LSD

LSD is commonly used as a recreational drug for its psychedelic effects.{{cite web|title=DrugFacts: Hallucinogens – LSD, Peyote, Psilocybin, and PCP |url=http://www.drugabuse.gov/publications/drugfacts/hallucinogens-lsd-peyote-psilocybin-pcp|publisher=National Institute on Drug Abuse |access-date=February 17, 2015|date=December 2014|archive-url=https://web.archive.org/web/20150216030833/http://www.drugabuse.gov/publications/drugfacts/hallucinogens-lsd-peyote-psilocybin-pcp |archive-date=February 16, 2015}}

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.{{cite book | title = Alcohol and Drugs in North America: A Historical Encyclopedia | veditors = Fahey D, Miller JS | isbn = 978-1-59884-478-8 | page = 375 }}San Francisco Chronicle September 20, 1966 Page One Stanislav Grof has written that religious and mystical experiences observed during LSD sessions appear similar to descriptions in sacred scriptures of great religions of the world and the texts of ancient civilizations.{{cite book| vauthors=Grof S, Grof JH| author-link1=Stanislav Grof| title=Realms of the Human Unconscious (Observations from LSD Research)| publisher=Souvenir Press (E & A) Ltd| year=1979| location=London| pages=13–14| url=http://www.csp.org/chrestomathy/realms_of3.html| isbn=978-0-285-64882-1| archive-url=https://web.archive.org/web/20071018164416/http://csp.org/chrestomathy/realms_of3.html| archive-date=October 18, 2007| access-date=November 18, 2007}}

{{See also|Lysergic acid diethylamide#Research}}

LSD currently has no approved uses in medicine.{{cite journal |vauthors=Nutt DJ, King LA, Nichols DE |title=Effects of Schedule I drug laws on neuroscience research and treatment innovation |journal=Nature Reviews. Neuroscience |volume=14 |issue=8 |pages=577–585 |date=August 2013 |pmid=23756634 |doi=10.1038/nrn3530 |s2cid=1956833}}{{Cite news |url=https://www.theguardian.com/science/2009/oct/23/lsd-ecstacy-health-benefits |title=Scientists study possible health benefits of LSD and ecstasy {{!}} Science |date=2016-07-23 |access-date=2016-07-23 |url-status= live |archive-url=https://web.archive.org/web/20160723155424/https://www.theguardian.com/science/2009/oct/23/lsd-ecstacy-health-benefits |archive-date=July 23, 2016 |newspaper=The Guardian |vauthors=Campbell D}} A meta analysis concluded that a single dose was shown to be effective at reducing alcohol consumption in people suffering from alcoholism. LSD has also been studied in depression, anxiety,{{Cite news |vauthors=Lustberg D |date=2022-10-14 |title=Acid for Anxiety: Fast and Lasting Anxiolytic Effects of LSD |url=https://psychedelicreview.com/acid-for-anxiety-fast-and-lasting-anxiolytic-effects-of-lsd/ |access-date=2022-12-01 |website=Psychedelic Science Review |language=en-US |archive-date=December 1, 2022 |archive-url=https://web.archive.org/web/20221201092629/https://psychedelicreview.com/acid-for-anxiety-fast-and-lasting-anxiolytic-effects-of-lsd/ |url-status=live }}{{cite journal |vauthors=Holze F, Gasser P, Müller F, Dolder PC, Liechti ME |title=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 |journal=Biological Psychiatry |date=September 2022 |volume=93 |issue=3 |pages=215–223 |doi=10.1016/j.biopsych.2022.08.025 |pmid=36266118 |s2cid=252095586 |doi-access=free}} and drug dependence, with positive preliminary results.{{cite journal |vauthors=Dos Santos RG, Osório FL, Crippa JA, Riba J, Zuardi AW, Hallak JE |title=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 |journal=Therapeutic Advances in Psychopharmacology |volume=6 |issue=3 |pages=193–213 |date=June 2016 |pmid=27354908 |pmc=4910400 |doi=10.1177/2045125316638008}}{{Cite web |title=History of LSD Therapy |url=https://druglibrary.org/schaffer/lsd/grofhist.htm |access-date=2022-11-07 |website=druglibrary.org |archive-date=November 7, 2022 |archive-url=https://web.archive.org/web/20221107004840/https://druglibrary.org/schaffer/lsd/grofhist.htm |url-status=live }}

{{See also|Psychedelic drug#Dosage}}

File:10 strip.jpg]]

LSD is an extraordinarily potent substance,{{cite book | vauthors = Liechti ME, Holze F | title = Disruptive Psychopharmacology | chapter = Dosing Psychedelics and MDMA | series = Curr Top Behav Neurosci | volume = 56 | pages = 3–21 | date = 2022 | pmid = 34734392 | doi = 10.1007/7854_2021_270 | isbn = 978-3-031-12183-8 | chapter-url = https://www.researchgate.net/publication/355943062}}{{cite book | vauthors = Nichols DE | title=Behavioral Neurobiology of Psychedelic Drugs | chapter=Chemistry and Structure–Activity Relationships of Psychedelics | series=Current Topics in Behavioral Neurosciences | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | volume=36 | date=2017 | pages=1–43 | isbn=978-3-662-55878-2 | doi=10.1007/7854_2017_475 | pmid=28401524 | chapter-url=https://bibliography.maps.org/resources/download/13937 | archive-url=https://web.archive.org/web/20250323072739/https://bibliography.maps.org/resources/download/13937 | archive-date=March 23, 2025 | quote=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.}} and is one of the most potent psychoactive drugs known. This means that it produces its pharmacological effects at very small doses, with its dose range measured in micrograms (μg); that is, millionths of a gram. Noticeable effects can occur with doses of LSD as low as 20{{nbsp}}μg, which is around 1/200th the mass of a grain of sand. LSD is approximately 200{{nbsp}}times as potent as psilocybin and 5,000{{nbsp}}times as potent as mescaline, meaning that it produces effects of similar magnitude at 1/200 and 1/5,000 times the respective doses.{{cite book | author = Albert Hofmann | chapter = Psychotomimetic Agents | pages = 169–235 | veditors = Burger A | title = Drugs Affecting the Central Nervous System | volume = 2 | date = 1968 | publisher = M. Dekker | location = New York | oclc = 245452885 | ol = OL13539506M | chapter-url = https://archive.org/details/drugsaffectingce0000edit/page/169/mode/1up | url = https://books.google.com/books?id=o_GMwgEACAAJ | quote = 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.}}

The usual dose range of LSD for psychedelic effects is 20 to 200{{nbsp}}μg. The typical intermediate and "good effect" dose for a psychedelic experience is 100{{nbsp}}μg (range 75–150{{nbsp}}μg, while 20 to 50{{nbsp}}μg is a low or "minidose" and 200{{nbsp}}μg is a high or ego-dissolution dose. A dose range as wide as 10 to 400{{nbsp}}μg has been reported.{{cite journal | vauthors = Luethi D, Liechti ME | title = Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics | journal = Int J Neuropsychopharmacol | volume = 21 | issue = 10 | pages = 926–931 | date = October 2018 | pmid = 29850881 | pmc = 6165951 | doi = 10.1093/ijnp/pyy047 }} LSD may also be used in microdosing.{{cite journal |vauthors=Polito V, Stevenson RJ |title=A systematic study of microdosing psychedelics |journal=PLOS ONE |volume=14 |issue=2 |pages=e0211023 |date=2019-02-06 |pmid=30726251 |pmc=6364961 |doi=10.1371/journal.pone.0211023 |bibcode=2019PLoSO..1411023P |doi-access=free}} In this context, it may be used at subthreshold or microdoses of less than 10{{nbsp}}μg.

The doses of LSD present in illicit LSD samples have decreased over time. In the mid-1960s, Owsley Stanley, the most important black market LSD manufacturer in the United States, distributed LSD at a standard concentration of 270{{nbsp}}μg,{{cite web| vauthors=Hidalgo E| year=2009| title=LSD Samples Analysis| publisher=Erowid| url=http://www.erowid.org/chemicals/lsd/lsd_article3.shtml| access-date=February 8, 2010| url-status=live| archive-url=https://web.archive.org/web/20100213145552/http://www.erowid.org/chemicals/lsd/lsd_article3.shtml| archive-date=February 13, 2010}} while street samples of the 1970s contained 30 to 300{{nbsp}}μg. By the 1980s, the amount had reduced to between 100 and 125{{nbsp}}μg, dropping more in the 1990s to the 20 to 80{{nbsp}}μg range,{{cite book |vauthors=Henderson LA, Glass WJ |title=LSD: Still with us after all these years |year=1994 |isbn=978-0-7879-4379-0 |publisher=Jossey-Bass |location=San Francisco}} and even further in the 2000s.{{cite web| author=Fire & Earth Erowid| date=Nov 2003| title=LSD Analysis – Do we know what's in street acid?| url=http://www.erowid.org/chemicals/lsd/lsd_article1.shtml| publisher=Erowid| access-date=February 8, 2010| archive-url=https://web.archive.org/web/20100126215446/http://www.erowid.org/chemicals/lsd/lsd_article1.shtml| archive-date=January 26, 2010| url-status=live}}

LSD produces a variety of physical, psychological, and sensory effects.

The primary immediate psychological effects of LSD are visual 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.{{cite journal | vauthors = El-Mallakh RS, Walker KL | title = Hallucinations, psuedohallucinations, and parahallucinations | journal = Psychiatry | volume = 73 | issue = 1 | pages = 34–42 | date = 2010 | pmid = 20235616 | doi = 10.1521/psyc.2010.73.1.34 }} 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.{{cite journal |vauthors=Majić T, Schmidt TT, Gallinat J |title=Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences? |journal=Journal of Psychopharmacology |volume=29 |issue=3 |pages=241–253 |date=March 2015 |pmid=25670401 |doi=10.1177/0269881114568040 |s2cid=16483172}} 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.{{cite web |work=Erowid |vauthors=Honig D |title=Frequently Asked Questions |url=http://www.erowid.org/chemicals/lsd/lsd_faq.shtml |archive-url=https://web.archive.org/web/20160212232436/https://www.erowid.org/chemicals/lsd/lsd_faq.shtml |archive-date=12 February 2016}}{{cite journal |vauthors=McGlothlin W, Cohen S, McGlothlin MS |title=Long lasting effects of LSD on normals |journal=Archives of General Psychiatry |volume=17 |issue=5 |pages=521–532 |date=November 1967 |pmid=6054248 |doi=10.1001/archpsyc.1967.01730290009002| url=http://www.maps.org/w3pb/new/1967/1967_mcglothlin_4655_1.pdf |archive-date=April 30, 2011 |archive-url=https://web.archive.org/web/20110430020912/http://www.maps.org/w3pb/new/1967/1967_mcglothlin_4655_1.pdf}}

Negative experiences, commonly known as "bad trips", can induce feelings of fear, agitation, anxiety, panic, and paranoia.{{cite journal | vauthors = Kopra EI, Ferris JA, Rucker JJ, McClure B, Young AH, Copeland CS, Winstock AR | title = Adverse experiences resulting in emergency medical treatment seeking following the use of lysergic acid diethylamide (LSD) | journal = Journal of Psychopharmacology | volume = 36 | issue = 8 | pages = 956–964 | date = August 2022 | pmid = 35672900 | pmc = 9353972 | doi = 10.1177/02698811221099650 }} 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.{{citation |title=Substance use – LSD |vauthors=Rogge T |date=21 May 2014 |access-date=14 July 2016 |publisher=MedlinePlus, U.S. National Library of Medicine |url=https://medlineplus.gov/ency/patientinstructions/000795.htm |url-status=live|archive-url=https://web.archive.org/web/20160728004220/https://medlineplus.gov/ency/patientinstructions/000795.htm|archive-date=July 28, 2016}}{{citation|title=LSD |author=CESAR |publisher=Center for Substance Abuse Research, University of Maryland |date=29 October 2013 |access-date=14 July 2016 |url=http://www.cesar.umd.edu/cesar/drugs/lsd.asp |archive-url=https://web.archive.org/web/20160715071823/http://www.cesar.umd.edu/cesar/drugs/lsd.asp |archive-date=July 15, 2016}}

LSD induces an animated sensory experience affecting senses, emotions, memories, time, and awareness. The effects range from subtle perceptual changes to profound cognitive shifts. Alterations in auditory and visual perception are common.{{cite journal |vauthors=Katz MM, Waskow IE, Olsson J |title=Characterizing the psychological state produced by LSD |journal=Journal of Abnormal Psychology |volume=73 |issue=1 |pages=1–14 |date=February 1968 |pmid=5639999 |doi=10.1037/h0020114 |citeseerx=10.1.1.409.4030}}

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.{{cite journal |journal=Archives of General Psychiatry |title=Subjective Reactions to Lysergic Acid Diethylamide (LSD-25) |date=May 1962 |volume=6 |issue=5 |pages=352–368 |doi=10.1001/archpsyc.1962.01710230020003 |vauthors=Linton HR, Langs RJ}}{{cite journal |vauthors=Parker LA |title=LSD produces place preference and flavor avoidance but does not produce flavor aversion in rats |journal=Behavioral Neuroscience |volume=110 |issue=3 | pages=503–508 |date=June 1996 |pmid=8888996 |doi=10.1037/0735-7044.110.3.503}}

There are reports of inanimate objects appearing animated, with static objects seeming to move in additional spatial dimensions.{{cite journal |vauthors=Oster G |title=Moiré patterns and visual hallucinations |journal=Psychedelic Review |date=1966 |volume=7 |pages=33–40 |url= https://maps.org/research-archive/psychedelicreview/n07/n07033osl.pdf |url-status=live |archive-date=19 April 2017 |archive-url=https://web.archive.org/web/20170419154504/http://www.maps.org/research-archive/psychedelicreview/n07/n07033osl.pdf}} The auditory effects of LSD may include echo-like distortions of sounds, and an intensified experience of music. Basic visual effects often resemble phosphenes and can be influenced by concentration, thoughts, emotions, or music.{{cite journal |vauthors=Kaelen M, Roseman L, Kahan J, Santos-Ribeiro A, Orban C, Lorenz R, Barrett FS, Bolstridge M, Williams T, Williams L, Wall MB, Feilding A, Muthukumaraswamy S, Nutt DJ, Carhart-Harris R |date=July 2016 |title=LSD modulates music-induced imagery via changes in parahippocampal connectivity |journal=European Neuropsychopharmacology |volume=26 |issue=7 |pages=1099–1109 |pmid=27084302 |doi=10.1016/j.euroneuro.2016.03.018 |s2cid=24037275}} Higher doses can lead to more intense sensory perception alterations, including synesthesia, perception of additional dimensions, and temporary dissociation.

File:Possible physical effects of lysergic acid diethylamide (LSD).svg

File:Mydriasis due to LSD usage.jpg (pupil dilation) due to usage of LSD.]]

LSD can induce physical effects such as pupil dilation, decreased appetite, increased sweating, and wakefulness. The physical reactions to LSD vary greatly and some may be a result of its psychological effects. Commonly observed symptoms include increased body temperature, blood sugar, and heart rate, as well as goose bumps, jaw clenching, dry mouth, and hyperreflexia. In cases of adverse reactions, users may experience numbness, weakness, nausea, and tremors.

The psychoactive effects of LSD last on average between 7 and 11{{nbsp}}hours, with a possible range of 4 to 22{{nbsp}}hours. Higher doses tend to lead to a longer duration of action. The onset of action when administered orally is 0.4 to 1.0{{nbsp}}hours on average, with a possible range of 0.1 to 1.8{{nbsp}}hours.

File:HarmCausedByDrugsTable.svg

File:Rational harm assessment of drugs radar plot.svg regarding 20 popular recreational drugs. LSD was ranked 14th in dependence, 15th in physical harm, and 13th in social harm.{{cite journal |vauthors=Nutt D, King LA, Saulsbury W, Blakemore C |title=Development of a rational scale to assess the harm of drugs of potential misuse |journal=Lancet |volume=369 |issue=9566 |pages=1047–53 |date=March 2007 |pmid=17382831 |doi=10.1016/s0140-6736(07)60464-4 |s2cid=5903121}}]]

LSD, a classical psychedelic, is deemed physiologically safe at standard dosages (50–200 μg) and its primary risks lie in psychological effects rather than physiological harm.{{cite journal |journal=Forensic Science International |vauthors=Nichols DE, Grob CS |doi=10.1016/j.forsciint.2018.01.006 |title=Is LSD Toxic? |volume=284 |pages=141–145 |date=March 2018 |pmid=29408722}} A 2010 study by David Nutt ranked LSD as significantly less harmful than alcohol, placing it near the bottom of a list assessing the harm of 20 drugs.{{cite journal |vauthors=Nutt DJ, King LA, Phillips LD |title=Drug harms in the UK: a multicriteria decision analysis |journal=Lancet |volume=376 |issue=9752 |pages=1558–65 |date=November 2010 |pmid=21036393 |doi=10.1016/s0140-6736(10)61462-6 |s2cid=5667719 |citeseerx=10.1.1.690.1283}}

LSD can induce panic 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 like schizophrenia.{{cite journal |vauthors=Krebs TS, Johansen PØ |title=Psychedelics and mental health: a population study |journal=PLOS ONE |volume=8 |issue=8 |pages=e63972 |date=2013-08-19 |pmid=23976938 |pmc=3747247 |doi=10.1371/journal.pone.0063972 |bibcode=2013PLoSO...863972K |veditors=Lu L |doi-access=free}}{{citation |title=What can we learn about schizophrenia from studying the human model, drug-induced psychosis?|vauthors=Murray RM, Paparelli A, Morrison PD, Marconi A, Di Forti M |journal=American Journal of Medical Genetics Part B |volume=162 |issue=7 |series=Special Issue: Identifying the Origins of Mental Illness: A Festschrift in Honor of Ming T. Tsuang |pages=661–670 |date=October 2013 |pmid=24132898 |s2cid=205326399 |doi=10.1002/ajmg.b.32177 |doi-access=free}} These hallucinogens can catalyze psychiatric disorders in predisposed individuals, although they do not tend to induce illness in emotionally healthy people.

