Lysergic acid diethylamide, commonly known asLSD (from GermanLysergsäurediethylamid) and by the slang namesacid andlucy, is asemisynthetichallucinogenic drug derived fromergot, known for its powerful psychological effects andserotonergic activity.[16] It was historically used inpsychiatry and 1960scounterculture; it is currently legally restricted but experiencing renewed scientific interest and increasing use.
When taken orally, LSD has an onset of action within 0.4 to 1.0 hours (range: 0.1–1.8 hours) and a duration of effect lasting 7 to 12 hours (range: 4–22 hours).[12][9] It is commonly administered via tabs ofblotter paper.[17] LSD is extremely potent, with noticeable effects at doses as low as 20micrograms and is sometimes taken in much smaller amounts formicrodosing. Despite widespread use, no fatal human overdoses have been documented. LSD is mainly used recreationally or for spiritual purposes.[18][19] LSD can cause mystical experiences.[20][21] LSD exerts its effects primarily through high-affinity binding to severalserotonin receptors, especially5-HT2A, and to a lesser extentdopaminergic andadrenergic receptors. LSD reduces oscillatory power in the brain'sdefault mode network and flattens brain hierarchy.[22][23] At higher doses, it can induce visual and auditory hallucinations,ego dissolution, andanxiety.[24][25] LSD use can cause adverse psychological effects such asparanoia anddelusions and may lead to persistent visual disturbances known ashallucinogen persisting perception disorder (HPPD).
Swiss chemistAlbert Hofmann first synthesized LSD in 1938 and discovered its powerfulpsychedelic effects in 1943 after accidental ingestion. It became widely studied in the 1950s and 1960s.[18][26] It was initially explored for psychiatric use due to its structural similarity to serotonin and safety profile.[27] It was used experimentally inpsychiatry for treatingalcoholism andschizophrenia.[28] By the mid-1960s, LSD became central to the youthcounterculture in places likeSan Francisco andLondon, influencing art, music, and social movements through events likeAcid Tests and figures such asOwsley Stanley andMichael Hollingshead. Its psychedelic effects inspired distinct visual art styles, music innovations, and caused a lasting cultural impact. However, its association with thecounterculture movement of the 1960s led to its classification as aSchedule I drug in the U.S. in 1970.[29] It was also listed as aSchedule I controlled substance by theUnited Nations in 1971 and remains without approved medical uses.[18]
Despite its legal restrictions, LSD remains influential in scientific and cultural contexts. Research on LSD declined due to cultural controversies by the 1960s, but has resurged since 2009. In 2024, the U.S.Food and Drug Administration designated a form of LSD (MM120) abreakthrough therapy forgeneralized anxiety disorder.[30] As of 2017, about 10% of people in the U.S. had used LSD at some point, with 0.7% having used it in the past year.[31] Usage rates have risen, with a 56.4% increase in adult use in the U.S. from 2015 to 2018.[32]
LSD is an extraordinarilypotent substance,[12][44][27][45] and is one of the most potent psychoactive drugs known.[27][45] This means that it produces itspharmacological effects at very small doses, with its dose range measured inmicrograms (μg); that is, millionths of a gram.[12][27] Noticeable effects can occur with doses of LSD as low as 20μg, which is around 1/200th the mass of a grain of sand.[12][44][27][18] LSD is approximately 200times as potent aspsilocybin and 5,000times as potent asmescaline, meaning that it produces effects of similar magnitude at 1/200 and 1/5,000 times the respective doses.[12][44][46]
The usual dose range of LSD for psychedelic effects is 20 to 200μg.[12][44] The typical intermediate and "good effect" dose for a psychedelic experience is 100μg (range 75–150μg, while 20 to 50μg is a low or "minidose" and 200μg is a high orego-dissolution dose.[12][44][9] A dose range as wide as 10 to 450μg has been reported.[47][48] LSD may also be used inmicrodosing.[49] In this context, it may be used at subthreshold or microdoses of less than 10μg.[12][44]
The doses of LSD present in illicit LSD samples have decreased over time. In the mid-1960s,Owsley Stanley, the most importantblack market LSD manufacturer in theUnited States, distributed LSD at a standard concentration of 270μg,[50] while street samples of the 1970s contained 30 to 300μg. By the 1980s, the amount had reduced to between 100 and 125μg, dropping more in the 1990s to the 20 to 80μg range,[51] and even further in the 2000s.[50][52]
The primary immediate psychological effects of LSD arevisual pseudo-hallucinations and altered thought, often referred to as "trips". These sensory alterations are considered pseudohallucinations because the subject does not perceive the patterns seen as being located in three-dimensional space outside the body.[53] LSD is not considered addictive. These effects typically begin within 20–30 minutes of oral ingestion, peak three to four hours after ingestion, and can last up to 20 hours, particularly with higher doses. An "afterglow" effect, characterized by an improved mood or perceived mental state, may persist for days or weeks following ingestion.[54] Positive experiences, or "good trips", are described as intensely pleasurable and can include feelings of joy, euphoria, an increased appreciation for life, decreased anxiety, a sense of spiritual enlightenment, and a feeling of interconnectedness with the universe.[55][56]
Negative experiences, commonly known as "bad trips", can induce feelings of fear, agitation, anxiety, panic, and paranoia.[9][57] While the occurrence of a bad trip is unpredictable, factors such as mood, surroundings, sleep, hydration, and social setting, collectively referred to as "set and setting", can influence the risk and are considered important in minimizing the likelihood of a negative experience.[58][59]
Alexander Shulgin did not includeexperience reports of LSD in his 1997 bookTiHKAL (Tryptamines I Have Known and Loved) due to the thousands of reports that already existed in the literature.[6]
LSD induces an animated sensory experience affecting senses, emotions, memories, time, and awareness. The effects range from subtle perceptual changes to profoundcognitive shifts. Alterations in auditory and visual perception are common.[60][61]
Users may experience enhanced visual phenomena, such as vibrant colors, objects appearing to morph, ripple or move, and geometric patterns on various surfaces. Changes in the perception of food's texture and taste are also noted, sometimes leading to aversion towards certain foods.[60][62]
There are reports of inanimate objects appearing animated, with static objects seeming to move in additional spatial dimensions.[63] The auditory effects of LSD may includeecho-like distortions of sounds, and an intensified experience of music. Basic visual effects often resemblephosphenes and can be influenced by concentration, thoughts, emotions, or music.[64] Higher doses can lead to more intense sensory perception alterations, including synesthesia, perception of additional dimensions, and temporarydissociation.
The psychoactive effects of LSD last on average between 7 and 11hours, with a possible range of 4 to 22hours.[12] Higher doses tend to lead to a longer duration of action.[12] Theonset of action when administered orally is 0.4 to 1.0hours on average, with a possible range of 0.1 to 1.8hours.[12] The time to peak effects given orally is 2.2 to 2.8hours on average, with a range of 1.3 to 6.5hours.[12]
Table from the 2010 ISCD study ranking various drugs (legal and illegal) based on statements by drug-harm experts. LSD was found to be the 18th most dangerous out of 20 considered.[67]Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged indelphic analysis regarding 20 popular recreational drugs. LSD was ranked 14th in dependence, 15th in physical harm, and 13th in social harm.[68]
LSD, a classical psychedelic, is deemed physiologically safe at standard doses (50–200 μg) and its primary risks lie in psychological effects rather than physiological harm.[69][70] A 2010 study byDavid Nutt ranked LSD as significantly less harmful thanalcohol, placing it near the bottom of a list assessing the harm of 20 drugs.[71]
LSD can inducepanic attacks or extreme anxiety, colloquially termed a "bad trip". Despite lower rates of depression and substance abuse found in psychedelic drug users compared to controls, LSD presents heightened risks for individuals with severe mental illnesses likeschizophrenia.[72][73] These hallucinogens can catalyze psychiatric disorders in predisposed individuals, although they do not tend to induce illness in emotionally healthy people.[69]
While research from the 1960s indicated increased suggestibility under the influence of LSD among both mentally ill and healthy individuals, recent documents suggest that the CIA and Department of Defense have discontinued research into LSD as a means of mind control.[74][75][76][non-primary source needed]
Flashbacks are psychological episodes where individuals re-experience some of LSD's subjective effects after the drug has worn off, persisting for days or months post-hallucinogen use.[77][78] These experiences are associated withhallucinogen persisting perception disorder (HPPD), where flashbacks occur intermittently or chronically, causing distress or functional impairment.[79]
The etiology of flashbacks is varied. Some cases are attributed tosomatic symptom disorder, where individuals fixate on normalsomatic experiences previously unnoticed prior to drug consumption.[80] Other instances are linked to associative reactions to contextual cues, similar to responses observed in individuals with past trauma or emotional experiences.[81] The risk factors for flashbacks remain unclear, but pre-existing psychopathologies may be significant contributors.[82]
Estimating the prevalence of HPPD is challenging. It is considered rare, with occurrences ranging from 1 in 20 users experiencing the transient and less severe type 1 HPPD, to 1 in 50,000 for the more concerning type 2 HPPD.[79] Contrary tointernet rumors, LSD is not stored long-term in thespinal cord or other parts of the body. Pharmacological evidence indicates LSD has a half-life of 175 minutes and is metabolized into water-soluble compounds like 2-oxo-3-hydroxy-LSD, eliminated through urine without evidence of long-term storage.[9] Clinical evidence also suggests that chronic use ofSSRIs can potentiate LSD-induced flashbacks, even months after stopping LSD use.[83]: 145
