (1): 53–8. doi:10.2174/1568007043482606. PMID   14965244.
  94. Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J (April 2011). "Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists". Neuroscience Letters. 493 (3): 76–9. doi:10.1016/j.neulet.2011.01.046. PMC   3064746 . PMID   21276828.
  95. Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, et al. (January 2007). "Functional selectivity and classical concepts of quantitative pharmacology". The Journal of Pharmacology and Experimental Therapeutics. 320 (1): 1–13. doi:10.1124/jpet.106.104463. PMID   16803859. S2CID   447937. Archived from the original on April 28, 2020. Retrieved August 14, 2019.
  96. BilZ0 (August 2005). "The Neuropharmacology of Hallucinogens: a technical overview". Erowid . Archived from the original on February 4, 2016.
  97. Svenningsson P, Nairn AC, Greengard P (October 2005). "DARPP-32 mediates the actions of multiple drugs of abuse". The AAPS Journal. 7 (2): E353-60. doi:10.1208/aapsj070235. PMC   2750972 . PMID   16353915. Archived from the original on October 29, 2012.
  98. "PDSP Ki Database". PDSP. Archived from the original on May 9, 2021. Retrieved January 20, 2020.
  99. Green JP, Johnson CL, Weinstein H, Maayani S (December 1977). "Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide". Proceedings of the National Academy of Sciences of the United States of America. 74 (12): 5697–701. Bibcode:1977PNAS...74.5697G. doi: 10.1073/pnas.74.12.5697 . PMC   431860 . PMID   23536.
  100. 1 2 Nichols DE, Frescas S, Marona-Lewicka D, Kurrasch-Orbaugh DM (September 2002). "Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD)". Journal of Medicinal Chemistry. 45 (19): 4344–9. doi:10.1021/jm020153s. PMID   12213075.
  101. 1 2 Chen Q, Tesmer JJ (January 2017). "A Receptor on Acid". Cell. 168 (3): 339–341. doi:10.1016/j.cell.2017.01.012. PMC   5520807 . PMID   28129534.
  102. 1 2 Aleksandrova L (October 5, 2020). "Crystal Structure of LSD and 5-HT2AR Part 2: Binding Details and Future Psychedelic Research Paths". Psychedelic Science Review. Archived from the original on March 29, 2021. Retrieved February 11, 2021.
  103. UNC Health Care (January 26, 2017). "This is LSD Attached to a Brain Cell Serotonin Receptor (Update)". Phys.org . Archived from the original on March 20, 2021. Retrieved November 4, 2019.
  104. Cell Press (January 26, 2017). "Structure of LSD and its receptor explains its potency". ScienceDaily . Archived from the original on May 28, 2021. Retrieved November 3, 2019.
  105. 1 2 Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, et al. (January 2017). "Crystal Structure of an LSD-Bound Human Serotonin Receptor". Cell. 168 (3): 377–389.e12. doi:10.1016/j.cell.2016.12.033. PMC   5289311 . PMID   28129538.
  106. 1 2 3 4 5 Shulgin A, Shulgin A (1997). "LSD". TiHKAL . Berkeley, California: Transform Press. ISBN   0-9630096-9-9. Archived from the original on October 15, 2008.
  107. 1 2 Hofmann A (1980). LSD—My Problem Child. McGraw-Hill. ISBN   0-07-029325-2. Archived from the original on December 15, 2017..
  108. Papac DI, Foltz RL (May–June 1990). "Measurement of lysergic acid diethylamide (LSD) in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry" (PDF). Journal of Analytical Toxicology. 14 (3): 189–90. doi:10.1093/jat/14.3.189. PMID   2374410. Archived from the original on April 29, 2011.
  109. Monte AP, Marona-Lewicka D, Kanthasamy A, Sanders-Bush E, Nichols DE (March 1995). "Stereoselective LSD-like activity in a series of d-lysergic acid amides of (R)- and (S)-2-aminoalkanes". Journal of Medicinal Chemistry. 38 (6): 958–66. doi:10.1021/jm00006a015. PMID   7699712.