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.{{cite web |url= http://www.gulfweb.org/bigdoc/rockrep.cfm#hallucinogens |title=Is Military Research Hazardous to Veterans Health? Lessons Spanning Half A Century, part F. HALLUCINOGENS |publisher=103rd Congress, 2nd Session-S. Prt. 103-97; Staff Report prepared for the committee on veterans' affairs |date=December 8, 1994 |vauthors=Rockefeller IV JD |location=West Virginia |archive-url=https://web.archive.org/web/20060813164326/http://gulfweb.org/bigdoc/rockrep.cfm#hallucinogens |archive-date=August 13, 2006 |access-date=December 13, 2018}}{{cite journal |vauthors=Middlefell R |title=The effects of LSD on body sway suggestibility in a group of hospital patients |journal=The British Journal of Psychiatry |volume=113 |issue=496 |pages=277–280 |date=March 1967 |pmid=6029626 |doi=10.1192/bjp.113.496.277 |s2cid=19439549 |url= http://www.lycaeum.org/research/researchpdfs/1489.pdf |archive-url=https://web.archive.org/web/20110430033215/http://www.lycaeum.org/research/researchpdfs/1489.pdf |archive-date=2011-04-30}}{{cite journal |vauthors=Sjoberg BM, Hollister LE |title=The effects of psychotomimetic drugs on primary suggestibility |journal=Psychopharmacologia |volume=8 |issue=4 |pages=251–262 |date=November 1965 |pmid=5885648 |doi=10.1007/BF00407857 |s2cid=15249061}}{{Primary source inline|date=June 2023}}

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.{{cite journal |vauthors=Halpern JH, Pope HG |title=Hallucinogen persisting perception disorder: what do we know after 50 years? |journal=Drug and Alcohol Dependence |volume=69 |issue=2 |pages=109–19 |date=March 2003 |pmid=12609692 |doi=10.1016/S0376-8716(02)00306-X}}{{cite journal |vauthors=Müller F, Kraus E, Holze F, Becker A, Ley L, Schmid Y, Vizeli P, Liechti ME, Borgwardt S |title=Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants |journal=Psychopharmacology |date=January 2022 |volume=239 |issue=6 |pages=1933–1943 |pmid=35076721 |doi=10.1007/s00213-022-06066-z |pmc=9166883 |s2cid=246276633}} These experiences are associated with hallucinogen persisting perception disorder (HPPD), where flashbacks occur intermittently or chronically, causing distress or functional impairment.

The etiology of flashbacks is varied. Some cases are attributed to somatic symptom disorder, where individuals fixate on normal somatic experiences previously unnoticed prior to drug consumption.{{cite journal |vauthors=Johansen PØ, Krebs TS |title=Psychedelics not linked to mental health problems or suicidal behavior: a population study |journal=Journal of Psychopharmacology |volume=29 |issue=3 |pages=270–279 |date=March 2015 |doi=10.1177/0269881114568039 |pmid=25744618 |s2cid=2025731}} Other instances are linked to associative reactions to contextual cues, similar to responses observed in individuals with past trauma or emotional experiences.{{cite book |vauthors=Holland D, Passie T |isbn=978-3-86135-207-5 |language=de |year=2011 |title=Flashback-Phänomene als Nachwirkung von Halluzinogeneinnahme |volume=2 |series=Bewusstsein – Kognition – Erleben |publisher=VWB Report |url=http://www.vwb-verlag.com/Katalog/m207.html |access-date=June 9, 2023 |archive-date=June 9, 2023 |archive-url=https://web.archive.org/web/20230609015208/http://www.vwb-verlag.com/Katalog/m207.html |url-status=live }} The risk factors for flashbacks remain unclear, but pre-existing psychopathologies may be significant contributors.{{cite journal |vauthors=Abraham HD, Duffy FH |date=October 1996 |title=Stable quantitative EEG difference in post-LSD visual disorder by split-half analysis: evidence for disinhibition |journal=Psychiatry Research |volume=67 |issue=3 |pages=173–87 |pmid=8912957 |doi=10.1016/0925-4927(96)02833-8 |s2cid=7587687}}

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. Contrary to internet rumors, LSD is not stored long-term in the spinal cord or other body parts. 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. Clinical evidence also suggests that chronic use of SSRIs can potentiate LSD-induced flashbacks, even months after stopping LSD use.{{cite book |title=Psychedelics as Psychiatric Medications |publisher=Oxford University Press |isbn=9780192678522 |url=https://books.google.com/books?id=7lazEAAAQBAJ |date=7 March 2023 |vauthors=Nutt DJ, Castle D |chapter=Drug-interaction with psychotropic drugs |access-date=May 21, 2023 |archive-date=May 21, 2023 |archive-url=https://web.archive.org/web/20230521000115/https://books.google.com/books?id=7lazEAAAQBAJ |url-status=live }}{{rp|145}}

LSD shows significant tachyphylaxis, with tolerance developing 24 hours after administration. The progression of tolerance at intervals shorter than 24 hours remains largely unknown.{{cite book |vauthors=Buchborn T, Grecksch G, Dieterich D, Hollt V |title=Neuropathology of Drug Addictions and Substance Misuse |doi=10.1016/B978-0-12-800212-4.00079-0 |chapter=Chapter 79 - Tolerance to Lysergic Acid Diethylamide: Overview, Correlates, and Clinical Implications |isbn=978-0-12-800212-4 |publisher=Academic Press |pages=848–849 |volume=2 |year=2016}} Tolerance typically resets to baseline after 3–4 days of abstinence.{{cite journal |title=A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects |vauthors=Dolder DS, Grünblatt E, Müller F, Borgwardt SJ, Liechti ME |date=28 June 2017 |doi=10.3389/fphar.2017.00423 |journal=Frontiers in Neuroscience |volume=8 |page=423 |pmid=28701958 |pmc=5487530 |doi-access=free}}{{cite journal |journal=Pain Practice |page=455 |volume=23 |issue=4 |issn=1533-2500 |doi=10.1111/papr.13203 |doi-access=free |vauthors=Kooijman NI, Willegers T, Reuser A, Mulleners WM, Kramers C, ((Vissers KCP)), ((van der Wal SEI)) |date=4 January 2023 |pmid=36597700 |title=Are psychedelics the answer to chronic pain: A review of current literature| s2cid=255470638 |hdl=2066/291903 |hdl-access=free}} Significant cross-tolerance occurs between LSD, mescaline and psilocybin.{{cite journal |vauthors=Wolbach AB, Isbell H, Miner EJ |date=March 1962 |title=Cross tolerance between mescaline and LSD-25, with a comparison of the mescaline and LSD reactions |journal=Psychopharmacologia |volume=3 |pages=1–14 |pmid=14007904 |doi=10.1007/BF00413101 |s2cid=23803624 |url=http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=2032&DocPartID=1893 |access-date=December 1, 2007 |archive-date=April 19, 2014 |archive-url=https://web.archive.org/web/20140419141528/http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=2032&DocPartID=1893}}{{cite journal |vauthors=Isbell H, Wolbach AB, Wikler A, Miner EJ |title=Cross tolerance between LSD and psilocybin |journal=Psychopharmacologia |volume=2 |issue=3 |pages=147–159 |year=1961 |doi=10.1007/BF00407974 |url=http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=1979&DocPartID=1843 |access-date=December 1, 2007 |pmid=13717955 |s2cid=7746880 |archive-date=March 15, 2016 |archive-url=https://web.archive.org/web/20160315102433/https://www.erowid.org/references/refs_view.php?a=showdocpartframe&c=ref&docpartid=1843&id=1979 |url-status=live }} A slight cross-tolerance to DMT is observed in humans highly tolerant to LSD.{{cite journal |vauthors=Rosenberg D, Isbell H, Miner E, Logan C |doi=10.1007/BF00413244 |date=7 August 1963 |title=The effect of N,N-dimethyltryptamine in human subjects tolerant to lysergic acid diethylamide |journal=Psychopharmacologia |volume=5 |issue=3 |pages=223–224 |pmid=14138757 |s2cid=32950588}} Tolerance to LSD also builds up with consistent use,{{cite journal |vauthors=Jonas S, Downer JD |title=Gross behavioural changes in monkeys following administration of LSD-25, and development of tolerance to LSD-25 |journal=Psychopharmacologia |volume=6 |issue=4 |pages=303–386 |date=October 1964 |pmid=4953438 |doi=10.1007/BF00413161 |s2cid=11768927}} and is believed to result from serotonin 5-HT_2A receptor downregulation. Researchers believe that tolerance returns to baseline after two weeks of not using psychedelics.{{cite journal |vauthors=Schlemmer RF, Nawara C, Heinze WJ, Davis JM, Advokat C |title=Influence of environmental context on tolerance to LSD-induced behavior in primates |journal=Biological Psychiatry |volume=21 |issue=3 |pages=314–317 |date=March 1986 |pmid=3947713 |doi=10.1016/0006-3223(86)90053-3 |s2cid=35508993}}

LSD is widely considered to be non-addictive, despite its potential for abuse.{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY |title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |year=2009 |publisher=McGraw-Hill Medical |location=New York |isbn=9780071481274 |pages=375 |edition=2nd |chapter=Chapter 15: Reinforcement and Addictive Disorders |quote=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) |url=https://books.google.com/books?id=PjgfBQAAQBAJ |access-date=June 12, 2023 |archive-date=August 28, 2023 |archive-url=https://web.archive.org/web/20230828020503/https://books.google.com/books?id=PjgfBQAAQBAJ |url-status=live }}{{cite journal |vauthors=Lüscher C, Ungless MA |title=The mechanistic classification of addictive drugs |journal=PLOS Medicine |volume=3 |issue=11 |pages=e437 |date=November 2006 |pmid=17105338 |pmc=1635740 |doi=10.1371/journal.pmed.0030437 |doi-access=free}} Attempts to train laboratory animals to self-administer LSD have been largely unsuccessful. Although tolerance to LSD builds up rapidly, a withdrawal syndrome does not appear, suggesting that a potential syndrome does not necessarily relate to the possibility of acquiring rapid tolerance to a substance.{{cite journal |vauthors=Balestrieri A, Fontanari D |date=September 1959 |doi=10.1001/archpsyc.1959.03590030063008 |pages=279–282 |pmid=13796178 |title=Acquired and crossed tolerance to mescaline, LSD-25, and BOL-148|journal=Archives of General Psychiatry | volume=1 |issue=3}} A report examining substance use disorder for DSM-IV noted that almost no hallucinogens produced dependence, unlike psychoactive drugs of other classes such as stimulants and depressants.{{cite journal |journal=Current Neuropharmacology |volume=17 |issue=2 |pages=1–15 |title=Ayahuasca: Psychological and Physiologic Effects, Pharmacology and Potential Uses in Addiction and Mental Illness |doi=10.2174/1570159X16666180125095902 |doi-access=free |issn=1875-6190 |vauthors=Hamill J, Hallak J, Dursun SD, Baker G |year=2019 |pmid=29366418| pmc=6343205}}{{cite journal |journal=Addiction |publisher=Society for the Study of Addiction |vauthors=Morgenstern J, Langenbucher J, Labouvie E |date=September 1994 |title=The generalizability of the dependence syndrome across substances: an examination of some properties of the proposed DSM-IV dependence criteria |volume=89 |issue=9 |pages=1105–1113 |doi=10.1111/j.1360-0443.1994.tb02787.x |pmid=7987187}}

The mutagenic potential of LSD is unclear. Overall, the evidence seems to point to limited or no effect at commonly used doses.{{cite journal |vauthors=Li JH, Lin LF |title=Genetic toxicology of abused drugs: a brief review |journal=Mutagenesis |volume=13 |issue=6 |pages=557–65 |date=November 1998 |pmid=9862186 |doi=10.1093/mutage/13.6.557 |doi-access=free}} Studies showed no evidence of teratogenic or mutagenic effects.

A potential risk of frequent repeated long-term use of LSD and other serotonergic psychedelics is cardiac fibrosis and valvulopathy due to serotonin 5-HT_2B receptor agonism.{{cite journal | vauthors = Tagen M, Mantuani D, van Heerden L, Holstein A, Klumpers LE, Knowles R | title = The risk of chronic psychedelic and MDMA microdosing for valvular heart disease | journal = J Psychopharmacol | volume = 37 | issue = 9 | pages = 876–890 | date = September 2023 | pmid = 37572027 | doi = 10.1177/02698811231190865 | url = }}{{cite journal | vauthors = Rouaud A, Calder AE, Hasler G | title = Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins | journal = J Psychopharmacol | volume = 38 | issue = 3 | pages = 217–224 | date = March 2024 | pmid = 38214279 | pmc = 10944580 | doi = 10.1177/02698811231225609 | url = }}{{cite journal | vauthors = Nahlawi A, Ptaszek LM, Ruskin JN | title = Cardiovascular effects and safety of classic psychedelics | journal = Nat Cardiovasc Res | volume = 4 | issue = 2 | pages = 131–144 | date = February 2025 | pmid = 39910289 | doi = 10.1038/s44161-025-00608-2 | url = }}{{cite journal | vauthors = Wsół A | title = Cardiovascular safety of psychedelic medicine: current status and future directions | journal = Pharmacol Rep | volume = 75 | issue = 6 | pages = 1362–1380 | date = December 2023 | pmid = 37874530 | pmc = 10661823 | doi = 10.1007/s43440-023-00539-4 | url = }}{{cite journal | vauthors = McIntyre RS | title = Serotonin 5-HT2B receptor agonism and valvular heart disease: implications for the development of psilocybin and related agents | journal = Expert Opin Drug Saf | volume = 22 | issue = 10 | pages = 881–883 | date = 2023 | pmid = 37581427 | doi = 10.1080/14740338.2023.2248883 | url = }} This may also be the case with microdosing. However, the risks are theoretical, and more research is needed to see if these complications can actually occur with psychedelics. A preliminary animal study found that chronic microdosing of LSD did not result in heart structure changes or valvulopathy in rodents.{{cite journal | vauthors = Effinger D, King J, Calderon J, Strong J, Thompson S | title = ACNP 63rd Annual Meeting: Poster Abstracts P609-P914: P680. Assessing the Potential Cardiovascular Risk of Microdosing Lysergic Acid Diethylamide in Mice | journal = Neuropsychopharmacology | volume = 49 | issue = Suppl 1 | pages = 418–594 (459–459) | date = December 2024 | pmid = 39643635 | doi = 10.1038/s41386-024-02013-y | url = | doi-access = free }} Research appears to be mixed on whether LSD is a potent serotonin 5-HT_2B receptor agonist or not, with some studies finding it to be essentially inactive.{{cite book | vauthors = Luethi D, Liechti ME | title=5-HT2B Receptors | chapter=Drugs of Abuse Affecting 5-HT2B Receptors | series=The Receptors | publisher=Springer International Publishing | publication-place=Cham | volume=35 | date=2021 | isbn=978-3-030-55919-9 | doi=10.1007/978-3-030-55920-5_16 | pages=277–289}}

{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

Some psychedelics, including LSD, are metabolized by the cytochrome P450 enzyme CYP2D6. Concurrent use of selective serotonin reuptake inhibitors (SSRIs), some of which are potent inhibitors of CYP2D6, with LSD may heighten the risk of serotonin syndrome.{{rp|145}} Chronic usage of SSRIs, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) is believed to diminish the subjective effects of psychedelics, likely due to 5-HT_2A receptor downregulation or desensitization induced by elevated serotonin levels.{{rp|145}} Contrary to the preceding notions however, a clinical study found that administration of LSD to people taking paroxetine, an SSRI and strong CYP2D6 inhibitor, increased LSD exposure by about 1.5-fold, was well-tolerated, and did not modify the pleasant subjective effects or physiological effects of LSD, whereas negative effects of LSD, including "bad drug effect", anxiety, and nausea, were reduced.{{cite journal | vauthors = Becker AM, Humbert-Droz M, Mueller L, Jelušić A, Tolev A, Straumann I, Avedisian I, Erne L, Thomann J, Luethi D, Grünblatt E, Meyer Zu Schwabedissen H, Liechti ME | title = Acute Effects and Pharmacokinetics of LSD after Paroxetine or Placebo Pre-Administration in a Randomized, Double-Blind, Cross-Over Phase I Trial | journal = Clin Pharmacol Ther | volume = | issue = | pages = | date = February 2025 | pmid = 40022427 | doi = 10.1002/cpt.3618 | url = | doi-access = free }} Similarly, a clinical study with LSD found that LSD levels were 75% higher in people with non-functional CYP2D6 (poor metabolizers) compared to those with functional CYP2D6.{{Cite journal |vauthors=Halman A, Kong G, Sarris J, Perkins D |date=January 2024 |title=Drug-drug interactions involving classic psychedelics: A systematic review |journal=J Psychopharmacol |volume=38 |issue=1 |pages=3–18 |doi=10.1177/02698811231211219 |pmc=10851641 |pmid=37982394}}{{cite journal | vauthors = Vizeli P, Straumann I, Holze F, Schmid Y, Dolder PC, Liechti ME | title = Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis | journal = Sci Rep | volume = 11 | issue = 1 | pages = 10851 | date = May 2021 | pmid = 34035391 | pmc = 8149637 | doi = 10.1038/s41598-021-90343-y | bibcode = 2021NatSR..1110851V | url = }} In contrast to certain other psychedelics, MAOIs do not inhibit the metabolism of or potentiate the effects of LSD and instead reduce its effects. Interactions between psychedelics and antipsychotics or anticonvulsants are not well-documented; however, co-use with mood stabilizers like lithium may induce seizures and dissociative effects, particularly in individuals with bipolar disorder.{{rp|146}}{{cite journal |journal=Drug and Alcohol Dependence |volume=239 |at=109586 |vauthors=Simonsson O, Goldberg SB, Chambers R, Osika W, Long DM, Hendricks PS |date=1 October 2022 |pmid=35981469 |pmc=9627432 |title=Prevalence and associations of classic psychedelic-related seizures in a population-based sample |doi=10.1016/j.drugalcdep.2022.109586}}{{cite journal |year=1967 |journal=Western Journal of Medicine |vauthors=Fisher D, Ungerleider J |pmid=4962683 |pmc=1502729 |volume=106 |issue=3 |pages=201–211 |title=Grand mal seizures following ingestion of LSD}} Lithium notably intensifies LSD reactions, potentially leading to acute comatose states when combined.