LSD shows significanttachyphylaxis, with tolerance developing 24 hours after administration. The progression of tolerance at intervals shorter than 24 hours remains largely unknown.[84] Tolerance typically resets to baseline after 3–4 days of abstinence.[85][86] Significant cross-tolerance occurs between LSD,mescaline andpsilocybin.[87][88] A slight cross-tolerance toDMT is observed in humans highly tolerant to LSD.[89] Tolerance to LSD also builds up with consistent use,[90] and is believed to result from serotonin 5-HT2Areceptor downregulation.[85] Researchers believe that tolerance returns to baseline after two weeks of not using psychedelics.[91]
LSD is widely considered to be non-addictive, despite its potential forabuse.[5][69][92][93] Attempts to train laboratory animals toself-administer LSD have been largely unsuccessful.[69] Although tolerance to LSD builds up rapidly, awithdrawal syndrome does not appear, suggesting that a potential syndrome does not necessarily relate to the possibility of acquiring rapid tolerance to a substance.[94] A report examiningsubstance use disorder forDSM-IV noted that almost no hallucinogens produced dependence, unlike psychoactive drugs of other classes such asstimulants anddepressants.[95][96]
Themutagenic potential of LSD is unclear. Overall, the evidence seems to point to limited or no effect at commonly used doses.[97] Studies showed no evidence ofteratogenic or mutagenic effects.[9]
A potential risk of frequent repeated long-term use of LSD and other serotonergic psychedelics iscardiac fibrosis andvalvulopathy due toserotonin5-HT2B receptoragonism.[98][99][100][101][102] This may also be the case withmicrodosing.[98][99][100] However, the risks are theoretical, and more research is needed to see if these complications can actually occur with psychedelics.[98][101] A preliminaryanimal study found that chronic microdosing of LSD did not result in heart structure changes or valvulopathy in rodents.[103] Research appears to be mixed on whether LSD is a potent serotonin 5-HT2B receptor agonist or not, with some studies finding it to be essentially inactive.[104]
LSD at typicalrecreational doses (~50–250μg) is considered to be verysafe in terms oftoxicity, with not a single toxicity-related death having been reported at such doses despite many millions of exposures.[110][111][112] In addition, LSD is considered to be a relatively non-toxic drug inoverdose.[110][111][112][9] It is estimated, based onanimal studies and humancase reports, that thelethal dose of LSD in humans is approximately 100mg, or about 1,000times the usual recreational dose of 100μg.[110][111] There have been a handful of reported cases of fatal overdose with LSD as of 2024.[110][111][112][9] However, critical review of the literature byDavid E. Nichols found that of five identified cases, one was not consistent with the effects of LSD but instead may have been another drug like25I-NBOMe, two involved normal doses of LSD in individuals who were placed inmaximal physical restraint (hogtied) by police followed by presumedpositional asphyxia and fatal cardiovascular collapse (hogtying being a practice that is associated with accidental death generally), and two were associated with massive LSD overdose involving doses of possibly more than 300mg.[110][111] Besides death due to toxicity, LSD is associated rarely with death viasuicide,accidents, orviolent encounters due to induction of abnormal behavior.[111][112]
In one well-known 1974case series, 8people accidentallyinsufflated two "lines" of nearly pure LSD powder that they thought werecocaine.[110][111][9][113][114] The exact doses of LSD were unknown, but were considered to be massive.[110][111][9] For context, a typical "line" of cocaine for insufflation is 50 to 100mg.[115] The individuals reported to the hospital within 10 to 15minutes, with five of themcomatose, three requiringintubation andmechanical ventilation, and the conscious individuals experiencing severehallucinogenic effects, among other toxic symptoms.[110][111][9][114] All of them completely recovered within 12hours and there were no deaths.[110][111][9][114] A subsequent 2020 case similarly involved accidental insufflation of a confirmed 55mg dose of LSD instead of cocaine, which was without adverse health consequences.[112][116] In other reports, a 5mg overdose of LSD produced severenausea andvomiting along with severe behavioral disturbances,[117][118] while a 10mg overdose was also non-fatal.[47][119]
Themedian lethal dose (LD50) of LSD in animals varies and is 50 to 60mg/kg in mice, 16.5mg/kg in rats, and 0.3mg/kg in rabbits all given byinjection.[112] A well-known 1962 instance of an elephant named Tusko given 297mg (~0.1mg/kg) LSD byintramuscular injection proved fatal.[127][112][119][128] These findings suggest that elephants may be much more sensitive to LSD in overdose than humans and other species.[127][112] However, this instance has been mired in criticism and controversy due to miscalculation of LSD dose and concomitant post-LSD administration ofpromazine andpentobarbital.[127][129] The experiment was repeated in two elephants with similar doses of LSD in 1984 without incident.[127][112][129]
Although LSD is relatively safe in overdose,25-NB (NBOMe) psychedelics like25I-NBOMe and25B-NBOMe are often sold as "LSD" and are highly toxic in overdose, with many reported severe intoxications and deaths.[133][131][134] Owing to their highpotency analogous to LSD, these drugs are also regularly sold as "LSD" inblotter papers.[135][136] Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,[137] and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".[138] Researchers state that the alleged physiological toxicity of LSD is likely due to psychoactive substances other than LSD.[70]
NBOMe compounds are reported to have a bitter taste,[138] are not active orally,[a] and are usually taken sublingually.[140] When NBOMes are administered sublingually,numbness of the tongue and mouth followed by a metallic chemical taste was observed, and researchers describe this physical side effect as one of the main discriminants between NBOMe compounds and LSD.[141][142][143] Despite its high potency, recreational doses of LSD have only produced low incidents of acute toxicity, but NBOMe compounds have extremely different safety profiles.[138][144] Testing withEhrlich's reagent gives a positive result for LSD and a negative result for NBOMe compounds.[145][146]
Affinities (Ki) of LSD for variousreceptors. The lower the value, 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, affinities that are above the line are unlikely to be involved in LSD's effects. Values are averages theKi Database.[147]
LSD binds to most serotonin receptor subtypes except for the serotonin5-HT3 and5-HT4 receptors.[12] However, some of these serotonin receptors may not be affected at typical brain concentrations of LSD.[69] In humans, recreational doses of LSD may affect5-HT1A,5-HT2A,5-HT2B,5-HT2C,5-HT5A, and5-HT6 receptors.[163] Although not present in humans,5-HT5B receptors found in rodents also have a high affinity for LSD.[164] The psychedelic effects of LSD are attributed to activation of 5-HT2A receptors.[165] Many but not all serotonin 5-HT2Aagonists arepsychedelics and serotonin 5-HT2Aantagonists block the psychedelic activity of LSD. LSD exhibitsfunctional selectivity at the serotonin 5-HT2A and 5-HT2C receptors in that it activates thesignal transduction enzymephospholipase A2 instead of activating the enzymephospholipase C as the endogenous ligand serotonin does.[166]
Exactly how LSD produces its effects is unknown, but it is thought that it works by increasingglutamate release in thecerebral cortex[69] and thereforeexcitation in this area, specifically inlayer V.[167] LSD, like many other drugs of recreational use, has been shown to activateDARPP-32-related pathways.[168] The drug enhances dopamine D2 receptorprotomer recognition andsignaling of D2–5-HT2A receptor complexes,[169] which may contribute to its psychotropic effects.[169] LSD has been shown to have low affinity forH1 receptors, displaying antihistamine effects, although the significance of this at doses used in humans is unknown.[170][171]
LSD is abiased agonist that induces a conformation in serotonin receptors that preferentially recruitsβ-arrestin overactivating G proteins.[172] LSD also has an exceptionally longresidence time when bound to serotonin receptors lasting hours, consistent with the long-lasting effects of LSD despite its relatively rapidclearance.[173][172] A crystal structure of the serotonin 5-HT2B receptor bound to LSD reveals an extracellular loop that forms a "lid" over the diethylamide end of the binding cavity and "traps" LSD in the binding pocket, which explains the slow rate of LSD unbinding from serotonin receptors.[173][174] The relatedlysergamidelysergic acid amide (LSA) that lacks the diethylamidemoiety is far less hallucinogenic in comparison.[174] Moreover, a specific residue in the binding pocket is partially responsible for the prolonged action of LSD, and this residue is found in the human protein but not in the receptors of rodents.[173]
LSD is an extraordinarilypotentpsychoactive drug and is among the most potent psychedelics known in humans.[27][45][47] The very high potency of LSD in producing psychedelic-like effects is also the case in animals, including rodents and monkeys.[47][175] It is unclear why LSD is so potent.[45][69][176] Theaffinity andactivational potency of LSD at the human serotonin 5-HT2A receptorin vitro is unremarkable compared to other psychedelics such asDOI andDOB.[45][69][176] There is no evidence for its greater potency being related topharmacokinetics ormetabolism.[69] It appears that theN,N-diethylamidemoiety of LSD fits into a sterically constrained region of the serotonin 5-HT2A receptor that specifically accommodates this moiety.[45][177][176]
An agonist is usually defined as a molecule that activates a receptor it binds to directly, according to that LSD binds to the TAAR1-receptor inside a dopaminergic neuron is meaning an acceleration of releasing endogenous dopamine from. So by assuming, that also the partial agonism at autoreceptors from LSD is mostly acting agonistic in these pathways, the overall activation of the dopamine system from LSD is very strong.[178]
Thecryo-EMstructures of the serotonin 5-HT2A receptor with LSD, as well as with various other psychedelics and serotonin 5-HT2A receptor agonists, have been solved and published byBryan L. Roth and colleagues.[184][185]