  110. "Erowid Morning Glory Vaults : Extraction of LSA (Method #1)". erowid.org. Archived from the original on September 26, 2014. Retrieved September 25, 2014.
  111. Kornfeld EC, Fornefeld EJ, Kline GB, Mann MJ, Morrison DE, Jones RG, Woodward RB (1956). "The Total Synthesis of Lysergic Acid". Journal of the American Chemical Society. 78 (13): 3087–3114. doi:10.1021/ja01594a039.
  112. Inuki S, Oishi S, Fujii N, Ohno H (November 2008). "Total synthesis of (+/-)-lysergic acid, lysergol, and isolysergol by palladium-catalyzed domino cyclization of amino allenes bearing a bromoindolyl group". Organic Letters. 10 (22): 5239–42. doi:10.1021/ol8022648. PMID   18956869.
  113. "Harvesting baker's yeast for aging-related therapeutics". ScienceDaily.
  114. Greiner T, Burch NR, Edelberg R (February 1958). "Psychopathology and psychophysiology of minimal LSD-25 dosage; a preliminary dosage-response spectrum". A.M.A. Archives of Neurology and Psychiatry. 79 (2): 208–10. doi:10.1001/archneurpsyc.1958.02340020088016. PMID   13497365.
  115. Meyer MA (April 2003). "Neurologic complications of anthrax: a review of the literature". Archives of Neurology. Schweiz. 60 (4): 483–8. doi: 10.1001/archneur.60.4.483 . PMID   12707059.
  116. Polito V, Stevenson RJ (February 6, 2019). "A systematic study of microdosing psychedelics". PLOS ONE. 14 (2): e0211023. Bibcode:2019PLoSO..1411023P. doi: 10.1371/journal.pone.0211023 . PMC   6364961 . PMID   30726251.
  117. 1 2 Hidalgo E (2009). "LSD Samples Analysis". Erowid. Archived from the original on February 13, 2010. Retrieved February 8, 2010.
  118. 1 2 Henderson LA, Glass WJ (1994). LSD: Still with us after all these years. San Francisco: Jossey-Bass. ISBN   978-0-7879-4379-0.
  119. Fire & Earth Erowid (2003). "LSD Analysis – Do we know what's in street acid?". Erowid. Archived from the original on January 26, 2010. Retrieved February 8, 2010.
  120. Li Z, McNally AJ, Wang H, Salamone SJ (October 1998). "Stability study of LSD under various storage conditions". Journal of Analytical Toxicology. 22 (6): 520–5. doi: 10.1093/jat/22.6.520 . PMID   9788528.
  121. R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 12th edition, Biomedical Publications, Foster City, CA, 2020, pp. 1197–1199.
  122. Dolder PC, Schmid Y, Steuer AE, Kraemer T, Rentsch KM, Hammann F, Liechti ME (October 2017). "Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects". Clinical Pharmacokinetics. 56 (10): 1219–1230. doi:10.1007/s40262-017-0513-9. PMC   5591798 . PMID   28197931.
  123. Hofmann 1980, p. 15
  124. Hofmann A (Summer 1969). Translated by Ott J. "LSD Ganz Persönlich" [LSD: Completely Personal]. MAPS (in German). 6 (69). Archived from the original on December 6, 2013.
  125. Nogrady T, Weaver DF (2005). Medicinal Chemistry: A Molecular and Biochemical Approach. Oxford University Press. p. 342. ISBN   978-0-19-028296-7. Archived from the original on March 8, 2021. Retrieved March 14, 2020.
  126. Nichols D (May 24, 2003). "Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day"". Hofmann Foundation. Archived from the original on September 22, 2007. Retrieved September 27, 2007.
