LSD: Difference between revisions
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{{Short description|Hallucinogenic drug}} |
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{{otheruses}} |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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{{Redirect-distinguish|Lsd|£sd}} |
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{{other uses}} |
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{{Use mdy dates|date=May 2016}} |
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{{Infobox drug |
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| Watchedfields = changed |
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| verifiedrevid = 629704081 |
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| drug_name = Lysergic acid diethylamide |
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| INN = Lysergide |
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| type = |
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| IUPAC_name = (6a''R'',9''R'')-''N'',''N''-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-''fg'']quinoline-9-carboxamide |
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| image = LSD Structure V2.svg |
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| alt = |
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| caption = [[Skeletal formula]] of LSD |
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| caption2 = 3D stick model of LSD |
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| Drugs.com = [https://www.drugs.com/illicit/lsd.html Reference] |
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| pregnancy_US = C |
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| MedlinePlus = |
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| licence_EU = |
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| licence_US = |
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| pregnancy_AU = |
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| pregnancy_category = C |
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| tradename = Delysid |
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| legal_AU = Schedule 9 |
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| legal_BR = F2 |
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| legal_CA = Schedule III |
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| legal_NZ = Class A |
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| legal_UK = Class A |
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| legal_UN = P I |
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| legal_US = Schedule I |
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| legal_DE = Anlage I |
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| addiction_liability = None<ref name="NHM-MDMA"/> |
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| legal_status = [[Illicit drug]] |
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| 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> |
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| routes_of_administration = [[By mouth]], [[Sublingual administration|sublingual]] |
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| 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> |
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<!--Pharmacokinetic data-->| bioavailability = 71%<ref name=Dol2015 /> |
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'''<small>D</small>-Lysergic Acid Diethylamide''', commonly called '''acid''', '''LSD''', or '''LSD-25''', is a powerful [[semisynthetic]] drug that can function either as a [[Hallucinogenic drug|hallucinogen]] or a [[psychedelic]] [[entheogen]]. A typical dose of LSD is only 100 [[microgram]]s, a tiny amount roughly equal to [[Orders of magnitude (mass)|one-tenth the weight]] of a grain of sand. LSD causes a powerful intensification and alteration of senses, feelings, memories, and self-awareness for 6 to 12 hours. In addition, LSD usually produces visual effects such as moving geometric patterns, "trails" behind moving objects, and brilliant colors. LSD usually does not produce [[hallucination]]s in the strict sense, but instead [[illusion]]s and vivid [[daydream]]-like [[Fantasy (psychology)|fantasies]]. At higher concentrations it can cause [[Synaesthesia|synaesthesia]]. |
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| protein_bound = Unknown<ref name=Pas2008 /> |
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| metabolism = [[Liver]] ([[CYP450]])<ref name=Dol2015 /> |
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| metabolites = 2-Oxo-3-hydroxy-LSD<ref name=Dol2015 /> |
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| 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> |
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| 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> |
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| elimination_half-life = 3.6 hours<ref name=Dol2015/><ref name=Muc2016/> |
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| excretion = [[Kidneys]]<ref name=Dol2015 /><ref name=Muc2016 /> |
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<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|??}} |
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The immediate effects are sometimes followed by long-lasting or even permanent changes in a user's [[Psychology|psychology]], point of view, and personality. LSD is [[Chemical synthesis|synthesized]] from [[lysergic acid]] and is sensitive to [[oxygen]], [[ultraviolet]] light, and [[chlorine]], especially in [[solution]]. In pure form it is colorless, odorless, and bitter. LSD is typically delivered orally, usually on a substrate such as absorbent blotter paper, a sugarcube, or [[gelatin]]. In all these preparations, LSD is tasteless. |
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| CAS_number = 50-37-3 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 6605 |
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| PubChem = 5761 |
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| IUPHAR_ligand = 17 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB04829 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 5558 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 8NA5SWF92O |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = C07542 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 263881 |
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| ATC_prefix = None |
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| PDB_ligand = 7LD |
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| class = [[Serotonergic psychedelic]] ([[hallucinogen]]) |
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<!--Chemical data-->| C = 20 |
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| H = 25 |
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| N = 3 |
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| O = 1 |
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| smiles = CCN(CC)C(=O)[C@H]1CN([C@@H]2Cc3c[nH]c4c3c(ccc4)C2=C1)C |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| 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 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = VAYOSLLFUXYJDT-RDTXWAMCSA-N |
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| synonyms = LSD, LSD-25, LAD, acid, lucy, among others |
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| melting_point = 80 |
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| melting_high = 85 |
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| 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|access-date=April 12, 2023|archive-date=April 12, 2023|archive-url=https://web.archive.org/web/20230412075752/https://pubchem.ncbi.nlm.nih.gov/compound/5761#section=Solubility|url-status=live}}</ref> |
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}} |
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'''Lysergic acid diethylamide''', commonly known as '''LSD''' (from German {{lang|de|Lysergsäure-diethylamid}}), is a potent [[psychedelic drug]] that intensifies thoughts, emotions, and sensory perception.<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 |issn=0031-6997}}</ref> Often referred to as '''acid''' or '''lucy''', LSD can cause mystical, spiritual, or religious experiences.<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><ref>{{cite journal | vauthors = Griffiths RR, Hurwitz ES, Davis AK, Johnson MW, Jesse R | title = Survey of subjective "God encounter experiences": Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT | journal = PLOS ONE | volume = 14 | issue = 4 | pages = e0214377 | date = 2019-04-23 | pmid = 31013281 | pmc = 6478303 | doi = 10.1371/journal.pone.0214377 | doi-access = free | bibcode = 2019PLoSO..1414377G }}</ref> At higher doses, it primarily induces visual and auditory hallucinations.<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 |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 }}</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 |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> LSD is not considered addictive, because it does not produce compulsive drug-seeking behavior.<ref>{{Cite web |title=LSD Fast Facts |url=https://www.justice.gov/archive/ndic/pubs4/4260/index.htm |access-date=2024-12-29 |website=www.justice.gov}}</ref> Using LSD can lead to adverse psychological reactions, such as anxiety, 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> Additionally, it may trigger "flashbacks," also known as [[hallucinogen persisting perception disorder]] (HPPD), where individuals experience persistent visual distortions after use.<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> |
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The effects of LSD begin within 30 minutes of ingestion and can last up to 20 hours, with most trips averaging 8–12 hours.<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 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> It is synthesized from [[lysergic acid]] and commonly administered via tabs of blotter paper.<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> LSD is mainly used recreationally or for spiritual purposes.<ref name="EU2018" /><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> As a serotonin receptor [[agonist]], LSD's precise effects are not fully understood, but it is known to alter the brain’s [[default mode network]], leading to its powerful psychedelic effects.<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 |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> |
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Introduced by [[Sandoz]] as a drug with various psychiatric uses, LSD quickly became a [[Psychedelic psychotherapy|therapeutic agent]] that appeared to show great promise. However, the extra-medical use of the drug in western society in the middle years of the twentieth century led to a political firestorm which resulted in the [[Hallucinogenic drug#Legal status|banning of the substance]] for recreational as well as medical and spiritual uses. |
