View source for Chemistry:LSD

{{Short description|Hallucinogenic drug}}
{{Hatnote inline|
}}
{{Infobox drug
| Watchedfields      = changed 
| verifiedrevid      = 629704081
| drug_name          = Lysergic acid diethylamide (LSD)
| INN                = Lysergide
| type               = 
| IUPAC_name         = (6a''R'',9''R'')-''N'',''N''-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-''fg'']quinoline-9-carboxamide
| image              = LSD skeletal formula.svg
| alt                = 
| caption            = [[Chemistry:Skeletal formula|Skeletal formula]] of LSD
| image2             = LSD-from-xtal-and-Spartan-PM3-3D-balls-web.png
| caption2           = [[Physics:Ball-and-stick model|Ball-and-stick model]] of LSD
| Drugs.com          = [https://www.drugs.com/illicit/lsd.html Reference]
| pregnancy_US       = C
| MedlinePlus        = 
| licence_EU         = 
| licence_US         = 
| pregnancy_AU       = 
| pregnancy_category = C
| tradename = Delysid
| legal_AU           = Schedule 9
| legal_BR           = F2
| legal_CA           = Schedule III
| legal_NZ           = Class A
| legal_UK           = Class A
| legal_UN           = P I
| legal_US           = Schedule I
| legal_DE           = Anlage I
| addiction_liability = None<ref name="NHM-MDMA"/>
| legal_status       = Illicit drug
| dependency_liability = Low<ref>{{cite book| vauthors = Halpern JH, Suzuki J, Huertas PE, Passie T | veditors = Price LH, Stolerman IP |title=Encyclopedia of Psychopharmacology A Springer Live Reference|date=June 7, 2014|publisher=Springer-Verlag Berlin Heidelberg|location=Heidelberg, Germany|isbn=978-3-642-27772-6|pages=1–5|quote=Hallucinogen abuse and dependence are known complications resulting from ... LSD and psilocybin. Users do not experience withdrawal symptoms, but the general criteria for substance abuse and dependence otherwise apply. Dependence is estimated in approximately 2 % of recent-onset users |doi=10.1007/978-3-642-27772-6_43-2|chapter=Hallucinogen Abuse and Dependence}}</ref>
| routes_of_administration = [[Medicine:Oral administration|By mouth]], [[Medicine:Sublingual administration|under the tongue]]
| pronounce          = {{IPA|/daɪ eθəl ˈæmaɪd/}}, {{IPA|/æmɪd/}}, or {{IPA|/eɪmaɪd/}}<ref>{{cite encyclopedia |url=http://www.collinsdictionary.com/dictionary/english/amide |title=Definition of "amide" |dictionary=Collins English Dictionary |access-date=January 31, 2015 |url-status=live |archive-url=https://web.archive.org/web/20150402115318/http://www.collinsdictionary.com/dictionary/english/amide |archive-date=April 2, 2015}}</ref><ref>{{cite web |url=https://www.ahdictionary.com/word/search.html?q=amide |title=American Heritage Dictionary Entry: amide |publisher=Ahdictionary.com |access-date=January 31, 2015 |archive-url=https://web.archive.org/web/20150402134025/https://www.ahdictionary.com/word/search.html?q=amide |archive-date=April 2, 2015}}</ref><ref>{{cite web |url=http://www.oxforddictionaries.com/us/definition/english/amide |title=amide – definition of amide in English from the ''Oxford Dictionary''|publisher=Oxforddictionaries.com |access-date=January 31, 2015 |archive-url=https://web.archive.org/web/20150402184403/http://www.oxforddictionaries.com/us/definition/english/amide |archive-date=April 2, 2015}}</ref>

<!--Pharmacokinetic data-->| bioavailability    = 71%<ref name=Dol2015 />
| protein_bound      = Unknown<ref name=Pas2008 />
| metabolism         = [[Biology:Liver|Liver]] ([[Biology:Cytochrome P450|CYP450]])<ref name=Dol2015 />
| metabolites        = 2-Oxo-3-hydroxy-LSD<ref name=Dol2015 />
| onset              = 30–40 minutes<ref>{{cite book|vauthors=Neinstein LS|title=Adolescent Health Care: A Practical Guide |date=2008|publisher=Lippincott Williams & Wilkins|isbn=9780781792561|pages=931|url=https://books.google.com/books?id=er8dQPxgcz0C&pg=PA931|language=en|access-date=January 27, 2017|archive-date=December 26, 2018|archive-url=https://web.archive.org/web/20181226025533/https://books.google.com/books?id=er8dQPxgcz0C&pg=PA931|url-status=live}}</ref>
| duration_of_action = 8–20 hours<ref>{{cite book|vauthors=Kranzler HR, Ciraulo DA|title=Clinical Manual of Addiction Psychopharmacology|publisher=American Psychiatric Pub|isbn=9781585626632|pages=216|url=https://books.google.com/books?id=TYddW0uzIRsC&pg=PA216|language=en|date=2 April 2007|access-date=January 27, 2017|archive-date=December 26, 2018|archive-url=https://web.archive.org/web/20181226025532/https://books.google.com/books?id=TYddW0uzIRsC&pg=PA216|url-status=live}}</ref>
| elimination_half-life = 3.6&nbsp;hours<ref name=Dol2015/><ref name=Muc2016/>
| excretion          = Kidneys<ref name=Dol2015 /><ref name=Muc2016 />

<!--Identifiers-->| CAS_number_Ref     = {{cascite|correct|??}}
| CAS_number         = 50-37-3
| ChEBI_Ref          = {{ebicite|correct|EBI}}
| ChEBI              = 6605
| PubChem            = 5761
| IUPHAR_ligand      = 17
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB04829
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 5558
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = 8NA5SWF92O
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C07542
| ChEMBL_Ref         = {{ebicite|correct|EBI}}
| ChEMBL             = 263881
| ATC_prefix         = None
| PDB_ligand         = 7LD
| class              = [[Unsolved:Hallucinogen|Hallucinogen]] ([[Chemistry:Psychedelic|psychedelic]])

<!--Chemical data-->| C                  = 20
| H                  = 25
| N                  = 3
| O                  = 1
| smiles             = CCN(CC)C(=O)[C@H]1CN([C@@H]2Cc3c[nH]c4c3c(ccc4)C2=C1)C
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| StdInChI           = 1S/C20H25N3O/c1-4-23(5-2)20(24)14-9-16-15-7-6-8-17-19(15)13(11-21-17)10-18(16)22(3)12-14/h6-9,11,14,18,21H,4-5,10,12H2,1-3H3/t14-,18-/m1/s1
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = VAYOSLLFUXYJDT-RDTXWAMCSA-N
| synonyms           = LSD, LSD-25, LAD, Acid, others
| melting_point      = 80
| melting_high       = 85
| solubility         = 67.02<ref>{{cite web |title=Lysergide|url=https://pubchem.ncbi.nlm.nih.gov/compound/5761#section=Solubility |website=pubchem.ncbi.nlm.nih.gov |language=en}}</ref>
}}
'''Lysergic acid diethylamide''', commonly known as '''LSD''' (from German {{lang|de|Lysergsäure-diethylamid}}), and known colloquially as '''acid''' or '''lucy''' is a potent [[Chemistry:Psychedelic drug|psychedelic drug]].<ref name="pmid26841800">{{cite journal |vauthors=Nichols DE |title=Psychedelics |journal=Pharmacological Reviews |volume=68 |issue=2 |pages=264–355 |date=April 2016 |pmid=26841800 |pmc=4813425 |doi=10.1124/pr.115.011478 |veditors=Barker EL}}</ref> Effects typically include intensified thoughts, emotions, and sensory perception.<ref name="NIH2016">{{cite web |title=What are hallucinogens? |date=January 2016 |url=https://www.drugabuse.gov/publications/drugfacts/hallucinogens |website=National Institute of Drug Abuse |access-date=April 24, 2016 |url-status=live |archive-url=https://web.archive.org/web/20160417180046/https://www.drugabuse.gov/publications/drugfacts/hallucinogens |archive-date=April 17, 2016}}</ref> At sufficiently high dosages LSD manifests primarily mental, visual, and auditory [[Unsolved:Hallucination|hallucination]]s.<ref name="LeptourgosFortier-Davy2020">{{cite journal |vauthors=Leptourgos P, Fortier-Davy M, Carhart-Harris R, Corlett PR, Dupuis D, Halberstadt AL, Kometer M, Kozakova E, LarØi F, Noorani TN, Preller KH, Waters F, Zaytseva Y, Jardri R |display-authors=4 |title=Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison |journal = Schizophrenia Bulletin |volume=46 |issue=6 |pages=1396–1408 |date=December 2020 |pmid=32944778 |pmc=7707069 |doi=10.1093/schbul/sbaa117 |quote=Thalamocortical connectivity was found altered in psychedelic states. Specifically, LSD was found to selectively increase effective connectivity from the thalamus to certain DMN areas, while other connections are attenuated. Furthermore, increased thalamic connectivity with the right fusiform gyrus and the anterior insula correlated with visual and auditory hallucinations (AH), respectively. }}</ref><ref name=":3">{{cite journal |vauthors=Holze F, Vizeli P, Ley L, Müller F, Dolder P, Stocker M, Duthaler U, Varghese N, Eckert A, Borgwardt S, Liechti ME |display-authors=4 |title=Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects |journal=Neuropsychopharmacology |volume=46 |issue=3 |pages=537–544 |date=February 2021 |pmid=33059356 |pmc=8027607 |doi=10.1038/s41386-020-00883-6}}</ref> Dilated pupils, increased blood pressure, and increased body temperature are typical.<ref name="EU2018" /> Effects typically begin within half an hour and can last for up to 20 hours (although on average, experiences last 8–12 hours).<ref name="EU2018" /><ref name=":1">{{Cite news |vauthors= Sloat S |date= 27 January 2017 |title= This is Why You Can't Escape an Hours-Long Acid Trip |work= Inverse |url= https://www.inverse.com/article/27067-lsd-acid-trip-brain-receptor-serotonin |url-status= live |access-date= 3 February 2020 |archive-date= June 11, 2021 |archive-url= https://web.archive.org/web/20210611212737/https://www.inverse.com/article/27067-lsd-acid-trip-brain-receptor-serotonin }}</ref> LSD is also capable of causing [[Unsolved:Psychedelic experience#Mystical experiences|mystical experiences]] and [[Philosophy:Ego death|ego dissolution]].<ref name=":3"/><ref>{{cite journal |vauthors=Liechti ME, Dolder PC, Schmid Y |title=Alterations of consciousness and mystical-type experiences after acute LSD in humans |journal=Psychopharmacology |volume=234 |issue=9–10 |pages=1499–1510 |date=May 2017 |pmid=27714429 |pmc=5420386 |doi=10.1007/s00213-016-4453-0}}</ref> It is used mainly as a recreational drug or for [[Chemistry:Entheogen|spiritual reasons]].<ref name="EU2018">{{cite web |title=LSD profile (chemistry, effects, other names, synthesis, mode of use, pharmacology, medical use, control status) |url=http://www.emcdda.europa.eu/publications/drug-profiles/lsd |website=EMCDDA |access-date=14 July 2018 |language=en |archive-date=April 28, 2021 |archive-url=https://web.archive.org/web/20210428113546/https://www.emcdda.europa.eu/publications/drug-profiles/lsd |url-status=live }}</ref><ref>{{cite news |vauthors=Gershon L |date=19 July 2016 |title=How LSD Went From Research to Religion |url=https://daily.jstor.org/how-lsd-went-from-research-to-religion/ |access-date=14 July 2018 |work=JSTOR Daily |archive-date=January 28, 2021 |archive-url=https://web.archive.org/web/20210128015545/https://daily.jstor.org/how-lsd-went-from-research-to-religion/ |url-status=live }}</ref> LSD is both the prototypical psychedelic and one of the "classical" psychedelics, being the psychedelic with the greatest scientific and cultural significance.<ref name="pmid26841800" /> LSD is synthesized as a solid compound, typically in the form of a powder or a crystalline material. This solid LSD is then dissolved in a liquid solvent, such as ethanol or distilled water, to create a solution. The liquid serves as a carrier for the LSD, allowing for accurate dosage and administration onto small pieces of blotter paper called tabs. LSD is typically either swallowed or held under the tongue.<ref name="NIH2016" /> In pure form, LSD is clear or white in color, has no smell, and is [[Chemistry:Crystalline|crystalline]].<ref name="NIH2016" /> It breaks down with exposure to ultraviolet light.<ref name="EU2018" />