  127. Hofmann A. "LSD My Problem Child". Archived from the original on January 11, 2010. Retrieved April 19, 2010.
  128. Hofmann A. "History Of LSD". Archived from the original on September 4, 2007. Retrieved September 27, 2007.
  129. "LSD: The Drug". U.S. Department of Justice, Drug Enforcement Administration. Archived from the original on April 27, 1999. Retrieved November 27, 2010.
  130. "The CIA's Secret Quest For Mind Control: Torture, LSD And A 'Poisoner In Chief'". NPR.org. Archived from the original on June 28, 2021. Retrieved October 6, 2019.
  131. Brecher EM, et al. (Editors of Consumer Reports Magazine) (1972). "How LSD was popularized". Druglibrary.org. Archived from the original on May 13, 2012. Retrieved June 20, 2012.
  132. Applebaum A (January 26, 2010). "Did The Death Of Communism Take Koestler And Other Literary Figures With It?". The Huffington Post . Archived from the original on July 14, 2011.
  133. "Out-Of-Sight! SMiLE Timeline". Archived from the original on February 1, 2010. Retrieved October 30, 2011.
  134. Veysey LR (1978). The Communal Experience: Anarchist and Mystical Communities in Twentieth-Century America . Chicago IL: University of Chicago Press. p. 437. ISBN   0-226-85458-2.
  135. United States Congress (October 24, 1968). "Staggers-Dodd Bill, Public Law 90-639" (PDF). Archived (PDF) from the original on May 9, 2010. Retrieved September 8, 2009.
  136. Gasser P (1994). "Psycholytic Therapy with MDMA and LSD in Switzerland". Archived from the original on October 11, 2009. Retrieved September 8, 2009.
  137. Feuer W (November 4, 2020). "Oregon becomes first state to legalize magic mushrooms as more states ease drug laws in 'psychedelic renaissance'". CNBC. Archived from the original on November 4, 2020. Retrieved November 7, 2020.
  138. DeRogatis J (2003). Turn On Your Mind: Four Decades of Great Psychedelic Rock. Milwaukie, Michigan: Hal Leonard. pp. 8–9. ISBN   0-634-05548-8.
  139. Gilliland J (1969). "Show 41 – The Acid Test: Psychedelics and a sub-culture emerge in San Francisco. [Part 1] : UNT Digital Library" (audio). Pop Chronicles . Digital.library.unt.edu. Archived from the original on June 29, 2011. Retrieved May 6, 2011.
  140. Hicks M (2000). Sixties Rock: Garage, Psychedelic, and Other Satisfactions Music in American Life. Chicago, IL: University of Illinois Press. p. 60. ISBN   0-252-06915-3.
  141. Mann J (2009). Turn on and Tune in: Psychedelics, Narcotics and Euphoriants. Royal Society of Chemistry. p. 87. ISBN   978-1-84755-909-8.
  142. Taylor M (March 22, 1996). "OBITUARY -- Ron Thelin". SFGate. Archived from the original on August 28, 2021. Retrieved May 13, 2020.
  143. Davis JC (January 2015). "The business of getting high: head shops, countercultural capitalism, and the marijuana legalization movement". The Sixties. 8 (1): 27–49. doi:10.1080/17541328.2015.1058480. hdl: 11603/7422 . S2CID   142795620.
  144. 1 2 Jarnow J (2016). Heads: A Biography of Psychedelic America. Da Capo Press. ISBN   9780306822551.
  145. Gilmore M (August 25, 2016). "Beatles' Acid Test: How LSD Opened the Door to 'Revolver'". Rolling Stone. Archived from the original on December 3, 2020. Retrieved December 9, 2021.
  146. "Keith Richards' Wildest Escapades: 19 Insane Tales From a Legendary Life". Rolling Stone. December 18, 2019. Archived from the original on December 9, 2021. Retrieved December 9, 2021.
  147. "The Moody Blues: stories of nights in technicolour satin and LSD". Classic Rock. January 20, 2021. Archived from the original on December 9, 2021. Retrieved December 9, 2021.