Neuroimaging studies usingresting statefMRI recently suggested that LSD changes the cortical functional architecture.[187] These modifications spatially overlap with the distribution of serotonergic receptors. In particular, increased connectivity and activity were observed in regions with high expression of5-HT2A receptor, while a decrease in activity and connectivity was observed in cortical areas that are dense with5-HT1A receptor.[188] Experimental data suggest that subcortical structures, particularly the thalamus, play a synergistic role with the cerebral cortex in mediating the psychedelic experience. LSD, through its binding to cortical 5-HT2A receptor, may enhance excitatory neurotransmission along frontostriatal projections and, consequently, reduce thalamic filtering of sensory stimuli towards the cortex.[189] This phenomenon appears to selectively involve ventral, intralaminar, and pulvinar nuclei.[189]
The oralbioavailability of LSD was crudely estimated as approximately 71% using previous data onintravenous administration of LSD.[10][14] The sample was equally divided between male and female subjects and there were no significant sex differences observed in the pharmacokinetics of LSD.[10][14] In a subsequent higher-quality 2025 study, the oral bioavailability of LSD was about 80%.[7][8]
Thepharmacokinetics 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.[10][14] In a sample of 16 healthy subjects, a single mid-range 200μg oral dose of LSD was found to produce meanmaximal concentrations of 4.5ng/mL at a median of 1.5hours (range 0.5–4hours) post-administration.[10][14]
A large meal before taking LSD has been found to result in circulating levels that were 50% lower than on an empty stomach.[9]
It has been said that there is a peculiar 40-minute lag beforeonset of the psychedelic effects of LSD when it is administeredintravenously.[177] This has been said to be related to time-dependent interactions of LSD with the serotonin 5-HT2A receptor.[177] However, contradicting the preceding claims, other sources have stated that intravenous injection of LSD results in onset of effects within a few minutes.[9][13][47] In a 2025 pharmacokinetic study comparing oral and intravenous LSD, the onset orally was about 45minutes and the onset by intravenous injection was about 2.5minutes.[7] In addition,intrathecal injection (intraspinal injection) is reported to have a virtually instantaneous onset of action.[9][13] However, in the 2025 study, time to maximal effects was about 2.5hours orally and about 1.2hours intravenously.[7] In an earlier 2016 study, intravenous LSD effects similarly peaked after about 1.7hours.[22][192] For comparison, intravenousdimethyltryptamine (DMT) given as abolus has been found to produce maximal effects after about 2minutes and intravenous psilocybin given over 60seconds after about 4minutes.[12][22] Doses of LSD are said to be similar by oral and injectable routes, with the exception of intrathecal injection in which the dose is reduced to about one-third of usual.[13]
Only 1% of the drug was eliminated inurine unchanged, whereas 13% was eliminated as O-H-LSD within 24hours.[10][14]
Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175minutes (about 3hours);[163] however, using more accurate techniques, Papac and Foltz (1990) reported that 1μg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1hours, with a peak plasma concentration of 5ng/mL at 3hours post-dose.[197] In a more modern 2015 study, concentrations of LSD decreased followingfirst-order kinetics with ahalf-life of 3.6 ± 0.9 hours and aterminal half-life of 8.9 ± 5.9 hours.[10][14]
The acute effects of LSD normally last between 6 and 12hours depending on dose, tolerance, and age.[6][9] In a modern study, the effects of the dose of LSD given lasted for up to 12hours and were closely correlated with the concentrations of LSD present in circulation over time, with no acutetolerance observed.[10][14]
The four possible stereoisomers of the LSD molecule. Only LSD (d-LSD) is active. The other, inactive isomers areiso-LSD (d-iso-LSD),l-LSD, andl-iso-LSD.
The 5S- orlevo- stereoisomers of lysergamides do not exist in nature and are not formed during the synthesis fromd-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 ofbases, as the alpha proton is acidic and can bedeprotonated and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated bychromatography and can be isomerized to LSD.
Pure salts of LSD aretriboluminescent, emitting small flashes of white light when shaken in the dark.[6] LSD is stronglyfluorescent and will glow bluish-white underUV light.
Albert Hofmann synthesized LSD in the following manner: (1) hydrazinolysis of ergotamine into D- and L-isolysergic acid hydrazide, (2) separation of the enantiomers with di-(p-toluyl)-D-tartaric acid to get D-isolysergic acid hydrazide, (3) enantiomerization into D-lysergic acid hydrazide, (4) substitution withHNO2 to D-lysergic acid azide and (5) finally substitution withdiethylamine to form D-lysergic acid diethylamide.[27]
"LSD," writes the chemistAlexander Shulgin, "is an unusually fragile molecule ... As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely."[6]
LSD has twolabile protons at the tertiary stereogenic C5 and C8 positions, rendering these centers prone toepimerisation. The C8 proton is more labile due to the electron-withdrawingcarboxamide attachment, but the removal of thechiral proton at the C5 position (which was once also an alpha proton of the parent moleculetryptophan) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with theindole ring.[citation needed]
LSD also hasenamine-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.[6] Thedouble bond between the 8-position and thearomatic ring, being conjugated with the indole ring, is susceptible tonucleophilic attacks by water oralcohol, especially in the presence of UV or other kinds of light. LSD often converts tolumi-LSD (10-hydroxy-9,10-dihydro-LSD), which is inactive in human beings.[6]
A controlled study was undertaken to determine the stability of LSD in pooled urine samples.[203]
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. The 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 the buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition ofEDTA.
Ehrlich's reagent can be used to test for the presence of LSD in a sample, turning purple upon reaction.[204]
LSD can be detected in concentrations larger than approximately 10% in a sample usingEhrlich's reagent and Hofmann's reagent. However, detecting LSD in human tissues is more challenging due to its active dose being significantly lower (inmicrograms) compared to most other drugs (inmilligrams).[205]
LSD may be quantified in urine for drug testing programs, in plasma or serum to confirm poisoning in hospitalized victims, or in whole blood for forensic investigations. The parent drug and its major metabolite are unstable in biofluids when exposed to light, heat, or alkaline conditions, necessitating protection from light, low-temperature storage, and quick analysis to minimize losses.[206] Maximum plasma concentrations are typically observed 1.4 to 1.5 hours after oral administration of 100μg and 200μg, respectively, with a plasma half-life of approximately 2.6 hours (ranging from 2.2 to 3.4 hours among test subjects).[207]
Due to its potency in microgram quantities, LSD is often not included in standard pre-employment urine or hair analyses.[205][208] However, advancedliquid chromatography–mass spectrometry methods can detect LSD in biological samples even after a single use.[208]
... 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[225]: 15
Swiss chemistAlbert Hofmann first synthesized LSD in 1938 fromlysergic acid, a chemical derived from thehydrolysis ofergotamine, analkaloid found inergot, a fungus that infects grain.[18][26] LSD was the 25th of variouslysergamides Hofmann synthesized from lysergic acid while trying to develop a newanaleptic, hence the alternate name LSD-25. Hofmann discovered its effects in humans on April 16, in 1943, after unintentionally ingesting an unknown amount, possibly absorbing it through his skin.[226][227][228] On April 19, 1943, Hofmann intentionally ingested 0.25 milligrams (250 micrograms) of LSD.[229] LSD was first published in thescientific literature by Hofmann and his colleaguepsychiatristWerner Stoll in 1943 and the hallucinogenic effects of LSD were first published by Stoll in 1947.[230][231][232][233][234]
LSD was subject to exceptional interest within the field ofpsychiatry in the 1950s and early 1960s, withSandoz distributing LSD to researchers under the trademark name Delysid in an attempt to find a marketable use for it.[227] During this period, LSD was controversially administered to hospitalised schizophrenic autistic children, with varying degrees of therapeutic success.[235][236][237][238] It was said to have been tried in every type of mental disorder by 1960.[47] LSD was also used in an attempt to curehomosexuality.[47] Most of the early studies of LSD for psychiatric conditions were of very low quality, often lacking evencontrol groups.[47] In 1975, it was concluded that LSD showed little difference fromplacebo for most conditions, but this conclusion was still based on low-quality evidence.[47]
According to declassified CIA documents, it's possible that the American agency spread LSD on civilians in Europe in the 50s.[240][241]
In the 1960s, LSD and other psychedelics were adopted by and became synonymous with thecounterculture movement due to their perceived ability to expand consciousness. This resulted in LSD being viewed as a cultural threat to American values and theVietnam War effort, and it was designated as aSchedule I (illegal for medical as well as recreational use) substance in 1968.[29] It was listed as aSchedule I controlled substance by theUnited Nations in 1971 and currently has no approved medical uses.[18] As of 2017[update], 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.[31] It was most popular in the 1960s to 1980s.[18] The use of LSD among US adults increased by 56.4% from 2015 to 2018.[242]
LSD was first synthesized on November 16, 1938[243] by Swiss chemistAlbert Hofmann at theSandoz Laboratories inBasel, Switzerland as part of a large research program searching for medically usefulergot alkaloid derivatives. The abbreviation "LSD" is from the German "Lysergsäurediethylamid".[244]