There have been no documented fatal human overdoses from LSD,{{cite journal |journal=Transformative Medicine |title=NBOMe Toxicity and Fatalities: A Review of the Literature |volume=1 |issue=1 |date=March 2022 |vauthors=Lipow M, Kaleem SZ, Espiridion E |pages=12–18 |s2cid=247888583 |doi=10.54299/tmed/msot8578 |doi-access=free |issn=2831-8978}} although there has been no "comprehensive review since the 1950s" and "almost no legal clinical research since the 1970s". A 5{{nbsp}}mg overdose of LSD (50{{nbsp}}times the usual dose) produced severe nausea and vomiting along with behavioral and emotional disturbances.{{cite journal | vauthors = Reynolds HH, Peterson GK | title = Psychophysiological effects of a large non-experimental dose of LSD-25 | journal = Psychol Rep | volume = 19 | issue = 1 | pages = 287–290 | date = August 1966 | pmid = 5942100 | doi = 10.2466/pr0.1966.19.1.287 | url = }} Eight individuals who had accidentally consumed an exceedingly high amount of LSD, mistaking it for cocaine, and had gastric levels of 1,000–7,000{{nbsp}}μg/100{{nbsp}}mL LSD tartrate and blood plasma levels up to 26{{nbsp}}μg/mL, had suffered from comatose states, vomiting, respiratory problems, hyperthermia, and light gastrointestinal bleeding; however, all of them survived without residual effects upon hospital intervention.{{cite journal | vauthors = Klock JC, Boerner U, Becker CE | title = Coma, Hyperthermia and Bleeding Associated with Massive LSD Overdose: A Report of Eight Cases | journal = The Western Journal of Medicine | date = March 1974 | volume = 120 | issue = 3 | pages = 183–188 | pmid = 4816396 | pmc = 1129381}}

Individuals experiencing a bad trip after LSD intoxication may present with severe anxiety and tachycardia, often accompanied by phases of psychotic agitation and varying degrees of delusions. Cases of death on a bad trip have been reported due to prone maximal restraint (commonly known as a hogtie) and positional asphyxia when the individuals were restrained by law enforcement personnel.

Massive doses are largely managed by symptomatic treatments, and agitation can be addressed with benzodiazepines.{{EMedicine|article|1011615|LSD Toxicity Treatment & Management|treatment}}{{cite journal |journal=Frontiers in Neuroscience |vauthors=Zawilska JB, Kacela M, Adamowicz P |doi=10.3389/fnins.2020.00078 |date=26 February 2020 |volume=14 |pmid=32174803 |title=NBOMes–Highly Potent and Toxic Alternatives of LSD |page=78 |pmc=7054380 |doi-access=free}} Reassurance in a calm, safe environment is beneficial.{{Cite journal |vauthors=Hartogsohn I |date=2017 |title=Constructing drug effects: A history of set and setting |journal=Drug Science, Policy and Law |language=en |volume=3 |pages=205032451668332 |doi=10.1177/2050324516683325 |s2cid=53373205 |issn=2050-3245 |doi-access=free}} Antipsychotics such as haloperidol are not recommended as they may have adverse psychotomimetic effects. Gastrointestinal decontamination with activated charcoal is of little use due to the rapid absorption of LSD, unless done within 30–60 minutes of ingesting exceedingly huge amounts. Administration of anticoagulants, vasodilators, and sympatholytics may be useful for treating ergotism.

The lethal oral dose of LSD in humans is estimated at 100 mg, based on LD₅₀ and lethal blood concentrations observed in rodent studies.

Many novel psychoactive substances of 25-NB (NBOMe) series, such as 25I-NBOMe and 25B-NBOMe, are regularly sold as LSD in blotter papers.{{cite journal |journal=Biochemical Pharmacology |vauthors=Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A |title=Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors |doi=10.1016/j.bcp.2018.09.024 |pmid=30261175 |pmc=6298744 |volume=158 |pages=27–34 |date=December 2018}}{{cite journal |journal=Journal of Analytical Toxicology |doi=10.1093/jat/bkv073 |pmc=4570937 |pmid=26378135 |title=Analysis of 25I-NBOMe, 25B-NBOMe, 25C-NBOMe and Other Dimethoxyphenyl-N-[(2-Methoxyphenyl) Methyl]Ethanamine Derivatives on Blotter Paper |vauthors=Poklis JL, Raso SA, Alford KN, Poklis A, Peace MR |date=Oct 2015 |volume=39 |issue=8 |pages=617–623}} NBOMe compounds are often associated with life-threatening toxicity and death.{{cite journal |journal=Clinical Toxicology |title=A cluster of 25B-NBOH poisonings following exposure to powder sold as lysergic acid diethylamide (LSD) |vauthors=Ivory ST, Rotella J, Schumann J, Greene SL |pages=966–969 |date=28 March 2022 |volume=60 |issue=8 |doi=10.1080/15563650.2022.2053150 |pmid=35343858 |s2cid=247764056}} Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,{{cite journal |journal=Frontiers in Pharmacology |date=12 December 2019 |vauthors=Miliano C, Marti M, Pintori N, Castelli MP, Tirri M, Arfè R, De Luca MA |title=Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe |volume=10 |page=1406 |pmid=31915427 |pmc=6921684 |doi=10.3389/fphar.2019.01406 |doi-access=free}} and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently". Researchers state that the alleged physiological toxicity of LSD is likely due to psychoactive substances other than LSD.

NBOMe compounds are reported to have a bitter taste, are not active orally,{{efn|The potency of N-benzylphenethylamines via buccal, sublingual, or nasal absorption is 50–100 greater (by weight) than oral route compared to the parent 2C-x compounds.{{cite journal |journal=Neurochemical Research |date=14 February 2014 |vauthors=Leth-Petersen S, Bundgaard C, Hansen M, Carnerup MA, Kehler J, Kristensen JL |title=Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability |volume=39 |issue=10 |pages=2018–2023 |doi=10.1007/s11064-014-1253-y |pmid=24519542| s2cid=254857910}} Researches hypothesize the low oral metabolic stability of N-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.}} and are usually taken sublingually.{{cite book |title=Neuropharmacology of New Psychoactive Substances |vauthors=Halberstadt AL |doi=10.1007/7854_2016_64 |date=18 January 2017 |isbn=978-3-319-52444-3 |publisher=Springer |chapter=Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens |series=Current Topics in Behavioral Neurosciences |volume=32 |pages=283–311 |pmid=28097528}} 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.{{cite journal |vauthors=Duffau B, Camargo C, Kogan M, Fuentes E, Kennedy Cassels B |journal=Journal of Chromatographic Science |volume=54 |issue=7 |date=August 2016 |pages=1153–1158 |title=Analysis of 25 C NBOMe in Seized Blotters by HPTLC and GC–MS |pmc=4941995 |pmid=27406128 |doi=10.1093/chromsci/bmw095 |doi-access=free}}{{cite journal |pmid=25105138 |pmc=4106087 |doi=10.1155/2014/734749 |title=25C-NBOMe: preliminary data on pharmacology, psychoactive effects, and toxicity of a new potent and dangerous hallucinogenic drug |journal=BioMed Research International |date=3 July 2014 |vauthors=Francesco SB, Ornella C, Gabriella A, Giuseppe V, Rita S, Flaminia BP, Eduardo C, Pierluigi S, Giovanni M, Guiseppe B, Fabrizio S |volume=2014 |page=734749 |doi-access=free}}{{cite book |title=Novel Psychoactive Substances: Classification, Pharmacology and Toxicology |chapter=Pharmacology and toxicology of N-Benzyl-phenylethylamines (25X-NBOMe) hallucinogens |vauthors=Potts AJ, ((Thomas SHL)), Hill SL |veditors=Dargan P, Wood D |doi=10.1016/B978-0-12-818788-3.00008-5 |isbn=978-0-12-818788-3 |pages=279–300 |edition=2nd |publisher=Academic Press |date=September 2021 |s2cid=240583877}} Despite its high potency, recreational doses of LSD have only produced low incidents of acute toxicity, but NBOMe compounds have extremely different safety profiles. Testing with Ehrlich's reagent gives a positive result for LSD and a negative result for NBOMe compounds.{{Cite journal | vauthors = Díaz Moreno M, Alarcón Ayala N, Estrada Y, Morris V, Quintero J |date=November 2022 |title=Échele Cabeza as a harm reduction project and activist movement in Colombia |url=https://www.emerald.com/insight/content/doi/10.1108/DHS-07-2022-0026/full/html |journal=Drugs, Habits and Social Policy |language=en |volume=23 |issue=3 |pages=263–276 |doi=10.1108/DHS-07-2022-0026 |issn=2752-6739}}{{cite journal | vauthors = Clancy L, Philp M, Shimmon R, Fu S | title = Development and validation of a color spot test method for the presumptive detection of 25-NBOMe compounds | journal = Drug Testing and Analysis | volume = 13 | issue = 5 | pages = 929–943 | date = May 2021 | pmid = 32744773 | doi = 10.1002/dta.2905 }}

File:LSDaffinities.GIF (K_i) of LSD for various receptors. 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 the K_i Database.]]

LSD is a serotonergic psychedelic and acts as a non-selective serotonin receptor modulator. It binds with high affinity to most of the serotonin receptors. The psychedelic effects of LSD are thought to be mediated specifically by activation of the serotonin 5-HT_2A receptor. However, a role of other serotonin receptors and targets in the effects of LSD cannot be ruled out and may be considered likely.{{cite journal | vauthors = Halberstadt AL, Geyer MA | title = Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens | journal = Neuropharmacology | volume = 61 | issue = 3 | pages = 364–381 | date = September 2011 | pmid = 21256140 | pmc = 3110631 | doi = 10.1016/j.neuropharm.2011.01.017 | url = }} Uniquely among serotonergic psychedelics, LSD also shows potentially significant affinity for the dopamine receptors, albeit much lower than for most of the serotonin receptors.{{cite journal | vauthors = Marona-Lewicka D, Thisted RA, Nichols DE | title = Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis | journal = Psychopharmacology | volume = 180 | issue = 3 | pages = 427–435 | date = July 2005 | pmid = 15723230 | doi = 10.1007/s00213-005-2183-9 | s2cid = 23565306 }}

LSD binds to most serotonin receptor subtypes except for the serotonin 5-HT₃ and 5-HT₄ receptors. However, some of these serotonin receptors may not be affected at typical brain concentrations of LSD. In humans, recreational doses of LSD may affect 5-HT_1A, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT_5A, and 5-HT₆ receptors. Although not present in humans, 5-HT_5B receptors found in rodents also have a high affinity for LSD.{{cite journal |vauthors=Nelson DL |title=5-HT5 receptors |journal=Current Drug Targets. CNS and Neurological Disorders |volume=3 |issue=1 |pages=53–58 |date=February 2004 |pmid=14965244 |doi=10.2174/1568007043482606}} The psychedelic effects of LSD are attributed to activation of 5-HT_2A receptors.{{cite journal |vauthors=Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J |title=Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists |journal=Neuroscience Letters |volume=493 |issue=3 |pages=76–79 |date=April 2011 |pmid=21276828 |pmc=3064746 |doi=10.1016/j.neulet.2011.01.046}} Many but not all serotonin 5-HT_2A agonists are psychedelics and serotonin 5-HT_2A antagonists block the psychedelic activity of LSD. LSD exhibits functional selectivity at the serotonin 5-HT_2A and 5-HT_2C receptors in that it activates the signal transduction enzyme phospholipase A2 instead of activating the enzyme phospholipase C as the endogenous ligand serotonin does.{{cite journal |vauthors=Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB |title=Functional selectivity and classical concepts of quantitative pharmacology |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=320 |issue=1 |pages=1–13 |date=January 2007 |pmid=16803859 |doi=10.1124/jpet.106.104463 |url=https://jpet.aspetjournals.org/content/320/1/1 |s2cid=447937 |access-date=June 11, 2023 |archive-date=June 11, 2023 |archive-url=https://web.archive.org/web/20230611010342/https://jpet.aspetjournals.org/content/320/1/1 |url-status=live }}

Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex and therefore excitation in this area, specifically in layer V.{{cite journal | vauthors = Aghajanian GK, Marek GJ | title = Serotonin and hallucinogens | journal = Neuropsychopharmacology | volume = 21 | issue = 2 Suppl | pages = 16S–23S | date = August 1999 | pmid = 10432484 | doi = 10.1016/S0893-133X(98)00135-3 | doi-access = free }} LSD, like many other drugs of recreational use, has been shown to activate DARPP-32-related pathways.{{cite journal | vauthors = Svenningsson P, Nairn AC, Greengard P | title = DARPP-32 mediates the actions of multiple drugs of abuse | journal = The AAPS Journal | volume = 7 | issue = 2 | pages = E353-60 | date = October 2005 | pmid = 16353915 | pmc = 2750972 | doi = 10.1208/aapsj070235 }} The drug enhances dopamine D₂ receptor protomer recognition and signaling of D₂–5-HT_2A receptor complexes,{{cite journal | vauthors = Borroto-Escuela DO, Romero-Fernandez W, Narvaez M, Oflijan J, Agnati LF, Fuxe K | title = Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes | journal = Biochemical and Biophysical Research Communications | volume = 443 | issue = 1 | pages = 278–84 | date = January 2014 | pmid = 24309097 | doi = 10.1016/j.bbrc.2013.11.104 }} which may contribute to its psychotropic effects. LSD has been shown to have low affinity for H1 receptors, displaying antihistamine effects, although the significance of this at doses used in humans is unknown.{{cite journal | vauthors = Green JP, Johnson CL, Weinstein H, Maayani S | title = Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 74 | issue = 12 | pages = 5697–701 | date = December 1977 | pmid = 23536 | pmc = 431860 | doi = 10.1073/pnas.74.12.5697 | bibcode = 1977PNAS...74.5697G | doi-access = free }}

LSD is a biased agonist that induces a conformation in serotonin receptors that preferentially recruits β-arrestin over activating G proteins.{{cite journal |vauthors=Chen Q, Tesmer JJ |title=A Receptor on Acid |journal=Cell |volume=168 |issue=3 |pages=339–341 |date=January 2017 |doi=10.1016/j.cell.2017.01.012 |pmid=28129534 |pmc=5520807}} 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.{{cite journal | vauthors = Roth BL, Gumpper RH | title = Psychedelics as Transformative Therapeutics | journal = Am J Psychiatry | volume = 180 | issue = 5 | pages = 340–347 | date = May 2023 | pmid = 37122272 | doi = 10.1176/appi.ajp.20230172 | url = https://cdr.lib.unc.edu/downloads/37720q20d| quote = 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.}} A crystal structure of the serotonin 5-HT_2B 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.{{cite journal | vauthors = Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, Lansu K, Schools ZL, Che T, Nichols DE, Shoichet BK, Dror RO, Roth BL | title = Crystal Structure of an LSD-Bound Human Serotonin Receptor | journal = Cell | volume = 168 | issue = 3 | pages = 377–389.e12 | date = January 2017 | pmid = 28129538 | pmc = 5289311 | doi = 10.1016/j.cell.2016.12.033 }} The related lysergamide lysergic acid amide (LSA) that lacks the diethylamide moiety is far less hallucinogenic in comparison. 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.

LSD is an extraordinarily potent psychoactive drug and is among the most potent psychedelics known in humans. It is unclear why LSD is so potent.{{cite journal | vauthors = Nichols DE | title = LSD and Its Lysergamide Cousins | pages = 80–87 | journal = The Heffter Review of Psychedelic Research | volume = 2 | date = 2001 | publisher = Heffter Research Institute | issn = 1534-9640 | url = https://www.heffter.org/wp-content/uploads/2020/04/chap6.pdf | quote = 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. [...]}} The affinity and activational potency of LSD at the human serotonin 5-HT_2A receptor in vitro is unremarkable compared to other psychedelics such as DOI and DOB. It appears that the N,N-diethylamide moiety of LSD fits into a sterically constrained region of the serotonin 5-HT_2A receptor that specifically accommodates this moiety.

LSD, like other psychedelics, has been found to increase the expression of genes related to synaptic plasticity and hence to have psychoplastogenic effects.{{cite journal | vauthors = Calder AE, Hasler G | title = Towards an understanding of psychedelic-induced neuroplasticity | journal = Neuropsychopharmacology | volume = 48 | issue = 1 | pages = 104–112 | date = January 2023 | pmid = 36123427 | pmc = 9700802 | doi = 10.1038/s41386-022-01389-z }} This is in part due to binding to brain-derived neurotrophic factor (BDNF) receptor tropomyosin receptor kinase B (TrkB).{{cite journal | vauthors = Moliner R, Girych M, Brunello CA, Kovaleva V, Biojone C, Enkavi G, Antenucci L, Kot EF, Goncharuk SA, Kaurinkoski K, Kuutti M, Fred SM, Elsilä LV, Sakson S, Cannarozzo C, Diniz CR, Seiffert N, Rubiolo A, Haapaniemi H, Meshi E, Nagaeva E, Öhman T, Róg T, Kankuri E, Vilar M, Varjosalo M, Korpi ER, Permi P, Mineev KS, Saarma M, Vattulainen I, Casarotto PC, Castrén E | title = Psychedelics promote plasticity by directly binding to BDNF receptor TrkB | journal = Nature Neuroscience | volume = 26 | issue = 6 | pages = 1032–1041 | date = June 2023 | pmid = 37280397 | doi = 10.1038/s41593-023-01316-5 | pmc = 10244169 }}

There appears to be no significant acute tolerance to the subjective effects of LSD.{{citation | author = Matthias Liechti | title = Pharmacology of novel psychoactive substances, MDMA, and LSD | work = Department of Biomedicine. Report 2014–2016 | pages=52–53 | date=2016 | url = https://biomedizin.unibas.ch/fileadmin/user_upload/biomedizin/research/fg_liechti_psychopharmacology_research/DBM_Report_2014-2016_liechti.pdf | quote = 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).}} Hence, its duration appears to be dictated by pharmacokinetics rather than by pharmacodynamics. This is in contrast to MDMA, which shows marked acute tolerance and a duration of effects that is shorter than its elimination half-life.