  148. "Totally gone: the story of the Small Faces' psychedelic masterpiece Ogdens' Nut Gone Flake". Classic Rock. November 3, 2020. Archived from the original on December 9, 2021. Retrieved December 9, 2021.
  149. "Was Syd Barrett an Acid Casualty?". Paste. May 2, 2017. Archived from the original on December 9, 2021. Retrieved December 9, 2021.
  150. Rubin R, Melnick JP (2007). Immigration and American Popular Culture: an Introduction. New York, NY: New York University Press. pp. 162–4. ISBN   978-0-8147-7552-3.
  151. Prown P, Newquist HP, Eiche JF (1997). Legends of Rock Guitar: the Essential Reference of Rock's Greatest Guitarists. London: Hal Leonard Corporation, 1997. p. 48. ISBN   0-7935-4042-9.
  152. Borthwick S, Moy R (2004). Popular Music Genres: an Introduction. Edinburgh: Edinburgh University Press. pp. 52–4. ISBN   0-7486-1745-0.
  153. DeRogatis J (2003). Turn On Your Mind: Four Decades of Great Psychedelic Rock. Milwaukie: Hal Leonard. p. 230. ISBN   0-634-05548-8.
  154. Unterberger R, Hicks S, Dempsey J (1999). Music USA: the rough guide. Rough Guides. pp.  391. ISBN   1-85828-421-X.
  155. St John G (2004). Rave Culture and Religion. Abingdon: Routledge. p. 52. ISBN   0-415-31449-6.
  156. Sheff D (2000). All We Are Saying: The Last Major Interview with John Lennon and Yoko Ono . New York: St. Martin's Press. ISBN   978-0-312-25464-3.
  157. Thompson T (June 16, 1967). "The New Far-Out Beatles". Life. Chicago: Time Inc. p. 101. Archived from the original on November 17, 2021. Retrieved December 8, 2016.
  158. McCartney P (June 19, 1967). "Interview with Paul McCartney". ITV Evening News (Interview). London: Independent Television News. Archived from the original on October 15, 2016. Retrieved May 7, 2017.
  159. "Final act of the United Nations Conference" (PDF). UN Convention on Psychotropic Substances. 1971. Archived from the original (PDF) on April 15, 2012.
  160. 1 2 "Poisons Standard". Therapeutic Goods Administration. Australian Government Department of Health. July 2016. Archived from the original on March 2, 2017.
  161. "Misuse of Drugs Act 1981" (PDF). Government of Western Australia. November 18, 2015. Archived from the original (PDF) on December 22, 2015.
  162. "Drugs and the law: Report of the inquiry into the Misuse of Drugs Act 1971". Runciman Report . London: Police Foundation. 2000. Archived from the original on January 30, 2016.
  163. "After the War on Drugs: Blueprint for Regulation". Transform Drug Policy Foundation. 2009. Archived from the original on October 5, 2013.
  164. From "LSD". Drug Enforcement Agency. U.S. Department of Justice. Archived from the original on October 5, 2009. Retrieved February 5, 2016. LSD is a Schedule I substance under the Controlled Substances Act.
  165. LSD Toxicity at eMedicine
  166. Neal v. United States, 516U.S.284 (1996)., originating from U.S. v. Neal, 46 F.3d 1405 (7th Cir. 1995)
  167. "Controlled Substances in Alphabetical Order" (PDF). dea.gov. U.S. Drug Enforcement Administration. Archived from the original (PDF) on April 17, 2016. Retrieved May 29, 2018.
  168. Blistein J (February 1, 2021). "Drug Decriminalization Goes Into Effect in Oregon". Rolling Stone. Archived from the original on April 26, 2021. Retrieved February 11, 2021.
  169. Jaeger K (June 29, 2021). "California Lawmakers Approve Bill To Legalize Psychedelics Possession In Committee". Marijuana Moment. Archived from the original on July 9, 2021. Retrieved July 8, 2021.