LSD'spsychedelic properties were discovered 5 years later when Hofmann himself accidentally ingested an unknown quantity of the chemical.[245] The first intentional ingestion of LSD occurred on April 19, 1943,[225] when Hofmann ingested 250μg of LSD. He said this would be a threshold dose based on the doses of other ergot alkaloids. Hofmann found the effects to be much stronger than he anticipated.[246] 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."[247] Sandoz would send the drug for free to researchers investigating its effects.[226]
'Effects of Lysergic Acid Diethylamide (LSD) on Troops Marching' – 16mm film produced by the United States military circa 1958
Beginning in the 1950s, the USCentral Intelligence Agency (CIA) began a research program code-namedProject MKUltra.[248] The CIA introduced LSD to the United States, purchasing the entire world's supply for $240,000 and propagating the LSD through CIAfront organizations to American hospitals, clinics, prisons, and research centers.[249] Experiments included administering LSD to CIA employees, military personnel, doctors, other government agents, prostitutes, mentally ill patients, and members of the general public to study their reactions, usually without the subjects' knowledge. The project was revealed in the US congressionalRockefeller Commission report in 1975. However, the extent of the experiments conducted under Project MKUltra are still mostly unknown, as acting CIA director Richard Helms destroyed many of the key documents related to MKUltra in 1973.[250]
In 1963, the Sandoz patents on LSD expired[51] and the Czech company Spofa began to produce the substance.[226] Sandoz stopped the production and distribution in 1965.[226]
Several figures, includingAldous Huxley,Timothy Leary, andAl Hubbard, had begun to advocate the consumption of LSD. LSD became central to the counterculture of the 1960s.[251] 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 andArthur Koestler,[252][253] and according to L. R. Veysey they profoundly influenced the thinking of the new generation of youth.[254]
On October 24, 1968, possession of LSD was made illegal in the United States.[255] The lastFDA 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.[256]
In November 2020, Oregon became the first US state to decriminalize possession of small amounts of LSD after voters approvedBallot Measure 110.[257]
By the mid-1960s, the youthcountercultures in California, particularly in San Francisco, had widely adopted the use of hallucinogenic drugs, including LSD. The first major underground LSD factory was established byOwsley Stanley.[258] Around this time, theMerry Pranksters, associated with novelistKen Kesey, organized theAcid Tests, events in San Francisco involving LSD consumption, accompanied by light shows and improvised music.[259][260] Their activities, including cross-country trips in a psychedelically-decorated bus and interactions with major figures of the beat movement, were later documented inTom Wolfe'sThe Electric Kool-Aid Acid Test (1968).[261]
In San Francisco's Haight-Ashbury neighborhood, the Psychedelic Shop was opened in January 1966 by brothers Ron and Jay Thelin to promote the safe use of LSD. This shop played a significant role in popularizing LSD in the area and establishingHaight-Ashbury as the epicenter of the hippie counterculture. The Thelins also organized theLove Pageant Rally in Golden Gate Park in October 1966, protesting against California's ban on LSD.[262][263]
A similar movement developed in London, led by British academicMichael Hollingshead, who first tried LSD in America in 1961. After experiencing LSD and interacting with notable figures such asAldous Huxley,Timothy Leary, andRichard Alpert, Hollingshead played a key role in the famous LSD research at Millbrook before moving to New York City for his experiments. In 1965, he returned to the UK and founded the World Psychedelic Center in Chelsea, London.[264]
Blotter art is an art form printed on perforated sheets of absorbentblotting paper infused with liquid LSD. The delivery method gained popularity following the banning of thehallucinogen LSD in the late 1960s. The use of graphics on blotter sheets originated as anunderground art form in the early 1970s, sometimes to help identify the dose, maker, or batch of LSD.
A drawing of a face, made under the effects of LSD.Dr. Oscar Janiger noted similarities between paintings made under the influence of the drug and those made by schizophrenics.
LSD art is anyart or visual displays inspired bypsychedelic experiences andhallucinations known to follow the ingestion of LSD (also known colloquially as acid).[265] Artists and scientists have been interested in the effect of LSD on drawing and painting since it first became available for legal use and general consumption.[266]
Psychedelic art for the cover of an issue of undergroundcounterculture newspaperHelix, 1967.
The influence of LSD in the realms of music and art became pronounced in the 1960s, especially through the Acid Tests and related events involving bands like theGrateful Dead,Jefferson Airplane, andBig Brother and the Holding Company. San Francisco-based artists such asRick Griffin,Victor Moscoso, andWes Wilson contributed to this movement through their psychedelic poster and album art.The Grateful Dead, in particular, became central to the culture of "Deadheads", with their music heavily influenced by LSD.[267]
Psychedelic music of the 1960s often sought to replicate the LSD experience, incorporating exotic instrumentation, electric guitars with effects pedals, and elaborate studio techniques. Artists and bands utilized instruments like sitars and tablas, and employed studio effects such as backward tapes, panning, and phasing.[269][270] Songs such asJohn Prine's "Illegal Smile" and the Beatles' "Lucy in the Sky with Diamonds" have been associated with LSD, although the latter's authors denied such claims.[271][page needed][272]
TheUnited NationsConvention on Psychotropic Substances of 1971 mandates that signing parties, including the United States, Australia, New Zealand, and most of Europe, prohibit LSD. Enforcement of these laws varies by country. The convention allows medical and scientific research with LSD.[277]
In Australia, LSD is classified as a Schedule 9 prohibited substance under the Poisons Standard (February 2017), indicating it may be abused or misused and its manufacture, possession, sale, or use should be prohibited except for approved research purposes.[278] In Western Australia, the Misuse of Drugs Act 1981 provides guidelines for possession and trafficking of substances like LSD.[279]
In Canada, LSD is listed under Schedule III of the Controlled Drugs and Substances Act. Unauthorized possession and trafficking of the substance can lead to significant legal penalties.[280]
In the United Kingdom, LSD is a Class A drug under the Misuse of Drugs Act 1971, making unauthorized possession and trafficking punishable by severe penalties. The Runciman Report and Transform Drug Policy Foundation have made recommendations and proposals regarding the legal regulation of LSD and other psychedelics.[281][282]
In the United States, LSD is classified as a Schedule I controlled substance under the Controlled Substances Act of 1970, making its manufacture, possession, and distribution illegal without a DEA license. The law considers LSD to have a high potential for abuse, no legitimate medical use, and to be unsafe even under medical supervision. The US Supreme Court case Neal v. United States (1995) clarified the sentencing guidelines related to LSD possession.[283]
Oregon decriminalized personal possession of small amounts of drugs, including LSD, in February 2021, and California has seen legislative efforts to decriminalize psychedelics.[284]
Mexico decriminalized the possession of small amounts of drugs, including LSD, for personal use in 2009. The law specifies possession limits and establishes that possession is not a crime within designated quantities.[285]
In the Czech Republic, possession of "amount larger than small" of LSD is criminalized, while possession of smaller amounts is a misdemeanor. The definition of "amount larger than small" is determined by judicial practice and specific regulations.[286][287]
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 precursorergotaminetartrate can produce 5–6kg of pure crystalline LSD; this corresponds to around 50–60million doses at 100μg. Because the masses involved are so small, concealing and transporting illicit LSD is much easier than smugglingcocaine,cannabis, or other illegal drugs.[288]
Manufacturing LSD requires laboratory equipment and experience in the field oforganic 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.[288] Ali Altaft, the lead chemist at theUniversity of Okara, inPunjab, Pakistan, performed the synthesis of LSD on video.[289]
LSD is produced in crystalline form and is then mixed withexcipients 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[clarification needed] forced a change totablet form. Appearing in 1968 as an orange tablet measuring about 6mm 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.[290]
Over some time, tablet dimensions, weight, shape and concentration of LSD evolved from large (4.5–8.1mm diameter), heavyweight (≥150μg), round, high concentration (90–350μg/tab) dose units to small (2.0–3.5mm diameter) lightweight (as low as 4.7μg/tab), variously shaped, lower concentration (12–85μg/tab, average range 30–40μg/tab) dose units. LSD tablet shapes have included cylinders, cones, stars, spacecraft, and heart shapes. The smallest tablets became known as "Microdots".[291]
After tablets came "computer acid" or "blotter paper LSD", typically made by dipping a preprinted sheet ofblotting paper into an LSD/water/alcohol solution.[290][291] More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975.[291] About the same time as blotter paper LSD came "Windowpane" (AKA "Clearlight"), which contained LSD inside a thingelatin square a quarter of an inch (6mm) across.[290] 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.[55][292] Authorities have encountered the drug in other forms—including powder or crystal, and capsule.[293]
Blotter art designs printed on blotter paper can serve to identify dose strengths, different batches, or makers.[294]
On the other hand, blotters without art may be considered safer by some, since there is no guarantee that theprinter ink used in clandestine production is edible or non-toxic for long-term exposure, and it is also possible for unscrupulous dealers to mimic reputable blotter art designs in order to boost sales.