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The drug was first synthesized by Swiss chemist [[Albert Hofmann]] in 1938 and became widely studied in the 1950s and 1960s.<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> It was used experimentally in [[psychiatry]] for treating [[alcoholism]] and [[schizophrenia]].<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> However, its association with the [[counterculture movement]] of the 1960s led to its classification as a [[Controlled Substances Act#Schedule I controlled substances|Schedule I]] drug in the U.S. 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 also listed as a [[Schedule 1 controlled substance|Schedule I controlled substance]] by the [[United Nations]] in 1971 and remains without approved medical uses.<ref name="EU2018" /> |
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[[Image:LSD blotter paper.jpg|thumb|350px|right|LSD blotter paper]] |
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Despite its legal restrictions, LSD remains influential in scientific and cultural contexts. Its therapeutic potential has been explored, particularly in treating mental health disorders.<ref name="pmid26841800" /><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> As of 2017, about 10% of people in the U.S. had used LSD at some point, with 0.7% having used it in the past year.<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> Usage rates have risen, with a 56.4% increase in adult use in the U.S. 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> |
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==Origin== |
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{{TOC limit}} |
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==Uses== |
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"LSD" is an abbreviation of the [[German language|German]] chemical name of the compound, ''<b>L</b>yserg<b>s</b>äure-<b>d</b>iäthylamid''. It was first synthesized in [[1938]] by [[Swiss]] [[chemistry|chemist]] Dr. [[Albert Hofmann]] in [[Basel]] at the [[Sandoz Laboratories]] as part of a large research program dealing with [[Ergoline|ergot alkaloid]] derivatives as cure for head aches. Its psychedelic properties were unknown until Hofmann, acting on a hunch, returned to work on the chemical 5 years later. He attributed the discovery to absorption through the skin of a microscopic amount of the 25th batch (hence the precise name "LSD-25") due to accidental contact on [[April 16]], which led to him testing it on himself for [[Psychoactive|psychoactivity]] ([http://www.psychedelic-library.org/child1.htm full story]). |
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===Recreational=== |
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Until [[1966]], LSD and [[psilocybin]] were provided by [[Sandoz Laboratories]] free of charge to interested scientists. The use of these compounds by psychiatrists to gain a better subjective understanding of the [[schizophrenia|schizophrenic]] experience was an accepted practice. Many clinical trials were conducted on the potential use of LSD in [[psychedelic psychotherapy]], generally with very positive results. LSD first became popular [[recreational drug use|recreationally]] among a small group of mental health professionals such as [[psychiatrist]]s and [[psychologists]] during the [[1950s]], as well as by socially prominent and politically powerful individuals such as [[Henry Luce|Henry]] and [[Clare Boothe Luce]]. |
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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> |
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===Spiritual=== |
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[[Cold War]] [[era]] [[intelligence service]]s were keenly interested in the possibilities of using LSD for [[interrogation]] and [[mind control]] ''(see [[MKULTRA|MK-ULTRA]])'', and also for large-scale [[social engineering (political science)|social engineering]] ''(see [[counterculture]])''. The [[CIA]] conducted extensive research on LSD, which alledgedly was mostly destroyed. |
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LSD can catalyze intense spiritual experiences and is thus considered an [[entheogen]]. Some users have reported [[out of body]] experiences. In 1966, [[Timothy Leary]] established the [[League for Spiritual Discovery]] with LSD as its [[sacrament]].<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> [[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|sacred scriptures]] of the great religions of the world and the texts of ancient [[civilization]]s.<ref name="Grof1979">{{cite book| vauthors=Grof S, Grof JH| author-link1=Stanislav Grof| title=Realms of the Human Unconscious (Observations from LSD Research)| publisher=Souvenir Press (E & A) Ltd| year=1979| location=London| pages=13–14| url=http://www.csp.org/chrestomathy/realms_of3.html| isbn=978-0-285-64882-1| archive-url=https://web.archive.org/web/20071018164416/http://csp.org/chrestomathy/realms_of3.html| archive-date=October 18, 2007| access-date=November 18, 2007}}</ref> |
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===Medical=== |
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Several mental health professionals, notably [[Harvard]] psychology professors Drs. [[Timothy Leary]] and Richard Alpert (later known as [[Ram Dass]]), became convinced of LSD's potential as a tool for spiritual growth, but accused of possession of a less than scientific spirit they were dismissed from the traditional psychological community, and as such cut off from scientific aquisition of the drug. Dr. Leary was then (alledgedly unbeknownst to himself) approached by agents of the CIA, who supplied him with such quantity of purified LSD-25, that he and Dr. Alpert/Ram Dass with infective spiritual-psychological fervor was more than indirect cause for the drug being made available to a much wider portion of the public - and as countercultural [[spirituality|spiritual]] [[guru]]s making LSD a household brand among the [[hippie]]s of the [[1960s]]. The drug was banned in the [[United States]] in [[1967]], for scientific therapeutic research as well as individual research and recreation. Many other countries quickly followed suit. |
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{{See also|Lysergic acid diethylamide#Research}} |
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LSD currently has no approved uses in [[Clinical practice|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]] concluded that a single dose was shown to be effective at reducing alcohol consumption in people suffering from [[alcoholism]].<ref name="Lysergic acid diethylamide LSD fo"/> LSD has also been studied in [[Depression (mood)|depression]], [[anxiety]],<ref name=":5">{{Cite news |vauthors=Lustberg D |date=2022-10-14 |title=Acid for Anxiety: Fast and Lasting Anxiolytic Effects of LSD |url=https://psychedelicreview.com/acid-for-anxiety-fast-and-lasting-anxiolytic-effects-of-lsd/ |access-date=2022-12-01 |website=Psychedelic Science Review |language=en-US |archive-date=December 1, 2022 |archive-url=https://web.archive.org/web/20221201092629/https://psychedelicreview.com/acid-for-anxiety-fast-and-lasting-anxiolytic-effects-of-lsd/ |url-status=live }}</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 |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 |archive-date=November 7, 2022 |archive-url=https://web.archive.org/web/20221107004840/https://druglibrary.org/schaffer/lsd/grofhist.htm |url-status=live }}</ref> |
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==Effects== |
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Since 1967, underground recreational and therapeutic LSD use has continued in many countries, supported by a black market and popular demand for the drug. Legal, academic research experiments on the effects and mechanisms of LSD are also conducted on occasion, but rarely involve human subjects. |
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LSD is exceptionally potent, with as little as 20 μg capable of producing a noticeable effect.<ref name="EU2018" /> |
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===Physical=== |
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[[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 |doi-broken-date=November 19, 2024 }}</ref>]] |
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[[File:Mydriasis due to LSD usage.jpg|alt=Patient with Mydriasis due to usage of LSD|thumb|upright=1.35|left|Patient with [[mydriasis]] (pupil dilation) due to usage of LSD]] |
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LSD can induce physical effects such as [[Mydriasis|pupil dilation]], decreased [[appetite]], increased [[sweating]], and [[wakefulness]]. The physical reactions to LSD vary greatly and some may be a result of its psychological effects. Commonly observed symptoms include increased [[body temperature]], [[blood sugar]], and [[heart rate]], as well as [[goose bumps]], [[Bruxism|jaw clenching]], [[dry mouth]], and [[hyperreflexia]]. In cases of adverse reactions, users may experience [[numbness]], [[weakness]], [[nausea]], and [[Tremor|tremors]].<ref name="EU2018" /> |
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===Psychological=== |
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LSD is by weight one of the most potent drugs yet discovered. Both subjective reports and pharmacological methods such as [[receptor binding assay]]s determine LSD to be, per [[mole (unit)|mole]], around 100 times more potent than [[Psilocybin|psilocybin]] and [[Psilocin|psilocin]] and around 4000 times more potent than [[Mescaline|mescaline]]. Dosages of LSD are measured in [[microgram]]s (µg), or millionths of a [[gram]]. By comparison, dosages of almost all other drugs, both recreational and medical, are measured in [[milligram]]s, or thousandths of a gram. |
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The primary immediate psychological effects of LSD are [[visual hallucination|visual pseudo-hallucination]]s and altered thought, often referred to as "trips". These sensory alterations are considered pseudohallucinations because the subject does not perceive the patterns seen as being located in three-dimensional space outside the body.<ref>{{cite journal | vauthors = El-Mallakh RS, Walker KL | title = Hallucinations, psuedohallucinations, and parahallucinations | journal = Psychiatry | volume = 73 | issue = 1 | pages = 34–42 | date = 2010 | pmid = 20235616 | doi = 10.1521/psyc.2010.73.1.34 }}</ref> LSD is not considered addictive.<ref>{{Cite web |title=LSD Fast Facts |url=https://www.justice.gov/archive/ndic/pubs4/4260/index.htm |access-date=2024-12-29 |website=www.justice.gov}}</ref> 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 (drug culture)|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=[[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> |
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Negative experiences, commonly known as "[[bad trip]]s", can induce feelings of fear, agitation, anxiety, panic, and paranoia.<ref name="Pas2008"/><ref name="kopra_adverse">{{cite journal | vauthors = Kopra EI, Ferris JA, Rucker JJ, McClure B, Young AH, Copeland CS, Winstock AR | title = Adverse experiences resulting in emergency medical treatment seeking following the use of lysergic acid diethylamide (LSD) | journal = Journal of Psychopharmacology | volume = 36 | issue = 8 | pages = 956–964 | date = August 2022 | pmid = 35672900 | pmc = 9353972 | doi = 10.1177/02698811221099650 }}</ref> 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> |