  170. Angell T (August 13, 2022). "California Senator Gives Up Psychedelics Reform Push For 2022 After Bill Gutted By Key Committee". Marijuana Moment. Retrieved August 20, 2022.
  171. "Ley de Narcomenudeo". El Pensador (in Spanish). October 17, 2009. Archived from the original on November 30, 2010.
  172. Tinajero JH, Angles CZ (October 2009). "The Law Against Small-Scale Drug Dealing A Doubtful Venture. Policy". Series on Legislative Reform of Drug Policies. Mexico. Archived from the original on April 2016.
  173. 1 2 Parliament of the Czech Republic (1998), Explanatory Report to Act No. 112/1998 Coll., which amends the Act No. 140/1961 Coll., the Criminal Code, and the Act No. 200/1990 Coll., on misdemeanors (in Czech), Prague "Podle čl. 36 Jednotné úmluvy o omamných látkách ze dne 31. března 1961 (č. 47/1965 Sb.) se signatáři zavazují k trestnímu postihu tam uvedených forem nakládání s drogami včetně jejich držby. Návrh upouští od dosavadní beztrestnosti držby omamných a psychotropních látek a jedů pro svoji potřebu. Dosavadní beztrestnost totiž eliminuje v řadě případů možnost postihu dealerů a distributorů drog."
  174. Supreme Court of the Czech Republic (February 25, 2012), 6 Tdo 156/2010 [NS 7078/2010]
  175. Government of the Czech Republic (2009), Regulation No. 467/2009 Coll., which defines for the purposes of the Criminal Code what is to be considered larger than small amount of narcotic and psychoactive substances and poisons (in Czech), Prague
  176. 1 2 "La nueva tabla para consumo de drogas es una guía para jueces". Archived from the original on June 22, 2013.
  177. "Dosis máximas de droga para consumo ya están vigentes". El Comercio . Archived from the original on June 24, 2013.
  178. "Ecuador: Aprueban tenencia de drogas para consumo". El Nuevo Herald . Archived from the original on June 25, 2013.
  179. "Ecuador could regulate the drug industry". Archived from the original on June 24, 2013.
  180. "LSD Price: How Much Is Acid Blotter, Sheet, Tab, Pyramid or Vial?". Addiction Resource. Archived from the original on August 28, 2021. Retrieved May 13, 2020.
  181. 1 2 DEA (2007). "LSD Manufacture – Illegal LSD Production". LSD in the United States. U.S. Department of Justice Drug Enforcement Administration. Archived from the original on August 29, 2007.
  182. 1 2 3 Stafford P (1992). "Chapter 1 – The LSD Family". Psychedelics Encyclopaedia (Third Expanded ed.). Ronin Publishing Inc. p. 62. ISBN   978-0-914171-51-5.
  183. 1 2 3 Laing RR, Beyerstein BL, Siegel JA (2003). "Chapter 2.2 – Forms of the Drug". Hallucinogens: A Forensic Drug Handbook. Academic Press. pp. 39–41. ISBN   978-0-12-433951-4. Archived from the original on February 2, 2021. Retrieved May 12, 2020.
  184. "Street Terms: Drugs and the Drug Trade". Office of National Drug Control Policy. April 5, 2005. Archived from the original on April 18, 2009. Retrieved January 31, 2007.
  185. DEA (2008). "Photo Library (page 2)". US Drug Enforcement Administration. Archived from the original on June 23, 2008. Retrieved June 27, 2008.
  186. MacLean JR, Macdonald DC, Ogden F, Wilby E (1967). "LSD-25 and mescaline as therapeutic adjuvants.". In Abramson H (ed.). The Use of LSD in Psychotherapy and Alcoholism. New York: Bobbs-Merrill. pp. 407–426.