'White on White' ('WoW') LSD blotters lacks blotter art (ink)
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.[295][296]
As a group, independent producers are of less concern to theDrug Enforcement Administration than the large-scale groups because their product reaches only local markets.[247]
Many LSD dealers and chemists describe a religious or humanitarian purpose that motivates their illicit activity. Nicholas Schou's bookOrange 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.[297]
In the second half of the 20th century, dealers and chemists loosely associated with theGrateful Dead likeOwsley Stanley,Nicholas Sand, Karen Horning, Sarah Maltzer, "Dealer McDope", andLeonard Pickard played an essential role in distributing LSD.[267]
LSD blotter acid mimic actually containing DOC.Different blotters which could possibly be mimics.
Since 2005, law enforcement in the United States and elsewhere has seized several chemicals and combinations of chemicals in blotter paper which were sold as LSD mimics, includingDOB,[298][299] a mixture ofDOC andDOI,[300]25I-NBOMe,[301] and a mixture ofDOC andDOB.[302] 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 achromatographic analysis of blotter paper containing2C-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.[303] Blotter LSD mimics can have relatively small dose squares; a sample of blotter paper containingDOC seized byConcord, California police had dose markings approximately 6mm apart.[304] Several deaths have been attributed to 25I-NBOMe.[305][306][307][308]
Some notable individuals have commented publicly on their experiences with LSD.[309][310] 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 topsychiatric treatment in the 1950s and 1960s. Still others describe experiences with illegal LSD, obtained for philosophic, artistic, therapeutic, spiritual, or recreational purposes.
W. H. Auden, the poet, said, "I myself have taken mescaline once and L.S.D. once. Aside from a slight schizophrenic dissociation of the I from the Not-I, including my body, nothing happened at all."[311] He also said, "LSD was a complete frost. … What it does seem to destroy is the power of communication. I have listened to tapes done by highly articulate people under LSD, for example, and they talk absolute drivel. They may have seen something interesting, but they certainly lose either the power or the wish to communicate."[312] He also said, "Nothing much happened but I did get the distinct impression that some birds were trying to communicate with me."[313]
James Cameron, the Canadian filmmaker, has said he experimented with LSD during his college years.[314]
Daniel Ellsberg, an American peace activist, says he has had several hundred experiences with psychedelics.[315]
Richard Feynman, a notable physicist atCalifornia Institute of Technology, tried LSD during his professorship at Caltech. Feynman largely sidestepped the issue when dictating his anecdotes; he mentions it in passing in the "O Americano, Outra Vez" section.[316][317]
Jerry Garcia stated in a July 3, 1989 interview forRelix Magazine, in response to the question "Have your feelings about LSD changed over the years?," "They haven't changed much. My feelings about LSD are mixed. It's something that I both fear and that I love at the same time. I never take any psychedelic, have a psychedelic experience, without having that feeling of, "I don't know what's going to happen." In that sense, it's still fundamentally an enigma and a mystery."[318]
Aldous Huxley, author ofBrave New World, became a user of psychedelics after moving toHollywood. He was at the forefront of the counterculture's use of psychedelic drugs, which led to his 1954 workThe Doors of Perception. Dying from cancer, he asked his wife on 22 November 1963 to inject him with 100μg of LSD. He died later that day.[320]
Steve Jobs, co-founder and former CEO ofApple Inc., said, "Taking LSD was a profound experience, one of the most important things in my life."[321]
Ernst Jünger, German writer and philosopher, throughout his life had experimented withdrugs such asether,cocaine, andhashish; and later in life he usedmescaline and LSD. These experiments were recorded comprehensively inAnnäherungen (1970,Approaches). The novelBesuch auf Godenholm (1952,Visit to Godenholm) is clearly influenced by his early experiments with mescaline and LSD. He met with LSD inventorAlbert Hofmann and they took LSD together several times. Hofmann's memoirLSD, My Problem Child describes some of these meetings.[322]
In a 2004 interview,Paul McCartney said thatThe Beatles' songs "Day Tripper" and "Lucy in the Sky with Diamonds" were inspired by LSD trips.[271]: 182 Nonetheless,John Lennon consistently stated over the course of many years that the fact that the initials of "Lucy in the Sky with Diamonds" spelled out L-S-D was a coincidence (he stated that the title came from a picture drawn by his sonJulian) and that the band members did not notice until after the song had been released, and Paul McCartney corroborated that story.[323]John Lennon,George Harrison, andRingo Starr also used the drug, although McCartney cautioned that "it's easy to overestimate the influence of drugs on the Beatles' music."[324]
Michel Foucault had an LSD experience with Simeon Wade inDeath Valley and later wrote "it was the greatest experience of his life, and that it profoundly changed his life and his work."[325][326] According to Wade, as soon as he came back to Paris, Foucault scrapped the second History of Sexuality's manuscript, and totally rethought the whole project.[327]
Oliver Sacks, aneurologist famous for writing best-selling case histories about his patients' disorders and unusual experiences, talks about his own experiences with LSD and other perception altering chemicals, in his book,Hallucinations.[330]
Alexander Shulgin, American chemist, told Albert Hofmann that he preferred LSD to2C-B.
LSD was initially explored forpsychiatric use due to its structural similarity to theneurotransmitterserotonin and itssafety profile.[27] In the 1950s and 1960s, it was used in psychiatry to enhancepsychotherapy, known aspsychedelic therapy. In theUnited States, the earliest research began in the 1950s.Albert Kurland and his colleagues published research on LSD's therapeutic potential to treatschizophrenia. InCanada,Humphry Osmond andAbram Hoffer completed LSD studies as early as 1952.[332] Somepsychiatrists, such asRonald A. Sandison, who pioneered its use atPowick Hospital in England, believed that LSD was especially useful at helping patients to "unblock" repressed subconscious material through otherpsychotherapeutic methods,[333] and also for treatingalcoholism.[334][335] One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producingself-acceptance and self-surrender,"[28] presumably by forcing the user to face issues and problems in that individual's psyche. By the 1960s however, controversies surrounding "hippie"counterculture began to deplete institutional support for continued studies.
In more recent years, there has been renewed clinical research on and interest in LSD for potential therapeutic uses.[336] This has been supported by several organizations, including theMultidisciplinary Association for Psychedelic Studies (MAPS), theBeckley Foundation, theHeffter Research Institute, and the Albert Hofmann Foundation, which exist to fund, encourage, and coordinate research into the medicinal and spiritual uses of LSD and related psychedelics.[337] New clinical LSD experiments in humans started in 2009 for the first time in 35 years.[336] As the drug is illegal in many areas of the world, potential medical uses have historically been difficult to study.[42] Investigational uses of LSD include the treatment ofalcoholism,[338]anxiety, anddepression, among other conditions.[339][38][39][93][340] Another use is alleviation of anxiety interminally illcancer patients.[38][336][341]
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, moderateconfusion and agitation, nausea,vomiting, and acting in a bizarre fashion.[37] A couple of reviews published in 2010 and 2014 concluded that conclusions drawn from most early trials are unreliable due to seriousmethodological flaws. These include the absence of adequatecontrol groups, lack of follow-up, and vague criteria fortherapeutic outcome. In many cases, studies failed to convincingly demonstrate whether the drug or the therapeutic interaction was responsible for any beneficial effects.[342][343] A 2020 meta-review indicated possible positive effects of LSD in reducing psychiatric symptoms, mainly in cases of alcoholism.[344]
LSD is apsychoplastogen, a compound capable of promoting rapid and sustainedneural plasticity, an action that hypothetically might be involved in its therapeutic benefits, although more research is needed to substantiate such notions.[347][348][349]
TheBritishcritical psychiatristJoanna Moncrieff has critiqued the use and study of psychedelics like LSD for treatment of psychiatric disorders, highlighting concerns including excessive hype around these drugs, questionable biologically-based theories of benefit, blurred lines between medical and recreational use, flawed clinical trial findings, financial conflicts of interest, strong expectancy effects and large placebo responses, small and short-term benefits over placebo, and their potential for difficult experiences and adverse effects, among others.[350]
In the 1950s and 1960s, some psychiatrists, such asOscar Janiger, explored the potential effect of LSD oncreativity. Experimental studies attempted to measure the effect of LSD on creative activity and aesthetic appreciation.[56][354][355][356] In 1966,James Fadiman conducted a study with the central question "How can psychedelics be used to facilitate problem solving?" This study attempted to solve 44 different problems and had 40 satisfactory solutions when the FDA banned all research into psychedelics. LSD was a key component of this study.[357][358]
^Thepotency ofN-benzylphenethylamines via buccal, sublingual, or nasal absorption is 50–100 greater (by weight) than oral route compared to the parent2C-x compounds.[139] Researches hypothesize the low oral metabolic stability ofN-benzylphenethylamines is likely causing the low bioavailability on the oral route, although the metabolic profile of this compounds remains unpredictable; therefore researches state that the fatalities linked to these substances may partly be explained by differences in the metabolism between individuals.[139]
^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.ISBN978-3-642-27772-6.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
^abMalenka 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 (2nd ed.). New York: McGraw-Hill Medical. p. 375.ISBN978-0-07-148127-4.Archived from the original on August 28, 2023. RetrievedJune 12, 2023.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)
^abcdefghijkMucke 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.PMID27392130.
^"Lysergide".pubchem.ncbi.nlm.nih.gov.Archived from the original on April 12, 2023. RetrievedApril 12, 2023.
^abcChwelos 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.PMID13810249.
^abUnited States Congress House Committee on Interstate and Foreign Commerce Subcommittee on Public Health and Welfare (1968).Increased Controls Over Hallucinogens and Other Dangerous Drugs. U.S. Government Printing Office.Archived from the original on July 13, 2020. RetrievedAugust 3, 2021.