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The dosage level that will produce a threshold hallucinogenic effect in humans is generally considered to be 25 micrograms, with the drug's effects becoming markedly more evident at higher dosages. In the late [[1990s]], LSD obtained during drug law enforcement operations in the [[United States]] has usually ranged between 20 and 80 micrograms per dose. During the [[1960s]], dosages were commonly 300 micrograms or more. |
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===Sensory=== |
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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 [[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> |
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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> |
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=== Physical === |
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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, and an intensified experience of music. 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 |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> Higher doses can lead to more intense sensory perception alterations, including synesthesia, perception of additional dimensions, and temporary [[Dissociation (psychology)|dissociation]]. |
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Physical reactions to LSD are highly variable and may include: [[uterus|uterine]] contractions, body [[temperature]] increase, elevated [[blood sugar]] levels, dry-mouth, [[goose bumps]], [[heart]]-rate increase, jaw clenching, [[nausea]], [[perspiration]], [[pupil]]-[[dilation]], [[saliva]]tion, [[mucus]] production, [[sleep]]lessness and [[tremor]]s. [[Cramps]] and [[muscle]] tension are also fairly commonly reported, but rather than being direct effects of LSD in the bloodstream, these symptoms are believed to be the result of awkward positions assumed by users experiencing fluctuations in their awareness of the passage of time and their own physical discomfort. |
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==Adverse effects== |
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LSD has been studied in the past as a painkiller for serious and chronic pain caused by cancer or other major trauma. Even at low (sub-psychedelic) dosages, it was found to be at least as effective as traditional opiates while being much longer lasting (pain reduction lasting as long as a week—''after'' peak effects had subsided). |
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[[File:HarmCausedByDrugsTable.svg|thumb|upright=1.35|Table from the 2010 ISCD study ranking various drugs (legal and illegal) based on statements by drug-harm experts. LSD was found to be the 18th most dangerous out of 20 considered.<ref name="Nutt_2010">{{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 = 1558–1565 | date = November 2010 | pmid = 21036393 | doi = 10.1016/S0140-6736(10)61462-6 | s2cid = 5667719 | citeseerx = 10.1.1.690.1283 }}</ref>]] |
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[[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>]] |
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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 (drug)|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> |
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=== Pharmacological === |
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===Psychological effects=== |
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LSD affects a huge number of receptors, including all dopamine receptor subtypes, all adrenoreceptor subtypes as well as many others. LSD binds to most serotonin receptor subtypes except for 5-HT<sub>3</sub> and 5-HT<sub>4</sub>. The hallucinogenic effects of LSD are attributed to its partial agonist effects at 5-HT<sub>2A</sub> receptors. Exactly how this produces hallucinations are unknown, but it is thought that it works by increasing excitation in cortical layers which facilitate the spread of information throughout the cortex. Through this, LSD causes parts of the brain which would not normally be activated by a given stimulus to become engaged. |
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====Mental disorders==== |
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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"/> |
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====Suggestibility==== |
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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}} |
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LSD's psychological effects ([[colloquially]] called a "trip") vary greatly from person to person, from one trip to another, and even as time passes during a single trip. Widely different effects emerge based on ''[[set and setting]]'' — the 'set' being the general mindset of the user, and the 'setting' being the physical and social environment in which the drug's effects are experienced. |
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====Flashbacks==== |
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An LSD trip can have long lasting or even permanent neutral, negative, and positive psychoemotional effects. LSD experiences can range from indescribably ecstatic to extraordinarily difficult; many difficult experiences (or "bad trips") result from a panicked user feeling that he or she has been permanently severed from [[reality]] and his or her [[ego]]. If the user is in a hostile or otherwise unsettling environment, or is not mentally prepared for the powerful distortions in perception and thought that the drug causes, effects are more likely to be unpleasant. |
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[[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-[[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 |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 [[hallucinogen persisting perception disorder]] (HPPD), where flashbacks occur intermittently or chronically, causing distress or functional impairment.<ref name="Halpern2018"/> |
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The etiology of flashbacks is varied. Some cases are attributed to [[somatic symptom disorder]], where individuals fixate on normal [[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 |access-date=June 9, 2023 |archive-date=June 9, 2023 |archive-url=https://web.archive.org/web/20230609015208/http://www.vwb-verlag.com/Katalog/m207.html |url-status=live }}</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> |
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Conversely, a pleasant, comfortable environment and a relaxed, balanced and open mindset will often result in a unique and extremely unusual experience. |
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Estimating the prevalence of HPPD is challenging. It is considered rare, with occurrences ranging from 1 in 20 users experiencing the transient and less severe type 1 HPPD, to 1 in 50,000 for the more concerning type 2 HPPD.<ref name="Halpern2018"/> Contrary to internet rumors, LSD is not stored long-term in the [[spinal cord]] or other body parts. Pharmacological evidence indicates LSD has a half-life of 175 minutes and is metabolized into water-soluble compounds like 2-oxo-3-hydroxy-LSD, eliminated through urine without evidence of long-term storage.<ref name="Pas2008"/> Clinical evidence also suggests that chronic use of [[SSRI]]s can potentiate LSD-induced flashbacks, even months after stopping LSD use.<ref name="drug-interaction">{{cite book |title=Psychedelics as Psychiatric Medications |publisher=[[Oxford University Press]] |isbn=9780192678522 |url=https://books.google.com/books?id=7lazEAAAQBAJ |date=7 March 2023 |vauthors=Nutt DJ, Castle D |chapter=Drug-interaction with psychotropic drugs |access-date=May 21, 2023 |archive-date=May 21, 2023 |archive-url=https://web.archive.org/web/20230521000115/https://books.google.com/books?id=7lazEAAAQBAJ |url-status=live }}</ref>{{rp|145}} |
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The sensory shifts caused by the drug can lead users to sit or lie in awkward positions for extended periods of time, resulting in muscle cramps and soreness that may mistakenly be attributed to the direct physical action of the drug. |
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===Drug interactions=== |
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Several psychedelics, including LSD, are metabolized by [[CYP2D6]]. Concurrent use of [[SSRIs]], potent inhibitors of CYP2D6, with LSD may heighten the risk of [[serotonin syndrome]].<ref name="drug-interaction"/>{{rp|145}} Chronic usage of SSRIs, [[Tricyclic antidepressant|TCA]]s, and [[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 [[antipsychotic]]s or [[anticonvulsant]]s are not well-documented; however, co-use with mood stabilizers like [[Lithium (medication)|lithium]] may induce [[seizure]]s and [[Dissociative disorder|dissociative effects]], particularly in individuals with [[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 |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" /> |
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Generally beginning within thirty to ninety minutes after ingestion and continuing for the following six to twelve hours, the user may experience anything from subtle changes in perception to overwhelming [[cognitive shift]]s and vivid [[illusion]]s |
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===Lethal dose=== |
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Sensory shifts include "high-level" sensory distortions such as warping of surfaces, appearance of moving geometrical patterns and textures on objects, blurred vision, image trailing, shape suggestibility, and color variations. Users often describe seeing new colors that they have not previously experienced, or colors may appear to have greater intensity. Perspective distortions may occur where items in the foreground appear to become part of the background, or the foreground and background may become temporarily indistinguishable. Changes in aural and visual perception are common, ranging from mild to overwhelming. |
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The lethal oral dose of LSD in humans is estimated at 100 mg, based on LD<sub>50</sub> and lethal blood concentrations observed in rodent studies.<ref name="pmid29408722" /> |
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===Tolerance=== |
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Higher doses often bring about shifts at a lower cognitive level - causing intense and fundamental distortions of sensory perception such as [[synaesthesia]], the experience of additional spatial or temporal dimensions, and temporary dissociation. |