  187. Ditman KS, Bailey JJ. "Evaluating LSD as a psychotherapeutic agent". In Hoffer A (ed.). A program for the treatment of alcoholism: LSD, malvaria, and nicotinic acid. pp. 353–402.
  188. ^ LSD: The Drug
  189. Schou N (2010). Orange Sunshine: The Brotherhood of Eternal Love and Its Quest to Spread Peace, Love, and Acid to the World . Thomas Dunne Books. ISBN   9780312551834.
  190. United States Drug Enforcement Administration (October 2005). "LSD Blotter Acid Mimic Containing 4-Bromo-2,5-dimethoxy-amphetamine (DOB) Seized Near Burns, Oregon" (PDF). Microgram Bulletin. 38 (10). Archived from the original (PDF) on October 18, 2012. Retrieved August 20, 2009.
  191. United States Drug Enforcement Administration (November 2006). "Intelligence Alert – Blotter Acid Mimics (Containing 4-Bromo-2,5-Dimethoxy-Amphetamine (DOB)) in Concord, California" (PDF). Microgram Bulletin. 39 (11): 136. Archived from the original (PDF) on October 18, 2012. Retrieved August 20, 2009.
  192. United States Drug Enforcement Administration (March 2008). "Unusual "Rice Krispie Treat"-Like Balls Containing Psilocybe Mushroom Parts in Warren County, Missouri" (PDF). Microgram Bulletin. 41 (3). Archived from the original (PDF) on October 17, 2012. Retrieved August 20, 2009.
  193. Iversen L (May 29, 2013). "Temporary Class Drug Order Report on 5-6APB and NBOMe compounds" (PDF). Advisory Council on the Misuse of Drugs. Gov.Uk. p. 14. Archived (PDF) from the original on September 21, 2013. Retrieved June 16, 2013.
  194. United States Drug Enforcement Administration (March 2009). ""Spice" – Plant Material(s) Laced With Synthetic Cannabinoids or Cannabinoid Mimicking Compounds". Microgram Bulletin. 42 (3). Archived from the original (PDF) on January 18, 2012. Retrieved August 20, 2009.
  195. United States Drug Enforcement Administration (November 2005). "Bulk Marijuana in Hazardous Packaging in Chicago, Illinois" (PDF). Microgram Bulletin. 38 (11). Archived from the original (PDF) on October 18, 2012. Retrieved August 20, 2009.
  196. United States Drug Enforcement Administration (December 2007). "SMALL HEROIN DISKS NEAR GREENSBORO, GEORGIA" (PDF). Microgram Bulletin. 40 (12). Archived from the original (PDF) on October 17, 2012. Retrieved August 20, 2009.
  197. Erowid. "25I-NBOMe (2C-I-NBOMe) Fatalities / Deaths". Drug Website. Erowid. Archived from the original on March 5, 2016. Retrieved February 28, 2016.
  198. Hastings D (May 6, 2013). "New drug N-bomb hits the street, terrifying parents, troubling cops". New York Daily News. Archived from the original on May 10, 2013. Retrieved May 7, 2013.
  199. Feehan C (January 21, 2016). "Powerful N-Bomb drug – responsible for spate of deaths internationally – responsible for hospitalisation of six in Cork". Irish Independent. Archived from the original on April 12, 2019. Retrieved January 22, 2016.
  200. Iversen L (May 29, 2013). "Temporary Class Drug Order Report on 5-6APB and NBOMe compounds" (PDF). Advisory Council on the Misuse of Drugs. Gov.Uk. Archived (PDF) from the original on September 21, 2013. Retrieved June 16, 2013.
  201. "The Albert Hofmann Foundation". Hofmann Foundation. Archived from the original on July 19, 2019. Retrieved September 27, 2007.
  202. "LSD & Psilocybin-Assisted Therapy for Anxiety". Archived from the original on May 11, 2018. Retrieved October 16, 2013.