LSD is pharmacologically considered to be non-addictive with a low potential for abuse. Adverse psychological reactions are possible, such as [[Medicine:Anxiety|anxiety]], [[Medicine:Paranoia|paranoia]], and delusions.<ref name="Pas2008">{{cite journal |vauthors = Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A |title=The pharmacology of lysergic acid diethylamide: a review |journal=CNS Neuroscience & Therapeutics |volume=14 |issue=4 |pages=295–314 |year=2008 |pmid=19040555 |pmc=6494066 |doi=10.1111/j.1755-5949.2008.00059.x}}</ref> In rare cases, LSD can induce "[[Philosophy:Flashback (psychology)|flashback]]s", known as [[Medicine:Hallucinogen persisting perception disorder|hallucinogen persisting perception disorder]], in which a person experiences apparent lasting or persistent visual hallucinations or perceptual distortions, such as [[Unsolved:Visual snow|visual snow]] and [[Medicine:Palinopsia|palinopsia]].<ref name="NIH2018C"/><ref name="Halpern2018">{{cite book |vauthors=Halpern JH, Lerner AG, Passie T |title=A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD. |series=Current Topics in Behavioral Neurosciences |date=2018 |volume=36 |pages=333–360 |isbn=978-3-662-55878-2 |doi=10.1007/7854_2016_457 |pmid=27822679}}</ref>

LSD is structurally related to substituted tryptamines, a class of compounds that includes [[Chemistry:Psilocybin|psilocybin]], the active compound found in psychedelic mushrooms. Thus, LSD shares some mechanisms of action and psychedelic effects with psilocybin and other tryptamines.<ref>{{cite journal |vauthors=Wong S, Yu AY, Fabiano N, Finkelstein O, Pasricha A, ((Jones BDM)), Rosenblat JD, Blumberger DW, Mulsant BH, Husain MI |display-authors=4 |journal=Journal of Psychoactive Drugs |title=Beyond Psilocybin: Reviewing the Therapeutic Potential of Other Serotonergic Psychedelics in Mental and Substance Use Disorders |pmid=37615379 |doi=10.1080/02791072.2023.2251133 |date=August 2023| pages=1–17 |s2cid=261098164}}</ref><ref>{{cite journal |vauthors=Walker SR, Pullella GA, Piggott MJ, Duggan PJ |journal=Australian Journal of Chemistry |title=Introduction to the chemistry and pharmacology of psychedelic drugs |doi=10.1071/CH23050 |date=July 2023| volume=76 |issue=5 |pages=236–257 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Mallaroni P, Mason NL, ((Vinckenbosch FRJ)), Ramaekers JG |journal=Psychopharmacology |volume=239 |pages=1783–1796 |title=The use patterns of novel psychedelics: experiential fingerprints of substituted phenethylamines, tryptamines and lysergamides |doi=10.1007/s00213-022-06142-4 |date=April 2022| issue=6 |pmid=35487983 |pmc=9166850 |doi-access=free}}</ref>

The effects of LSD are thought to stem primarily from it being an [[Biology:Agonist|agonist]] at the [[Biology:5-HT2A receptor|5-HT<sub>2A</sub>]] [[Chemistry:Serotonin receptor|serotonin receptor]]. While exactly how LSD exerts its effects by agonism at this receptor is not fully understood, corresponding increased [[Chemistry:Glutamic acid|glutamatergic]] neurotransmission and reduced [[Biology:Default mode network|default mode network]] activity are thought to be key mechanisms of action.<ref name="Pas2008"/><ref name="pmid26841800"/><ref name="pmid14761703">{{cite journal |vauthors=Nichols DE |title=Hallucinogens |journal=Pharmacology & Therapeutics |volume=101 |issue=2 |pages=131–181 |date=February 2004 |pmid=14761703 |doi=10.1016/j.pharmthera.2003.11.002 |issn=1879-016X}}</ref><ref>{{Cite journal |vauthors=Girn M, Roseman L, Bernhardt B, Smallwood J, Carhart-Harris R, Spreng RN |display-authors=4 |date=2020-05-03|title=Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex |journal=bioRxiv |s2cid=233346402 |doi=10.1101/2020.05.01.072314 |doi-access=free}}</ref><ref name="pmid27071089">{{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 |display-authors=4 |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}}</ref> LSD also binds to [[Biology:Dopamine receptor|dopamine]] [[Biology:Dopamine receptor D1|D<sub>1</sub>]] and [[Biology:Dopamine receptor D2|D<sub>2</sub>]] receptors, which is thought to contribute to reports of LSD being more stimulating than compounds such as psilocybin.<ref name="pmid24309097"/><ref name="nichols_closes_shop"/>

LSD was first synthesized by Swiss chemist Albert Hofmann in 1938 from [[Chemistry:Lysergic acid|lysergic acid]], a chemical derived from the [[Chemistry:Hydrolysis|hydrolysis]] of [[Chemistry:Ergotamine|ergotamine]], an [[Chemistry:Alkaloid|alkaloid]] found in [[Biology:Ergot|ergot]], a fungus that infects grain.<ref name="EU2018" /><ref name="NIH2018C">{{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}}</ref> LSD was the 25th of various [[Chemistry:Lysergamides|lysergamides]] Hofmann synthesized from lysergic acid while trying to develop a new analeptic, hence the alternate name LSD-25. Hofmann discovered its effects in humans in 1943, after unintentionally ingesting an unknown amount, possibly absorbing it through his skin.<ref name="Hofmann2009">{{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}}</ref><ref name="Lee1992">{{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}}</ref><ref name="Ettinger2017">{{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}}</ref> LSD was subject to exceptional interest within the field of [[Biology:Psychiatry|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.<ref name="Lee1992" />

LSD-assisted [[Medicine:Psychotherapy|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 [[Medicine:Alcoholism|alcoholism]], with promising results.<ref name="Lee1992"/><ref>{{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}}</ref><ref name="Use of d-lysergic acid diethylamide">{{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}}</ref><ref name="Lysergic acid diethylamide LSD fo">{{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}}</ref> Osmond coined the term "psychedelic" (lit. ''mind manifesting'') as a term for LSD and related [[Unsolved:Hallucinogen|hallucinogen]]s, superseding the previously held "[[Medicine:Psychotomimetic|psychotomimetic]]" model in which LSD was believed to mimic [[Medicine:Schizophrenia|schizophrenia]]. In contrast to schizophrenia, LSD can induce [[Philosophy:Transcendence#Contemporary philosophy|transcendent]] experiences, or mental states that transcend the experience of everyday consciousness, with lasting psychological benefit.<ref name="pmid26841800" /><ref name="Lee1992" /> During this time, the Central Intelligence Agency (CIA) began using LSD in the research project [[Social:Project MKUltra|Project MKUltra]], which used psychoactive substances to aid interrogation. The CIA administered LSD to unwitting test subjects in order to observe how they would react, the most well-known example of this being [[Unsolved:Operation Midnight Climax|Operation Midnight Climax]].<ref name="Lee1992" /> LSD was one of several psychoactive substances evaluated by the [[Organization:Chemical Corps|U.S. Army Chemical Corps]] as possible non-lethal incapacitants in the [[Social:Edgewood Arsenal human experiments|Edgewood Arsenal human experiments]].<ref name="Lee1992" />

In the 1960s, LSD and other psychedelics were adopted by, and became synonymous with, the [[Philosophy:Counterculture of the 1960s|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.<ref>{{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}}</ref> It was listed as a Schedule 1 controlled substance by the {{wipe|United Nations}} in 1971 and currently has no approved medical uses.<ref name="EU2018" /> {{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.<ref name="NIH2018B">{{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}}</ref> It was most popular in the 1960s to 1980s.<ref name="EU2018" /> The use of LSD among US adults increased 56.4% from 2015 to 2018.<ref>{{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}}</ref>

==Uses==

===Recreational===
LSD is commonly used as a recreational drug.<ref>{{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}}</ref>