The cryo-EM structures of the serotonin 5-HT_2A receptor with LSD, as well as with various other psychedelics and serotonin 5-HT_2A receptor agonists, have been solved and published by Bryan L. Roth and colleagues.{{cite journal | vauthors = Gumpper RH, Jain MK, Kim K, Sun R, Sun N, Xu Z, DiBerto JF, Krumm BE, Kapolka NJ, Kaniskan HÜ, Nichols DE, Jin J, Fay JF, Roth BL | title = The structural diversity of psychedelic drug actions revealed | journal = Nature Communications | volume = 16 | issue = 1 | pages = 2734 | date = March 2025 | pmid = 40108183 | doi = 10.1038/s41467-025-57956-7 | pmc = 11923220 | bibcode = 2025NatCo..16.2734G }}{{cite conference | vauthors = Gumpper RH, DiBerto J, Jain M, Kim K, Fay J, Roth BL | title = Structures of Hallucinogenic and Non-Hallucinogenic Analogues of the 5-HT2A Receptor Reveals Molecular Insights into Signaling Bias | conference = University of North Carolina at Chapel Hill Department of Pharmacology Research Retreat September 16th, 2022 – William and Ida Friday Center | date = September 2022 | url = https://www.med.unc.edu/pharm/wp-content/uploads/sites/930/2022/07/COMPLETE-PHARM-RETREAT-PROGRAM-2022-UPDATE.pdf#page=37}}

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| caption1 = Resting state fMRI BOLD-contrast imaging shows increased primary visual cortex (V1) cerebral blood flow (CBF) and increased V1 resting state functional connectivity (RSFC), which correlated more strongly with the visual hallucinatory aspect of the LSD experience. Increased V1 RSFC also correlated with visual analogue scale (VAS) ratings of simple hallucinations and the magnitude of CBF observed in the visual cortex correlated positively with ratings of complex imagery on the LSD-induced altered state of consciousness (ASC).{{cite journal |vauthors=Carhart-Harris RL, Muthukumaraswamy S, Roseman L, Kaelen M, Droog W, Murphy K, Tagliazucchi E, Schenberg EE, Nest T, Orban C, Leech R, Williams LT, Williams TM, Bolstridge M, Sessa B, McGonigle J, Sereno MI, Nichols D, Hellyer PJ, Hobden P, Evans J, Singh KD, Wise RG, Curran HV, Feilding A, Nutt DJ |title=Neural correlates of the LSD experience revealed by multimodal neuroimaging |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=113 |issue=17 |pages=4853–4858 |date=11 April 2016 |pmid=27071089 |pmc=4855588 |doi=10.1073/pnas.1518377113 |bibcode=2016PNAS..113.4853C |doi-access=free}}

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| image2 = FMRI PH RSFC LSD.png

| caption2 = Resting state fMRI BOLD-contrast imaging shows decreased bilateral parahippocampal (PH) resting state functional connectivity (RSFC), which correlated with the ego-dissolution aspect of the LSD experience. A significant relationship was also found between decreased posterior cingulate cortex (PCC) alpha power and default mode network (DMN) disintegration with ego-dissolution.

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Neuroimaging studies using resting state fMRI recently suggested that LSD changes the cortical functional architecture.{{cite journal | vauthors = Singleton SP, Luppi AI, Carhart-Harris RL, Cruzat J, Roseman L, Nutt DJ, Deco G, Kringelbach ML, Stamatakis EA, Kuceyeski A |title = Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape|journal = Nat Commun |volume=13 | issue=1 | page=5812 | date=Oct 2022 | pmid=36192411 | doi = 10.1038/s41467-022-33578-1 | pmc=9530221 | bibcode=2022NatCo..13.5812S | doi-access=free }} These modifications spatially overlap with the distribution of serotoninergic receptors. In particular, increased connectivity and activity were observed in regions with high expression of 5-HT_2A receptor, while a decrease in activity and connectivity was observed in cortical areas that are dense with 5-HT_1A receptor.{{cite journal |vauthors=Delli Pizzi S, Chiacchiaretta P, Sestieri C, Ferretti A, Onofrj M, Della Penna S, Roseman L, Timmermann C, Nutt DJ, Carhart-Harris RL, Sensi SL |title=Spatial Correspondence of LSD-Induced Variations on Brain Functioning at Rest With Serotonin Receptor Expression |journal=Biol Psychiatry Cogn Neurosci Neuroimaging |volume=8 |issue=7 |pages=768–776 |date=July 2023 |pmid=37003409 |doi=10.1016/j.bpsc.2023.03.009 |s2cid=257862535}} 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-HT_2A receptor, may enhance excitatory neurotransmission along frontostriatal projections and, consequently, reduce thalamic filtering of sensory stimuli towards the cortex.{{cite journal |vauthors=Delli Pizzi S, Chiacchiaretta P, Sestieri C, Ferretti A, Tullo MG, Della Penna S, Martinotti G, Onofrj M, Roseman L, Timmermann C, Nutt DJ, Carhart-Harris RL, Sensi SL |title=LSD-induced changes in the functional connectivity of distinct thalamic nuclei |journal=NeuroImage |volume=283 |page=120414 |date=Dec 2023 |pmid=37858906 |doi=10.1016/j.neuroimage.2023.120414 |doi-access=free}} This phenomenon appears to selectively involve ventral, intralaminar, and pulvinar nuclei.

The acute effects of LSD normally last between 6 and 12{{nbsp}}hours depending on dosage, tolerance, and age.{{cite book |vauthors=Shulgin A, Shulgin A |author-link1=Alexander Shulgin |author-link2=Ann Shulgin |chapter-url=http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml |archive-date=15 October 2008 |archive-url=http://archive.wikiwix.com/cache/20081015082653/http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml |chapter=LSD |title=TiHKAL |location=Berkeley, CA |publisher=Transform Press |date=1997 |isbn=0-9630096-9-9}} Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175 minutes (about 3 hours).{{cite journal |vauthors=Aghajanian GK, Bing OH |title=Persistence of lysergic acid diethylamide in the plasma of human subjects |journal=Clinical Pharmacology and Therapeutics |volume=5 |issue=5 |pages=611–614 |year=1964 |pmid=14209776 |doi=10.1002/cpt196455611| url=http://www.maps.org/w3pb/new/1964/1964_aghajanian_2224_1.pdf |s2cid=29438767 |archive-url= https://web.archive.org/web/20090327144227/http://www.maps.org/w3pb/new/1964/1964_aghajanian_2224_1.pdf |archive-date=March 27, 2009}} 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.{{cite journal |vauthors=Papac DI, Foltz RL |title=Measurement of lysergic acid diethylamide (LSD) in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry |journal=Journal of Analytical Toxicology |volume=14 |issue=3 |pages=189–190 |date=May–June 1990 |pmid=2374410 |doi=10.1093/jat/14.3.189 |url=http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=6265&DocPartID=6624 |url-status=live|format=PDF |archive-date=April 29, 2011|archive-url=https://web.archive.org/web/20110429060433/http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=6265&DocPartID=6624}}

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. 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. 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.

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. 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. 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. The oral bioavailability of LSD was crudely estimated as approximately 71% using previous data on intravenous administration of LSD. The sample was equally divided between male and female subjects and there were no significant sex differences observed in the pharmacokinetics of LSD.

A large meal before taking LSD has been found to result in circulating levels that were 50% lower than on an empty stomach.

It has been said that there is a peculiar 40-minute lag before onset of the psychedelic effects of LSD when it is administered intravenously. This has been said to be related to time-dependent interactions of LSD with the serotonin 5-HT_2A receptor. However, contradicting the preceding claims, other sources have stated that intravenous injection of LSD results in onset of effects within a few minutes. In addition, intrathecal injection (intraspinal injection) is reported to have a virtually instantaneous onset of action. Doses of LSD are said to be similar by oral and injectable routes, with the exception of intrathecal injection in which the dosage is reduced to about one-third of usual.

File:Lysergide stereoisomers structural formulae v.2.png

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,{{Cite book |title=Handbook of Medical Hallucinogens |date=2021 |publisher=Guilford Publications |isbn=9781462545452 |pages=160 |language=en |chapter=LSD |chapter-url=https://mcb.berkeley.edu/labs2/presti/sites/mcb.berkeley.edu.labs2.presti/files/u3/2021%20LSD%20Chapter%20Panik%20Presti.pdf |access-date=March 14, 2024 |archive-date=March 14, 2024 |archive-url=https://web.archive.org/web/20240314163910/https://mcb.berkeley.edu/labs2/presti/sites/mcb.berkeley.edu.labs2.presti/files/u3/2021%20LSD%20Chapter%20Panik%20Presti.pdf |url-status=live }} has the absolute configuration (5R,8R). 5S stereoisomers 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. LSD is strongly fluorescent and will glow bluish-white under UV light.

LSD is an ergoline derivative. It is commonly synthesized by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride{{cite journal |vauthors=Monte AP, Marona-Lewicka D, Kanthasamy A, Sanders-Bush E, Nichols DE |date=March 1995 |title=Stereoselective LSD-like activity in a series of d-lysergic acid amides of (R)- and (S)-2-aminoalkanes |journal=Journal of Medicinal Chemistry |volume=38 |issue=6 |pages=958–66 |pmid=7699712 |doi=10.1021/jm00006a015}} and peptide coupling reagents.{{cite journal |vauthors=Nichols DE, Frescas S, Marona-Lewicka D, Kurrasch-Orbaugh DM |date=September 2002 |title=Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD) |journal=Journal of Medicinal Chemistry |volume=45 |issue=19 |pages=4344–9 |pmid=12213075 |doi=10.1021/jm020153s}} Lysergic acid is made by alkaline hydrolysis of lysergamides like ergotamine, a substance usually derived from the ergot fungus on agar plate. Lysergic acid can also be produced synthetically, although these processes are not used in clandestine manufacture due to their low yields and high complexity.{{cite journal |vauthors=Kornfeld EC, Fornefeld EJ, Kline GB, Mann MJ, Morrison DE, Jones RG, Woodward RB |title=The Total Synthesis of Lysergic Acid |journal=Journal of the American Chemical Society |volume=78 |issue=13 |pages=3087–3114 |year=1956 |doi=10.1021/ja01594a039|bibcode=1956JAChS..78.3087K }}{{cite journal |vauthors=Inuki S, Oishi S, Fujii N, Ohno H |title=Total synthesis of (+/-)-lysergic acid, lysergol, and isolysergol by palladium-catalyzed domino cyclization of amino allenes bearing a bromoindolyl group |journal=Organic Letters |volume=10 |issue=22 |pages=5239–42 |date=November 2008 |pmid=18956869 |doi=10.1021/ol8022648 |url=https://figshare.com/articles/journal_contribution/2663242}}

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 with HNO₂ to D-lysergic acid azide and (5) finally substitution with diethylamine to form D-lysergic acid diethylamide.

The precursor for LSD, lysergic acid, has been produced by GMO baker's yeast.{{cite web |author=((National University of Singapore, Yong Loo Lin School of Medicine)) |date=10 February 2022 |title=Harvesting baker's yeast for aging-related therapeutics |website=ScienceDaily |url=https://www.sciencedaily.com/releases/2022/02/220210154135.htm |access-date=2023-05-04 |archive-date=November 27, 2022 |archive-url=https://web.archive.org/web/20221127230250/https://www.sciencedaily.com/releases/2022/02/220210154135.htm |url-status=live }} Journal Reference: {{cite journal |vauthors=Wong G, Lim LR, Tan YQ, Go MK, Bell DJ, Freemont PS, Yew WS |title=Reconstituting the complete biosynthesis of D-lysergic acid in yeast |journal=Nature Communications |volume=13 |issue=1 |pages=712 |date=February 2022 |doi=10.1038/s41467-022-28386-6 |pmid=35132076 |pmc=8821704 |bibcode=2022NatCo..13..712W}}

"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."

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 the 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|date=May 2011}}

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. 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.

A controlled study was undertaken to determine the stability of LSD in pooled urine samples.{{cite journal | vauthors = Li Z, McNally AJ, Wang H, Salamone SJ | title = Stability study of LSD under various storage conditions | journal = Journal of Analytical Toxicology | volume = 22 | issue = 6 | pages = 520–5 | date = October 1998 | pmid = 9788528 | doi = 10.1093/jat/22.6.520 | doi-access = free }}

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 of EDTA.

File:LSD Ehrlich reagent test.jpg can be used to test for the presence of LSD in a sample, turning purple upon reaction.{{cite web |url=https://www.emcdda.europa.eu/publications/drug-profiles/lsd_en |title=Lysergide (LSD) drug profile |website=European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) |access-date=15 May 2023 |url-status=live |archive-url=https://web.archive.org/web/20230202152854/https://www.emcdda.europa.eu/publications/drug-profiles/lsd_en |archive-date=2 February 2023}}]]

LSD can be detected in concentrations larger than approximately 10% in a sample using Ehrlich's reagent and Hofmann's reagent. However, detecting LSD in human tissues is more challenging due to its active dosage being significantly lower (in micrograms) compared to most other drugs (in milligrams).{{Cite journal | vauthors = Appel JB, Whitehead WE, Freedman DX |date= July 1968 |title=Motivation and the behavioral effects of LSD |journal=Psychonomic Science |language=en |volume=12 |issue=7 |pages=305–306 |doi=10.3758/BF03331322 |s2cid=144527673 |issn=0033-3131|doi-access=free }}

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.R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 12th edition, Biomedical Publications, Foster City, CA, 2020, pp. 1197–1199. Maximum plasma concentrations are typically observed 1.4 to 1.5 hours after oral administration of 100 μg and 200 μg, respectively, with a plasma half-life of approximately 2.6 hours (ranging from 2.2 to 3.4 hours among test subjects).{{cite journal | vauthors = Dolder PC, Schmid Y, Steuer AE, Kraemer T, Rentsch KM, Hammann F, Liechti ME | title = Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects | journal = Clinical Pharmacokinetics | volume = 56 | issue = 10 | pages = 1219–1230 | date = October 2017 | pmid = 28197931 | doi = 10.1007/s40262-017-0513-9 | pmc = 5591798 }}

Due to its potency in microgram quantities, LSD is often not included in standard pre-employment urine or hair analyses.{{cite journal |vauthors=Jiaming Z, Xin W, Jiali Z, Hang R, Yunli Z, Ping X |title=Concentrations of LSD, 2-oxo-3-hydroxy-LSD, and iso-LSD in hair segments of 18 drug abusers |journal=Forensic Science International |volume=344 |date=March 2023 |pmid=36753839 |doi=10.1016/j.forsciint.2023.111578| s2cid=256574276}} However, advanced liquid chromatography–mass spectrometry methods can detect LSD in biological samples even after a single use.