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LSD shows significant [[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=[[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> Significant cross-tolerance occurs between LSD, [[mescaline]] and [[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 |archive-date=March 15, 2016 |archive-url=https://web.archive.org/web/20160315102433/https://www.erowid.org/references/refs_view.php?a=showdocpartframe&c=ref&docpartid=1843&id=1979 |url-status=live }}</ref> A slight cross-tolerance to [[DMT]] is observed in humans highly tolerant to LSD.<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> 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> [[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> |
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===Addiction and dependence liability=== |
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====Spiritual==== |
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LSD is widely considered to be non-addictive, despite its potential for [[Substance abuse|abuse]].<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 |access-date=June 12, 2023 |archive-date=August 28, 2023 |archive-url=https://web.archive.org/web/20230828020503/https://books.google.com/books?id=PjgfBQAAQBAJ |url-status=live }}</ref><ref name="pmid14761703"/><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><ref name="clinicalLSD"/> Attempts to train laboratory animals to [[Self-administration|self-administer]] LSD have been largely unsuccessful.<ref name="pmid14761703"/> Although tolerance to LSD builds up rapidly, a [[withdrawal syndrome]] does not appear, suggesting that a potential syndrome does not necessarily relate to the possibility of acquiring rapid tolerance to a substance.<ref>{{cite journal |vauthors=Balestrieri A, Fontanari D |date=September 1959 |doi=10.1001/archpsyc.1959.03590030063008 |pages=279–282 |pmid=13796178 |title=Acquired and crossed tolerance to mescaline, LSD-25, and BOL-148|journal=Archives of General Psychiatry | volume=1 |issue=3}}</ref> A report examining [[substance use disorder]] for [[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 [[depressant]]s.<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> |
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LSD is considered an [[entheogen]] because it often catalyzes intense spiritual experiences where users feel they have come into contact with a greater spiritual or cosmic order. It is common for users to believe that they have achieved insights into the way the mind works and some experience permanent or long-lasting changes in their life perspectives. Some users consider LSD a religious sacrament, or a powerful tool for access to the divine. Many books have been written comparing the LSD trip to the state of [[enlightenment (Buddhism)|enlightenment]] of [[eastern philosophy]]. |
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===Cancer and pregnancy=== |
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Such supposed mystical experiences under the influence of LSD have been observed and documented by researchers such as [[Timothy Leary]] and [[Stanislav Grof]]. |
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The [[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/> |
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==Overdose== |
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===Acute duration=== |
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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, and had gastric levels of 1000–7000 μg LSD tartrate per 100 mL and [[blood plasma]] levels up to 26 μg/ml, had suffered from [[Coma#Causes|comatose states]], vomiting, respiratory problems, [[hyperthermia]], and light [[gastrointestinal bleeding]]; however, all of them survived without residual effects upon hospital intervention.<ref name="Pas2008"/><ref>{{cite journal | vauthors = Klock JC, Boerner U, Becker CE | title = Coma, Hyperthermia and Bleeding Associated with Massive LSD Overdose: A Report of Eight Cases | journal = The Western Journal of Medicine | date = March 1974 | volume = 120 | issue = 3 | pages = 183–188 | pmid = 4816396 | pmc = 1129381}}</ref> |
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Individuals experiencing a bad trip after LSD intoxication may present with severe anxiety and tachycardia, often accompanied by phases of psychotic agitation and varying degrees of delusions.<ref name="pmid29408722" /> Cases of death on a bad trip have been reported due to [[hogtie#Human uses|prone maximal restraint]] (commonly known as a hogtie) and [[positional asphyxia]] when the individuals were restrained by [[law enforcement personnel]].<ref name="pmid29408722" /> |
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LSD's primary effects normally last from 6 to 12 hours. One characteristic feature of LSD is that with higher doses, the duration of the experience increases, but not the intensity. It is typical for users of LSD to be unable to sleep restfully until at least 12 hours have passed, and they do not feel completely "back to normal" until after getting one or two full nights of restful sleep, although they will exhibit no outward signs of impairment after the drug has worn off. |
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Massive doses are largely managed by [[symptomatic treatment]]s, and agitation can be addressed with [[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 [[Set and setting|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> [[Typical antipsychotic|Antipsychotics]] such as [[haloperidol]] are not recommended as they may have adverse [[Psychotomimetism|psychotomimetic effects]].<ref name="Medscape" /> Gastrointestinal decontamination with [[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 [[ergotism]].<ref name="Medscape" /> |
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LSD has an extremely short half life in the body. Most of the drug's already minuscule dose is eliminated before the trip is even over, suggesting that LSD triggers some sort of neurochemical cascade rather than acting directly to produce its effects. |
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===Designer drug overdose=== |
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Anecdotal reports indicate that administration of [[Thorazine]] or similar [[typical antipsychotic]] tranquilizers will not end an LSD trip, but rather will just immobilize the patient. |
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Many [[Designer drug|novel psychoactive substances]] of [[25-NB]] (NBOMe) series, such as [[25I-NBOMe]] and [[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 |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 compounds 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 |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"/> |
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NBOMe compounds are reported to have a bitter taste,<ref name="Lipow22"/> are not active orally,{{efn|The [[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 [[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 |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 |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 its 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"/> Testing with [[Ehrlich's reagent]] gives a positive result for LSD and a negative result for NBOMe compounds.<ref>{{Cite journal | vauthors = Díaz Moreno M, Alarcón Ayala N, Estrada Y, Morris V, Quintero J |date=November 2022 |title=Échele Cabeza as a harm reduction project and activist movement in Colombia |url=https://www.emerald.com/insight/content/doi/10.1108/DHS-07-2022-0026/full/html |journal=[[Drugs, Habits and Social Policy]] |language=en |volume=23 |issue=3 |pages=263–276 |doi=10.1108/DHS-07-2022-0026 |issn=2752-6739}}</ref><ref>{{cite journal | vauthors = Clancy L, Philp M, Shimmon R, Fu S | title = Development and validation of a color spot test method for the presumptive detection of 25-NBOMe compounds | journal = Drug Testing and Analysis | volume = 13 | issue = 5 | pages = 929–943 | date = May 2021 | pmid = 32744773 | doi = 10.1002/dta.2905 }}</ref> |
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=== Physical dangers === |
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==Pharmacology== |
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Although LSD is generally considered nontoxic, other dangers may arise from bad judgments made during the experience. As with many drugs, while under the influence of LSD the ability to make sensible judgments and understand common dangers can be impaired, making the user susceptible to personal injury. |
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===Pharmacodynamics=== |
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If an individual attempts to drive a car or operate machinery under the influence of the drug, that individual's absorption in inner experiences may lead to accidents and injury. |
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[[File:LSDaffinities.GIF|thumb|right|300px|[[Affinity (pharmacology)|Affinities]] (K<sub>i</sub>) of LSD for various [[receptor (biochemistry)|receptor]]s. The lower the value, the more strongly LSD binds to that receptor (i.e., with higher affinity). The horizontal line represents an approximate value for human plasma concentrations of LSD, and hence, affinities that are above the line are unlikely to be involved in LSD's effects. Values are averages the [[Ki Database|K<sub>i</sub> Database]].<ref name="PDSPKiDatabase" />]] |
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{| class="wikitable floatright" style="font-size:small;" |
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There is also some indication that LSD may trigger a [[fugue state|dissociative fugue]] state in individuals who are taking certain classes of [[antidepressants]] such as [[lithium salt]]s and [[Tricyclic antidepressant|tricyclics]]. In such a state, the user has an impulse to wander, and may not be aware of his or her actions, which can lead to physical injury. [[MAOI]]s and [[Selective serotonin reuptake inhibitor|SSRIs]] are believed to interact more benignly, tending to diminish LSD's subjective effects greatly. |
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|+ {{Nowrap|Activities of LSD}} |
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|- |
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! [[Biological target|Target]] !! [[Affinity (pharmacology)|Affinity]] (K<sub>i</sub>, nM) |
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|- |
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| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 0.64–7.3 |
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|- |
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| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || 3.9 |
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|- |
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| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 3.9–14 |
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|- |
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| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || 93 |
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|- |
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| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 0.48–21 (K<sub>i</sub>)<br />0.24–225 ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}})<br />23–84% ({{Abbrlink|E<sub>max</sub>|maximal efficacy}}) |