===Spiritual===
LSD can catalyze intense spiritual experiences and is thus considered an [[Chemistry:Entheogen|entheogen]]. Some users have reported out of body experiences. In 1966, [[Biography:Timothy Leary|Timothy Leary]] established the League for Spiritual Discovery with LSD as its [[Religion:Sacrament|sacrament]].<ref>{{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 }}</ref><ref>''San Francisco Chronicle'' September 20, 1966 Page One</ref> [[Biography:Stanislav Grof|Stanislav Grof]] has written that religious and mystical experiences observed during LSD sessions appear to be [[Empirical research|phenomenologically]] indistinguishable from similar descriptions in the sacred scriptures of the great religions of the world and the texts of ancient [[Social:Civilization|civilization]]s.<ref name="Grof1979">{{cite book| vauthors=Grof S, Grof JH|  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}}</ref>

===Medical===
LSD currently has no approved uses in medicine.<ref name=Nutt2009>{{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}}</ref><ref>{{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}}</ref> A [[Meta-analysis|meta analysis]] concluded that a single dose was shown to be effective at reducing alcohol consumption in people suffering from [[Medicine:Alcoholism|alcoholism]].<ref name="Lysergic acid diethylamide LSD fo"/> LSD has also been studied in depression, anxiety,<ref name=":5">{{Cite web |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}}</ref><ref name=":6">{{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}}</ref> and drug dependence, with positive preliminary results.<ref>{{cite journal |vauthors=Dos Santos RG, Osório FL, Crippa JA, Riba J, Zuardi AW, Hallak JE |display-authors=4 |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}}</ref><ref>{{Cite web |title=History of LSD Therapy |url=https://druglibrary.org/schaffer/lsd/grofhist.htm |access-date=2022-11-07 |website=druglibrary.org}}</ref>

==Effects==
LSD is exceptionally potent, with as little as 20 μg capable of producing a noticeable effect.<ref name="EU2018" />

===Physical===
[[File:Possible physical effects of lysergic acid diethylamide (LSD).svg|thumb|upright=1.35|left|Some symptoms reported for LSD<ref name=NIDA>{{cite web |date=June 2009 |title=Hallucinogens – LSD, Peyote, Psilocybin, and PCP |publisher=The National Institute on Drug Abuse (NIDA) |url=http://www.nida.nih.gov/infofacts/hallucinogens.html |work=NIDA InfoFacts|archive-date=21 November 2009|archive-url=https://web.archive.org/web/20091121195932/http://www.nida.nih.gov/infofacts/hallucinogens.html}}</ref><ref name=Schiff>{{cite journal |vauthors=Schiff PL |title=Ergot and its alkaloids |journal=American Journal of Pharmaceutical Education |volume=70 |issue=5 |pages=98 |date=October 2006 |pmid=17149427 |pmc=1637017 |doi=10.5688/aj700598 }}</ref>]]
[[File:Mydriasis due to LSD usage.jpg|alt=Patient with Mydriasis due to usage of LSD|thumb|upright=1.35|left|Patient with [[Medicine:Mydriasis|mydriasis]] (pupil dilation) due to usage of LSD]]
LSD can induce physical effects such as [[Medicine:Mydriasis|pupil dilation]], decreased [[Medicine:Appetite|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 [[Medicine:Goose bumps|goose bumps]], jaw clenching, dry mouth, and hyperreflexia. In cases of adverse reactions, users may experience numbness, weakness, nausea, and tremors.<ref name="EU2018" />

===Psychological===
The primary immediate psychological effects of LSD are visual hallucinations and [[Philosophy:Illusion|illusion]]s, often referred to as "trips". 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.<ref>{{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}}</ref> 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.<ref name="erowid-faq">{{cite web |work=[[Organization:Erowid|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}}</ref><ref name="PMID6054248">{{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}}</ref>

Conversely, negative experiences, known as "bad trips," can induce feelings of fear, anxiety, panic, paranoia, and even [[Medicine:Suicidal ideation|suicidal ideation]].<ref name="cdasa" /> 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.<ref name=MedlinePlus>{{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}}</ref><ref name=CESAR>{{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}}</ref>

===Sensory===
LSD induces an animated sensory experience affecting senses, emotions, memories, time, and awareness, lasting from 6 to 20 hours, with the duration dependent on dosage and individual tolerance. Effects typically commence within 30 to 90 minutes post-ingestion, ranging from subtle perceptual changes to profound [[Philosophy:Cognitive shift|cognitive shift]]s. Alterations in auditory and visual perception are common.<ref name="linton-langs"/><ref>{{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}}</ref>

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.<ref name="linton-langs">{{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}}</ref><ref>{{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}}</ref>

There are reports of inanimate objects appearing animated, with static objects seeming to move in additional spatial dimensions.<ref>{{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}}</ref> The auditory effects of LSD may include echo-like distortions of sounds. Basic visual effects often resemble phosphenes and can be influenced by concentration, thoughts, emotions, or music.<ref>{{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 |display-authors=4 |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}}</ref> Auditory effects may include echo-like distortions and an intensified experience of music. Higher doses can lead to more intense sensory perception alterations, including synesthesia, perception of additional dimensions, and temporary [[Medicine:Dissociation (psychology)|dissociation]].

==Adverse effects==
[[File:Rational harm assessment of drugs radar plot.svg|thumb|upright=1.35|Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in [[Delphi method|delphic analysis]] regarding 20 popular recreational drugs. LSD was ranked 14th in dependence, 15th in physical harm, and 13th in social harm.<ref>{{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}}</ref>]]

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.<ref name="pmid14761703"/><ref name="pmid29408722">{{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}}</ref> 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.<ref name="pmid21036393">{{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}}</ref>

===Psychological effects===
====Mental disorders====
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.<ref>{{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}}</ref><ref name="Murray">{{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}}</ref> These hallucinogens can catalyze psychiatric disorders in predisposed individuals, although they do not tend to induce illness in emotionally healthy people.<ref name="pmid14761703"/> Several behavioral-related fatalities and suicides have been associated with LSD.<ref>{{cite web |title=LSD |publisher=National Library of Medicine |website=TOXNET – Toxicology Data Network – HSDB Database |url=https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3920 |access-date=21 March 2018 |archive-date=March 22, 2018 |archive-url=https://web.archive.org/web/20180322021122/https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3920}}</ref>

====Suggestibility====
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.<ref>{{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}}</ref><ref>{{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}}</ref><ref>{{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}}</ref>{{Primary source inline|date=June 2023}}

====Flashbacks====
[[Philosophy:Flashback (psychology)|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-[[Unsolved:Hallucinogen|hallucinogen]] use.<ref name="Halpern2003">{{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}}</ref><ref>{{cite journal |vauthors=Müller F, Kraus E, Holze F, Becker A, Ley L, Schmid Y, Vizeli P, Liechti ME, Borgwardt S |display-authors=4 |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}}</ref> These experiences are associated with [[Medicine:Hallucinogen persisting perception disorder|hallucinogen persisting perception disorder]], where flashbacks occur intermittently or chronically, causing distress or functional impairment.<ref name="Halpern2018"/>

The etiology of flashbacks is varied. Some cases are attributed to [[Medicine:Somatic symptom disorder|somatic symptom disorder]], where individuals fixate on normal [[Biology:Somatic nervous system|somatic]] experiences previously unnoticed prior to drug consumption.<ref>{{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}}</ref> Other instances are linked to associative reactions to contextual cues, similar to responses observed in individuals with past trauma or emotional experiences.<ref>{{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}}</ref> The risk factors for flashbacks remain unclear, but pre-existing psychopathologies may be significant contributors.<ref>{{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}}</ref>

Estimating the prevalence of [[Medicine:Hallucinogen persisting perception disorder|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.<ref name="Halpern2018"/> Contrary to internet rumors, LSD is not stored long-term in the [[Biology:Spinal cord|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.<ref name="Pas2008"/> Clinical evidence also suggests that chronic use of SSRIs can potentiate LSD-induced flashbacks, even months after stopping LSD use.<ref name="drug-interaction">{{cite book |title=Psychedelics as Psychiatric Medications |publisher=[[Organization:Oxford University Press|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}}</ref>{{rp|145}}

===Drug-interactions===
Several psychedelics, including LSD, are metabolized by [[Biology:CYP2D6|CYP2D6]]. Concurrent use of [[Chemistry:Selective serotonin reuptake inhibitor|SSRIs]], potent inhibitors of CYP2D6, with LSD may heighten the risk of [[Medicine:Serotonin syndrome|serotonin syndrome]].<ref name="drug-interaction"/>{{rp|145}} Chronic usage of SSRIs, [[Chemistry:Tricyclic antidepressant|TCA]]s, and [[Biology:Monoamine oxidase inhibitor|MAOI]]s is believed to diminish the subjective effects of psychedelics, likely due to SSRI-induced 5-HT<sub>2A</sub> receptor downregulation and MAOI-induced 5-HT<sub>2A</sub> receptor desensitization.<ref name="Pas2008"/><ref name="drug-interaction"/>{{rp|145}} Interactions between psychedelics and [[Chemistry:Antipsychotic|antipsychotic]]s or [[Chemistry:Anticonvulsant|anticonvulsant]]s are not well-documented; however, co-use with mood stabilizers like [[Chemistry:Lithium (medication)|lithium]] may induce [[Medicine:Seizure|seizure]]s and [[Medicine:Dissociative disorder|dissociative effects]], particularly in individuals with [[Medicine:Bipolar disorder|bipolar disorder]].<ref name="drug-interaction"/>{{rp|146}}<ref>{{cite journal |journal=Drug and Alcohol Dependence |volume=239 |at=109586 |vauthors=Simonsson O, Goldberg SB, Chambers R, Osika W, Long DM, Hendricks PS |display-authors=4 |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}}</ref><ref>{{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}}</ref> Lithium notably intensifies LSD reactions, potentially leading to acute comatose states when combined.<ref name="Pas2008" />

===Fatal dose===
Lethal oral dose of LSD in humans is estimated at 100&nbsp;mg, based on LD<sub>50</sub> and lethal blood concentrations observed in rodent studies.<ref name="pmid29408722" />