{{Main|Lysergamides|Lysergamides#Simplified or partial lysergamides}}

A variety of LSD analogues are known.{{cite book | vauthors = Shulgin AT | chapter=Basic Pharmacology and Effects | pages=67–137 | veditors = Laing RR | title=Hallucinogens: A Forensic Drug Handbook | publisher=Elsevier Science | series=Forensic Drug Handbook Series | year=2003 | isbn=978-0-12-433951-4 | url=https://books.google.com/books?id=l1DrqgobbcwC | chapter-url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 | access-date=1 February 2025}}{{cite journal | vauthors = Jacob P, Shulgin AT | title = Structure-activity relationships of the classic hallucinogens and their analogs | journal = NIDA Res Monogr | volume = 146 | issue = | pages = 74–91 | date = 1994 | pmid = 8742795 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 }}{{cite book |vauthors=Shulgin AT | chapter=Chemistry of Psychotomimetics | pages = 3–29 | veditors = Hoffmeister F, Stille G | title=Psychotropic Agents, Part III: Alcohol and Psychotomimetics, Psychotropic Effects of Central Acting Drugs | series=Handbook of Experimental Pharmacology | publisher=Springer Berlin Heidelberg |location=Berlin |date=1982 | volume=55 / 3 |isbn=978-3-642-67772-4 | oclc = 8130916 | doi=10.1007/978-3-642-67770-0_1 | url = https://books.google.com/books?id=mrT8CAAAQBAJ | chapter-url = https://bitnest.netfirms.com/external/10.1007/978-3-642-67770-0_1}}{{cite book | author = Alexander T. Shulgin | chapter = Hallucinogens | pages = 1109–1137 | chapter-url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6ac0c892ee380436f614d3aae0686ef617b2e0c5 | veditors = Burger A, Wolf ME | title = Burger's Medicinal Chemistry | edition = 4 | volume = 3 | date = 1980 | publisher = Wiley | location = New York | isbn = 978-0-471-01572-7 | oclc = 219960627 | url = https://books.google.com/books?id=2b3wAAAAMAAJ}}{{CiteTiHKAL}} Many of them retain psychedelic effects similarly to LSD, although most have reduced potency and none are notably more potent than LSD.{{cite thesis | vauthors = Mangner TJ | degree = Ph.D. | publisher = University of Michigan | title=Potential Psychotomimetic Antagonists. N,n -diethyl-1-methyl-3-aryl-1, 2, 5, 6-tetrahydropyridine-5-carboxamides. | date=1978 | doi=10.7302/11268 | url=https://www.proquest.com/openview/f845a6810749d00f70305960adfde737/ | archive-url=https://web.archive.org/web/20250330031605/https://media.proquest.com/media/hms/ORIG/2/9yQxJ?cit%3Aauth=MANGNER%2C+THOMAS+JOSEPH&cit%3Atitle=POTENTIAL+PSYCHOTOMIMETIC+ANTAGONISTS.+N%2CN+...&cit%3Apub=ProQuest+Dissertations+and+Theses&cit%3Avol=&cit%3Aiss=&cit%3Apg=&cit%3Adate=1978&ic=true&cit%3Aprod=ProQuest+Dissertations+%26+Theses+Global&_a=ChgyMDI1MDMzMDAzMDAzNTMxOTo3ODkyMzgSBjEwNjkyNRoKT05FX1NFQVJDSCILNzYuMTc0LjAuNTcqBTE4NzUwMgkzMDI5MDU4NjE6DURvY3VtZW50SW1hZ2VCATBSBk9ubGluZVoCRlRiA1BGVGoAcgB6AIIBJVAtMTAxMDI2OC0xMDA1MS1DVVNUT01FUi1udWxsLTcwOTY2NDmSAQZPbmxpbmXKAW9Nb3ppbGxhLzUuMCAoV2luZG93cyBOVCAxMC4wOyBXaW42NDsgeDY0KSBBcHBsZVdlYktpdC81MzcuMzYgKEtIVE1MLCBsaWtlIEdlY2tvKSBDaHJvbWUvMTM0LjAuMC4wIFNhZmFyaS81MzcuMzbSARZEaXNzZXJ0YXRpb25zICYgVGhlc2VzmgIHUHJlUGFpZKoCK09TOkVNUy1NZWRpYUxpbmtzU2VydmljZS1nZXRNZWRpYVVybEZvckl0ZW3KAhNEaXNzZXJ0YXRpb24vVGhlc2lz0gIBWfICAPoCAU6CAwNXZWKKAxxDSUQ6MjAyNTAzMzAwMzAwMzUzMTk6NTcyNjc1&_s=QP3F3liRMGFAbHtX3wDWE8eO1gs%3D#page=22 | archive-date=30 March 2025}} Examples include ergine (lysergic acid amide; LSA), ergonovine (ergometrine), methylergonovine (methylergometrine), methysergide, ETH-LAD, AL-LAD, 1-methyl-LSD (MLD-41), and LA-SS-Az (LSZ), among many others.{{cite book | vauthors = Rutschmann J, Stadler PA | chapter=Chemical Background | veditors=Berde B, Schild HO | title=Ergot Alkaloids and Related Compounds | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | date=1978 | isbn=978-3-642-66777-0 | doi=10.1007/978-3-642-66775-6_2 | pages=29–85 | series=Handbook of Experimental Pharmacology (HEP) | volume=49}}{{cite book | vauthors = Fanchamps A | chapter=Some Compounds With Hallucinogenic Activity | veditors=Berde B, Schild HO | title=Ergot Alkaloids and Related Compounds | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | date=1978 | isbn=978-3-642-66777-0 | doi=10.1007/978-3-642-66775-6_8 | pages=567–614 | series=Handbook of Experimental Pharmacology (HEP) | volume=49 | chapter-url=https://bibliography.maps.org/resources/download/8769| archive-url=https://web.archive.org/web/20250330033128/https://bibliography.maps.org/resources/download/8769 | archive-date=March 30, 2025 }} Presumed or known prodrugs of LSD, including 1A-LSD (ALD-52), 1P-LSD, and 1V-LSD, have been developed or encountered.{{cite journal | vauthors = Schifano F, Vento A, Scherbaum N, Guirguis A | title = Stimulant and hallucinogenic novel psychoactive substances; an update | journal = Expert Rev Clin Pharmacol | volume = 16 | issue = 11 | pages = 1109–1123 | date = 2023 | pmid = 37968919 | doi = 10.1080/17512433.2023.2279192 | url = | hdl = 2299/27223 | hdl-access = free }}{{cite journal | vauthors = Ponce JC | title=The use of prodrugs as drugs of abuse | journal=WIREs Forensic Science | volume=6 | issue=3 | date=2024 | issn=2573-9468 | doi=10.1002/wfs2.1514 | doi-access=free | page=}} Some non-hallucinogenic LSD analogues, such as lisuride and 2-bromo-LSD (BOL-148), are known as well.{{cite journal | vauthors = Gumpper RH, Nichols DE | title = Chemistry/structural biology of psychedelic drugs and their receptor(s) | journal = Br J Pharmacol | volume = | issue = | pages = | date = October 2024 | pmid = 39354889 | doi = 10.1111/bph.17361 | url = }}{{cite journal | vauthors = Nichols DE | title=Structure–activity relationships of serotonin 5-HT 2A agonists | journal=Wiley Interdisciplinary Reviews: Membrane Transport and Signaling | volume=1 | issue=5 | date=2012 | issn=2190-460X | doi=10.1002/wmts.42 | doi-access=free | pages=559–579 | access-date=22 March 2025 | url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=e28e0e22c3145af5a787c34fbedbaa8f81e1ed6b}} They are lower-efficacy serotonin 5-HT_2A receptor partial agonists and can notably act as hallucinogen antagonists against LSD.{{cite journal | vauthors = Pfaff RC, Huang X, Marona-Lewicka D, Oberlender R, Nichols DE | title = Lysergamides revisited | journal = NIDA Res Monogr | volume = 146 | issue = | pages = 52–73 | date = 1994 | pmid = 8742794 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=57}} In addition to lysergamide derivatives, simplified or "partial" LSD analogues, such as NDTDI, N-DEAOP-NMT, and DEIMDHPCA, are known.{{cite book | veditors=Gordon M | title=Psychopharmacological Agents: Use, Misuse and Abuse | series=Medicinal Chemistry: A Series of Monographs | volume=4 | vauthors = Shulgin AT | chapter=Psychotomimetic Agents | date=1976 | isbn=978-0-12-290559-9 | doi=10.1016/b978-0-12-290559-9.50011-9 | pages=59–146 | publisher=Academic Press | url=https://bitnest.netfirms.com/external/10.1016/B978-0-12-290559-9.50011-9 | quote = 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.}}{{cite thesis | vauthors = Nichols DE | title = Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid | date = May 1973 | publisher = University of Iowa | pages = 23 | oclc = 1194694085 | url = https://bitnest.netfirms.com/external/Theses/Nichols1973#page=32}}{{cite journal | vauthors = Campaigne E, Knapp DR | title = Structural analogs of lysergic acid | journal = J Pharm Sci | volume = 60 | issue = 6 | pages = 809–814 | date = June 1971 | pmid = 4942861 | doi = 10.1002/jps.2600600602 | url = }}{{cite patent | country = WO | number = 2021076572 | inventor = Olsen DE, Dunlap L, Wagner F, Chytil M, Powell NA | status = | title = Ergoline-like compounds for promoting neural plasticity | pubdate = 22 April 2021 | gdate = | fdate = 14 October 2020 | pridate = 14 October 2020 | assign1 = Delix Therapeutics, Inc. | assign2 = The Regents of the University of California | url =https://patents.google.com/patent/WO2021076572/ }}

{{Quote box| quote= ... 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.|source= —Albert Hofmann, on his first experience with LSD{{cite book | vauthors = Hofmann A |url=http://www.psychedelic-library.org/child.htm |title=LSD—My Problem Child |access-date=April 19, 2010 |via=The Psychedelic Library |archive-url=https://web.archive.org/web/20171215043651/http://www.psychedelic-library.org/child.htm |archive-date=15 December 2017 |url-status=live |publisher=McGraw-Hill |date=1980 |isbn=0-07-029325-2}}{{rp|p=15}}|width=25em}}

{{Main|History of LSD}}

Swiss chemist Albert Hofmann first synthesized LSD in 1938 from lysergic acid, a chemical derived from the hydrolysis of ergotamine, an alkaloid found in ergot, a fungus that infects grain.{{cite web |title=Commonly Abused Drugs Charts |url=https://www.drugabuse.gov/drugs-abuse/commonly-abused-drugs-charts#lsd |website=National Institute on Drug Abuse |access-date=14 July 2018 |date=2 July 2018 |url-status=live |archive-url=https://web.archive.org/web/20200301183029/https://www.drugabuse.gov/drugs-abuse/commonly-abused-drugs-charts#lsd |archive-date=March 1, 2020}} 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 on April 16, in 1943, after unintentionally ingesting an unknown amount, possibly absorbing it through his skin.{{Cite book |vauthors=Hofmann A |title=LSD, my problem child: reflections on sacred drugs, mysticism, and science |location=Santa Cruz, CA |publisher=Multidisciplinary Association for Psychedelic Studies |year=2009 |isbn=978-0-9798622-2-9 |edition=4th |oclc=610059315}}{{Cite book |vauthors=Lee MA, Shlain B |title=Acid dreams: the complete social history of LSD: the CIA, the Sixties, and beyond |date=1992 |publisher=Grove Weidenfeld |isbn=0-8021-3062-3 |location=New York |oclc=25281992}}{{cite book |vauthors=Ettinger RH |title=Psychopharmacology |date=2017 |publisher=Psychology Press |isbn=978-1-351-97870-5 |page=226 |language=en |url=https://books.google.com/books?id=XT4lDwAAQBAJ&pg=PA226 |access-date=September 27, 2021 |url-status=live |archive-url=https://web.archive.org/web/20210927002241/https://books.google.com/books?id=XT4lDwAAQBAJ&pg=PA226 |archive-date=September 27, 2021}} On April 19, 1943, Hofmann intentionaly ingested 0.25 milligrams (250 micrograms) of LSD.{{Cite magazine | vauthors = Calderon T |date=2018-04-19 |title=Flashback: LSD Creator Albert Hofmann Drops Acid for the First Time |url=https://www.rollingstone.com/culture/culture-news/flashback-lsd-creator-albert-hofmann-drops-acid-for-the-first-time-629085/ |access-date=2025-02-10 |magazine=Rolling Stone |language=en-US}} LSD was first published in the scientific literature by Hofmann and his colleague psychiatrist Werner Stoll in 1943 and the hallucinogenic effects of LSD were first published by Stoll in 1947.{{cite book | vauthors = Gach J | title=History of Psychiatry and Medical Psychology | chapter=Biological Psychiatry in the Nineteenth and Twentieth Centuries | publisher=Springer US | publication-place=Boston, MA | date=2008 | isbn=978-0-387-34707-3 | doi=10.1007/978-0-387-34708-0_12 | pages=381–418 | url=https://www.timothydavidson.com/Library/Books/Wallace-2008-History%20of%20Psychiatry%20and%20Medical%20Psychology/Wallace%20and%20Gach-2008-History%20of%20Psychiatry%20and%20Medical%20Psychology.pdf#page=413 | archive-url=https://web.archive.org/web/20250319140308/https://www.timothydavidson.com/Library/Books/Wallace-2008-History%20of%20Psychiatry%20and%20Medical%20Psychology/Wallace%20and%20Gach-2008-History%20of%20Psychiatry%20and%20Medical%20Psychology.pdf#page=413 | archive-date=March 19, 2025 | quote=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.]}}{{cite magazine | title = High Times Greats: Interview With Albert Hofmann, The Man Who First Synthesized LSD | date = 10 January 2020 | orig-date = July 1976 | magazine = High Times | url = https://web.archive.org/web/20200110215454/https://hightimes.com/culture/albert-hofmann-lsd-interview/ | quote = 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.}}{{cite journal | vauthors = Stoll A, Hofmann A | title=Partialsynthese von Alkaloiden vom Typus des Ergobasins. (6. Mitteilung über Mutterkornalkaloide) | trans-title=Partial synthesis of ergobasine-type alkaloids. (6th report on ergot alkaloids) | journal=Helvetica Chimica Acta | volume=26 | issue=3 | date=3 May 1943 | issn=0018-019X | doi=10.1002/hlca.19430260326 | pages=944–965}}{{cite journal | vauthors = Stoll WA | title = 11. Lysergsäure-diäthylamid, ein Phantastikum aus der Mutterkorngruppe | trans-title = 11. Lysergic Acid Diethylamide, a Hallucinogen From the Ergot Group | journal = Schweizer Archiv für Neurologie und Psychiatrie | volume = 60 | issue = | date = 1947 | pages = 279–323 | issn = 0258-7661 | url = https://bibliography.maps.org/resources/download/16963| archive-url = https://web.archive.org/web/20250401005831/https://bibliography.maps.org/resources/download/16963 | archive-date = April 1, 2025 }}{{cite journal | vauthors = Stoll W | title = Ein neues, in sehr kleinen Mengen wirksames Phantastikum | trans-title = A New Phantasticum, Effective in Very Tiny Amounts | journal = Schweizer Archiv für Neurologie und Psychiatrie | volume = 64 | issue = | date = 1949 | pages = 483–484 | issn = 0258-7661 | url = https://bibliography.maps.org/resources/download/16676| archive-url = https://web.archive.org/web/20250401012040/https://bibliography.maps.org/resources/download/16676 | archive-date = April 1, 2025 }}

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. During this period, LSD was controversially administered to hospitalised schizophrenic autistic children, with varying degrees of therapeutic success.{{cite journal | vauthors = Freedman AM, Ebin EV, Wilson EA | title = Autistic schizophrenic children. An experiment in the use of d-lysergic acid diethylamide (LSD-25) | journal = Archives of General Psychiatry | volume = 6 | issue = 3 | pages = 203–213 | date = March 1962 | pmid = 13894863 | doi = 10.1001/archpsyc.1962.01710210019003 }}{{cite journal | vauthors = Simmons JQ, Leiken SJ, Lovaas OI, Schaeffer B, Perloff B | title = Modification of autistic behavior with LSD-25 | journal = The American Journal of Psychiatry | volume = 122 | issue = 11 | pages = 1201–1211 | date = May 1966 | pmid = 5325567 | doi = 10.1176/ajp.122.11.1201 }}{{cite journal | vauthors = Sigafoos J, Green VA, Edrisinha C, Lancioni GE | title = Flashback to the 1960s: LSD in the treatment of autism | journal = Developmental Neurorehabilitation | volume = 10 | issue = 1 | pages = 75–81 | date = 2007 | pmid = 17608329 | doi = 10.1080/13638490601106277 }}{{cite journal | vauthors = Abramson HA | title = The use of LSD (d-lysergic acid diethylamide) in the therapy of children (a brief review) | journal = The Journal of Asthma Research | volume = 5 | issue = 2 | pages = 139–143 | date = December 1967 | pmid = 4865578 | doi = 10.3109/02770906709104325 }}

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.{{Cite web |title=Psychiatric Research with Hallucinogens |website=www.druglibrary.org |url=https://www.druglibrary.org/schaffer/lsd/grob.htm |access-date=2021-07-26|archive-date=July 26, 2021|archive-url=https://web.archive.org/web/20210726203733/https://www.druglibrary.org/schaffer/lsd/grob.htm |url-status=live}}{{cite journal |vauthors=Chwelos N, Blewett DB, Smith CM, Hoffer A |title=Use of d-lysergic acid diethylamide in the treatment of alcoholism |journal=Quarterly Journal of Studies on Alcohol |volume=20 |issue=3 |pages=577–590 |date=September 1959 |pmid=13810249 |doi=10.15288/qjsa.1959.20.577}}{{cite journal |vauthors=Krebs TS, Johansen PØ |title=Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials |journal=Journal of Psychopharmacology |volume=26 |issue=7 |pages=994–1002 |date=July 2012 |pmid=22406913 |doi=10.1177/0269881112439253 |s2cid=10677273}} Osmond coined the term "psychedelic" (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 can induce transcendent experiences, or mental states that transcend the experience of everyday consciousness, with lasting psychological benefit. 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 to observe how they would react, the most well-known example of this being Operation Midnight Climax. 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.

According to declassified CIA documents, it's possible that the american agency spread LSD on civilians in Europe in the 50s.{{Cite web |date=2010-03-11 |title=French bread spiked with LSD in CIA experiment |url=https://www.telegraph.co.uk/news/worldnews/europe/france/7415082/French-bread-spiked-with-LSD-in-CIA-experiment.html |access-date=2025-04-01 |website=The Telegraph |language=en}}{{Cite news |date=2010-08-23 |title=Pont-Saint-Esprit poisoning: Did the CIA spread LSD? |url=https://www.bbc.com/news/world-10996838 |access-date=2025-04-01 |work=BBC News |language=en-GB}}

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.{{Cite book |author=United States Congress House Committee on Interstate and Foreign Commerce Subcommittee on Public Health and Welfare |url=https://books.google.com/books?id=qbY6xQEACAAJ |title=Increased Controls Over Hallucinogens and Other Dangerous Drugs |date=1968 |publisher=U.S. Government Printing Office |access-date=August 3, 2021|archive-date=July 13, 2020 |archive-url=https://web.archive.org/web/20200713014802/https://books.google.com/books?id=qbY6xQEACAAJ|url-status=live}} It was listed as a Schedule I controlled substance by the United Nations in 1971 and currently has no approved medical uses. {{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.{{cite web|author=National Institute on Drug Abuse|title=Hallucinogens |url=https://www.drugabuse.gov/drugs-abuse/hallucinogens |access-date=14 July 2018|archive-date=June 3, 2020|archive-url=https://web.archive.org/web/20200603125635/https://www.drugabuse.gov/drugs-abuse/hallucinogens|url-status=live}} It was most popular in the 1960s to 1980s. The use of LSD among US adults increased by 56.4% from 2015 to 2018.{{cite journal |vauthors=Yockey RA, Vidourek RA, King KA |title=Trends in LSD use among US adults: 2015–2018 |journal=Drug and Alcohol Dependence |volume=212 |pages=108071 |date=July 2020 |pmid=32450479 |doi=10.1016/j.drugalcdep.2020.108071 |s2cid=218893155}}

LSD was first synthesized on November 16, 1938{{cite journal |vauthors=Hofmann A |author-link=Albert Hofmann| translator=Ott J |title=LSD Ganz Persönlich |trans-title=LSD: Completely Personal |date=Summer 1969 |url=http://www.maps.org/news-letters/v06n3/06346hof.html |journal=MAPS |volume=6 |issue=69 |language=de |archive-url=https://web.archive.org/web/20131206032629/http://www.maps.org/news-letters/v06n3/06346hof.html |archive-date=6 December 2013}} 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".{{cite book |url=https://books.google.com/books?id=TNXeDAAAQBAJ&pg=PT342 |title=Medicinal Chemistry: A Molecular and Biochemical Approach |vauthors=Nogrady T, Weaver DF |date=2005 |publisher=Oxford University Press |isbn=978-0-19-028296-7 |page=342 |language=en |access-date=March 14, 2020 |url-status=live |archive-url=https://web.archive.org/web/20210308133740/https://www.google.com/books/edition/Medicinal_Chemistry/TNXeDAAAQBAJ?hl=en&gbpv=1&dq=%22LysergS%C3%A4ureDiethylamid%22+abreviation+LSD&pg=PT342 |archive-date=March 8, 2021}}

Image:Albert Hofmann.jpg in 2006.]]

LSD's psychedelic properties were discovered 5 years later when Hofmann himself accidentally ingested an unknown quantity of the chemical.{{cite web |title=Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" |url=http://www.erowid.org/general/conferences/conference_mindstates4_nichols.shtml |access-date=September 27, 2007 |vauthors=Nichols D |date=May 24, 2003 |website=Hofmann Foundation |archive-date=September 22, 2007 |archive-url=https://web.archive.org/web/20070922215008/http://www.erowid.org/general/conferences/conference_mindstates4_nichols.shtml |url-status=live}} The first intentional ingestion of LSD occurred on April 19, 1943, 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.{{cite web |url=http://www.a1b2c3.com/drugs/lsd01.htm|title=History Of LSD |access-date=September 27, 2007 |vauthors=Hofmann A |archive-url=https://web.archive.org/web/20070904212518/http://www.a1b2c3.com/drugs/lsd01.htm |archive-date=September 4, 2007}} 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."{{cite report |date=Oct 1995 |chapter=LSD: The Drug |title=LSD in the United States |publisher=U.S. Department of Justice, Drug Enforcement Administration |chapter-url=http://www.usdoj.gov/dea/pubs/lsd/lsd-4.htm |access-date=November 27, 2010 |archive-date=April 27, 1999 |archive-url=https://web.archive.org/web/19990427145322/http://www.usdoj.gov/dea/pubs/lsd/lsd-4.htm}} Sandoz would send the drug for free to researchers investigating its effects.