^Fahey DM, Miller JS (August 27, 2013). Fahey D, Miller JS (eds.).Alcohol and Drugs in North America: A Historical Encyclopedia. Bloomsbury Academic. p. 375.ISBN978-1-59884-478-8.
^abNutt DJ, King LA, Nichols DE (August 2013). "Effects of Schedule I drug laws on neuroscience research and treatment innovation".Nature Reviews. Neuroscience.14 (8):577–585.doi:10.1038/nrn3530.PMID23756634.S2CID1956833.
^abcdefNichols DE (2017)."Chemistry and Structure–Activity Relationships of Psychedelics".Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 1–43.doi:10.1007/7854_2017_475.ISBN978-3-662-55878-2.PMID28401524. Archived fromthe original on March 23, 2025.Although LSD is the most well-known psychedelic, only a very few structural modifications can be made to its structure, and nearly all of those attenuate its activity by about an order of magnitude. In addition, there is a paucity of structure–activity data for ergolines, principally due to the synthetic difficulty inherent in their chemistry. [...] Although LSD is the most potent psychedelic agent in humans, its affinity and potency at the human 5-HT2A receptor is rather unremarkable compared with much simpler molecules such as DOI. [...] Because of its structural complexity and tedious approaches to its total synthesis, only a few structural modifications of LSD have been reported. [...] Unfortunately, only a few of them have been assessed in human psychopharmacology, most being much less active than LSD itself.
^Albert Hofmann (1968)."Psychotomimetic Agents". In Burger A (ed.).Drugs Affecting the Central Nervous System. Vol. 2. New York: M. Dekker. pp. 169–235.OCLC245452885.OL13539506M.Subsequent experiments on volunteers of the Sandoz research laboratories confirmed the extraordinary activity of lysergic acid diethylamide on the human psyche. These showed that the effective oral dose of LSD in human beings is 0.03—0.05 mg. [...] LSD is by far the most active and most specific psychotomimetic. It is about 5,000—10,000 times more active than mescaline or about 100–200 times more active than psilocybin.
^El-Mallakh RS, Walker KL (2010). "Hallucinations, psuedohallucinations, and parahallucinations".Psychiatry.73 (1):34–42.doi:10.1521/psyc.2010.73.1.34.PMID20235616.
^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):241–253.doi:10.1177/0269881114568040.PMID25670401.S2CID16483172.
^Rogge T (May 21, 2014),Substance use – LSD, MedlinePlus, U.S. National Library of Medicine,archived from the original on July 28, 2016, retrievedJuly 14, 2016
^CESAR (October 29, 2013),LSD, Center for Substance Abuse Research, University of Maryland, archived fromthe original on July 15, 2016, retrievedJuly 14, 2016
^abLinton HR, Langs RJ (May 1962). "Subjective Reactions to Lysergic Acid Diethylamide (LSD-25)".Archives of General Psychiatry.6 (5):352–368.doi:10.1001/archpsyc.1962.01710230020003.
^Parker LA (June 1996). "LSD produces place preference and flavor avoidance but does not produce flavor aversion in rats".Behavioral Neuroscience.110 (3):503–508.doi:10.1037/0735-7044.110.3.503.PMID8888996.
^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, Special Issue: Identifying the Origins of Mental Illness: A Festschrift in Honor of Ming T. Tsuang,162 (7):661–670,doi:10.1002/ajmg.b.32177,PMID24132898,S2CID205326399
^Sjoberg BM, Hollister LE (November 1965). "The effects of psychotomimetic drugs on primary suggestibility".Psychopharmacologia.8 (4):251–262.doi:10.1007/BF00407857.PMID5885648.S2CID15249061.
^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.PMID12609692.
^abHalpern 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.ISBN978-3-662-55878-2.PMID27822679.
^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.PMID25744618.S2CID2025731.
^Buchborn T, Grecksch G, Dieterich D, Hollt V (2016). "Chapter 79 - Tolerance to Lysergic Acid Diethylamide: Overview, Correlates, and Clinical Implications".Neuropathology of Drug Addictions and Substance Misuse. Vol. 2.Academic Press. pp. 848–849.doi:10.1016/B978-0-12-800212-4.00079-0.ISBN978-0-12-800212-4.
^Rosenberg D, Isbell H, Miner E, Logan C (August 7, 1963). "The effect of N,N-dimethyltryptamine in human subjects tolerant to lysergic acid diethylamide".Psychopharmacologia.5 (3):223–224.doi:10.1007/BF00413244.PMID14138757.S2CID32950588.
^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):303–386.doi:10.1007/BF00413161.PMID4953438.S2CID11768927.
^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):314–317.doi:10.1016/0006-3223(86)90053-3.PMID3947713.S2CID35508993.
^Balestrieri A, Fontanari D (September 1959). "Acquired and crossed tolerance to mescaline, LSD-25, and BOL-148".Archives of General Psychiatry.1 (3):279–282.doi:10.1001/archpsyc.1959.03590030063008.PMID13796178.
^Morgenstern J, Langenbucher J, Labouvie E (September 1994). "The generalizability of the dependence syndrome across substances: an examination of some properties of the proposed DSM-IV dependence criteria".Addiction.89 (9). Society for the Study of Addiction:1105–1113.doi:10.1111/j.1360-0443.1994.tb02787.x.PMID7987187.
^abcTagen M, Mantuani D, van Heerden L, Holstein A, Klumpers LE, Knowles R (September 2023). "The risk of chronic psychedelic and MDMA microdosing for valvular heart disease".J Psychopharmacol.37 (9):876–890.doi:10.1177/02698811231190865.PMID37572027.
^McIntyre RS (2023). "Serotonin 5-HT2B receptor agonism and valvular heart disease: implications for the development of psilocybin and related agents".Expert Opin Drug Saf.22 (10):881–883.doi:10.1080/14740338.2023.2248883.PMID37581427.
^Luethi D, Liechti ME (2021). "Drugs of Abuse Affecting 5-HT2B Receptors".5-HT2B Receptors. The Receptors. Vol. 35. Cham: Springer International Publishing. pp. 277–289.doi:10.1007/978-3-030-55920-5_16.ISBN978-3-030-55919-9.
^abcKlock JC, Boerner U, Becker CE (1975). "Coma, hyperthermia, and bleeding associated with massive LSD overdose, a report of eight cases".Clin Toxicol.8 (2):191–203.doi:10.3109/15563657508988063.PMID1149410.
^Goldstein RA, DesLauriers C, Burda A, Johnson-Arbor K (February 2009). "Cocaine: history, social implications, and toxicity: a review".Semin Diagn Pathol.26 (1):10–17.doi:10.1053/j.semdp.2008.12.001.PMID19292024.When "snorted," a typical "line" of cocaine contains approximately 50-100 mg of parent compound, although it is often "cut" or adulterated with other substances.20
^abShulgin AT (1976). "Psychotomimetic Agents". In Gordon M (ed.).Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. Vol. 4. Academic Press. pp. 59–146.doi:10.1016/b978-0-12-290559-9.50011-9.ISBN978-0-12-290559-9.The largest number of structural analogs of LSD that have been prepared involve the opening of one or more of the rings of the parent lysergic acid system. [...] A recent review covers this chemistry (Campaigne and Knapp, 1971), but there is apparently no human psychopharmacology as yet known.
^Reynolds HH, Peterson GK (August 1966). "Psychophysiological effects of a large non-experimental dose of LSD-25".Psychol Rep.19 (1):287–290.doi:10.2466/pr0.1966.19.1.287.PMID5942100.
^abMalcolm B, Thomas K (June 2022). "Serotonin toxicity of serotonergic psychedelics".Psychopharmacology (Berl).239 (6):1881–1891.doi:10.1007/s00213-021-05876-x.PMID34251464.
^abTap SC, Thomas K, Páleníček T, Stenbæk DS, Oliveira-Maia AJ, van Dalfsen J, et al. (September 2025)."Concomitant use of antidepressants and classic psychedelics: A scoping review".J Psychopharmacol.39 (10) 02698811251368360: 2698811251368360.doi:10.1177/02698811251368360.PMC12572353.PMID40937732.Importantly, the idea of increased risk for developing serotonin syndrome and/or serotonin toxicity, when [antidepressants (ADs)] are co-administered with high doses of psychedelics, has recently been challenged, in part because classic psychedelics are partial agonists of the 5-HT2A receptor and would also compete for serotonin binding (Malcolm and Thomas, 2022; Rickli et al., 2016; Sarparast et al., 2022). Based on this clinical rationale, the concomitant use of ADs and classic psychedelics may be preferred, or patients could temporarily reduce the dose of ADs around dosing days with psychedelics to have minimal interactions. Simultaneously, the competition for 5-HT2A receptors could impede the biological action of psychedelics during concomitant use of ADs and potentially limit efficacy (Halman et al., 2024), particularly as the 5-HT2A receptor induces neuroplasticity (Cameron et al., 2023; Ly et al., 2018; Vargas et al., 2023).{{cite journal}}: CS1 maint: article number as page number (link)
^abcLeonard JB, Anderson B, Klein-Schwartz W (December 2018). "Does getting high hurt? Characterization of cases of LSD and psilocybin-containing mushroom exposures to national poison centers between 2000 and 2016".J Psychopharmacol.32 (12):1286–1294.doi:10.1177/0269881118793086.PMID30182795.