===Tolerance===
LSD shows significant [[Chemistry:Tachyphylaxis|tachyphylaxis]], with tolerance developing 24 hours after administration. The progression of tolerance at intervals shorter than 24 hours remains largely unknown.<ref>{{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=[[Company:Academic Press|Academic Press]] |pages=848–849 |volume=2 |year=2016}}</ref> Tolerance typically resets to baseline after 3–4 days of abstinence.<ref name="pmid28701958">{{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}}</ref><ref>{{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}}</ref> Cross-tolerance occurs between LSD, [[Biology:Mescaline|mescaline]], [[Chemistry:Psilocybin|psilocybin]],<ref name="isbell_mescaline">{{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}}</ref><ref name="isbell_psilocybin">{{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}}</ref> and to some degree DMT.{{efn|Although cross-tolerance to DMT is noted as negligible,<ref>{{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}}</ref> some reports suggest that LSD-tolerant individuals showed undiminished responses to DMT.<ref>{{cite journal |vauthors=Strassman RJ, Qualls CR, Berg LM |title=Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans |journal=Biological Psychiatry |volume=39 |issue=9 |date=1 May 1996 |pages=784–785 |doi=10.1016/0006-3223(95)00200-6 |pmid=8731519 |s2cid=3220559 |url=https://www.sciencedirect.com/science/article/abs/pii/0006322395002006}}</ref>}} Tolerance to LSD also builds up with consistent use,<ref name="springer">{{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}}</ref> and is believed to result from serotonin 5-HT<sub>2A</sub> [[Biology:Downregulation and upregulation#Downregulation and upregulation of receptors|receptor downregulation]].<ref name="pmid28701958" /> Researchers believe that tolerance returns to baseline after two weeks of not using psychedelics.<ref name=lsdtol>{{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}}</ref>

===Addiction and dependence liability===
The NIH states that LSD is addictive,<ref name=NIH2018C/> while most other sources state it is not.<ref name="pmid29408722"/><ref name="Lus2006">{{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}}</ref> A 2009 textbook states that it "rarely produce[s] compulsive use."<ref name="NHM-MDMA">{{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}}</ref> A 2006 review states it is readily abused, but does not result in addiction.<ref name=Lus2006/> There are no recorded successful attempts to train animals to self-administer LSD in laboratory settings.<ref name="pmid14761703"/> A study reports that although tolerance to LSD builds up rapidly, a [[Medicine:Withdrawal syndrome|withdrawal syndrome]] does not appear, suggesting that a potential syndrome does not necessarily relate to the possibility of acquiring rapid tolerance to a substance.<ref>{{cite journal |journal=Addiction Medicine Physicians and Medicinal Cannabinoids |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| volume=1 |issue=3}}</ref> A report examining [[Medicine:Substance use disorder|substance use disorder]] for [[Medicine:Diagnostic and Statistical Manual of Mental Disorders|DSM-IV]] noted that almost no hallucinogens produced dependence, unlike psychoactive drugs of other classes such as stimulants and depressants.<ref name="pmid29366418">{{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}}</ref><ref>{{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}}</ref>

===Cancer and pregnancy===
The [[Biology:Mutagenesis|mutagenic]] potential of LSD is unclear. Overall, the evidence seems to point to limited or no effect at commonly used doses.<ref>{{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}}</ref> Studies showed no evidence of teratogenic or mutagenic effects.<ref name=Pas2008/>

==Overdose==
There have been no documented fatal human overdoses from LSD,<ref name="Pas2008"/><ref name="Lipow22">{{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}}</ref> although there has been no "comprehensive review since the 1950s" and "almost no legal clinical research since the 1970s".<ref name="Pas2008"/> Eight individuals who had accidentally consumed an exceedingly high amount of LSD, mistaking it for cocaine, had plasma levels of 1000–7000 μg per 100 mL [[Biology:Blood plasma|blood plasma]] had suffered from [[Medicine:Coma#Causes|comatose states]], vomiting, respiratory problems, [[Medicine:Hyperthermia|hyperthermia]], and light [[Medicine:Gastrointestinal bleeding|gastrointestinal bleeding]]; however, all of them survived without residual effects upon hospital intervention.<ref name="Pas2008"/>

Individuals experiencing a bad trip after LSD intoxication may be presented with severe anxiety, tachycardia, often accompanied by phases of psychotic agitation and varying degrees of delusions which seem to overlap with [[Social:Excited delirium|excited delirium]] (ExDS); however individuals experiencing ExDS may suddenly die, whereas there are no reported cases of sudden death from a bad trip.<ref name="pmid29408722" /> However, cases of death on a bad trip have been reported due to prone maximal restraint (PMR) and [[Medicine:Positional asphyxia|positional asphyxia]] when the individuals were held restraint by [[Social:Law enforcement officer|law enforcement personnel]].<ref name="pmid29408722" />

Massive doses are largely managed by [[Medicine:Symptomatic treatment|symptomatic treatment]]s, and agitation can be addressed with [[Chemistry:Benzodiazepine|benzodiazepine]]s.<ref name="Medscape">{{EMedicine|article|1011615|LSD Toxicity Treatment & Management|treatment}}</ref><ref>{{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}}</ref> Reassurance in a calm, safe environment is beneficial.<ref>{{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}}</ref> [[Chemistry:Typical antipsychotic|Antipsychotic agents]] such as neuroleptics and [[Chemistry:Haloperidol|haloperidol]] are not recommended as they may have adverse [[Medicine:Psychotomimetism|psychotomimetic effects]].<ref name="Medscape" /> Gastrointestinal decontamination with [[Chemistry:Activated charcoal (medication)|activated charcoal]] is of little use due to the rapid absorption of LSD, unless done within 30–60 minutes of ingesting exceedingly huge amounts.<ref name="Medscape" /> Administration of anticoagulants, vasodilators, and sympatholytics may be useful for treating [[Medicine:Ergotism|ergotism]].<ref name="Medscape" />

===Designer drug overdose===
Many [[Chemistry:Designer drug|novel psychoactive substances]] of [[Chemistry:25-NB|25-NB]] (NBOMe) series, such as [[Chemistry:25I-NBOMe|25I-NBOMe]] and [[Chemistry:25B-NBOMe|25B-NBOMe]], are regularly sold as LSD in blotter papers.<ref name="pmid30261175">{{cite journal |journal=Biochemical Pharmacology |vauthors=Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A |display-authors=4 |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}}</ref><ref>{{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}}</ref> NBOMe coumpounds are often associated with life-threatening toxicity and death.<ref name="pmid30261175"/><ref name="pmid35343858">{{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}}</ref> Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,<ref name="pmid31915427">{{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 |display-authors=4 |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}}</ref> and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".<ref name="Lipow22"/> Researchers state that the alleged physiological toxicity of LSD is likely due to psychoactive substances other than LSD.<ref name="pmid29408722"/> NBOMe compounds are reported to have a bitter taste,<ref name="Lipow22"/> and are not active orally,{{efn|The [[Chemistry:Potency (pharmacology)|potency]] of ''N''-benzylphenethylamines via buccal, sublingual, or nasal absorption is 50–100 greater (by weight) than oral route compared to the parent [[Chemistry:2C (psychedelics)|2C-x]] compounds.<ref name="pmid24519542">{{cite journal |journal=Neurochemical Research |date=14 February 2014 |vauthors=Leth-Petersen S, Bundgaard C, Hansen M, Carnerup MA, Kehler J, Kristensen JL |display-authors=4 |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}}</ref> 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.<ref name="pmid24519542"/>}} and are usually taken sublingually.<ref name="pmid28097528">{{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}}</ref> 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.<ref>{{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}}</ref><ref>{{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 |display-authors=4 |volume=2014 |page=734749 |doi-access=free}}</ref><ref>{{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}}</ref> Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity, but NBOMe compounds have extremely different safety profiles.<ref name="Lipow22"/><ref name="pmid35343858"/> [[Chemistry:Ehrlich's reagent|Ehrlich's reagent]] can be used to test for the presence of LSD.<ref name="LSDEMCDDA"/>

==Pharmacology==

===Pharmacodynamics===
[[File:LSDaffinities.GIF|thumb|Binding affinities of LSD for various receptors. The lower the [[Chemistry:Dissociation constant|dissociation constant]] (K<sub>i</sub>), the more strongly LSD binds to that receptor (i.e. with higher affinity). The horizontal line represents an approximate value for human plasma concentrations of LSD, and hence, receptor affinities that are above the line are unlikely to be involved in LSD's effect. Data averaged from data from the [[Company:Ki Database|K<sub>i</sub> Database]]

{| class="wikitable sortable mw-collapsible"
|+Binding affinity for various serotonin receptors
!Receptor
!K<sub>i</sub> (nM)
|-
|[[Biology:5-HT1A receptor|5-HT<sub>1A</sub>]]
|1.1
|-
|[[Biology:5-HT2A receptor|5-HT<sub>2A</sub>]]
|2.9
|-
|[[Biology:5-HT2B receptor|5-HT<sub>2B</sub>]]
|4.9
|-
|[[Biology:5-HT2C receptor|5-HT<sub>2C</sub>]]
|23
|-
|[[Biology:5-HT5A receptor|5-HT<sub>5A</sub>]]
|9
|-
|[[Biology:5-HT6 receptor|5-HT<sub>6</sub>]]
|2.3
|}
]]

Most [[Chemistry:Serotonergic psychedelic|serotonergic psychedelic]]s are not significantly [[Chemistry:Dopaminergic|dopaminergic]], and LSD is therefore atypical in this regard. The agonism of the [[Biology:Dopamine receptor D2|D<sub>2</sub> receptor]] by LSD may contribute to its psychoactive effects in humans.<ref name="nichols_closes_shop">{{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 = 427–35 | date = July 2005 | pmid = 15723230 | doi = 10.1007/s00213-005-2183-9 | s2cid = 23565306 }}</ref>