  203. DEA Public Affairs (November 16, 2001). "DEA – Publications – LSD in the US – The Drug". Web.petabox.bibalex.org. Archived from the original on April 27, 1999. Retrieved November 27, 2010.
  204. Bogenschutz MP (March 2013). "Studying the effects of classic hallucinogens in the treatment of alcoholism: rationale, methodology, and current research with psilocybin". Current Drug Abuse Reviews. 6 (1): 17–29. doi:10.2174/15733998113099990002. PMID   23627783.
  205. "LSD Therapy for Persons Suffering From Major Depression - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. February 8, 2021. Archived from the original on June 11, 2021. Retrieved March 9, 2021.
  206. Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, et al. (April 2021). "Trial of Psilocybin versus Escitalopram for Depression". The New England Journal of Medicine. 384 (15): 1402–1411. doi:10.1056/NEJMoa2032994. PMID   33852780. S2CID   233243518.
  207. de Vos CM, Mason NL, Kuypers KP (2021). "Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics". Frontiers in Psychiatry. 12: 724606. doi: 10.3389/fpsyt.2021.724606 . PMC   8461007 . PMID   34566723.
  208. Lukasiewicz K, Baker JJ, Zuo Y, Lu J (2021). "Serotonergic Psychedelics in Neural Plasticity". Frontiers in Molecular Neuroscience. 14: 748359. doi: 10.3389/fnmol.2021.748359 . PMC   8545892 . PMID   34712118.
  209. Calder AE, Hasler G (September 2022). "Towards an understanding of psychedelic-induced neuroplasticity". Neuropsychopharmacology. 48 (1): 104–112. doi:10.1038/s41386-022-01389-z. PMC   9700802 . PMID   36123427. S2CID   252381170.
  210. Cohen, S. (1959). The therapeutic potential of LSD-25. A Pharmacologic Approach to the Study of the Mind, p251–258.
  211. "Use of d-lysergic acid diethylamide in the treatment of alcoholism". Archived from the original on February 24, 2021. Retrieved June 20, 2012.
  212. "Use of d-Lysergic Acid Diethylamide in the Treatment of Alcoholism". Hofmann.org. November 14, 2003. Archived from the original on February 3, 2012. Retrieved February 22, 2012.
  213. Frood A (March 9, 2012). "LSD helps to treat alcoholism". Nature News. doi:10.1038/nature.2012.10200. S2CID   137367650. Archived from the original on March 8, 2021. Retrieved December 25, 2020.
  214. Vollenweider FX, Kometer M (September 2010). "The neurobiology of psychedelic drugs: implications for the treatment of mood disorders". Nature Reviews. Neuroscience. 11 (9): 642–51. doi:10.1038/nrn2884. PMID   20717121. S2CID   16588263.
  215. Baumeister D, Barnes G, Giaroli G, Tracy D (August 2014). "Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles". Therapeutic Advances in Psychopharmacology. 4 (4): 156–69. doi:10.1177/2045125314527985. PMC   4104707 . PMID   25083275.
  216. "LSD-Assisted Psychotherapy". MAPS. Archived from the original on May 11, 2018. Retrieved October 3, 2016.
  217. Liechti ME (October 2017). "Modern Clinical Research on LSD". Neuropsychopharmacology. 42 (11): 2114–2127. doi:10.1038/npp.2017.86. PMC   5603820 . PMID   28447622.
  218. Carhart-Harris R (April 20, 2021). "Psychedelics are transforming the way we understand depression and its treatment". The Guardian. Archived from the original on June 11, 2021. Retrieved May 16, 2021.
  219. Sessa B (November 2008). "Is it time to revisit the role of psychedelic drugs in enhancing human creativity?". Journal of Psychopharmacology. 22 (8): 821–7. doi:10.1177/0269881108091597. PMID   18562421. S2CID   1908638.