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|- |
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| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 0.98–30 (K<sub>i</sub>)<br />8.9–12,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />13–71% ({{Abbr|E<sub>max</sub>|maximal efficacy}}) |
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|- |
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| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 1.1–48 (K<sub>i</sub>)<br />0.85 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />26–79% ({{Abbr|E<sub>max</sub>|maximal efficacy}}) |
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|- |
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| [[5-HT3 receptor|5-HT<sub>3</sub>]] || >10,000 |
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|- |
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| [[5-HT4 receptor|5-HT<sub>4</sub>]] || 1,000 (rat) |
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|- |
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| [[5-HT5A receptor|5-HT<sub>5A</sub>]] || 9.0 |
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|- |
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| [[5-HT5B receptor|5-HT<sub>5B</sub>]] || 3.2 (rat) |
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|- |
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| [[5-HT6 receptor|5-HT<sub>6</sub>]] || 2.3–6.9 |
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|- |
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| [[5-HT7 receptor|5-HT<sub>7</sub>]] || 6.3–6.6 |
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|- |
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| [[Alpha-1A adrenergic receptor|α<sub>1A</sub>]] || 670–1,128 |
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|- |
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| [[Alpha-1B adrenergic receptor|α<sub>1B</sub>]] || 8,677 |
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|- |
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| [[Alpha-1D adrenergic receptor|α<sub>1D</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[Alpha-2A adrenergic receptor|α<sub>2A</sub>]] || 12–46 |
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|- |
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| [[Alpha-2B adrenergic receptor|α<sub>2B</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[Alpha-2C adrenergic receptor|α<sub>2C</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[Beta-1 adrenergic receptor|β<sub>1</sub>]] || 140–1,601 |
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|- |
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| [[Beta-2 adrenergic receptor|β<sub>2</sub>]] || 740–3,461 |
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|- |
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| [[Beta-3 adrenergic receptor|β<sub>3</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[D1 receptor|D<sub>1</sub>]] || 177–340 |
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|- |
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| [[D2 receptor|D<sub>2</sub>]] || 110–126 |
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|- |
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| [[D3 receptor|D<sub>3</sub>]] || 27 |
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|- |
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| [[D4 receptor|D<sub>4</sub>]] || 56–158 |
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|- |
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| [[D5 receptor|D<sub>5</sub>]] || 344 |
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|- |
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| [[H1 receptor|H<sub>1</sub>]] || 1,100–1,540 |
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|- |
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| [[H2 receptor|H<sub>2</sub>]]–[[H4 receptor|H<sub>4</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[Muscarinic acetylcholine M1 receptor|M<sub>1</sub>]]–[[Muscarinic acetylcholine M5 receptor|M<sub>5</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[I1 receptor|I<sub>1</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[Sigma-1 receptor|σ<sub>1</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[Sigma-2 receptor|σ<sub>2</sub>]] || {{Abbr|ND|No data}} |
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|- |
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| [[Trace amine-associated receptor 1|TAAR1]] || 450 (K<sub>i</sub>) (rat)<br />10,000 (K<sub>i</sub>) (mouse)<br />>20,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) (human) |
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|- |
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| {{Abbrlink|SERT|Serotonin transporter}} || >30,000 (K<sub>i</sub>)<br />>100,000 ({{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}}) |
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|- |
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| {{Abbrlink|NET|Norepinephrine transporter}} || 5,600–>30,000 (K<sub>i</sub>)<br />>100,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}}) |
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|- |
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| {{Abbrlink|DAT|Dopamine transporter}} || >30,000 (K<sub>i</sub>)<br />>100,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}}) |
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|- class="sortbottom" |
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| colspan="2" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise noted. '''Refs:''' <ref name="PDSPKiDatabase">{{cite web | title=PDSP Database | website=UNC | url=https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=lsd&kiAllRadio=all&doQuery=Submit+Query | language=zu | access-date=11 December 2024}}</ref><ref name="BindingDB">{{cite web | vauthors = Liu T | title=BindingDB BDBM21342 (4R,7R)-N,N-diethyl-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide::CHEMBL263881::LSD::LSD 25::LSD,(+)::LSD,l-::Lysergic Acid Diethylamide::Lysergic Acid Diethylamide Tartrate::US20240166618, Compound LSD::[3H]-LSD::d-Isolysergic acid amide | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=21342 | access-date=11 December 2024}}</ref><ref name="HolzeSinghLiechti2024">{{cite journal | vauthors = Holze F, Singh N, Liechti ME, D'Souza DC | title = Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile | journal = Biol Psychiatry Cogn Neurosci Neuroimaging | volume = 9 | issue = 5 | pages = 472–489 | date = May 2024 | pmid = 38301886 | doi = 10.1016/j.bpsc.2024.01.007 | url = | doi-access = free }}</ref><ref name="Ray2010">{{cite journal | vauthors = Ray TS | title = Psychedelics and the human receptorome | journal = PLOS ONE | volume = 5 | issue = 2 | pages = e9019 | date = February 2010 | pmid = 20126400 | pmc = 2814854 | doi = 10.1371/journal.pone.0009019 | doi-access = free | bibcode = 2010PLoSO...5.9019R | url = }}</ref><ref name="RickliLuethiReinisch2015">{{cite journal | vauthors = Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) | journal = Neuropharmacology | volume = 99 | issue = | pages = 546–553 | date = December 2015 | pmid = 26318099 | doi = 10.1016/j.neuropharm.2015.08.034 | url = http://edoc.unibas.ch/56163/1/20170921163006_59c3cceeb8e5d.pdf}}</ref><ref name="RickliMoningHoener2016">{{cite journal | vauthors = Rickli A, Moning OD, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens | journal = Eur Neuropsychopharmacol | volume = 26 | issue = 8 | pages = 1327–1337 | date = August 2016 | pmid = 27216487 | doi = 10.1016/j.euroneuro.2016.05.001 | url = http://edoc.unibas.ch/53326/1/20170117174852_587e4af45b658.pdf}}</ref><br /><ref name="LuethiTrachselHoener2018">{{cite journal | vauthors = Luethi D, Trachsel D, Hoener MC, Liechti ME | title = Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs) | journal = Neuropharmacology | volume = 134 | issue = Pt A | pages = 141–148 | date = May 2018 | pmid = 28720478 | doi = 10.1016/j.neuropharm.2017.07.012 | url = https://edoc.unibas.ch/57358/1/20170920150712_59c2680084ec5.pdf}}</ref><ref name="JanowskyEshlemanJohnson2014">{{cite journal | vauthors = Janowsky A, Eshleman AJ, Johnson RA, Wolfrum KM, Hinrichs DJ, Yang J, Zabriskie TM, Smilkstein MJ, Riscoe MK | title = Mefloquine and psychotomimetics share neurotransmitter receptor and transporter interactions in vitro | journal = Psychopharmacology (Berl) | volume = 231 | issue = 14 | pages = 2771–2783 | date = July 2014 | pmid = 24488404 | pmc = 4097020 | doi = 10.1007/s00213-014-3446-0 | url = }}</ref><ref name="Wsół2023">{{cite journal | vauthors = Wsół A | title = Cardiovascular safety of psychedelic medicine: current status and future directions | journal = Pharmacol Rep | volume = 75 | issue = 6 | pages = 1362–1380 | date = December 2023 | pmid = 37874530 | pmc = 10661823 | doi = 10.1007/s43440-023-00539-4 | url = }}</ref><ref name="EganGrindeDupre2000">{{cite journal | vauthors = Egan C, Grinde E, Dupre A, Roth BL, Hake M, Teitler M, Herrick-Davis K | title = Agonist high and low affinity state ratios predict drug intrinsic activity and a revised ternary complex mechanism at serotonin 5-HT(2A) and 5-HT(2C) receptors | journal = Synapse | volume = 35 | issue = 2 | pages = 144–150 | date = February 2000 | pmid = 10611640 | doi = 10.1002/(SICI)1098-2396(200002)35:2<144::AID-SYN7>3.0.CO;2-K | url = }}</ref><ref name="PorterBenwellLamb1999">{{cite journal | vauthors = Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ | title = Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells | journal = Br J Pharmacol | volume = 128 | issue = 1 | pages = 13–20 | date = September 1999 | pmid = 10498829 | pmc = 1571597 | doi = 10.1038/sj.bjp.0702751 | url = }}</ref><ref name="SimmlerBuchyChaboz2016">{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = }}</ref> |
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Most [[serotonergic psychedelic]]s are not significantly [[dopaminergic]], and LSD is therefore atypical in this regard. The agonism of the [[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> |
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=== Flashbacks === |
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LSD binds to most serotonin receptor subtypes except for the [[5-HT3 receptor|5-HT<sub>3</sub>]] and [[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 [[Molar concentration|nM]].<ref name="pmid14761703"/> In humans, recreational doses of LSD can affect [[5-HT1A receptor|5-HT<sub>1A</sub>]] (K<sub>i</sub> = 1.1 nM), [[5-HT2A receptor|5-HT<sub>2A</sub>]] (K<sub>i</sub> = 2.9 nM), [[5-HT2B receptor|5-HT<sub>2B</sub>]] (K<sub>i</sub> = 4.9 nM), [[5-HT2C receptor|5-HT<sub>2C</sub>]] (K<sub>i</sub> = 23 nM), [[5-HT5A receptor|5-HT<sub>5A</sub>]] (K<sub>i</sub> = 9 nM [in cloned rat tissues]), and [[5-HT6 receptor|5-HT<sub>6</sub> receptors]] (K<sub>i</sub> = 2.3 nM).<ref name="Aghajanian" /> Although not present in humans, [[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 [[Crosstalk (biology)|cross-activation]] of 5-HT<sub>2A</sub> [[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> [[agonist]]s are [[psychedelics]] and 5-HT<sub>2A</sub> [[Receptor antagonist|antagonists]] block the psychedelic activity of LSD. LSD exhibits [[functional selectivity]] at the 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors in that it activates the [[signal transduction]] enzyme [[phospholipase A2]] instead of activating the enzyme [[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 |title=Functional selectivity and classical concepts of quantitative pharmacology |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=320 |issue=1 |pages=1–13 |date=January 2007 |pmid=16803859 |doi=10.1124/jpet.106.104463 |url=https://jpet.aspetjournals.org/content/320/1/1 |s2cid=447937 |access-date=June 11, 2023 |archive-date=June 11, 2023 |archive-url=https://web.archive.org/web/20230611010342/https://jpet.aspetjournals.org/content/320/1/1 |url-status=live }}</ref> |