LSD binds to most serotonin receptor subtypes except for the [[Biology:5-HT3 receptor|5-HT<sub>3</sub>]] and [[Biology:5-HT4 receptor|5-HT<sub>4</sub> receptor]]s. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20&nbsp;[[Physics:Molar concentration|nM]].<ref name="pmid14761703"/> In humans, recreational doses of LSD can affect [[Biology:5-HT1A receptor|5-HT<sub>1A</sub>]] (K<sub>i</sub> = 1.1 nM), [[Biology:5-HT2A receptor|5-HT<sub>2A</sub>]] (K<sub>i</sub> = 2.9 nM), [[Biology:5-HT2B receptor|5-HT<sub>2B</sub>]] (K<sub>i</sub> = 4.9 nM), [[Biology:5-HT2C receptor|5-HT<sub>2C</sub>]] (K<sub>i</sub> = 23 nM), [[Biology:5-HT5A receptor|5-HT<sub>5A</sub>]] (K<sub>i</sub> = 9 nM [in cloned rat tissues]), and [[Biology:5-HT6 receptor|5-HT<sub>6</sub> receptors]] (K<sub>i</sub> = 2.3 nM).<ref name="Aghajanian" /> Although not present in humans, [[Biology:5-HT5B receptor|5-HT<sub>5B</sub> receptors]] found in rodents also have a high affinity for LSD.<ref>{{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}}</ref> The psychedelic effects of LSD are attributed to [[Biology:Crosstalk|cross-activation]] of 5-HT<sub>2A</sub> [[Biology:GPCR oligomer|receptor heteromers]].<ref>{{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}}</ref> Many but not all 5-HT<sub>2A</sub> [[Biology:Agonist|agonist]]s are [[Chemistry:Psychedelic drug|psychedelics]] and 5-HT<sub>2A</sub> [[Biology:Receptor antagonist|antagonists]] block the psychedelic activity of LSD. LSD exhibits [[Biology:Functional selectivity|functional selectivity]] at the 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors in that it activates the [[Biology:Signal transduction|signal transduction]] enzyme [[Biology:Phospholipase A2|phospholipase A2]] instead of activating the enzyme [[Biology:Phospholipase C|phospholipase C]] as the endogenous ligand serotonin does.<ref>{{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 |display-authors=4 |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}}</ref>

Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing glutamate release in the [[Biology:Cerebral cortex|cerebral cortex]]<ref name="pmid14761703"/> and therefore [[Biology:Excitatory postsynaptic potential|excitation]] in this area, specifically in layer V.<ref>{{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 }}</ref> LSD, like many other drugs of recreational use, has been shown to activate DARPP-32-related pathways.<ref>{{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 }}</ref> The drug enhances dopamine D<sub>2</sub> receptor [[Biology:Protomer|protomer]] recognition and [[Biology:Cell signaling|signaling]] of D<sub>2</sub>–5-HT<sub>2A</sub> receptor complexes,<ref name="pmid24309097">{{cite journal | vauthors = Borroto-Escuela DO, Romero-Fernandez W, Narvaez M, Oflijan J, Agnati LF, Fuxe K |display-authors=4 | 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 }}</ref> which may contribute to its psychotropic effects.<ref name="pmid24309097" /> LSD has been shown to have low affinity for H1 receptors, displaying antihistamine effects.<ref>{{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 }}</ref><ref name="synth2"/>

LSD is a biased agonist that induces a conformation in serotonin receptors that preferentially recruits β-arrestin over [[Biology:Gs alpha subunit|activating G protein]]s.<ref name="Chen_2017">{{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}}</ref> LSD also has an exceptionally long [[Biology:Residence time#Pharmacology|residence time]] when bound to serotonin receptors lasting hours, consistent with the long lasting effects of LSD despite its relatively rapid [[Clearance (pharmacology)|clearance]].<ref name="Chen_2017" /> A crystal structure of 5-HT<sub>2B</sub> bound to LSD reveals an extracellular loop that forms a lid over the diethylamide end of the binding cavity which explains the slow rate of LSD unbinding from serotonin receptors.<ref name="WackerWang2017">{{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 | display-authors = 4 | 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 }}</ref> The related lysergamide lysergic acid amide (LSA) that lacks the diethylamide [[Chemistry:Moiety|moiety]] is far less hallucinogenic in comparison.<ref name="WackerWang2017" />

===Pharmacokinetics===
[[File:FMRI V1 RSFC LSD.png|thumb|upright=1.35|[[Physics:Resting state fMRI|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 visual cortex correlated positively with ratings of complex imagery on the LSD-induced altered state of consciousness (ASC).<ref name="pmid27071089"/>]]
[[File:FMRI PH RSFC LSD.png|thumb|upright=1.35|[[Physics:Resting state fMRI|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.<ref name="pmid27071089" />]]
The effects of LSD normally last between 6 and 12 hours depending on dosage, tolerance, and age.{{Medical citation needed|date=June 2023}}<ref name="tihkal">{{cite book |vauthors=Shulgin A, Shulgin A |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=[[Chemistry:TiHKAL|TiHKAL]] |location=Berkeley, CA |publisher=Transform Press |date=1997 |isbn=0-9630096-9-9}}</ref> Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175&nbsp;minutes (about 3&nbsp;hours).<ref name="Aghajanian">{{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}}</ref> However, using more accurate techniques, Papac and Foltz (1990) reported that 1&nbsp;µg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1&nbsp;hours, with a peak plasma concentration of 5&nbsp;ng/mL at 3&nbsp;hours post-dose.<ref name="Papac">{{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}}</ref>

The [[Medicine:Pharmacokinetics|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.<ref name=Dol2015 /><ref name=Muc2016 /> In a sample of 16 healthy subjects, a single mid-range 200&nbsp;μg oral dose of LSD was found to produce mean [[Medicine:Cmax (pharmacology)|maximal concentration]]s of 4.5&nbsp;ng/mL at a median of 1.5&nbsp;hours (range 0.5–4&nbsp;hours) post-administration.<ref name=Dol2015 /><ref name=Muc2016 /> Concentrations of LSD decreased following first-order kinetics with a [[Physics:Half-life|half-life]] of 3.6±0.9 hours and a terminal half-life of 8.9±5.9 hours.<ref name=Dol2015 /><ref name=Muc2016 />

The effects of the dose of LSD given lasted for up to 12&nbsp;hours and were closely correlated with the concentrations of LSD present in circulation over time, with no acute [[Chemistry:Drug tolerance|tolerance]] observed.<ref name=Dol2015 /><ref name=Muc2016 /> Only 1% of the drug was eliminated in [[Biology:Urine|urine]] unchanged, whereas 13% was eliminated as the major [[Biology:Metabolite|metabolite]] 2-oxo-3-hydroxy-LSD (O-H-LSD) within 24&nbsp;hours.<ref name=Dol2015 /><ref name=Muc2016 /> O-H-LSD is formed by [[Biology:Cytochrome P450|cytochrome P450]] [[Biology:Enzyme|enzyme]]s, although the specific enzymes involved are unknown, and it does not appear to be known whether O-H-LSD is pharmacologically active or not.<ref name=Dol2015 /><ref name=Muc2016 /> The oral [[Chemistry:Bioavailability|bioavailability]] of LSD was crudely estimated as approximately 71% using previous data on intravenous administration of LSD.<ref name=Dol2015 /><ref name=Muc2016 /> The sample was equally divided between male and female subjects and there were no significant sex differences observed in the pharmacokinetics of LSD.<ref name=Dol2015 /><ref name=Muc2016 />

===Mechanisms of action===
Neuroimaging studies using resting state fMRI recently suggested that LSD changes the cortical functional architecture.<ref name="Singleton SP">{{cite journal | vauthors = Singleton SP, Luppi AI, Carhart-Harris RL, Cruzat J, Roseman L, Nutt DJ, Deco G, Kringelbach ML, Stamatakis EA, Kuceyeski A |display-authors=4 |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 }}</ref> These modifications spatially overlap with the distribution of serotoninergic receptors. In particular, increased connectivity and activity were observed in regions with high expression of [[Biology:5-HT2A receptor|5-HT<sub>2A</sub>]] receptor, while a decrease in activity and connectivity was observed in cortical areas that are dense with [[Biology:5-HT1A receptor|5-HT<sub>1A</sub>]] receptor.<ref name="Delli Pizzi S BP:CNNI">{{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 |display-authors=4 |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}}</ref> 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 [[Biology:5-HT2A receptor|5-HT<sub>2A</sub>]] receptor, may enhance excitatory neurotransmission along frontostriatal projections and, consequently, reduce thalamic filtering of sensory stimuli towards the cortex.<ref name="Delli Pizzi S NeuroImage">{{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 |display-authors=4 |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}}</ref> This phenomenon appears to selectively involve ventral, intralaminar, and pulvinar nuclei.<ref name="Delli Pizzi S NeuroImage"/>

==Chemistry==
[[File:Lysergide stereoisomers structural formulae v.2.png|thumb|upright=1.35|The four possible stereoisomers of LSD. Only (+)-LSD is psychoactive.]]

LSD is a [[Biology:Chirality|chiral]] compound with two [[Chemistry:Stereocenter|stereocenter]]s at the [[Chemistry:Carbon|carbon]] atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)-<small>D</small>-LSD,{{citation needed|reason=incorrect stereochemical notation small capital D|date=September 2018}} has the [[Chemistry:Absolute configuration|absolute configuration]] (5''R'',8''R''). 5''S'' stereoisomers of lysergamides do not exist in nature and are not formed during the synthesis from [[Chemistry:Descriptor#dl|''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-[[Chemistry:Tryptophan|tryptophan]], the precursor to all biosynthetic ergoline compounds.

However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of [[Chemistry:Base|bases]], as the alpha proton is acidic and can be [[Chemistry:Deprotonation|deprotonated]] and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated by [[Physics:Chromatography|chromatography]] and can be isomerized to LSD.

Pure salts of LSD are triboluminescent, emitting small flashes of white light when shaken in the dark.<ref name="tihkal" /> LSD is strongly fluorescent and will glow bluish-white under UV light.