  220. Janiger O, Dobkin de Rios M (1989). "LSD and creativity". Journal of Psychoactive Drugs. 21 (1): 129–34. doi:10.1080/02791072.1989.10472150. PMID   2723891. Archived from the original on October 3, 2009.
  221. Stafford PG, Golightly BH (1967). LSD, the problem-solving psychedelic. ASIN   B0006BPSA0. Archived from the original on April 17, 2012.
  222. "Psychiater Gasser bricht sein Schweigen". Basler Zeitung. July 28, 2009. Archived from the original on October 6, 2011. Retrieved June 19, 2011.
  223. LSD-Assisted Psychotherapy "LSD-Assisted Psychotherapy". Archived from the original on May 11, 2018. Retrieved February 5, 2017.
  224. Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, Burbach KF, Soltanzadeh Zarandi S, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, Olson DE (2018). "Psychedelics promote structural and functional neural plasticity". Cell Reports. 23 (11): 3170–3182. doi:10.1016/j.celrep.2018.05.022. PMC   6082376 . PMID   29898390.
  225. Dolan EW (August 11, 2022). "Neuroscience research suggests LSD might enhance learning and memory by promoting brain plasticity". PsyPost. Retrieved September 12, 2022.
  226. Whelan A, Johnson MI (May 2018). "Lysergic acid diethylamide and psilocybin for the management of patients with persistent pain: a potential role?" (PDF). Pain Management. 8 (3): 217–229. doi:10.2217/pmt-2017-0068. PMID   29722608. S2CID   19160293. Archived (PDF) from the original on October 8, 2020. Retrieved August 22, 2020.
  227. "Famous LSD users". The Good Drugs Guide. Archived from the original on October 7, 2008. Retrieved October 20, 2008.
  228. "People on psychedelics". Archived from the original on April 21, 2013. Retrieved November 1, 2012.
  229. Mason D (Autumn 2015). "Review: Awe for Auden". The Hudson Review. The Hudson Review, Inc. 68 (3): 492–500.
  230. Auden WH (November 15, 1971). "W. H. Auden at Swathmore; An hour of questions and answers with Auden". Exhibition notes from the W.H. Auden Collection. the Swarthmore College Library. Archived from the original on June 11, 2021. Retrieved February 23, 2021.
  231. MacMonagle N (February 17, 2007). "A Master of Memorable speech". The Irish Times.
  232. Meyer A (January 24, 2022). "Daniel Ellsberg Talks Psychedelics, Consciousness and World Peace". Lucid News. Archived from the original on January 29, 2022. Retrieved January 29, 2022.
  233. Feynman RP (1985). Leighton R (ed.). Surely You're Joking, Mr. Feynman!: Adventures of a Curious Character. W. W. Norton. ISBN   978-0-393-01921-6. OCLC   10925248.
  234. Gleick J (1992). Genius: The Life and Science of Richard Feynman. Pantheon Books. ISBN   978-0-679-40836-9. OCLC   243743850.
  235. Alderson J (April 20, 2010). "Q&A with Jerry Garcia: Portrait of an Artist as a Tripper". Relix Magazine. Archived from the original on May 21, 2010. Retrieved June 29, 2013.
  236. "The Bill Gates Interview". Playboy. July 1994. Archived from the original on July 7, 2014.
  237. Colman D (October 2011). "Aldous Huxley's LSD Death Trip". Archived from the original on November 12, 2011. Retrieved November 1, 2011.
  238. Bosker B (October 21, 2011). "The Steve Jobs Reading List: The Books And Artists That Made The Man". Huffington Post. Archived from the original on October 22, 2011. Retrieved October 23, 2011.
  239. "LSD, My Problem Child · Radiance from Ernst Junger". www.psychedelic-library.org. Archived from the original on May 12, 2021. Retrieved April 17, 2021.
  240. Sheff 2000, p. 182.
  241. "Is 'Lucy in the Sky with Diamonds' Code for LSD?". Snopes.com. February 15, 1998. Retrieved June 20, 2012.