File:Effects_of_Lysergic_Acid_Diethylamide_(LSD)_on_Troops_Marching.webm

Beginning in the 1950s, the US Central Intelligence Agency (CIA) began a research program code-named Project MKUltra.{{Cite book | vauthors = Marks J |title=The Search for the Manchurian Candidate: The CIA and Mind Control |date=1978 |publisher=Times Books |isbn=07139-12790 |location=U.S.A. |pages=57}} 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.{{cite news |title=The CIA's Secret Quest For Mind Control: Torture, LSD And A 'Poisoner In Chief' |url=https://www.npr.org/2019/09/09/758989641/the-cias-secret-quest-for-mind-control-torture-lsd-and-a-poisoner-in-chief |website=NPR.org |access-date=6 October 2019 |language=en |archive-date=June 28, 2021 |archive-url=https://web.archive.org/web/20210628081520/https://www.npr.org/2019/09/09/758989641/the-cias-secret-quest-for-mind-control-torture-lsd-and-a-poisoner-in-chief |url-status=live }} 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 congressional Rockefeller 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.{{Cite book | vauthors = Marks J |title=The Search for The Manchurian Candidate: The CIA and Mind Control |publisher=Times Books |year=1978 |publication-date=1978 |pages=97 |language=English}}

In 1963, the Sandoz patents on LSD expired and the Czech company Spofa began to produce the substance. Sandoz stopped the production and distribution in 1965.

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.{{cite web |url=http://www.druglibrary.org/schaffer/Library/studies/cu/CU50.html |title=How LSD was popularized |vauthors=Brecher EM |collaboration=Editors of Consumer Reports Magazine |date=1972 |publisher=Druglibrary.org |access-date=20 June 2012 |url-status=live |archive-url=https://web.archive.org/web/20120513233708/http://druglibrary.org/schaffer/Library/studies/cu/CU50.html |archive-date= 13 May 2012}} 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,{{cite web |vauthors=Applebaum A |author-link=Anne Applebaum |url=http://www.huffingtonpost.com/2010/01/26/did-the-death-of-communis_n_435939.html |title=Did The Death Of Communism Take Koestler And Other Literary Figures With It? |work=The Huffington Post |date=26 January 2010 |archive-url=http://archive.wikiwix.com/cache/20110714161713/http://www.huffingtonpost.com/2010/01/26/did-the-death-of-communis_n_435939.html |archive-date=14 July 2011}}{{cite web |title=Out-Of-Sight! SMiLE Timeline |url=http://pages.cthome.net/tobelman/The_Out-Of-Sight_SMiLE_Site.html|access-date=October 30, 2011|archive-url=https://web.archive.org/web/20100201234435/http://pages.cthome.net/tobelman/The_Out-Of-Sight_SMiLE_Site.html |archive-date=February 1, 2010}} and according to L. R. Veysey they profoundly influenced the thinking of the new generation of youth.{{cite book |vauthors=Veysey LR |title=The Communal Experience: Anarchist and Mystical Communities in Twentieth-Century America |location=Chicago IL |publisher=University of Chicago Press |date=1978 |isbn=0-226-85458-2 |page=437}}

On October 24, 1968, possession of LSD was made illegal in the United States.{{cite web |url=http://www.erowid.org/psychoactives/law/law_fed_staggers-dodd.pdf |author=United States Congress |title=Staggers-Dodd Bill, Public Law 90-639 |date=October 24, 1968 |access-date=September 8, 2009 |url-status=live |archive-url=https://web.archive.org/web/20100509025200/http://www.erowid.org/psychoactives/law/law_fed_staggers-dodd.pdf |archive-date=May 9, 2010}} 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.{{cite web |url=http://www.maps.org/news-letters/v05n3/05303psy.html |vauthors=Gasser P |title=Psycholytic Therapy with MDMA and LSD in Switzerland |year=1994 |access-date=September 8, 2009 |url-status=live | archive-date=October 11, 2009 |archive-url=https://web.archive.org/web/20091011083518/http://www.maps.org/news-letters/v05n3/05303psy.html}}

In November 2020, Oregon became the first US state to decriminalize possession of small amounts of LSD after voters approved Ballot Measure 110.{{Cite web|title=Oregon becomes first state to legalize magic mushrooms as more states ease drug laws in 'psychedelic renaissance'|vauthors=Feuer W|date=November 4, 2020 |url=https://www.cnbc.com/2020/11/04/oregon-becomes-first-state-to-legalize-magic-mushrooms-as-more-states-ease-drug-laws.html |website=CNBC|access-date=November 7, 2020 |url-status=live|archive-date=November 4, 2020|archive-url=https://web.archive.org/web/20201104155737/https://www.cnbc.com/2020/11/04/oregon-becomes-first-state-to-legalize-magic-mushrooms-as-more-states-ease-drug-laws.html}}

By the mid-1960s, the youth countercultures in California, particularly in San Francisco, had widely adopted the use of hallucinogenic drugs, including LSD. The first major underground LSD factory was established by Owsley Stanley.{{cite book |vauthors=DeRogatis J |title=Turn On Your Mind: Four Decades of Great Psychedelic Rock |location=Milwaukie, Michigan |publisher=Hal Leonard |date=2003 |isbn=0-634-05548-8 |pages=8–9}} Around this time, the Merry Pranksters, associated with novelist Ken Kesey, organized the Acid Tests, events in San Francisco involving LSD consumption, accompanied by light shows and improvised music.{{cite web |url=https://digital.library.unt.edu/ark:/67531/metadc19800/m1/ |title=Show 41 – The Acid Test: Psychedelics and a sub-culture emerge in San Francisco. [Part 1] : UNT Digital Library | vauthors = Gilliland J |year=1969 |author-link=John Gilliland |website=Pop Chronicles |publisher=Digital.library.unt.edu |format=audio |access-date=May 6, 2011 |url-status=live |archive-url=http://archive.wikiwix.com/cache/20110629170356/https://digital.library.unt.edu/ark:/67531/metadc19800/m1/ |archive-date=June 29, 2011}}{{cite book | vauthors = Hicks M | title = Sixties Rock: Garage, Psychedelic, and Other Satisfactions Music in American Life | location = Chicago, IL | publisher = University of Illinois Press | date = 2000 | isbn = 0-252-06915-3 | page = 60 }} Their activities, including cross-country trips in a psychedelically decorated bus and interactions with major figures of the beat movement, were later documented in Tom Wolfe's The Electric Kool-Aid Acid Test (1968).{{cite book | vauthors = Mann J | title = Turn on and Tune in: Psychedelics, Narcotics and Euphoriants | publisher = Royal Society of Chemistry | date = 2009 | isbn = 978-1-84755-909-8 | page = 87 }}

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 establishing Haight-Ashbury as the epicenter of the hippie counterculture. The Thelins also organized the Love Pageant Rally in Golden Gate Park in October 1966, protesting against California's ban on LSD.{{Cite web|title=OBITUARY — Ron Thelin |url=https://www.sfgate.com/news/article/OBITUARY-Ron-Thelin-2989153.php |vauthors=Taylor M |date=1996-03-22 |website=SFGate |access-date=2020-05-13 |url-status=live |archive-date=August 28, 2021 |archive-url=https://web.archive.org/web/20210828153344/https://www.sfgate.com/news/article/OBITUARY-Ron-Thelin-2989153.php}}{{cite journal |vauthors=Davis JC |title=The business of getting high: head shops, countercultural capitalism, and the marijuana legalization movement. |journal=The Sixties |date=January 2015 |volume=8 |issue=1 |pages=27–49 |doi=10.1080/17541328.2015.1058480 |hdl=11603/7422 |s2cid=142795620 |hdl-access=free}}

A similar movement developed in London, led by British academic Michael Hollingshead, who first tried LSD in America in 1961. After experiencing LSD and interacting with notable figures such as Aldous Huxley, Timothy Leary, and Richard 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.{{cite book | vauthors = Conners P |title=White Hand Society - The Psychedelic Partnership of Timothy Leary and Allen Ginsberg |publisher=City Lights Books |year=2010 |isbn=9780872865358 |page=[https://archive.org/details/isbn_9780872865358/page/148 148] |url-access=registration |url=https://archive.org/details/isbn_9780872865358/page/148 }}

File:Helix, v.2, no.6, Dec. 1, 1967 - DPLA - 85798bf5973acd2aa823cbc257dfae2a (page 1).jpg newspaper Helix, 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 the Grateful Dead, Jefferson Airplane, and Big Brother and the Holding Company. San Francisco-based artists such as Rick Griffin, Victor Moscoso, and Wes 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.

In the United Kingdom, Michael Hollingshead, reputed for introducing LSD to various artists and musicians like Storm Thorgerson, Donovan, Keith Richards, and members of the Beatles, played a significant role in the drug's proliferation in the British art and music scene. Despite LSD's illegal status from 1966, it was widely used by groups including the Beatles, the Rolling Stones, and the Moody Blues. Their experiences influenced works such as the Beatles' Sgt. Pepper's Lonely Hearts Club Band and Cream's Disraeli Gears, featuring psychedelic-themed music and artwork.{{cite magazine |vauthors=Gilmore M |url=https://www.rollingstone.com/feature/beatles-acid-test-how-lsd-opened-the-door-to-revolver-251417/ |title=Beatles' Acid Test: How LSD Opened the Door to 'Revolver' |magazine=Rolling Stone |date=August 25, 2016 |access-date=December 9, 2021 |archive-date=December 3, 2020 |archive-url=https://web.archive.org/web/20201203211257/https://www.rollingstone.com/feature/beatles-acid-test-how-lsd-opened-the-door-to-revolver-251417/ |url-status=live}}

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.{{cite book |vauthors=Rubin R, Melnick JP |title=Immigration and American Popular Culture: an Introduction |location=New York, NY |publisher=New York University Press |date=2007 |isbn=978-0-8147-7552-3 |pages=162–4}}{{cite book |vauthors=Prown P, Newquist HP, Eiche JF |title=Legends of Rock Guitar: the Essential Reference of Rock's Greatest Guitarists |location=London |publisher=Hal Leonard Corporation, 1997 |isbn=0-7935-4042-9 |pages=48 |year=1997}} Songs such as John 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.{{cite book |vauthors=Sheff D |year=2000 |author-link=David Sheff |title=All We Are Saying: The Last Major Interview with John Lennon and Yoko Ono |publisher=St. Martin's Press |location=New York |isbn=978-0-312-25464-3 |url=https://archive.org/details/allwearesayingla00lenn |url-access=registration}}{{page needed|date=January 2024}}{{cite magazine |vauthors=Thompson T |date=16 June 1967 |title=The New Far-Out Beatles |magazine=Life |url=https://books.google.com/books?id=lVYEAAAAMBAJ&pg=101 |location=Chicago |publisher=Time Inc. |pages=101 |access-date=8 Dec 2016 |archive-date=November 17, 2021 |archive-url=https://web.archive.org/web/20211117042255/https://books.google.com/books?id=lVYEAAAAMBAJ&pg=101 |url-status=live}}

Contemporary artists influenced by LSD include Keith Haring in the visual arts,{{cite book |title=Keith Haring: Journey of the Radiant Baby |url=https://books.google.com/books?id=PElY27UXXkYC |publisher=Bunker Hill Publishing |year=2006 |isbn=1593730527 |vauthors=Haring K |page=25 |access-date=December 5, 2023 |archive-date=October 2, 2023 |archive-url=https://web.archive.org/web/20231002134101/https://books.google.com/books?id=PElY27UXXkYC |url-status=live }} various electronic dance music creators,{{cite news |url=https://www.vice.com/en/article/newv7g/why-drugs-genres-match-mdma-raves-shrooms-psychedelia-rap-lean |publisher=Vice |author=Daisy Jones |date=5 June 2017 |title=Why Certain Drugs Make Specific Genres Sound So Good |access-date=December 5, 2023 |archive-date=December 5, 2023 |archive-url=https://web.archive.org/web/20231205200458/https://www.vice.com/en/article/newv7g/why-drugs-genres-match-mdma-raves-shrooms-psychedelia-rap-lean |url-status=live }} and the jam band Phish.{{cite web |url=https://liveforlivemusic.com/features/phish-matisyahu-nyc/ |title=Phishin' With Matisyahu: How LSD "Turned My Entire World Inside Out" |author=Kendall Deflin |date=22 June 2017 |access-date=December 5, 2023 |archive-date=September 30, 2023 |archive-url=https://web.archive.org/web/20230930095840/https://liveforlivemusic.com/features/phish-matisyahu-nyc/ |url-status=live }} The 2018 Leo Butler play All You Need is LSD is inspired by the author's interest in the history of LSD.{{Cite web |title=How LSD influenced Western culture |url=https://www.bbc.com/culture/article/20181016-how-lsd-influenced-western-culture |access-date=2024-01-08 |website=www.bbc.com |date=October 17, 2018 |archive-date=November 27, 2020 |archive-url=https://web.archive.org/web/20201127003729/https://www.bbc.com/culture/article/20181016-how-lsd-influenced-western-culture |url-status=live }}

The United Nations Convention 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.{{cite web |work=UN Convention on Psychotropic Substances |date=1971 |url=http://www.unodc.org/pdf/convention_1971_en.pdf |title=Final act of the United Nations Conference |archive-url=https://web.archive.org/web/20120415011336/http://www.unodc.org/pdf/convention_1971_en.pdf |archive-date=15 April 2012}}

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.{{cite web |url=https://www.legislation.gov.au/Details/F2017L00057 |title=Poisons Standard |date=July 2016 |archive-url=https://web.archive.org/web/20170302025331/https://www.legislation.gov.au/Details/F2017L00057 |archive-date=2 March 2017 |work=Therapeutic Goods Administration |publisher=Australian Government Department of Health}} In Western Australia, the Misuse of Drugs Act 1981 provides guidelines for possession and trafficking of substances like LSD.{{cite web |title=Misuse of Drugs Act 1981 |date=18 November 2015 |url=http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument:28280P/$FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B06-e0-00%5D.pdf?OpenElement |publisher=Government of Western Australia |archive-url=https://web.archive.org/web/20151222180141/http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument%3A28280P/%24FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B06-e0-00%5D.pdf?OpenElement |archive-date=22 December 2015}}

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.{{cite web|url=http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-26.html#h-30 |title=Controlled Drugs and Substances Act |access-date=December 15, 2013 |publisher=Canadian Department of Justice |year=1996 |author=Canadian government |website=Justice Laws |archive-url=https://web.archive.org/web/20131215170432/http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-26.html |archive-date=December 15, 2013 }}

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.{{cite web |url=http://www.druglibrary.org/schaffer/Library/studies/runciman/pf3.htm |title=Drugs and the law: Report of the inquiry into the Misuse of Drugs Act 1971 |archive-url=https://web.archive.org/web/20160130144204/http://www.druglibrary.org/schaffer/Library/studies/runciman/pf3.htm |archive-date=30 January 2016 |location=London |publisher=Police Foundation |date=2000 |work=Runciman Report}}{{cite web |url=http://www.tdpf.org.uk/blueprint%20download.htm |title=After the War on Drugs: Blueprint for Regulation |archive-url=https://web.archive.org/web/20131005145241/http://www.tdpf.org.uk/blueprint%20download.htm |archive-date=5 October 2013 |work=Transform Drug Policy Foundation |date=2009}}

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.{{cite court| litigants=Neal v. United States| reporter=U.S.| vol=516| opinion=284| pinpoint=| court=| year=1996| url=https://www.law.cornell.edu/supct/html/94-9088.ZO.html| archive-url=https://web.archive.org/web/20160409213251/https://www.law.cornell.edu/supct/html/94-9088.ZO.html| url-status=live}}, originating from U.S. v. Neal, 46 F.3d 1405 (7th Cir. 1995)

Oregon decriminalized personal possession of small amounts of drugs, including LSD, in February 2021, and California has seen legislative efforts to decriminalize psychedelics.{{Cite web|vauthors=Jaeger K|date=2021-06-29|title=California Lawmakers Approve Bill To Legalize Psychedelics Possession In Committee|url=https://www.marijuanamoment.net/california-lawmakers-approve-bill-to-legalize-psychedelics-possession-in-committee/|access-date=2021-07-08|website=Marijuana Moment|language=en-US|archive-date=July 9, 2021|archive-url=https://web.archive.org/web/20210709172122/https://www.marijuanamoment.net/california-lawmakers-approve-bill-to-legalize-psychedelics-possession-in-committee/|url-status=live}}

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.{{cite web |url=http://www.elpensador.com.mx/2009/10/17/Ley-de-Narcomenudeo/ |title=Ley de Narcomenudeo |archive-url=https://web.archive.org/web/20101130224127/http://www.elpensador.com.mx/2009/10/17/Ley-de-Narcomenudeo/ |archive-date=30 November 2010 |language=es |work=El Pensador |date=17 October 2009}}

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.{{cite report |publisher=Parliament of the Czech Republic |year=1998 |title=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 |location=Prague |language=cs}}{{Citation |author=Supreme Court of the Czech Republic |author-link=Supreme Court of the Czech Republic |date=25 February 2012 |title=6 Tdo 156/2010 [NS 7078/2010]}}

File:LSDLabGlassware.jpg

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.{{cite web|author=DEA |year=2007 |title=LSD Manufacture – Illegal LSD Production |url=https://fas.org/irp/agency/doj/dea/product/lsd/lsd-5.htm |website=LSD in the United States |publisher=U.S. Department of Justice Drug Enforcement Administration |archive-url=https://web.archive.org/web/20070829023659/https://fas.org/irp/agency/doj/dea/product/lsd/lsd-5.htm|archive-date=August 29, 2007}}

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. Ali Altaft, the lead chemist at the University of Okara, in Punjab, Pakistan, performed the synthesis of LSD on video.{{Cite web | vauthors = Maravelias P |date=2024-12-18 |title=Willy Myco Just Released the First-Ever Video Demonstrating How to Synthesize LSD |url=https://doubleblindmag.com/willy-myco-lsd-synthesis-in-pakistan/ |access-date=2025-02-10 |website=DoubleBlind Mag |language=en-US}}

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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{{clarification needed|date=September 2024}} 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.{{cite book |vauthors=Stafford P |year=1992 |title=Psychedelics Encyclopaedia |chapter=Chapter 1 – The LSD Family |pages=62 |edition=3rd |publisher=Ronin Publishing |isbn=978-0-914171-51-5}}

Over some time, tablet dimensions, weight, shape and concentration of LSD evolved from large (4.5–8.1 mm diameter), heavyweight (≥150 mg), round, high concentration (90–350 μg/tab) dosage units to small (2.0–3.5 mm diameter) lightweight (as low as 4.7 mg/tab), variously shaped, lower concentration (12–85 μg/tab, average range 30–40 μg/tab) dosage units. LSD tablet shapes have included cylinders, cones, stars, spacecraft, and heart shapes. The smallest tablets became known as "Microdots."{{cite book |vauthors=Laing RR, Beyerstein BL, Siegel JA |year=2003 |title=Hallucinogens: A Forensic Drug Handbook |chapter=Chapter 2.2 – Forms of the Drug |chapter-url=https://books.google.com/books?id=l1DrqgobbcwC |pages=39–41 |publisher=Academic Press |isbn=978-0-12-433951-4 |access-date=May 12, 2020 |archive-date=February 2, 2021 |archive-url=https://web.archive.org/web/20210202134552/https://books.google.com/books?id=l1DrqgobbcwC |url-status=live}}

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. More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975. 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. 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.{{cite web| title=Street Terms: Drugs and the Drug Trade| date=April 5, 2005| url=http://www.whitehousedrugpolicy.gov/streetterms/ByType.asp?intTypeID=6| publisher=Office of National Drug Control Policy| access-date=January 31, 2007| url-status=live| archive-url=https://web.archive.org/web/20090418031446/http://www.whitehousedrugpolicy.gov/streetTerms/ByType.asp?intTypeID=6| archive-date=April 18, 2009}} Authorities have encountered the drug in other forms—including powder or crystal, and capsule.{{cite web |author=DEA |year=2008 |title=Photo Library (page 2) |publisher=US Drug Enforcement Administration |url=http://www.usdoj.gov/dea/photo_library2.html#lsd |access-date=June 27, 2008 |archive-url=https://web.archive.org/web/20080623111640/http://www.usdoj.gov/dea/photo_library2.html |archive-date=June 23, 2008}}

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.{{cite book |vauthors=MacLean JR, Macdonald DC, Ogden F, Wilby E |chapter=LSD-25 and mescaline as therapeutic adjuvants. |veditors=Abramson H |title=The Use of LSD in Psychotherapy and Alcoholism |publisher=Bobbs-Merrill |location=New York |date=1967 |pages=407–426}}{{cite book |vauthors=Ditman KS, Bailey JJ |chapter=Evaluating LSD as a psychotherapeutic agent |veditors=Hoffer A |title=A program for the treatment of alcoholism: LSD, malvaria, and nicotinic acid |pages=353–402}}

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.