===Synthesis===
LSD is an [[Chemistry:Ergoline|ergoline]] derivative. It is commonly synthesized by reacting diethylamine with an activated form of [[Chemistry:Lysergic acid|lysergic acid]]. Activating reagents include [[Chemistry:Phosphoryl chloride|phosphoryl chloride]]<ref name="synth1">{{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}}</ref> and peptide coupling reagents.<ref name="synth2">{{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}}</ref> Lysergic acid is made by alkaline [[Chemistry:Hydrolysis|hydrolysis]] of lysergamides like [[Chemistry:Ergotamine|ergotamine]], a substance usually derived from the [[Biology:Ergot|ergot]] [[Biology:Fungus|fungus]] on [[Organization:Agar plate|agar plate]]; or, theoretically possible, but impractical and uncommon, from [[Chemistry:Ergine|ergine]] (lysergic acid amide, LSA) extracted from [[Biology:Morning glory|morning glory]] seeds.<ref name="erowid">{{cite web |url=http://www.erowid.org/plants/morning_glory/morning_glory_extraction1.shtml |title=Extraction of LSA (Method #1) |publisher=Erowid |access-date=September 25, 2014 |archive-url=https://web.archive.org/web/20140926235219/http://www.erowid.org/plants/morning_glory/morning_glory_extraction1.shtml |archive-date=September 26, 2014 |url-status=live}}</ref> Lysergic acid can also be produced synthetically, although these processes are not used in clandestine manufacture due to their low yields and high complexity.<ref>{{cite journal |vauthors=Kornfeld EC, Fornefeld EJ, Kline GB, Mann MJ, Morrison DE, Jones RG, Woodward RB |display-authors=4 |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}}</ref><ref>{{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}}</ref>

====Research====
The precursor for LSD, [[Chemistry:Lysergic acid|lysergic acid]], has been produced by GMO [[Biology:Baker's yeast|baker's yeast]].<ref>{{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}} '''Journal Reference:''' {{cite journal |vauthors=Wong G, Lim LR, Tan YQ, Go MK, Bell DJ, Freemont PS, Yew WS |display-authors=4 |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}}</ref>

===Dosage===
[[File:10 strip.jpg|thumb|White on White blotters (WoW) for [[Medicine:Sublingual administration|sublingual administration]]]]
A single dose of LSD may be between 40 and 500 micrograms—an amount roughly equal to one-tenth the mass of a grain of sand. Threshold effects can be felt with as little as 25 micrograms of LSD.<ref name="greiner">{{cite journal |vauthors=Greiner T, Burch NR, Edelberg R |title=Psychopathology and psychophysiology of minimal LSD-25 dosage; a preliminary dosage-response spectrum |journal=A.M.A. Archives of Neurology and Psychiatry |volume=79 |issue=2 |pages=208–10 |date=February 1958 |pmid=13497365 |doi=10.1001/archneurpsyc.1958.02340020088016}}</ref><ref>{{cite journal |vauthors=Meyer MA |title=Neurologic complications of anthrax: a review of the literature |journal=Archives of Neurology |volume=60 |issue=4 |pages=483–8 |date=April 2003 |pmid=12707059 |doi=10.1001/archneur.60.4.483 |doi-access=free |place=Schweiz}}</ref> The practice of using sub-threshold doses is called [[Chemistry:Psychedelic microdosing|microdosing]].<ref>{{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}}</ref> Dosages of LSD are measured in micrograms (µg), or millionths of a gram.

In the mid-1960s, the most important [[Finance:Black market|black market]] LSD manufacturer (Owsley Stanley) distributed LSD at a standard concentration of 270&nbsp;µg,<ref name="LSD Samples Analysis">{{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}}</ref> 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 20–80&nbsp;µg range,<ref name="henderson-glass">{{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}}</ref> and even more in the 2000s (decade).<ref name="LSD Samples Analysis" /><ref>{{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}}</ref>

===Reactivity and degradation===
"LSD," writes the chemist Alexander Shulgin, "is an unusually fragile molecule ... As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely."<ref name="tihkal" />

LSD has two [[Chemistry:Lability|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 [[Chemistry:Carboxamide|carboxamide]] attachment, but removal of the [[Chirality|chiral]] proton at the C5 position (which was once also an alpha proton of the parent molecule [[Chemistry:Tryptophan|tryptophan]]) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with the [[Chemistry:Indole|indole]] ring.{{Citation needed|date=May 2011}}

LSD also has [[Chemistry:Enamine|enamine]]-type reactivity because of the electron-donating effects of the indole ring. Because of this, [[Chemistry:Chlorine|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.<ref name="tihkal" /> The [[Chemistry:Covalent bond|double bond]] between the 8-position and the [[Chemistry:Aromatic hydrocarbon|aromatic ring]], being conjugated with the indole ring, is susceptible to [[Chemistry:Nucleophile|nucleophilic]] attacks by water or [[Chemistry:Alcohol|alcohol]], especially in the presence of UV or other kinds of light. LSD often converts to "lumi-LSD," which is inactive in human beings.<ref name="tihkal" />

A controlled study was undertaken to determine the stability of LSD in pooled urine samples.<ref>{{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 }}</ref>
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&nbsp;°C for up to four weeks. After four weeks of incubation, a 30% loss in LSD concentration at 37&nbsp;°C and up to a 40% at 45&nbsp;°C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. It was also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of [[Chemistry:EDTA|EDTA]].

===Detection===
[[File:LSD Ehrlich reagent test.jpg|thumb|Ehrlich's reagent can be used to test for the presence of LSD in a sample, turning purple upon reaction.<ref name="LSDEMCDDA">{{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}}</ref>]]

LSD can be detected in concentrations larger than approximately 10% in a sample using [[Chemistry:Ehrlich's reagent|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).<ref name="ReferenceA">{{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 }}</ref>

LSD may be quantified in urine for drug abuse 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.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 12th edition, Biomedical Publications, Foster City, CA, 2020, pp. 1197–1199.</ref> Maximum plasma concentrations are typically observed 1.4 to 1.5 hours after oral administration of 100&nbsp;µg and 200&nbsp;µg, respectively, with a plasma half-life of approximately 2.6 hours (ranging from 2.2 to 3.4 hours among test subjects).<ref>{{cite journal | vauthors = Dolder PC, Schmid Y, Steuer AE, Kraemer T, Rentsch KM, Hammann F, Liechti ME |display-authors=4 | 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 }}</ref>

Due to its potency in microgram quantities, LSD is often not included in standard pre-employment urine or hair analyses.<ref name="ReferenceA"/><ref name="pmid36753839">{{cite journal |vauthors=Jiaming Z, Xin W, Jiali Z, Hang R, Yunli Z, Ping X |display-authors=4 |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}}</ref> However, advanced [[Physics:Liquid chromatography–mass spectrometry|liquid chromatography–mass spectrometry]] methods can detect LSD in biological samples even after a single use.<ref name="pmid36753839"/>

==History==
{{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, [[Physics:Kaleidoscope|kaleidoscopic]] play of colors. After some two hours this condition faded away.|source= —Albert Hofmann, on his first experience with LSD<ref name="hofmann1980">{{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}}</ref>{{rp|p=15}}|width=25em}}

LSD was first synthesized on November 16, 1938<ref>{{cite journal |vauthors=Hofmann A | 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}}</ref> by Swiss chemist Albert Hofmann at the Sandoz Laboratories in [[Place:Basel|Basel]], Switzerland as part of a large research program searching for medically useful [[Chemistry:Ergoline|ergot alkaloid]] derivatives. The abbreviation "LSD" is from the German "Lysergsäurediethylamid".<ref>{{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}}</ref>

[[Image:Albert Hofmann.jpg|thumb|Albert Hofmann in 2006]]
LSD's [[Chemistry:Psychedelic drug|psychedelic]] properties were discovered 5 years later when Hofmann himself accidentally ingested an unknown quantity of the chemical.<ref name="hyponichols">{{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}}</ref> The first intentional ingestion of LSD occurred on April 19, 1943,<ref name="hofmann1980" /> 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.<ref name="histlsd">{{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}}</ref> 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."<ref name="LSD: The Drug">{{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}}</ref> Sandoz would send the drug for free to researchers investigating its effects.<ref name="Hofmann2009"/>

[[File:Effects_of_Lysergic_Acid_Diethylamide_(LSD)_on_Troops_Marching.webm|thumb|left|upright=1.35|'Effects of Lysergic Acid Diethylamide (LSD) on Troops Marching' – 16mm film produced by the United States military circa 1958]]
Beginning in the 1950s, the US Central Intelligence Agency (CIA) began a research program code named [[Social:Project MKUltra|Project MKUltra]]. The CIA introduced LSD to the United States, purchasing the entire world's supply for $240,000 and propagating the LSD through CIA front organizations to American hospitals, clinics, prisons and research centers.<ref>{{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 }}</ref> Experiments included administering LSD to CIA employees, military personnel, doctors, other government agents, prostitutes, mentally ill patients, and members of the general public in order to study their reactions, usually without the subjects' knowledge. The project was revealed in the US congressional Rockefeller Commission report in 1975.

In 1963, the Sandoz patents on LSD expired<ref name="henderson-glass"/> and the Czech company Spofa began to produce the substance.<ref name="Hofmann2009" /> Sandoz stopped the production and distribution in 1965.<ref name="Hofmann2009" />

Several figures, including [[Biography:Aldous Huxley|Aldous Huxley]], [[Biography:Timothy Leary|Timothy Leary]], and Al Hubbard, had begun to advocate the consumption of LSD. LSD became central to the counterculture of the 1960s.<ref>{{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}}</ref> In the early 1960s the use of LSD and other hallucinogens was advocated by new proponents of consciousness expansion such as Leary, Huxley, [[Biography:Alan Watts|Alan Watts]] and [[Biography:Arthur Koestler|Arthur Koestler]],<ref>{{cite web |vauthors=Applebaum A |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}}</ref><ref>{{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}}</ref> and according to L. R. Veysey they profoundly influenced the thinking of the new generation of youth.<ref>{{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}}</ref>

On October 24, 1968, possession of LSD was made illegal in the United States.<ref>{{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}}</ref> The last [[Organization:Food and Drug Administration|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.<ref>{{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}}</ref>

In November 2020, Oregon became the first US state to decriminalize possession of small amounts of LSD after voters approved Ballot Measure 110.<ref>{{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}}</ref>

==Society and culture==
===Counterculture===
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.<ref name=DeRogatispp8-9>{{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}}</ref> 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.<ref name=pc41>{{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&#93; : UNT Digital Library | vauthors = Gilliland J |year=1969 |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}}</ref><ref name=Hicks2000p60>{{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 }}</ref> 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).<ref name=Mann2009p87>{{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 }}</ref>