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There is also a commonly reported possibility of "flashbacks", a psychological phenomenon in which an individual experiences an episode of some of the subjective effects of LSD (this may be a positive or negative experience) long after the drug has been consumed and worn off -- sometimes weeks or months afterward. Flashbacks is an example of a [[Hallucinogen Persisting Perception Disorder]], a [[DSM-IV]] diagnosis. Several journal articles have described the disorder (see, for example, ''Adverse consequences of lysergic acid diethylamide'', H.D. Abraham and A. Aldridge, Addiction 1993, 88:1327-1334). Several studies have tried to determine how likely a "normal user" (that is a user not suffering from known psychiatric conditions) of LSD is to experience flashbacks. The larger studies include (''Flashback phenomena in basic trainees who enter the US Air Force'', Blumenfield, Military Medicine, 136, 39-41, 1971) and (''LSD Flashbacks and Ego Functioning'', Naditch, M & Fenwick, Journal of Abnormal Psychology, Vol. 86, No 4, 352-359, 1977), arriving at figures of 20% and 28%, respectively. |
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Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing [[Glutamate (neurotransmitter)|glutamate]] release in the [[cerebral cortex]]<ref name="pmid14761703"/> and therefore [[Excitatory postsynaptic potential|excitation]] in this area, specifically in [[Cortical layers|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 [[protomer]] recognition and [[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 | 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"/> |
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Debate continues over the nature and causes of flashbacks. Some say flashbacks are a manifestation of [[post-traumatic stress disorder]], not directly related to LSD's mechanism, and varying according to the susceptibility of the individual to the disorder. Many emotionally intense experiences can lead to flashbacks when a person is reminded acutely of the original experience. |
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LSD is a [[biased agonist]] that induces a conformation in serotonin receptors that preferentially recruits [[β-arrestin]] over [[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 [[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 | 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 [[Moiety (chemistry)|moiety]] is far less hallucinogenic in comparison.<ref name="WackerWang2017" /> |
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Several [[Drug urban legends|urban legends]] claim that flashbacks are the result of trace amounts of LSD or related chemicals being dislodged and released into the body after having been crystallized and stored in fat or spinal fluid cells. However, scientific research has disproven this conjecture; LSD (which is water soluble) is metabolized in the liver, as with many other drugs, and its metabolites are excreted normally in the [http://www.erowid.org/chemicals/lsd/lsd_myth1.shtml urine]. |
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LSD, like other psychedelics, has been found to increase the expression of genes related to synaptic plasticity.<ref>{{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 }}</ref> This is in part due to binding to brain-derived neurotrophic factor (BDNF) receptor TrkB.<ref>{{cite journal | vauthors = Moliner R, Girych M, Brunello CA, Kovaleva V, Biojone C, Enkavi G, Antenucci L, Kot EF, Goncharuk SA, Kaurinkoski K, Kuutti M, Fred SM, Elsilä LV, Sakson S, Cannarozzo C, Diniz CR, Seiffert N, Rubiolo A, Haapaniemi H, Meshi E, Nagaeva E, Öhman T, Róg T, Kankuri E, Vilar M, Varjosalo M, Korpi ER, Permi P, Mineev KS, Saarma M, Vattulainen I, Casarotto PC, Castrén E | title = Psychedelics promote plasticity by directly binding to BDNF receptor TrkB | journal = Nature Neuroscience | volume = 26 | issue = 6 | pages = 1032–1041 | date = June 2023 | pmid = 37280397 | doi = 10.1038/s41593-023-01316-5 | pmc = 10244169 }}</ref> |
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=== Psychoses === |
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====Mechanisms of action==== |
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There are numerous reported cases of LSD inducing or triggering a psychosis in people that were apparently healthy prior to taking LSD. In most cases, the psychosis is of short duration, but in other cases it may be chronic, possibly even permanent. While it is clear that LSD has some relation to psychosis, it is difficult to determine if LSD in itself induces psychosis or if it merely triggers latent conditions that would have manifested themselves sooner or later. Several studies have tried to estimate the prevalence of LSD-induced prolonged psychosis arriving at numbers of around 4 in 1000 individuals. |
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| caption1 = [[Resting state fMRI]] [[Blood-oxygen-level-dependent imaging|BOLD-contrast imaging]] shows increased [[primary visual cortex]] (V1) [[Cerebral circulation|cerebral blood flow]] (CBF) and increased V1 [[Resting state fMRI#Functional|resting state functional connectivity]] (RSFC), which correlated more strongly with the visual hallucinatory aspect of the LSD experience. Increased V1 RSFC also correlated with [[visual analogue scale]] (VAS) ratings of simple hallucinations and the magnitude of CBF observed in the visual cortex correlated positively with ratings of complex imagery on the LSD-induced [[altered state of consciousness]] (ASC).<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 |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> |
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| image2 = FMRI PH RSFC LSD.png |
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| caption2 = [[Resting state fMRI]] [[Blood-oxygen-level-dependent imaging|BOLD-contrast imaging]] shows decreased [[Parahippocampal gyrus|bilateral parahippocampal]] (PH) [[Resting state fMRI#Functional|resting state functional connectivity]] (RSFC), which correlated with the [[Ego death|ego-dissolution]] aspect of the LSD experience. A significant relationship was also found between decreased [[posterior cingulate cortex]] (PCC) [[Alpha wave|alpha power]] and [[default mode network]] (DMN) disintegration with ego-dissolution.<ref name="pmid27071089" /> |
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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 |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 [[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 [[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 |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 [[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 |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"/> |
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== Addiction potential == |
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===Pharmacokinetics=== |
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LSD is not considered addictive, in that its users do not exhibit the medical community's commonly accepted definitions of [[addiction]] and physical dependence. Rapid tolerance build-up prevents regular use, and there is cross-tolerance shown between LSD, [[mescaline]] and [[psilocybin]]. This tolerance diminishes after a few days' abstention from use. |
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The acute effects of LSD normally last between 6 and 10 hours depending on dosage, tolerance, and age.<ref name="tihkal">{{cite book |vauthors=Shulgin A, Shulgin A |author-link1=Alexander Shulgin |author-link2=Ann Shulgin |chapter-url=http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml |archive-date=15 October 2008 |archive-url=http://archive.wikiwix.com/cache/20081015082653/http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml |chapter=LSD |title=[[TiHKAL]] |location=Berkeley, CA |publisher=Transform Press |date=1997 |isbn=0-9630096-9-9}}</ref><ref>{{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 | date = 2008-11-11 | pmid = 19040555 | pmc = 6494066 | doi = 10.1111/j.1755-5949.2008.00059.x }}</ref> Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175 minutes (about 3 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 μg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1 hours, with a peak plasma concentration of 5 ng/mL at 3 hours post-dose.<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> |
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The [[pharmacokinetics]] of LSD were not properly determined until 2015, which is not surprising for a drug with the kind of low-μg potency that LSD possesses.<ref name=Dol2015 /><ref name=Muc2016 /> In a sample of 16 healthy subjects, a single mid-range 200 μg oral dose of LSD was found to produce mean [[Cmax (pharmacology)|maximal concentration]]s of 4.5 ng/mL at a median of 1.5 hours (range 0.5–4 hours) post-administration.<ref name=Dol2015 /><ref name=Muc2016 /> Concentrations of LSD decreased following [[first-order kinetics]] with a [[half-life]] of 3.6±0.9 hours and a [[terminal half-life]] of 8.9±5.9 hours.<ref name=Dol2015 /><ref name=Muc2016 /> |
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Many experts consider drugs such as LSD to be a sort of anti-drug (encourages users to stop using drugs), as it forces the user to face issues and problems in that individual's psyche. In contrast, the harder drugs ([[alcohol]], [[heroin]], and [[cocaine]]) are used to [[escapism|escape]] from reality. Studies in the 1950s in using LSD to treat alcoholism professed a 50% success rate. [[Alcoholics Anonymous]], on the other hand, has a success rate of 5% or less. |
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The effects of the dose of LSD given lasted for up to 12 hours and were closely correlated with the concentrations of LSD present in circulation over time, with no acute [[drug tolerance|tolerance]] observed.<ref name=Dol2015 /><ref name=Muc2016 /> Only 1% of the drug was eliminated in [[urine]] unchanged, whereas 13% was eliminated as the major [[metabolite]] 2-oxo-3-hydroxy-LSD (O-H-LSD) within 24 hours.<ref name=Dol2015 /><ref name=Muc2016 /> O-H-LSD is formed by [[cytochrome P450]] [[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 [[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 /> |
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== History == |
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==Chemistry== |