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.{{cite book| vauthors=Schou N |title=Orange Sunshine: The Brotherhood of Eternal Love and Its Quest to Spread Peace, Love, and Acid to the World |date=2010 |publisher=Thomas Dunne Books |url=https://archive.org/details/orangesunshinebr00scho_0 |url-access=registration |isbn=9780312551834}}

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.{{cite book| vauthors=Jarnow J |title=Heads: A Biography of Psychedelic America |date=2016 |publisher=Da Capo Press |isbn=9780306822551}}

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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,{{Cite journal |journal=Microgram Bulletin |date=October 2005 |author=United States Drug Enforcement Administration |volume=38 |issue=10 |url=http://www.justice.gov/dea/pr/micrograms/2005/mg1005.pdf |title=LSD Blotter Acid Mimic Containing 4-Bromo-2,5-dimethoxy-amphetamine (DOB) Seized Near Burns, Oregon |access-date=August 20, 2009 |archive-url=https://web.archive.org/web/20121018052304/http://www.justice.gov/dea/pr/micrograms/2005/mg1005.pdf |archive-date=October 18, 2012}}{{Cite journal |journal=Microgram Bulletin |date=November 2006 |volume=39 |issue=11 |author=United States Drug Enforcement Administration |page=136 |title=Intelligence Alert – Blotter Acid Mimics (Containing 4-Bromo-2,5-Dimethoxy-Amphetamine (DOB)) in Concord, California |url=http://www.justice.gov/dea/pr/micrograms/2006/mg1106.pdf |access-date=August 20, 2009 |archive-url=https://web.archive.org/web/20121018052155/http://www.justice.gov/dea/pr/micrograms/2006/mg1106.pdf |archive-date=October 18, 2012}} a mixture of DOC and DOI,{{Cite journal |journal=Microgram Bulletin |date=March 2008 |volume=41 |issue=3 |author=United States Drug Enforcement Administration |url=http://www.justice.gov/dea/pr/micrograms/2008/mg0308.pdf |title=Unusual "Rice Krispie Treat"-Like Balls Containing Psilocybe Mushroom Parts in Warren County, Missouri |access-date=August 20, 2009 |archive-url=https://web.archive.org/web/20121017234315/http://www.justice.gov/dea/pr/micrograms/2008/mg0308.pdf |archive-date=October 17, 2012}} 25I-NBOMe,{{cite web| vauthors=Iversen L |title=Temporary Class Drug Order Report on 5-6APB and NBOMe compounds |url=https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/204808/J_TCDO_report_on_5-6APB_and_NBOMe_compounds.pdf |website=Advisory Council on the Misuse of Drugs |publisher=Gov.Uk |access-date=June 16, 2013 |date=May 29, 2013 |pages=14 |url-status=live |archive-url=https://web.archive.org/web/20130921234700/https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/204808/J_TCDO_report_on_5-6APB_and_NBOMe_compounds.pdf|archive-date=September 21, 2013}} and a mixture of DOC and DOB.{{Cite journal |journal=Microgram Bulletin |date=March 2009 |volume=42 |issue=3 |author=United States Drug Enforcement Administration |url=http://www.justice.gov/dea/pr/micrograms/2009/mg0309.pdf |title="Spice" – Plant Material(s) Laced With Synthetic Cannabinoids or Cannabinoid Mimicking Compounds |access-date=August 20, 2009 |archive-url=https://web.archive.org/web/20120118165818/http://www.justice.gov/dea/programs/forensicsci/microgram/mg0309/mg0309.html |archive-date=January 18, 2012}} 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.{{Cite journal |journal=Microgram Bulletin |date=November 2005 |volume=38 |issue=11 |author=United States Drug Enforcement Administration |url=http://www.justice.gov/dea/pr/micrograms/2005/mg1105.pdf |title=Bulk Marijuana in Hazardous Packaging in Chicago, Illinois |access-date=August 20, 2009 |archive-url=https://web.archive.org/web/20121018052300/http://www.justice.gov/dea/pr/micrograms/2005/mg1105.pdf |archive-date=October 18, 2012}} 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.{{Cite journal |journal=Microgram Bulletin |date=December 2007 |volume=40 |issue=12 |author=United States Drug Enforcement Administration |url=http://www.justice.gov/dea/pr/micrograms/2007/mg1207.pdf |title=SMALL HEROIN DISKS NEAR GREENSBORO, GEORGIA |access-date=August 20, 2009 |archive-url=https://web.archive.org/web/20121017234332/http://www.justice.gov/dea/pr/micrograms/2007/mg1207.pdf |archive-date=October 17, 2012}} Several deaths have been attributed to 25I-NBOMe.{{cite web |url=https://www.erowid.org/chemicals/2ci_nbome/2ci_nbome_death.shtml |title=25I-NBOMe (2C-I-NBOMe) Fatalities / Deaths |publisher=Erowid |access-date=February 28, 2016 |author=Erowid |url-status=live |archive-url=https://web.archive.org/web/20160305193143/https://www.erowid.org/chemicals/2ci_nbome/2ci_nbome_death.shtml |archive-date=March 5, 2016}}{{cite news| vauthors=Hastings D |title=New drug N-bomb hits the street, terrifying parents, troubling cops |url=http://www.nydailynews.com/news/national/new-synthetic-hallucinogen-n-bomb-killing-users-cops-article-1.1336327 |access-date=May 7, 2013 |newspaper=New York Daily News |date=May 6, 2013 |url-status=live|archive-url=https://web.archive.org/web/20130510103039/http://www.nydailynews.com/news/national/new-synthetic-hallucinogen-n-bomb-killing-users-cops-article-1.1336327|archive-date=May 10, 2013}}{{cite news|vauthors=Feehan C |title=Powerful N-Bomb drug – responsible for spate of deaths internationally – responsible for hospitalisation of six in Cork |url=http://www.independent.ie/irish-news/powerful-nbomb-drug-responsible-for-spate-of-deaths-internationally-responsible-for-hospitalisation-of-six-in-cork-34384507.html|access-date=January 22, 2016|newspaper=Irish Independent|date=January 21, 2016 |archive-date=April 12, 2019|archive-url=https://web.archive.org/web/20190412203933/https://www.independent.ie/irish-news/powerful-nbomb-drug-responsible-for-spate-of-deaths-internationally-responsible-for-hospitalisation-of-six-in-cork-34384507.html|url-status=live}}{{cite web |vauthors=Iversen L |title=Temporary Class Drug Order Report on 5-6APB and NBOMe compounds |url=https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/204808/J_TCDO_report_on_5-6APB_and_NBOMe_compounds.pdf |website=Advisory Council on the Misuse of Drugs |publisher=Gov.Uk |access-date=June 16, 2013 |date=May 29, 2013 |url-status=live |archive-url=https://web.archive.org/web/20130921234700/https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/204808/J_TCDO_report_on_5-6APB_and_NBOMe_compounds.pdf |archive-date=September 21, 2013}}

Some notable individuals have commented publicly on their experiences with LSD.{{cite web |title=Famous LSD users |url=http://www.thegooddrugsguide.com/articles/famous_users/lsd.htm |publisher=The Good Drugs Guide |access-date=2008-10-20 |url-status=live |archive-url=https://web.archive.org/web/20081007023344/http://www.thegooddrugsguide.com/articles/famous_users/lsd.htm |archive-date=October 7, 2008}}{{cite web |url=http://popwiki.net |title=People on psychedelics |access-date=2012-11-01 |url-status=live |archive-url=https://web.archive.org/web/20130421145334/http://popwiki.net/ |archive-date=April 21, 2013}} 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.

• 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."{{cite journal | vauthors = Mason D | title = Review: Awe for Auden | journal = The Hudson Review | volume = 68 | issue = 3 | date = Autumn 2015 | pages = 492–500 | publisher = The Hudson Review, Inc. }} 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."{{cite web | url = http://www.swarthmore.edu/library/auden/QandA_pt6.html | vauthors = Auden WH | title = W. H. Auden at Swathmore; An hour of questions and answers with Auden | date = 15 November 1971 | work = Exhibition notes from the W.H. Auden Collection | publisher = the Swarthmore College Library | access-date = February 23, 2021 | archive-date = June 11, 2021 | archive-url = https://web.archive.org/web/20210611212901/http://www.swarthmore.edu/library/auden/QandA_pt6.html | url-status = live }} He also said, "Nothing much happened but I did get the distinct impression that some birds were trying to communicate with me."{{cite news | url = https://www.irishtimes.com/news/a-master-of-memorable-speech-1.1195982 | vauthors = MacMonagle N | title = A Master of Memorable speech | newspaper = The Irish Times | date = 17 February 2007 }}
• James Cameron, the Canadian filmmaker, has said he experimented with LSD during his college years.{{Cite web |date=2010-01-10 |title=The Impossible Reality of James Cameron |url=https://rollingstoneindia.com/james-cameron/ |access-date=2025-03-24 |website=Rolling Stone India |language=en-US}}
• Daniel Ellsberg, an American peace activist, says he has had several hundred experiences with psychedelics.{{Cite web| vauthors=Meyer A |date=2022-01-24 |title=Daniel Ellsberg Talks Psychedelics, Consciousness and World Peace |url=https://www.lucid.news/daniel-ellsberg-talks-psychedelics-consciousness-and-world-peace/|access-date=2022-01-29|website=Lucid News|language=en-US|archive-date=January 29, 2022|archive-url=https://web.archive.org/web/20220129143452/https://www.lucid.news/daniel-ellsberg-talks-psychedelics-consciousness-and-world-peace/|url-status=live}}
• Richard Feynman, a notable physicist at California 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.{{cite book | vauthors = Feynman RP |title=Surely You're Joking, Mr. Feynman!: Adventures of a Curious Character | veditors = Leighton R |publisher=W. W. Norton |year=1985 |isbn=978-0-393-01921-6 |oclc=10925248|title-link=Surely You're Joking, Mr. Feynman! }}{{cite book | vauthors = Gleick J |author-link=James Gleick |title=Genius: The Life and Science of Richard Feynman |publisher=Pantheon Books |year=1992|isbn=978-0-679-40836-9 |oclc=243743850}}
• Jerry Garcia stated in a July 3, 1989 interview for Relix 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."{{cite web|url=http://www.relix.com/features/2010/04/20/q-a-with-jerry-garcia-portrait-of-an-artist-as-a-tripper?3 |title=Q&A with Jerry Garcia: Portrait of an Artist as a Tripper |publisher=Relix Magazine |date=April 20, 2010 |access-date=2013-06-29 | vauthors = Alderson J |archive-url=https://web.archive.org/web/20100521033451/http://www.relix.com/features/2010/04/20/q-a-with-jerry-garcia-portrait-of-an-artist-as-a-tripper?3 |archive-date=May 21, 2010}}
• Bill Gates implied in an interview with Playboy that he tried LSD during his youth.{{cite magazine |title= The Bill Gates Interview |magazine= Playboy |date= July 1994 |url= http://www.playboy.com/playground/view/50-years-of-the-playboy-interview-bill-gates |archive-url= https://web.archive.org/web/20140707190401/http://www.playboy.com/playground/view/50-years-of-the-playboy-interview-bill-gates |archive-date= July 7, 2014}}
• Aldous Huxley, author of Brave New World, became a user of psychedelics after moving to Hollywood. He was at the forefront of the counterculture's use of psychedelic drugs, which led to his 1954 work The Doors of Perception. Dying from cancer, he asked his wife on 22 November 1963 to inject him with 100 μg of LSD. He died later that day.{{cite news |vauthors=Colman D |title=Aldous Huxley's LSD Death Trip |newspaper=Open Culture |date=October 2011 |url=http://www.openculture.com/2011/10/aldous_huxleys_lsd_death_trip.html |access-date=1 November 2011 |url-status=live |archive-url=https://web.archive.org/web/20111112140024/http://www.openculture.com/2011/10/aldous_huxleys_lsd_death_trip.html |archive-date=November 12, 2011}}
• Steve Jobs, co-founder and former CEO of Apple Inc., said, "Taking LSD was a profound experience, one of the most important things in my life."{{Cite news | vauthors = Bosker B |title=The Steve Jobs Reading List: The Books And Artists That Made The Man |newspaper=Huffington Post |url=http://www.huffingtonpost.com/2011/10/21/the-steve-jobs-reading-list-the-books_n_1024021.html |access-date=23 October 2011 |date=21 October 2011 |url-status=live |archive-url=https://web.archive.org/web/20111022123850/http://www.huffingtonpost.com/2011/10/21/the-steve-jobs-reading-list-the-books_n_1024021.html |archive-date=October 22, 2011}}
• Ernst Jünger, German writer and philosopher, throughout his life had experimented with drugs such as ether, cocaine, and hashish; and later in life he used mescaline and LSD. These experiments were recorded comprehensively in Annäherungen (1970, Approaches). The novel Besuch auf Godenholm (1952, Visit to Godenholm) is clearly influenced by his early experiments with mescaline and LSD. He met with LSD inventor Albert Hofmann and they took LSD together several times. Hofmann's memoir LSD, My Problem Child describes some of these meetings.{{cite web|title=LSD, My Problem Child · Radiance from Ernst Junger|website=www.psychedelic-library.org |url=http://www.psychedelic-library.org/child7.htm |access-date=April 17, 2021|archive-date=May 12, 2021|archive-url=https://web.archive.org/web/20210512173700/http://www.psychedelic-library.org/child7.htm|url-status=live}}
• In a 2004 interview, Paul McCartney said that The Beatles' songs "Day Tripper" and "Lucy in the Sky with Diamonds" were inspired by LSD trips.{{rp|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 son Julian) and that the band members did not notice until after the song had been released, and Paul McCartney corroborated that story.{{cite web |date=1998-02-15 |title=Is 'Lucy in the Sky with Diamonds' Code for LSD? |url=https://www.snopes.com/fact-check/lucy-in-the-sky-with-diamonds/ |access-date=2012-06-20 |website=Snopes.com |publisher= |archive-date=December 20, 2021 |archive-url=https://web.archive.org/web/20211220152957/https://www.snopes.com/fact-check/lucy-in-the-sky-with-diamonds/ |url-status=live }} John Lennon, George Harrison, and Ringo Starr also used the drug, although McCartney cautioned that "it's easy to overestimate the influence of drugs on the Beatles' music."{{cite magazine |title=The Truth Behind "LSD" |vauthors=Matus V |date=June 2004 |magazine=The Weekly Standard |url=https://www.washingtonexaminer.com/weekly-standard/the-truth-behind-lsd |access-date=November 3, 2019 |url-status=live |archive-date=March 8, 2021 |archive-url=https://web.archive.org/web/20210308185326/https://www.washingtonexaminer.com/weekly-standard/the-truth-behind-lsd}}
• Michel Foucault had an LSD experience with Simeon Wade in Death Valley and later wrote "it was the greatest experience of his life, and that it profoundly changed his life and his work."{{Cite web|url=http://www.openculture.com/2017/09/when-michel-foucault-tripped-on-acid-in-death-valley-and-called-it-the-greatest-experience-of-my-life-1975.html|title=When Michel Foucault Tripped on Acid in Death Valley and Called It "The Greatest Experience of My Life"|date=September 1975|website=Open Culture|language=en-US|access-date=2019-04-27|archive-date=March 15, 2021|archive-url=https://web.archive.org/web/20210315225234/https://openculture.com/2017/09/when-michel-foucault-tripped-on-acid-in-death-valley-and-called-it-the-greatest-experience-of-my-life-1975.html|url-status=live}}{{Cite news |url=https://lareviewofbooks.org/article/blowing-the-philosophers-fuses-michel-foucaults-lsd-trip-in-the-valley-of-death/|title=Blowing The Philosopher's Fuses: Michel Foucault's LSD Trip in The Valley of Death|vauthors=Penner J|website=Los Angeles Review of Books|date=June 17, 2019 |language=en-US|access-date=11 April 2021|archive-date=April 11, 2021|archive-url=https://web.archive.org/web/20210411165642/https://lareviewofbooks.org/article/blowing-the-philosophers-fuses-michel-foucaults-lsd-trip-in-the-valley-of-death/#_ftnref4|url-status=live}} Wade: "We fell silent to listen to Stockhausen's Songs 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". 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.{{Cite book|title=Foucault in California: [A True Story-–Wherein the Great French Philosopher Drops Acid in the Valley of Death]| vauthors=Wade S |publisher=Heyday Books |year=2019 |isbn=9781597144636}} In a letter to Wade, dated 16 September 1978, Foucault authorised the book's publication and added: "How could I not love you?"
• Kary Mullis is reported to credit LSD with helping him develop DNA amplification technology, for which he received the Nobel Prize in Chemistry in 1993.{{Cite magazine| url=https://www.wired.com/science/discoveries/news/2006/01/70015 |title=LSD: The Geek's Wonder Drug? |access-date=2008-03-11 |vauthors=Harrison A |date=2006-01-16 |magazine=Wired |quote=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. |url-status=live |archive-url=https://web.archive.org/web/20080505100508/http://www.wired.com/science/discoveries/news/2006/01/70015 |archive-date=May 5, 2008}}
• Carlo Rovelli, an Italian theoretical physicist and writer, has credited his use of LSD with sparking his interest in theoretical physics.{{Cite web|vauthors=Higgins C|date=2018-04-14|title='There is no such thing as past or future': physicist Carlo Rovelli on changing how we think about time |website=The Guardian |url=http://www.theguardian.com/books/2018/apr/14/carlo-rovelli-exploding-commonsense-notions-order-of-time-interview |access-date=2022-02-06|archive-date=January 11, 2022|archive-url=https://web.archive.org/web/20220111094136/https://www.theguardian.com/books/2018/apr/14/carlo-rovelli-exploding-commonsense-notions-order-of-time-interview|url-status=live}}
• Oliver Sacks, a neurologist 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.{{cite book |vauthors=Sacks O |date=2012 |title=Hallucinations |publisher=Vintage Books |page=106 |url=https://www.oliversacks.com/books-by-oliver-sacks/hallucinations/ |isbn=978-0-307-94743-7 |quote=On the West Coast in the early 1960s LSD and morning glory seeds were readily available, so I sampled those, too. |access-date=June 30, 2018 |url-status=live |archive-date=April 21, 2021 |archive-url=https://web.archive.org/web/20210421064209/https://www.oliversacks.com/books-by-oliver-sacks/hallucinations/}}
• Alexander Shulgin, American chemist, told Albert Hofmann that he preferred LSD to 2C-B.
• Matt Stone and Trey Parker, creators of the TV series South Park, claimed to have shown up at the 72nd Academy Awards, at which they were nominated for Best Original Song, under the influence of LSD.{{cite web | vauthors = Bose SD |title=When Trey Parker and Matt Stone went to the Oscars on LSD Swapnil Dhruv Bose |date=December 27, 2021 |website=FarOutMagazine.co.uk |url=https://faroutmagazine.co.uk/when-trey-parker-and-matt-stone-went-to-the-oscars-on-lsd/ |access-date=January 20, 2022 |url-status=live |archive-date=January 20, 2022 |archive-url=https://web.archive.org/web/20220120001258/https://faroutmagazine.co.uk/when-trey-parker-and-matt-stone-went-to-the-oscars-on-lsd/}}