In San Francisco's Haight-Ashbury neighborhood, the Psychedelic Shop was opened in January 1966 by brothers Ron and Jay Thelin to promote 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.<ref>{{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}}</ref><ref>{{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}}</ref>

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 [[Biography:Aldous Huxley|Aldous Huxley]], [[Biography:Timothy Leary|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 own experiments. In 1965, he returned to the UK and founded the World Psychedelic Center in Chelsea, London.<ref>{{cite book |last1=Conners |first1=Peter |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 }}</ref>

===Music and Art===
[[File:Hell0 Darinzo.jpg|thumb|Psychedelic art aims to capture the experiences of psychedelic trips.]]
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.<ref name=Jarnow/>

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.<ref>{{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}}</ref>

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 backwards tapes, panning, and phasing.<ref>{{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}}</ref><ref>{{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}}</ref> 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.<ref name=Sheff>{{cite book |vauthors=Sheff D |year=2000 |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}}</ref>{{page needed|date=January 2024}}<ref name="life">{{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}}</ref>

Contemporary artists influenced by LSD include Keith Haring in the visual arts,<ref>{{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 |first=Keith |last=Haring |page=25}}</ref> various electronic dance music creators,<ref>{{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}}</ref> and the jam band Phish.<ref>{{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}}</ref> The 2018 Leo Butler play ''All You Need is LSD'' is inspired by the author's interest in the history of LSD.<ref>{{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}}</ref>

===Legal status===
The {{wipe|United Nations}} [[Medicine:Convention on Psychotropic Substances|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.<ref>{{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}}</ref>

====Australia====
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.<ref name="Poisons Standard">{{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}}</ref> In Western Australia, the Misuse of Drugs Act 1981 provides guidelines for possession and trafficking of substances like LSD.<ref>{{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}}</ref>

====Canada====
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.<ref name="cdasa">{{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 }}</ref>

====United Kingdom====
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.<ref>{{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}}</ref><ref>{{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}}</ref>

====United States====
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.<ref>{{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}}, originating from U.S. v. Neal, 46 F.3d 1405 (7th Cir. 1995)</ref>

Oregon decriminalized personal possession of small amounts of drugs, including LSD, in February 2021, and California has seen legislative efforts to decriminalize psychedelics.<ref>{{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}}</ref>

====Mexico====
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.<ref>{{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}}</ref>

====Czech Republic====
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.<ref name="Cz expl rep">{{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}}</ref><ref>{{Citation |author=Supreme Court of the Czech Republic |date=25 February 2012 |title=6 Tdo 156/2010 [NS 7078/2010]}}</ref>

===Economics===

====Production====
[[File:LSDLabGlassware.jpg|thumb|Glassware seized by the DEA]]

An active dose of LSD is very minute, allowing a large number of doses to be synthesized from a comparatively small amount of raw material. Twenty five kilograms of precursor [[Chemistry:Ergotamine|ergotamine]] [[Chemistry:Tartrate|tartrate]] can produce 5–6&nbsp;kg of pure crystalline LSD; this corresponds to around 50–60&nbsp;million doses at 100&nbsp;µg. Because the masses involved are so small, concealing and transporting illicit LSD is much easier than smuggling [[Biology:Cocaine|cocaine]], [[Biology:Cannabis (drug)|cannabis]], or other illegal drugs.<ref name="DEA-pub">{{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}}{{Dead link|date=January 2015}}</ref>

Manufacturing LSD requires laboratory equipment and experience in the field of [[Chemistry:Organic chemistry|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.<ref name="DEA-pub"/>

=====Forms=====
[[File:5 LSD blotters.png|thumb|Five doses of LSD, often called a "five strip"]]

LSD is produced in crystalline form and is then mixed with [[Chemistry:Excipient|excipient]]s or redissolved for production in ingestible forms. Liquid solution is either distributed in small vials or, more commonly, sprayed onto or soaked into a distribution medium. Historically, LSD solutions were first sold on sugar cubes, but practical considerations forced a change to [[Medicine:Tablet (pharmacy)|tablet]] form. Appearing in 1968 as an orange tablet measuring about 6&nbsp;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.<ref name=Stafford1992>{{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}}</ref>

Over a period of time, tablet dimensions, weight, shape and concentration of LSD evolved from large (4.5–8.1&nbsp;mm diameter), heavyweight (≥150&nbsp;mg), round, high concentration (90–350&nbsp;µg/tab) dosage units to small (2.0–3.5&nbsp;mm diameter) lightweight (as low as 4.7&nbsp;mg/tab), variously shaped, lower concentration (12–85&nbsp;µg/tab, average range 30–40&nbsp;µg/tab) dosage units. LSD tablet shapes have included cylinders, cones, stars, spacecraft, and heart shapes. The smallest tablets became known as "Microdots."<ref name=Laing2003>{{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}}</ref>

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.<ref name=Stafford1992/><ref name=Laing2003/> More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975.<ref name=Laing2003/> About the same time as blotter paper LSD came "Windowpane" (AKA "Clearlight"), which contained LSD inside a thin [[Biology:Gelatin|gelatin]] square a quarter of an inch (6&nbsp;mm) across.<ref name=Stafford1992/> <!-- Please do not add any street names here unless you can provide evidence for their notability and importance! Additions not referenced to a reliable source will be removed immediately. The goal of an encyclopedia is to provide a "ready reference" of key concepts, not give an exhaustive list of every detail.--> 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.<ref name="erowid-faq"/><ref>{{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}}</ref> Authorities have encountered the drug in other forms—including powder or crystal, and capsule.<ref>{{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}}</ref>

=====Modern distribution=====
LSD manufacturers and traffickers in the United States can be categorized into two groups: A few large-scale producers, and an equally limited number of small, clandestine chemists, consisting of independent producers who, operating on a comparatively limited scale, can be found throughout the country.<ref>{{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}}</ref><ref>{{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}}</ref>

As a group, independent producers are of less concern to the [[Organization:Drug Enforcement Administration|Drug Enforcement Administration]] than the large-scale groups because their product reaches only local markets.<ref name="LSD: The Drug"/>

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.<ref>{{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}}</ref>

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

====={{anchor|N-Bomb}} Mimics=====
[[File:Docpsychadelic.jpg|thumb|LSD blotter acid mimic actually containing DOC]]
[[File:Lysergic.JPG|thumb|Different blotters which could possibly be mimics]]

Since 2005, law enforcement in the United States and elsewhere has seized several chemicals and combinations of chemicals in blotter paper which were sold as LSD mimics, including DOB,<ref name="microgram october 2005">{{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}}</ref><ref name="microgram november 2006">{{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}}</ref> a mixture of [[Chemistry:2,5-Dimethoxy-4-chloroamphetamine|DOC]] and DOI,<ref name="microgram march 2008">{{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}}</ref> [[Chemistry:25I-NBOMe|25I-NBOMe]],<ref name="ACMD Report">{{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}}</ref> and a mixture of [[Chemistry:2,5-Dimethoxy-4-chloroamphetamine|DOC]] and DOB.<ref name="microgram march 2009">{{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}}</ref> 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 [[Physics:Chromatography|chromatographic]] analysis of blotter paper containing [[Chemistry:2C-C|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.<ref name="microgram november 2005">{{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}}</ref> Blotter LSD mimics can have relatively small dose squares; a sample of blotter paper containing [[Chemistry:2,5-Dimethoxy-4-chloroamphetamine|DOC]] seized by Concord, California police had dose markings approximately 6&nbsp;mm apart.<ref name="microgram december 2007">{{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}}</ref> Several deaths have been attributed to 25I-NBOMe.<ref name="Erowid25I-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}}</ref><ref name="NY Daily news">{{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}}</ref><ref name="Ireland injuries">{{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}}</ref><ref name="ACMD Report2">{{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}}</ref>

==Research==
In the United States the earliest research began in the 1950s. For instance, with his colleagues Albert Kurland published research on LSD's therapeutic potential in treating to schizophrenia. In Canada began Humphrey Osmond and Abram Hoffer completed LSD studies as early as 1952.<ref>{{Cite journal |last=Dyck |first=Ericka |date=1965 |title=Flashback: Psychiatric Experimentation with LSD in Historical Perspective. |journal=Canadian Journal of Psychiatry |volume=50 |issue=7}}</ref>  By the 1960s, controversies surrounding "hippie" counter culture began to deplete institutional support for continued studies.

Currently, a number of organizations—including the Beckley Foundation, MAPS, Heffter Research Institute and the Albert Hofmann Foundation—exist to fund, encourage and coordinate research into the medicinal and spiritual uses of LSD and related psychedelics.<ref>{{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}}</ref> New clinical LSD experiments in humans started in 2009 for the first time in 35 years.<ref name="new research">{{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}}</ref> As it is illegal in many areas of the world, potential medical uses are difficult to study.<ref name=Nutt2009/>

In 2001 the [[Organization:Drug Enforcement Administration|United States Drug Enforcement Administration]] stated that LSD "produces no aphrodisiac effects, does not increase creativity, has no lasting positive effect in treating [[Medicine:Alcoholism|alcoholics]] or criminals, does not produce a "model psychosis", and does not generate immediate personality change."<ref name="LSD: The Drug"/> More recently, experimental uses of LSD have included the treatment of alcoholism,<ref name=":0">{{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}}</ref> pain and cluster headache relief,<ref name=Pas2008/> and prospective studies on depression.<ref>{{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}}</ref><ref>{{cite journal |vauthors=Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, Martell J, Blemings A, Erritzoe D, Nutt DJ |display-authors=4 |title=Trial of Psilocybin versus Escitalopram for Depression |journal=The New England Journal of Medicine |volume=384 |issue=15 |pages=1402–1411 |date=April 2021 |pmid=33852780 |doi=10.1056/NEJMoa2032994 |s2cid =233243518 |doi-access=free}}</ref>

A 2020 meta-review indicated possible positive effects of LSD in reducing psychiatric symptoms, mainly in cases of alcoholism.<ref>{{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}}</ref> There is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits.<ref name="pmid36123427">{{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}}</ref><ref name="pmid35060714">{{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}}</ref>