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LSD was first synthesized in 1938, recognized as a potent consciousness-altering agent in 1943, and distributed as a drug in the mid-forties. It is closely related to two plants traditionally used as [[entheogen|entheogens]], the ergot fungus, thought by some to have been used as the trigger for the mystical experiences reported by participants at the [[Eleusinian mysteries]] in [[Ancient Greece]], and [[Morning glory seeds]], used by [[Native Americans]] in [[Central America]] for divination and other spiritual purposes. |
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[[File:Lysergide stereoisomers structural formulae v.2.png|thumb|upright=1.35|The four possible stereoisomers of LSD. Only (+)-LSD is psychoactive.]] |
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LSD is a [[chirality (chemistry)|chiral]] compound with two [[stereocenter]]s at the [[carbon]] atoms C-5 and C-8, so that theoretically four different [[optical isomerism|optical isomers]] of LSD could exist. LSD, also called (+)-''d''-LSD,<ref>{{Cite book |title=Handbook of Medical Hallucinogens |date=2021 |publisher=Guilford Publications |isbn=9781462545452 |pages=160 |language=en |chapter=LSD |chapter-url=https://mcb.berkeley.edu/labs2/presti/sites/mcb.berkeley.edu.labs2.presti/files/u3/2021%20LSD%20Chapter%20Panik%20Presti.pdf |access-date=March 14, 2024 |archive-date=March 14, 2024 |archive-url=https://web.archive.org/web/20240314163910/https://mcb.berkeley.edu/labs2/presti/sites/mcb.berkeley.edu.labs2.presti/files/u3/2021%20LSD%20Chapter%20Panik%20Presti.pdf |url-status=live }}</ref> has the [[absolute configuration]] (5''R'',8''R''). 5''S'' stereoisomers of lysergamides do not exist in nature and are not formed during the synthesis from [[Descriptor (chemistry)#dl|''d'']]-lysergic acid. [[Retrosynthesis|Retrosynthetically]], the C-5 stereocenter could be analysed as having the same configuration of the alpha carbon of the naturally occurring amino acid L-[[tryptophan]], the precursor to all biosynthetic ergoline compounds. |
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Its medical uses ranged from facilitating [[psychotherapy]] to treating [[autism|autistic children]], [[alcoholism|alcoholics]], and [[depression|depressed people]]. It was also used for spiritual purposes in both formal and informal settings, and it eventually became widely used as a recreational substance. Due to its powerful and unpredictable effects, especially outside of controlled environments, it was blamed for mishaps, accidents, and irreversible mental damage which was claimed to have occurred as a result of its use. It also was seen as the driving force behind a social revolution that threatened mainstream values. As a result, powerful political forces joined to counter its effects, and it was banned in the [[United States]] in [[1967]] and in the rest of the world shortly thereafter. |
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However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of [[base (chemistry)|bases]], as the alpha proton is acidic and can be [[deprotonated]] and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated by [[chromatography]] and can be isomerized to LSD. |
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''See [[History of LSD]], and [[Entheogen]]'' |
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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]]. |
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==Chemistry== |
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===Synthesis=== |
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LSD is an [[ergoline]] derivative. It is commonly synthesized by reacting [[diethylamine]] with an activated form of [[lysergic acid]]. Activating reagents include [[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 reagent]]s.<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 [[hydrolysis]] of lysergamides like [[ergotamine]], a substance usually derived from the [[ergot]] [[fungus]] on [[agar plate]]; or, theoretically possible, but impractical and uncommon, from [[ergine]] (lysergic acid amide, LSA) extracted from [[morning glory]] seeds.<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 |title=The Total Synthesis of Lysergic Acid |journal=Journal of the American Chemical Society |volume=78 |issue=13 |pages=3087–3114 |year=1956 |doi=10.1021/ja01594a039|bibcode=1956JAChS..78.3087K }}</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> |
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<table border="1" cellpadding="2" cellspacing="0" align="right" style="margin-left:1em"> |
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====Research==== |
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<tr><th colspan="2" align=center bgcolor="#cccccc">'''LSD'''</th></tr> |
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The precursor for LSD, [[lysergic acid]], has been produced by [[GMO]] [[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 |archive-date=November 27, 2022 |archive-url=https://web.archive.org/web/20221127230250/https://www.sciencedaily.com/releases/2022/02/220210154135.htm |url-status=live }} '''Journal Reference:''' {{cite journal |vauthors=Wong G, Lim LR, Tan YQ, Go MK, Bell DJ, Freemont PS, Yew WS |title=Reconstituting the complete biosynthesis of D-lysergic acid in yeast |journal=Nature Communications |volume=13 |issue=1 |pages=712 |date=February 2022 |doi=10.1038/s41467-022-28386-6 |pmid=35132076 |pmc=8821704 |bibcode=2022NatCo..13..712W}}</ref> |
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===Dosage=== |
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<tr><td>[[IUPAC nomenclature|Chemical name]]</td><td align="center"><small>D</small>-Lysergic acid diethylamide<br>or:<br><small>(6a''R'',9''R'')-''N'',''N''-diethyl-7-methyl-<br>4,6,6a,7,8,9-hexahydroindolo<br>[4,3-''fg'']quinoline-9-carboxamide</small></td></tr> |
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[[File:10 strip.jpg|thumb|White on White blotters (WoW) for [[sublingual administration]]]] |
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A single dose of LSD is typically 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 [[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. |
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In the mid-1960s, the most important [[black market]] LSD manufacturer ([[Owsley Stanley]]) distributed LSD at a standard concentration of 270 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 μg. By the 1980s, the amount had reduced to between 100 and 125 μg, dropping more in the 1990s to the 20–80 μg range,<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> |
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<tr><td>[[Chemical formula]]</td><td>C<sub>20</sub>H<sub>25</sub>N<sub>3</sub>O</td></tr> |
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===Reactivity and degradation=== |
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<tr><td>[[Molecular mass]]</td><td>323.43 g/mol</td></tr> |
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"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" /> |
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LSD has two [[labile]] protons at the tertiary stereogenic C5 and C8 positions, rendering these centers prone to [[epimerisation]]. The C8 proton is more labile due to the electron-withdrawing [[carboxamide]] attachment, but the removal of the [[chiral]] proton at the C5 position (which was once also an alpha proton of the parent molecule [[tryptophan]]) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with the [[indole]] ring.{{Citation needed|date=May 2011}} |
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<tr><td>[[Melting point]]</td><td>80 - 85 °C</td></tr> |
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LSD also has [[enamine]]-type reactivity because of the electron-donating effects of the indole ring. Because of this, [[chlorine]] destroys LSD molecules on contact; even though chlorinated tap water contains only a slight amount of chlorine, the small quantity of compound typical to an LSD solution will likely be eliminated when dissolved in tap water.<ref name="tihkal" /> The [[covalent bond|double bond]] between the 8-position and the [[aromatic hydrocarbon|aromatic ring]], being conjugated with the indole ring, is susceptible to [[nucleophilic]] attacks by water or [[alcohol (chemistry)|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" /> |
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<tr><td>[[CAS registry number|CAS number]]</td><td>50-37-3</td></tr> |
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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> |
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<tr><td>[[Simplified molecular input line entry specification|SMILES]]</td><td><small>O=[C@@](N(CC)CC)[C@H]<br>1CN(C)[C@](C2=C1)([H])<br>CC3=CNC4=C3C2=CC=C4</small></td></tr> |
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The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. These studies demonstrated no significant loss in LSD concentration at 25 °C for up to four weeks. After four weeks of incubation, a 30% loss in LSD concentration at 37 °C and up to a 40% at 45 °C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. The stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. It was also demonstrated that trace amounts of metal ions in the buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of [[EDTA]]. |
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===Detection=== |
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<tr><td colspan="2" align="center">[[Image:Lsd-structure.png|The chemical structure of LSD]]</td></tr> |
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[[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>]] |
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LSD can be detected in concentrations larger than approximately 10% in a sample using [[Ehrlich's reagent]] and [[Hofmann's reagent]]. However, detecting LSD in human tissues is more challenging due to its active dosage being significantly lower (in [[micrograms]]) compared to most other drugs (in [[milligrams]]).<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> |
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</table> |
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LSD may be quantified in urine for drug testing programs, in plasma or serum to confirm poisoning in hospitalized victims, or in whole blood for forensic investigations. The parent drug and its major metabolite are unstable in biofluids when exposed to light, heat, or alkaline conditions, necessitating protection from light, low-temperature storage, and quick analysis to minimize losses.<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 μg and 200 μg, respectively, with a plasma half-life of approximately 2.6 hours (ranging from 2.2 to 3.4 hours among test subjects).<ref>{{cite journal | vauthors = Dolder PC, Schmid Y, Steuer AE, Kraemer T, Rentsch KM, Hammann F, Liechti ME | title = Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects | journal = Clinical Pharmacokinetics | volume = 56 | issue = 10 | pages = 1219–1230 | date = October 2017 | pmid = 28197931 | doi = 10.1007/s40262-017-0513-9 | pmc = 5591798 }}</ref> |