^Rudin D, Liechti ME, Luethi D (September 2021). "Molecular and clinical aspects of potential neurotoxicity induced by new psychoactive stimulants and psychedelics".Exp Neurol.343 113778.doi:10.1016/j.expneurol.2021.113778.PMID34090893.
^Soto-Angona Ó, Fortea A, Fortea L, Martínez-Ramírez M, Santamarina E, López FJ, et al. (August 2024). "Do classic psychedelics increase the risk of seizures? A scoping review".Eur Neuropsychopharmacol.85:35–42.doi:10.1016/j.euroneuro.2024.05.002.PMID38917636.
^Herian M, Świt P (January 2023). "25X-NBOMe compounds - chemistry, pharmacology and toxicology. A comprehensive review".Crit Rev Toxicol.53 (1):15–33.doi:10.1080/10408444.2023.2194907.PMID37115704.
^abLeth-Petersen S, Bundgaard C, Hansen M, Carnerup MA, Kehler J, Kristensen JL (February 14, 2014). "Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability".Neurochemical Research.39 (10):2018–2023.doi:10.1007/s11064-014-1253-y.PMID24519542.S2CID254857910.
^Halberstadt AL (January 18, 2017). "Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens".Neuropharmacology of New Psychoactive Substances. Current Topics in Behavioral Neurosciences. Vol. 32. Springer. pp. 283–311.doi:10.1007/7854_2016_64.ISBN978-3-319-52444-3.PMID28097528.
^Potts AJ, Thomas SHL, Hill SL (September 2021). "Pharmacology and toxicology of N-Benzyl-phenylethylamines (25X-NBOMe) hallucinogens". In Dargan P, Wood D (eds.).Novel Psychoactive Substances: Classification, Pharmacology and Toxicology (2nd ed.). Academic Press. pp. 279–300.doi:10.1016/B978-0-12-818788-3.00008-5.ISBN978-0-12-818788-3.S2CID240583877.
^Clancy L, Philp M, Shimmon R, Fu S (May 2021). "Development and validation of a color spot test method for the presumptive detection of 25-NBOMe compounds".Drug Testing and Analysis.13 (5):929–943.doi:10.1002/dta.2905.PMID32744773.
^Egan C, Grinde E, Dupre A, Roth BL, Hake M, Teitler M, et al. (February 2000). "Agonist high and low affinity state ratios predict drug intrinsic activity and a revised ternary complex mechanism at serotonin 5-HT(2A) and 5-HT(2C) receptors".Synapse.35 (2):144–150.doi:10.1002/(SICI)1098-2396(200002)35:2<144::AID-SYN7>3.0.CO;2-K.PMID10611640.
^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):427–435.doi:10.1007/s00213-005-2183-9.PMID15723230.S2CID23565306.
^abBorroto-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.Bibcode:2014BBRC..443..278B.doi:10.1016/j.bbrc.2013.11.104.PMID24309097.
^abNichols 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.PMID12213075.
^abcRoth BL, Gumpper RH (May 2023)."Psychedelics as Transformative Therapeutics".Am J Psychiatry.180 (5):340–347.doi:10.1176/appi.ajp.20230172.PMID37122272.We now have molecular-level details regarding how psychedelic drugs interact with and activate 5-HT2A receptors (39) (Figure 2B). Studies on a related serotonin receptor (5-HT2B) have clarified how LSD can stabilize distinct signaling complexes (40, 41). A key finding of these studies was the discovery that once LSD binds to the 5-HT2A receptor, a lid is formed over the binding pocket, which "traps" LSD for several hours (39, 40) (Figure 2B). These findings imply that at least part of the reason for the long duration of action of drugs like LSD is the trapping of the receptor via conformational changes that occur after drug binding. These studies also showed that this prolonged action of LSD is due in part to a specific residue within the binding pocket, which is found in humans but not in mice or rats (39). This residue (Ser242) also is essential for the high-affinity interactions of LSD, psilocybin, and perhaps other such drugs at the human and nonhuman primate 5-HT2A receptors.
^abcNichols DE (2001)."LSD and Its Lysergamide Cousins"(PDF).The Heffter Review of Psychedelic Research.2.Heffter Research Institute:80–87.ISSN1534-9640.Indeed, the potency of LSD at the 5-HT2A receptor is not as great as that of some of the amphetamine hallucinogens such as DOB or DOI, yet its human potency is about ten times greater. [...] Furthermore, there is a cavity within these receptors that accommodates and is complementary to the activating drug, in this case LSD. What we are forced to conclude is that the area within the receptor that binds to the diethylamide function of LSD is a specific region that must be just large enough to contain the diethyl groups. [...]
^abcdGumpper RH, Nichols DE (October 2024). "Chemistry/structural biology of psychedelic drugs and their receptor(s)".Br J Pharmacol bph.17361.doi:10.1111/bph.17361.PMID39354889.
^Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, et al. (July 2025)."The polypharmacology of psychedelics reveals multiple targets for potential therapeutics"(PDF).Neuron.113 (19): 3129–3142.e9.doi:10.1016/j.neuron.2025.06.012.PMID40683247.Recent studies have suggested that psychedelics such as LSD directly interact with TrkB with high affinity, promoting BDNF-mediated neuroplasticity and antidepressant-like effects via allosteric potentiation of BDNF signaling in active synapses.8 To investigate this, we screened LSD across 450 human kinases, including TrkB, but found no significant interactions between LSD and any tested human kinases. Further experiments in transfected cells revealed no effect of LSD or psilocin on BDNF-mediated activation of a TrkB reporter. We note that similar negative preliminary results, which have not yet been published in a peer-reviewed journal, were recently reported by Boltaev et al.63
^abcMatthias Liechti (2016),"Pharmacology of novel psychoactive substances, MDMA, and LSD"(PDF),Department of Biomedicine. Report 2014–2016, pp. 52–53,LSD produced subjective drug effects that lasted up to 12h (Fig. 3a) and correlated well with the concentrations of LSD in the blood plasma over time (Fig. 3b and c). The half-life of LSD in plasma was 3.5 h. In contrast to LSD, the half-life of MDMA is longer (8h) but the effects of MDMA last only up to 6h despite the continued presence of the substance in the body (Fig. 3d). Thus, there is marked acute tolerance to the effects of MDMA. [...] Fig. 3: Pharmacokinetics-Pharmacodynamics of LSD. LSD effects last up to 12h (a) corresponding to its plasma-concentration time curve (b) and exhibiting no hysteresis in the LSD concentration-effect plot (c). In contrast, the MDMA concentration-effect plot shows pronounced hysteresis consistent with acute tolerance (d).
^Delli Pizzi S, Chiacchiaretta P, Sestieri C, Ferretti A, Onofrj M, Della Penna S, et al. (July 2023). "Spatial Correspondence of LSD-Induced Variations on Brain Functioning at Rest With Serotonin Receptor Expression".Biol Psychiatry Cogn Neurosci Neuroimaging.8 (7):768–776.doi:10.1016/j.bpsc.2023.03.009.PMID37003409.S2CID257862535.
^abcMeyer MR, Maurer HH (February 2011). "Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse".Pharmacogenomics.12 (2):215–233.doi:10.2217/pgs.10.171.PMID21332315.It is rapidly metabolized to the following five metabolites which have been identified in urine or blood from human users: N-demethyl-LSD (nor-LSD), 2-oxoLSD, 2-oxo-3-hydroxy-LSD, 13-hydroxyLSD and 14-hydroxy-LSD [187–189]. The 13- and 14-hydroxy metabolites are additionally excreted as glucuronides [188]. [...] 2-oxo-3-hydroxy-LSD was shown to be the main human urinary metabolite with concentrations four- to 40-times higher than that of LSD [187,188,191]. As concluded by Yu in his review on indolalkylamines, almost nothing is known regarding the contribution of specific drug-metabolizing enzymes to the production of individual LSD metabolites in humans.
^abcMaurer HH, Meyer MR (April 18, 2012). "Drugs of Abuse (Including Designer Drugs)".Metabolism of Drugs and Other Xenobiotics. Wiley. pp. 429–463.doi:10.1002/9783527630905.ch16.ISBN978-3-527-32903-8. RetrievedJune 7, 2025.[LSD] is metabolized to the following five metabolites: N-demethyl-LSD (nor-LSD), 2-oxo-LSD, 2-oxo-3-hydroxy-LSD, 13-hydroxy-LSD, and 14-hydroxy-LSD [72–74]. The 13- and 14-hydroxy metabolites are additionally excreted as glucuronides [74]. 2-Oxo-3-hydroxy-LSD was shown to be the main human urinary metabolite with concentrations 4–40 times higher than that of LSD [73–75]. In incubations of LSD with human liver microsomes and hepatocytes, 2,3-dihydroxy-LSD could be identified [71]. So far, the contribution and importance of specific enzymes in the formation of the LSD main metabolites such as 2-oxo-3-hydroxy-LSD still remains unclear.
^Luethi D, Hoener MC, Krähenbühl S, Liechti ME, Duthaler U (June 2019). "Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use".Biochem Pharmacol.164:129–138.doi:10.1016/j.bcp.2019.04.013.PMID30981875.
^"LSD"(PDF).Handbook of Medical Hallucinogens. Guilford Publications. 2021. p. 160.ISBN978-1-4625-4545-2.Archived(PDF) from the original on March 14, 2024. RetrievedMarch 14, 2024.