===Psychedelic therapy===
In the 1950s and 1960s, LSD was used in psychiatry to enhance psychotherapy, known as [[Unsolved:Psychedelic therapy|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 [[Medicine:Psychotherapy|psychotherapeutic]] methods,<ref>Cohen, S. (1959). "The therapeutic potential of LSD-25". ''A Pharmacologic Approach to the Study of the Mind'', p. 251–258.</ref> and also for treating alcoholism.<ref>{{cite journal |title=Use of d-Lysergic Acid Diethylamide in the Treatment of Alcoholism |journal=Quart. 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}}</ref><ref>{{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}}</ref> One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing [[Philosophy:Self-acceptance|self-acceptance]] and self-surrender,"<ref name="Use of d-lysergic acid diethylamide"/> 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 [[Methodology|methodological]] flaws. These include the absence of adequate control groups, lack of followup, and vague criteria for [[Chemistry:Therapy|therapeutic]] outcome.  In many cases studies failed to convincingly demonstrate whether the drug or the therapeutic interaction was responsible for any beneficial effects.<ref>{{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}}</ref><ref>{{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}}</ref>

In recent years, organizations like the Multidisciplinary Association for Psychedelic Studies have renewed clinical research of LSD.<ref name="new research"/>

It has been proposed that LSD be studied for use in the therapeutic setting, particularly in anxiety.<ref name=":5"/><ref name=":6"/><ref name="clinicalLSD">{{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}}</ref><ref>{{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?utm_term=6ab4fa802d5ac7404da3d7218f1d1f2a&utm_campaign=GuardianTodayUS&utm_source=esp&utm_medium=Email&CMP=GTUS_email |archive-date=June 11, 2021|url-status=live}}</ref>

===Other uses===
In the 1950s and 1960s, some psychiatrists (e.g. Oscar Janiger) explored the potential effect of LSD on creativity. Experimental studies attempted to measure the effect of LSD on creative activity and aesthetic appreciation.<ref name="PMID6054248"/><ref name="PMID18562421">{{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}}</ref><ref name="PMID2723891">{{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}}</ref><ref name="Stafford-Golightly">{{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}}</ref> 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.<ref>{{cite web |title=Scientific Problem Solving with Psychedelics – James Fadiman | website=[[Company:YouTube|YouTube]] |url=https://www.youtube.com/watch?v=KtL5fafpRKc |access-date=2023-05-02 |language=en}}</ref><ref>{{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}}</ref>

Since 2008 there has been ongoing research into using LSD to alleviate anxiety for [[Medicine:Terminal illness|terminally ill]] cancer patients coping with their impending deaths.<ref name=":5" /><ref name="new research"/><ref>{{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}}</ref>

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 [[Medicine:Confusion|confusion]] and agitation, nausea, [[Medicine:Vomiting|vomiting]], and acting in a bizarre fashion.<ref name="Lysergic acid diethylamide LSD fo"/>

LSD has been used as a treatment for [[Medicine:Cluster headache|cluster headache]]s with positive results in some small studies.<ref name=Pas2008/>

Recently, researchers discovered that LSD is a potent psychoplastogen, a compound capable of promoting rapid and sustained neural plasticity that may have wide-ranging therapeutic benefit.<ref name=Ly2018>{{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 |display-authors=4 |year=2018 |volume=23 |issue=11 |pages=3170–3182 |doi=10.1016/j.celrep.2018.05.022 |pmid=29898390 |pmc=6082376 }}</ref> LSD has been shown to increase markers of neuroplasticity in human brain [[Biology:Organoid|organoid]]s and improve memory performance in human subjects.<ref>{{Cite web |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 |website=PsyPost |language=en-US}}</ref>

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.<ref name=lsdpain>{{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}}</ref>

==Notable individuals==
Some notable individuals have commented publicly on their experiences with LSD.<ref>{{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}}</ref><ref>{{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}}</ref> 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."<ref>{{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. }}</ref> 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."<ref>{{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 }}</ref> He also said, "Nothing much happened but I did get the distinct impression that some birds were trying to communicate with me."<ref>{{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 }}</ref>
* Daniel Ellsberg, an American peace activist, says he has had several hundred experiences with psychedelics.<ref>{{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}}</ref>
* [[Biography:Richard Feynman|Richard Feynman]], a notable physicist at [[Organization:California Institute of Technology|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.<ref>{{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! }}</ref><ref>{{cite book | vauthors = Gleick J |title=Genius: The Life and Science of Richard Feynman |publisher=Pantheon Books |year=1992|isbn=978-0-679-40836-9 |oclc=243743850}}</ref>
* 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."<ref>{{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}}</ref>
* [[Biography:Bill Gates|Bill Gates]] implied in an interview with ''Playboy'' that he tried LSD during his youth.<ref>{{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}}</ref>
* [[Biography:Aldous Huxley|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&nbsp;µg of LSD. He died later that day.<ref name=OpenCulture>{{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}}</ref>
* [[Biography:Steve Jobs|Steve Jobs]], co-founder and former CEO of [[Company:Apple Inc.|Apple Inc.]], said, "Taking LSD was a profound experience, one of the most important things in my life."<ref>{{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}}</ref>
* Ernst Jünger, German writer and philosopher, throughout his life had experimented with drugs such as [[Chemistry:Diethyl ether|ether]], [[Biology:Cocaine|cocaine]], and [[Chemistry:Hashish|hashish]]; and later in life he used [[Biology:Mescaline|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.<ref>{{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}}</ref>
* 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.<ref name=Sheff/>{{rp|182}} Nonetheless, [[Biography:John Lennon|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.<ref>{{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=}}</ref> [[Biography:John Lennon|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."<ref name="weeklystandard">{{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}}</ref>
*[[Biography:Michel Foucault|Michel Foucault]] had an LSD experience with Simeon Wade in the [[Earth:Death Valley|Death Valley]] and later wrote "it was the greatest experience of his life, and that it profoundly changed his life and his work."<ref>{{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}}</ref><ref>{{Cite web |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".</ref> 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.<ref>{{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?"</ref>
* [[Biography:Kary Mullis|Kary Mullis]] is reported to credit LSD with helping him develop [[Biology:Polymerase chain reaction|DNA amplification]] technology, for which he received the Nobel Prize in Chemistry in 1993.<ref>{{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}}</ref>
* [[Biography:Carlo Rovelli|Carlo Rovelli]], an Italian [[Physics:Theoretical physics|theoretical physicist]] and writer, has credited his use of LSD with sparking his interest in theoretical physics.<ref>{{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}}</ref>
* 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''.<ref>{{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/}}</ref>
* Matt Stone and [[Biography:Trey Parker|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.<ref>{{cite web |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/}}</ref>

== See also ==
{{div col |colwidth=15em}}
* [[Chemistry:1P-LSD|1P-LSD]]
* [[Chemistry:1cP-LSD|1cP-LSD]]
* LSD art
* Owsley Stanley
* [[Chemistry:Psychedelic microdosing|Psychedelic microdosing]]
* [[Unsolved:Psychedelic therapy|Psychedelic therapy]]
* Psychoplastogen
* Urban legends about LSD
{{div col end}}

== Notes ==
{{notelist}}

== References ==
{{reflist|refs=
<ref name=Dol2015>{{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}}</ref>
<ref name=Muc2016>{{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}}</ref>
}}

== Further reading ==
{{refbegin}}
* {{cite web | vauthors = Bebergal P | url =  http://thephoenix.com/Boston/News/62230-Will-Harvard-drop-acid-again/ | title = Will Harvard drop acid again? Psychedelic research returns to Crimsonland | work = The Phoenix | location = Boston | date = 2 June 2008 | archive-url = https://web.archive.org/web/20080920154506/http://thephoenix.com/Boston/News/62230-Will-Harvard-drop-acid-again/ | archive-date = September 20, 2008 }}
* {{cite journal | vauthors = Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A | title = The pharmacology of lysergic acid diethylamide: a review | journal = CNS Neuroscience & Therapeutics | volume = 14 | issue = 4 | pages = 295–314 | year = 2008 | pmid = 19040555 | pmc = 6494066 | doi = 10.1111/j.1755-5949.2008.00059.x }}
* {{cite report | vauthors= Winstock AR, Timmerman C, Davies E, Maier LJ, Zhuparris A, Ferris JA, Barratt MJ, Kuypers K | display-authors = 4 | date = 2021 | url = https://www.globaldrugsurvey.com/wp-content/uploads/2021/03/GDS2020-Psychedelics-report.pdf | title = Global Drug Survey (GDS) 2020 Psychedelics Key Findings Report }}
{{refend}}

== External links ==
{{commons|LSD}}
* [http://www.emcdda.europa.eu/publications/drug-profiles/lsd Drug Profiles: LSD] European Monitoring Centre for Drugs and Drug Addiction
* [http://www.erowid.org/chemicals/lsd/lsd.shtml LSD-25] at [[Organization:Erowid|Erowid]]
* [https://psychonautwiki.org/wiki/LSD LSD] at PsychonautWiki
* [http://tihkal.info/read.php?domain=tk&id=26 LSD entry in TiHKAL • info] {{Webarchive|url=https://web.archive.org/web/20210828153345/https://isomerdesign.com/PiHKAL/read.php?domain=tk&id=26 |date=August 28, 2021 }}
* [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Lysergic+acid+diethylamide U.S. National Library of Medicine: Drug Information Portal – Lysergic acid diethylamide]

===Documentaries===
* [http://www.nfb.ca/film/hofmanns_potion ''Hofmann's Potion''] a documentary on the origins of LSD, 2002
* {{YouTube|hZdz0G4lG6k|Power & Control LSD in The Sixties}}, documentary film directed by Aron Ranen, 2006<!-- This video was uploaded to YouTube by the director -->
* [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]'' Netflix docuseries, 2022

{{Drug use}}
{{Hallucinogens}}
{{Navboxes
| title = [[Chemistry:Pharmacodynamics|Pharmacodynamics]]
| titlestyle = background:#ccccff
| list1 = 
{{Adrenergic receptor modulators}}
{{Dopamine receptor modulators}}
{{Serotonin receptor modulators}}
}}
{{Ergolines}}


{{DEFAULTSORT:Lysergic Acid Diethylamide}}
[[Category:Dopamine agonists]]
[[Category:Entheogens]]
[[Category:Light-sensitive chemicals]]
[[Category:Mind control]]
[[Category:Serotonin receptor agonists]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|LSD}}