In the United States, the earliest research began in the 1950s. Albert Kurland and his colleagues published research on LSD's therapeutic potential to treat schizophrenia. In Canada, Humphry Osmond and Abram Hoffer completed LSD studies as early as 1952.{{Cite journal | vauthors = Dyck E |date=1965 |title=Flashback: Psychiatric Experimentation with LSD in Historical Perspective. |journal=Canadian Journal of Psychiatry |volume=50 |issue=7}} By the 1960s, controversies surrounding "hippie" counterculture began to deplete institutional support for continued studies.

Currently, several 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.{{cite web |url=http://www.hofmann.org/ |title=The Albert Hofmann Foundation |access-date=September 27, 2007 |website=Hofmann Foundation |archive-url=https://web.archive.org/web/20190719174636/http://www.hofmann.org/ |archive-date=July 19, 2019}} New clinical LSD experiments in humans started in 2009 for the first time in 35 years.{{cite web|title=LSD-Assisted Psychotherapy |website=MAPS |url=http://www.maps.org/research/psilo-lsd |access-date=October 16, 2013|url-status=deviated |archive-url=https://web.archive.org/web/20180511060129/http://www.maps.org/research/psilo-lsd|archive-date=May 11, 2018}} As it is illegal in many areas of the world, potential medical uses are difficult to study.

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." More recently, experimental uses of LSD have included the treatment of alcoholism,{{cite journal |vauthors=Bogenschutz MP |date=March 2013 |title=Studying the effects of classic hallucinogens in the treatment of alcoholism: rationale, methodology, and current research with psilocybin |journal=Current Drug Abuse Reviews |volume=6 |issue=1 |pages=17–29 |pmid=23627783 |doi=10.2174/15733998113099990002}} pain and cluster headache relief,{{Cite web | vauthors = Jarow O |date=2024-05-15 |title=Psychedelics could treat some of the worst chronic pain in the world |url=https://www.vox.com/future-perfect/2024/5/15/24156372/psychedelics-chronic-pain-cluster-headache-medicine-lsd-psilocybin |access-date=2024-05-25 |website=Vox |language=en-US |archive-date=May 25, 2024 |archive-url=https://web.archive.org/web/20240525084603/https://www.vox.com/future-perfect/2024/5/15/24156372/psychedelics-chronic-pain-cluster-headache-medicine-lsd-psilocybin |url-status=live }}{{Cite web |title=RFA-AG-25-004: Safety and Early Efficacy Studies of Psychedelic-Assisted Therapy for Chronic Pain in Older Adults (UG3/UH3 Clinical Trial Required) |url=https://grants.nih.gov/grants/guide/rfa-files/RFA-AG-25-004.html |access-date=2024-05-25 |website=grants.nih.gov |archive-date=May 25, 2024 |archive-url=https://web.archive.org/web/20240525084606/https://grants.nih.gov/grants/guide/rfa-files/RFA-AG-25-004.html |url-status=live }} and prospective studies on depression.{{Cite journal |title=LSD Therapy for Persons Suffering From Major Depression - Full Text View |url=https://clinicaltrials.gov/ct2/show/NCT03866252 |access-date=2021-03-09 |website=ClinicalTrials.gov |date=February 8, 2021 |language=en |archive-date=June 11, 2021 |archive-url=https://web.archive.org/web/20210611214216/https://clinicaltrials.gov/ct2/show/NCT03866252 |url-status=live}}

A 2020 meta-review indicated possible positive effects of LSD in reducing psychiatric symptoms, mainly in cases of alcoholism.{{cite journal |title=Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials |vauthors=Fuentes JJ, Fonseca F, Elices M, Farré M, Torrens M |pmid=32038315 |pmc=6985449 |journal=Frontiers in Psychiatry |doi=10.3389/fpsyt.2019.00943 |volume=10 |date=January 2020 |page=943 |doi-access=free}} There is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits.{{cite journal |vauthors=Calder AE, Hasler G |title=Towards an understanding of psychedelic-induced neuroplasticity |journal=Neuropsychopharmacology |volume=48 |issue=1 |pages=104–112 |date=January 2023 |pmid=36123427 |pmc=9700802 |doi=10.1038/s41386-022-01389-z |doi-access=free}}{{cite journal |vauthors=Olson DE |title=Biochemical Mechanisms Underlying Psychedelic-Induced Neuroplasticity |journal=Biochemistry |volume=61 |issue=3 |pages=127–136 |date=February 2022 |pmid=35060714 |pmc=9004607 |doi=10.1021/acs.biochem.1c00812}}

{{See also|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,Cohen, S. (1959). "The therapeutic potential of LSD-25". A Pharmacologic Approach to the Study of the Mind, p. 251–258. and also for treating alcoholism.{{cite journal |title=Use of d-Lysergic Acid Diethylamide in the Treatment of Alcoholism |journal=Q. J. Stud. Alcohol |volume=20 |pages=577–590 |vauthors=Chwelos N, Blewett DB, Smith CM, Hoffer A |date=1959 |issue=3 |doi=10.15288/qjsa.1959.20.577 |pmid=13810249 |url=http://www.erowid.org/references/texts/show/1852docid1733 |access-date=June 20, 2012 |archive-url=https://web.archive.org/web/20210224135151/https://www.erowid.org/references/texts/show/1852docid1733 |archive-date=February 24, 2021 |url-status=live}} Via {{cite web |title=Abstract |url=http://www.hofmann.org/papers/blewett_1.html |access-date=February 22, 2012 |url-status=live |archive-url=https://web.archive.org/web/20120203022019/http://www.hofmann.org/papers/blewett_1.html |archive-date=February 3, 2012 |website=Hofmann.org}}{{Cite journal |vauthors=Frood A |date=2012-03-09 |title=LSD helps to treat alcoholism |journal=Nature News |url=http://www.nature.com/news/lsd-helps-to-treat-alcoholism-1.10200 |doi=10.1038/nature.2012.10200 |s2cid=137367650 |access-date=December 25, 2020 |archive-date=March 8, 2021 |archive-url=https://web.archive.org/web/20210308135250/https://www.nature.com/news/lsd-helps-to-treat-alcoholism-1.10200 |url-status=live}} One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender," 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 follow-up, 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.{{cite journal |vauthors=Vollenweider FX, Kometer M |title=The neurobiology of psychedelic drugs: implications for the treatment of mood disorders |journal=Nature Reviews. Neuroscience |volume=11 |issue=9 |pages=642–51 |date=September 2010 |pmid=20717121 |doi=10.1038/nrn2884 |s2cid=16588263}}{{cite journal |vauthors=Baumeister D, Barnes G, Giaroli G, Tracy D |title=Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles |journal=Therapeutic Advances in Psychopharmacology |volume=4 |issue=4 |pages=156–69 |date=August 2014 |pmid= 25083275 |pmc=4104707 |doi=10.1177/2045125314527985}}

In recent years, organizations like the Multidisciplinary Association for Psychedelic Studies (MAPS) have renewed clinical research of LSD.

It has been proposed that LSD be studied for use in the therapeutic setting, particularly in anxiety.{{cite journal |vauthors=Liechti ME |title=Modern Clinical Research on LSD |journal=Neuropsychopharmacology |volume=42 |issue=11 |pages=2114–2127 |date=October 2017 |pmid=28447622 |pmc=5603820 |doi=10.1038/npp.2017.86}}{{Cite news |title=Psychedelics are transforming the way we understand depression and its treatment |date=April 20, 2021 |newspaper=The Guardian |vauthors=Carhart-Harris R |url=https://www.theguardian.com/commentisfree/2021/apr/20/psychedelics-depression-treatment-psychiatry-psilocybin |access-date=16 May 2021 |archive-url=https://web.archive.org/web/20210611212734/https://www.theguardian.com/commentisfree/2021/apr/20/psychedelics-depression-treatment-psychiatry-psilocybin|archive-date=June 11, 2021|url-status=live}} In 2024, the FDA designated a form of LSD as a breakthrough therapy to treat generalized anxiety disorder which is being developed by MindMed.{{Cite web | vauthors = Terry K |date=2024-03-26 |title=FDA Opens the Door to Clinical Use of LSD |url=https://www.webmd.com/mental-health/news/20240326/fda-opens-the-door-clinical-use-lsd |access-date=2024-05-25 |website=WebMD |language=en |archive-date=May 25, 2024 |archive-url=https://web.archive.org/web/20240525075810/https://www.webmd.com/mental-health/news/20240326/fda-opens-the-door-clinical-use-lsd |url-status=live }}

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.{{cite journal |vauthors=Sessa B |title=Is it time to revisit the role of psychedelic drugs in enhancing human creativity? |journal=Journal of Psychopharmacology |volume=22 |issue=8 |pages=821–827 |date=November 2008 |pmid=18562421 |s2cid=1908638 |doi=10.1177/0269881108091597}}{{cite journal |vauthors=Janiger O, Dobkin de Rios M |title=LSD and creativity |journal=Journal of Psychoactive Drugs |volume=21 |issue=1 |pages=129–134 |year=1989 |pmid=2723891 |doi=10.1080/02791072.1989.10472150 |url= http://www.erowid.org/culture/characters/janiger_oscar/janiger_oscar.shtml |archive-url=https://web.archive.org/web/20091003005533/http://www.erowid.org/culture/characters/janiger_oscar/janiger_oscar.shtml |archive-date=October 3, 2009 |url-status=live}}{{cite book |title=LSD, the problem-solving psychedelic |vauthors=Stafford PG, Golightly BH |year=1967 |url=http://www.psychedelic-library.org/staf3.htm |url-status=live |archive-url=https://web.archive.org/web/20120417105503/http://www.psychedelic-library.org//staf3.htm |archive-date =April 17, 2012}} In 1966 Dr. 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.{{cite web |title=Scientific Problem Solving with Psychedelics – James Fadiman |website=YouTube |date=May 29, 2013 |url=https://www.youtube.com/watch?v=KtL5fafpRKc |access-date=2023-05-02 |language=en |archive-date=September 8, 2019 |archive-url=https://web.archive.org/web/20190908090741/https://www.youtube.com/watch?v=KtL5fafpRKc |url-status=live }}{{cite book |vauthors=Fadiman J |title=The psychedelic explorer's guide: safe, therapeutic, and sacred journeys |date=2018 |publisher=Tantor Media |isbn=978-1-9773-7476-9 |oclc=1031461623}}

Since 2008 there has been ongoing research into using LSD to alleviate anxiety for terminally ill cancer patients coping with their impending deaths.{{Cite news |url=http://bazonline.ch/wissen/medizin-und-psychologie/Psychiater-Gasser-bricht-sein-Schweigen/story/25732295|title=Psychiater Gasser bricht sein Schweigen|date=July 28, 2009 |newspaper=Basler Zeitung|access-date=June 19, 2011|archive-url=https://web.archive.org/web/20111006122541/http://bazonline.ch/wissen/medizin-und-psychologie/Psychiater-Gasser-bricht-sein-Schweigen/story/25732295|archive-date=October 6, 2011}}

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.

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

LSD is a potent psychoplastogen, a compound capable of promoting rapid and sustained neural plasticity that may have wide-ranging therapeutic benefit.{{cite journal |title=Psychedelics promote structural and functional neural plasticity |journal=Cell Reports |vauthors=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 |year=2018 |volume=23 |issue=11 |pages=3170–3182 |doi=10.1016/j.celrep.2018.05.022 |pmid=29898390 |pmc=6082376 }} LSD has been shown to increase markers of neuroplasticity in human brain organoids and improve memory performance in human subjects.{{Cite news |vauthors=Dolan EW |date=2022-08-11 |title=Neuroscience research suggests LSD might enhance learning and memory by promoting brain plasticity |url=https://www.psypost.org/2022/08/neuroscience-research-suggests-lsd-might-enhance-learning-and-memory-by-promoting-brain-plasticity-63701 |access-date=2022-09-12 |newspaper=Psypost - Psychology News |language=en-US |archive-date=August 26, 2022 |archive-url=https://web.archive.org/web/20220826005449/https://www.psypost.org/2022/08/neuroscience-research-suggests-lsd-might-enhance-learning-and-memory-by-promoting-brain-plasticity-63701 |url-status=live }}

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.{{cite journal |vauthors=Whelan A, Johnson MI |title=Lysergic acid diethylamide and psilocybin for the management of patients with persistent pain: a potential role? |journal=Pain Management |volume=8 |issue=3 |pages=217–229 |date=May 2018 |pmid=29722608 |doi=10.2217/pmt-2017-0068 |s2cid=19160293 |url=http://eprints.leedsbeckett.ac.uk/4843/1/LysergicAcidDiethylamide%28LSD%29andPsilocybinAM-JOHNSON.pdf |access-date=August 22, 2020 |archive-date=October 8, 2020 |archive-url=https://web.archive.org/web/20201008201515/http://eprints.leedsbeckett.ac.uk/4843/1/LysergicAcidDiethylamide%28LSD%29andPsilocybinAM-JOHNSON.pdf |url-status=live}}

{{Portal|1960s}}

• LSD art

{{Notelist}}

{{Reflist|refs=

{{cite journal |vauthors=Dolder PC, Schmid Y, Haschke M, Rentsch KM, Liechti ME |title=Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans |journal=The International Journal of Neuropsychopharmacology |volume=19 |issue=1 |pages=pyv072 |date=June 2015 |pmid=26108222 |pmc=4772267 |doi=10.1093/ijnp/pyv072}}

{{cite journal |vauthors=Mucke HA |title=From Psychiatry to Flower Power and Back Again: The Amazing Story of Lysergic Acid Diethylamide |journal=Assay and Drug Development Technologies |volume=14 |issue=5 |pages=276–281 |date=July 2016 |pmid=27392130 |doi=10.1089/adt.2016.747}}

}}

• {{cite book | title = LSD: My Problem Child | author = Albert Hofmann | url = https://books.google.com/books?id=e5wQAQAAIAAJ | year = 1980| publisher = McGraw-Hill | isbn = 978-0-07-029325-0 }}

{{Wikiquote|LSD}}

{{Commons}}

• [https://isomerdesign.com/pihkal/explore/5026 LSD - Isomer Design]
• [http://www.erowid.org/chemicals/lsd/lsd.shtml LSD-25] {{Webarchive|url=https://web.archive.org/web/20081015023231/http://www.erowid.org/chemicals/lsd/lsd.shtml |date=October 15, 2008 }} at Erowid
• [https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml LSD] {{Webarchive|url=https://web.archive.org/web/20151118232537/https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml |date=November 18, 2015 }} at TiHKAL by Alexander Shulgin
• [https://psychonautwiki.org/wiki/LSD LSD] {{Webarchive|url=https://web.archive.org/web/20220831090729/https://psychonautwiki.org/wiki/LSD |date=August 31, 2022 }} at PsychonautWiki
• [https://tripsitter.com/lsd/ LSD (Acid): Ultimate Guide To the World’s Most Famous Psychedelic - Tripsitter]

• [http://www.nfb.ca/film/hofmanns_potion Hofmann's Potion] {{Webarchive|url=https://web.archive.org/web/20210616120006/http://www.nfb.ca/film/hofmanns_potion/ |date=June 16, 2021 }} a documentary on the origins of LSD, 2002
• [https://web.archive.org/web/20091106130407/http://channel.nationalgeographic.com/series/explorer/4094/Overview Inside LSD] National Geographic Channel, 2009
• [https://www.netflix.com/de-en/title/80229847 How to Change Your Mind] {{Webarchive|url=https://web.archive.org/web/20220616180919/https://www.netflix.com/de-en/title/80229847 |date=June 16, 2022 }} Netflix docuseries, 2022

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