^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.PMID7699712.
^Kornfeld EC, Fornefeld EJ, Kline GB, Mann MJ, Morrison DE, Jones RG, et al. (1956). "The Total Synthesis of Lysergic Acid".Journal of the American Chemical Society.78 (13):3087–3114.Bibcode:1956JAChS..78.3087K.doi:10.1021/ja01594a039.
^abJiaming Z, Xin W, Jiali Z, Hang R, Yunli Z, Ping X (March 2023). "Concentrations of LSD, 2-oxo-3-hydroxy-LSD, and iso-LSD in hair segments of 18 drug abusers".Forensic Science International.344 111578.doi:10.1016/j.forsciint.2023.111578.PMID36753839.S2CID256574276.
^Rutschmann J, Stadler PA (1978). "Chemical Background". In Berde B, Schild HO (eds.).Ergot Alkaloids and Related Compounds. Handbook of Experimental Pharmacology (HEP). Vol. 49. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 29–85.doi:10.1007/978-3-642-66775-6_2.ISBN978-3-642-66777-0.
^Schifano F, Vento A, Scherbaum N, Guirguis A (2023). "Stimulant and hallucinogenic novel psychoactive substances; an update".Expert Rev Clin Pharmacol.16 (11):1109–1123.doi:10.1080/17512433.2023.2279192.hdl:2299/27223.PMID37968919.
^abcdHofmann A (2009).LSD, my problem child: reflections on sacred drugs, mysticism, and science (4th ed.). Santa Cruz, CA: Multidisciplinary Association for Psychedelic Studies.ISBN978-0-9798622-2-9.OCLC610059315.
^abcdefLee MA, Shlain B (1992).Acid dreams: the complete social history of LSD: the CIA, the Sixties, and beyond. New York: Grove Weidenfeld.ISBN0-8021-3062-3.OCLC25281992.
^Gach J (2008). "Biological Psychiatry in the Nineteenth and Twentieth Centuries".History of Psychiatry and Medical Psychology(PDF). Boston, MA: Springer US. pp. 381–418.doi:10.1007/978-0-387-34708-0_12.ISBN978-0-387-34707-3. Archived fromthe original(PDF) on March 19, 2025.In 1938 the Swiss chemist Albert Hofmann produced lysergic acid diethylamide (LSD)—the first, and most prominent, of these chemically synthesized agents—in the course of a systematic investigation of partially synthetic amides of lysergic acid in the Sandoz Pharmaceutical Laboratories in Basel (Hofmann 1970). [Taking] LSD by accident in 1943, Hofmann discovered its psychoactivity. He then experimented with it on himself and found that it produced a peculiar restlessness, extreme activity of the imagination, and an uninterrupted stream of images. Hofmann did not publish the results of his experiment, though he became quite famous later. Hofmann and Arthur Stoll, the head of the Sandoz pharmaceutical laboratory in Basle, published the first paper on the synthesis of LSD in 1943, while Stoll went on to publish the first paper on the effects of lysergic diethylamide acid in 1947. [...] Stoll, Arthur and Hofmann, Albert. 1943. Partialsynthese von Alkaloiden vom Typus des Ergobasins. Helv. Chim. Acta 26:944. Stoll, Arthur. 1947. Lysergsäure-diäthylamid, ein Phantastikum aus der Mutterkorngruppe. Schweiz. Arch. Neurol. Psychiat. 60:279. [The first paper on the hallucinogenic effect of LSD.]
^Michael Horowitz (July 1976)."Interview: Albert Hofmann".High Times. No. 11. pp. 24–28, 31, 81. Archived fromthe original on May 5, 2025.High Times: Why was it four years from your discovery of the psychic effects of LSD [in 1943] until your report was published? [...] Hofmann: [...] After confirmation of the action of this extraordinary compound by volunteers of the Sandoz staff, Professor Arthur Stoll, who was then head of the Sandoz pharmaceutical department, asked me if I would permit his son, Werner A. Stoll—who was starting his career at the psychiatric hospital of the University of Zurich—to submit this new agent to a fundamental psychiatric study on normal volunteers and on psychiatric patients. This investigation took a rather long time, [...] This excellent and comprehensive study was not published until 1947.
^Stoll A, Hofmann A (May 3, 1943). "Partialsynthese von Alkaloiden vom Typus des Ergobasins. (6. Mitteilung über Mutterkornalkaloide)" [Partial synthesis of ergobasine-type alkaloids. (6th report on ergot alkaloids)].Helvetica Chimica Acta.26 (3):944–965.Bibcode:1943HChAc..26..944S.doi:10.1002/hlca.19430260326.ISSN0018-019X.
^Freedman AM, Ebin EV, Wilson EA (March 1962). "Autistic schizophrenic children. An experiment in the use of d-lysergic acid diethylamide (LSD-25)".Archives of General Psychiatry.6 (3):203–213.doi:10.1001/archpsyc.1962.01710210019003.PMID13894863.
^Simmons JQ, Leiken SJ, Lovaas OI, Schaeffer B, Perloff B (May 1966). "Modification of autistic behavior with LSD-25".The American Journal of Psychiatry.122 (11):1201–1211.doi:10.1176/ajp.122.11.1201.PMID5325567.
^Sigafoos J, Green VA, Edrisinha C, Lancioni GE (2007). "Flashback to the 1960s: LSD in the treatment of autism".Developmental Neurorehabilitation.10 (1):75–81.doi:10.1080/13638490601106277.PMID17608329.
^Abramson HA (December 1967). "The use of LSD (d-lysergic acid diethylamide) in the therapy of children (a brief review)".The Journal of Asthma Research.5 (2):139–143.doi:10.3109/02770906709104325.PMID4865578.
^abc"LSD: The Drug". LSD in the United States (Report). U.S. Department of Justice, Drug Enforcement Administration. October 1995. Archived fromthe original on April 27, 1999. RetrievedNovember 27, 2010.
^Marks J (1978).The Search for the Manchurian Candidate: The CIA and Mind Control. U.S.A.: Times Books. p. 57.ISBN07139-12790.
^Marks J (1978).The Search for The Manchurian Candidate: The CIA and Mind Control. Times Books. p. 97.
^Brecher EM, et al. (Editors of Consumer Reports Magazine) (1972)."How LSD was popularized". Druglibrary.org.Archived from the original on May 13, 2012. RetrievedJune 20, 2012.
^Hicks M (2000).Sixties Rock: Garage, Psychedelic, and Other Satisfactions Music in American Life. Chicago, IL: University of Illinois Press. p. 60.ISBN0-252-06915-3.
^Mann J (2009).Turn on and Tune in: Psychedelics, Narcotics and Euphoriants. Royal Society of Chemistry. p. 87.ISBN978-1-84755-909-8.
^Rubin R, Melnick JP (2007).Immigration and American Popular Culture: an Introduction. New York, NY: New York University Press. pp. 162–4.ISBN978-0-8147-7552-3.
^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.ISBN0-7935-4042-9.
^Thompson T (June 16, 1967)."The New Far-Out Beatles".Life. Chicago: Time Inc. p. 101.Archived from the original on November 17, 2021. RetrievedDecember 8, 2016.
^"Poisons Standard".Therapeutic Goods Administration. Australian Government Department of Health. July 2016. Archived fromthe original on March 2, 2017.
^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 (Report) (in Czech). Prague: Parliament of the Czech Republic. 1998.
^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.
^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.
^Penner J (June 17, 2019)."Blowing The Philosopher's Fuses: Michel Foucault's LSD Trip in The Valley of Death".Los Angeles Review of Books.Archived from the original on April 11, 2021. RetrievedApril 11, 2021. Wade: "We fell silent to listen to Stockhausen'sSongs of Youth. Zabriskie Point was filled with the sound of a kindergarten playground overlaid with electric tonalities.Kontakte followed.Glissandos bounced off the stars, which glowed like incandescent pinballs. Foucault turned to Michael and said this is the first time he really understood what Stockhausen had achieved".
^Wade S (2019).Foucault in California: [A True Story-–Wherein the Great French Philosopher Drops Acid in the Valley of Death]. Heyday Books.ISBN978-1-59714-463-6. In a letter to Wade, dated 16 September 1978, Foucault authorised the book's publication and added: "How could I not love you?"
^Harrison A (January 16, 2006)."LSD: The Geek's Wonder Drug?".Wired.Archived from the original on May 5, 2008. RetrievedMarch 11, 2008.Like Herbert, many scientists and engineers also report heightened states of creativity while using LSD. During a press conference on Friday, Hofmann revealed that he was told by Nobel-prize-winning chemist Kary Mullis that LSD had helped him develop the polymerase chain reaction that helps amplify specific DNA sequences.
^Sacks O (2012).Hallucinations.Vintage Books. p. 106.ISBN978-0-307-94743-7.Archived from the original on April 21, 2021. RetrievedJune 30, 2018.On the West Coast in the early 1960s LSD and morning glory seeds were readily available, so I sampled those, too.
^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.PMID23627783.
^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.PMID20717121.S2CID16588263.
^Sessa B (November 2008). "Is it time to revisit the role of psychedelic drugs in enhancing human creativity?".Journal of Psychopharmacology.22 (8):821–827.doi:10.1177/0269881108091597.PMID18562421.S2CID1908638.
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