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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 |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 [[liquid chromatography–mass spectrometry]] methods can detect LSD in biological samples even after a single use.<ref name="pmid36753839"/> |
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LSD is an example of an [[ergoline]] derivative. It is commonly produced from [[Lysergic acid|lysergic acid]], which is made from the tartrate salt of [[ergotamine]], a substance derived from the [[ergot]] [[fungus]] on [[rye]], or from ergine (lysergic acid amide), a chemical found in [[morning glory]] seeds. Although theoretically possible, manufacture of LSD from morning glory seeds is not economically feasible and these seeds have never been found to be a successful starting material for LSD production. |
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==History== |
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[[Image:LSDLabGlassware.jpg|left|thumb|Glassware seized by the DEA from Pickard and Apperson's laboratory]] |
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{{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, [[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}} |
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{{Main|History of LSD}} |
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Only a small amount of ergotamine tartrate is required to produce LSD in large batches. For example, 25 kilograms of ergotamine tartrate can produce 5 or 6 kilograms of pure LSD crystal that, under ideal circumstances, could be processed into 100 million dosage units (at 50 micrograms per dose), more than enough to meet what is believed to be the entire annual U.S. demand for the drug. LSD manufacturers need only create a small quantity of the substance and, thus, enjoy the advantages of ease of concealment and transport not available to traffickers of other illegal drugs, primarily [[marijuana]] and [[cocaine]]. |
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Swiss chemist [[Albert Hofmann]] first synthesized LSD in 1938 from [[lysergic acid]], a chemical derived from the [[hydrolysis]] of [[ergotamine]], an [[alkaloid]] found in [[ergot]], a fungus that infects grain.<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 [[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 [[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" /> During this period, LSD was controversially administered to hospitalised schizophrenic autistic children, with varying degrees of therapeutic success.<ref>{{cite journal | vauthors = Freedman AM, Ebin EV, Wilson EA | title = Autistic schizophrenic children. An experiment in the use of d-lysergic acid diethylamide (LSD-25) | journal = Archives of General Psychiatry | volume = 6 | issue = 3 | pages = 203–213 | date = March 1962 | pmid = 13894863 | doi = 10.1001/archpsyc.1962.01710210019003 }}</ref><ref>{{cite journal | vauthors = Simmons JQ, Leiken SJ, Lovaas OI, Schaeffer B, Perloff B | title = Modification of autistic behavior with LSD-25 | journal = The American Journal of Psychiatry | volume = 122 | issue = 11 | pages = 1201–1211 | date = May 1966 | pmid = 5325567 | doi = 10.1176/ajp.122.11.1201 }}</ref><ref>{{cite journal | vauthors = Sigafoos J, Green VA, Edrisinha C, Lancioni GE | title = Flashback to the 1960s: LSD in the treatment of autism | journal = Developmental Neurorehabilitation | volume = 10 | issue = 1 | pages = 75–81 | date = 2007 | pmid = 17608329 | doi = 10.1080/13638490601106277 }}</ref><ref>{{cite journal | vauthors = Abramson HA | title = The use of LSD (d-lysergic acid diethylamide) in the therapy of children (a brief review) | journal = The Journal of Asthma Research | volume = 5 | issue = 2 | pages = 139–143 | date = December 1967 | pmid = 4865578 | doi = 10.3109/02770906709104325 }}</ref> |
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LSD-assisted [[psychotherapy]] was used in the 1950s and early 1960s by psychiatrists such as [[Humphry Osmond]], who pioneered the application of LSD to the treatment of [[alcoholism]], with promising results.<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 [[hallucinogen]]s, superseding the previously held "[[psychotomimetic]]" model in which LSD was believed to mimic [[schizophrenia]]. In contrast to schizophrenia, LSD can induce [[Transcendence (philosophy)#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 [[Project MKUltra]], which used [[psychoactive substances]] to aid [[interrogation]]. The CIA administered LSD to unwitting test subjects to observe how they would react, the most well-known example of this being [[Operation Midnight Climax]].<ref name="Lee1992" /> LSD was one of several psychoactive substances evaluated by the [[U.S. Army Chemical Corps]] as possible non-lethal incapacitants in the [[Edgewood Arsenal human experiments]].<ref name="Lee1992" /> |
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Manufacturing LSD is time consuming and dangerous. Relatively sophisticated and expensive laboratory equipment is required, and it takes from 2 to 3 days to produce 30 to 100 grams of pure compound. Some of the reactions necessary may cause significant explosions if not performed properly by a trained [[organic chemistry|organic chemist]]. It is believed that LSD usually is not produced in large quantities, but rather in a series of small batches. Production of LSD in small batches also minimizes the loss of precursor chemicals in case a synthetic step doesn't work as expected. |
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In the 1960s, LSD and other psychedelics were adopted by and became synonymous with, the [[counterculture movement]] due to their perceived ability to expand consciousness. This resulted in LSD being viewed as a cultural threat to American values and the [[Vietnam War|Vietnam war effort]], and it was designated as a [[List of Schedule I drugs (US)|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|Schedule I controlled substance]] by the [[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 by 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> |
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=== Forms of LSD === |
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LSD was first synthesized on November 16, 1938<ref>{{cite journal |vauthors=Hofmann A |author-link=Albert Hofmann| translator=Ott J |title=LSD Ganz Persönlich |trans-title=LSD: Completely Personal |date=Summer 1969 |url=http://www.maps.org/news-letters/v06n3/06346hof.html |journal=MAPS |volume=6 |issue=69 |language=de |archive-url=https://web.archive.org/web/20131206032629/http://www.maps.org/news-letters/v06n3/06346hof.html |archive-date=6 December 2013}}</ref> by Swiss chemist [[Albert Hofmann]] at the [[Sandoz]] Laboratories in [[Basel]], Switzerland as part of a large research program searching for medically useful [[ergot alkaloid]] derivatives. The abbreviation "LSD" is from the German "Lysergsäurediethylamid".<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> |
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LSD is produced in crystalline form and then mixed with excipients or diluted as a liquid for production in ingestible forms. Often, LSD is sold in tablet form (usually small tablets known as microdots), on sugar cubes, in thin squares of gelatin (commonly referred to as window panes), and most commonly, as blotter paper (sheets of paper soaked in or impregnated with LSD, covered with colorful designs or artwork, and perforated into small squares of individual dosage units). LSD is sold under more than 80 street names including acid, blotter, doses and trips, as well as names that reflect the designs on the sheets of blotter paper. On occasion, authorities have encountered the drug in other forms-- including powder or crystal, liquid, and capsule-- and laced on other substances. More than 200 types of LSD tablets have been encountered since [[1969]] and more than 350 paper designs have been acquired since [[1975]]. Designs range from simple five-point stars in black and white to exotic artwork in full four-color print. |
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[[Image:Albert Hofmann.jpg|thumb|[[Albert Hofmann]] in 2006]] |
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== Legal status == |
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LSD's [[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"/> |
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[[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]] |
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The [[United Nations]] [[Convention on Psychotropic Substances]] (adopted in [[1971]]) requires its parties to prohibit LSD. Hence, it is illegal in all parties to the convention, which includes the [[United States]] and most of [[Europe]]. However, enforcement of extant laws varies from country to country. |
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Beginning in the 1950s, the US [[Central Intelligence Agency]] (CIA) began a research program code-named [[Project MKUltra]]. The CIA introduced LSD to the United States, purchasing the entire world's supply for $240,000 and propagating the LSD through CIA [[front organizations]] to American hospitals, clinics, prisons, and research centers.<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 to study their reactions, usually without the subjects' knowledge. The project was revealed in the US congressional [[United States President's Commission on CIA activities within the United States|Rockefeller Commission report]] in 1975. |
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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" /> |
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LSD is easy to conceal and smuggle. A tiny vial can contain thousands of doses. Not much money is made from retail-level sales of LSD, so the drug is typically not associated with the violent [[organized crime|organized criminal]] organizations involved in [[cocaine]] and [[opiate]] smuggling. |
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Several figures, including [[Aldous Huxley]], [[Timothy Leary]], and [[Alfred Matthew Hubbard|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, [[Alan Watts]] and [[Arthur Koestler]],<ref>{{cite web |vauthors=Applebaum A |author-link=Anne Applebaum |url=http://www.huffingtonpost.com/2010/01/26/did-the-death-of-communis_n_435939.html |title=Did The Death Of Communism Take Koestler And Other Literary Figures With It? |work=[[The Huffington Post]] |date=26 January 2010 |archive-url=http://archive.wikiwix.com/cache/20110714161713/http://www.huffingtonpost.com/2010/01/26/did-the-death-of-communis_n_435939.html |archive-date=14 July 2011}}</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> |
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Unlike alcohol prohibition, LSD prohibition does not make an exception for religious use, presumably because nontraditional entheogen-centered religions are extremely uncommon and not generally accepted by modern societies. By contrast, the United States government permits some tribes of Southwestern [[American Indian]]s to cultivate and use hallucinogenic [[peyote]] cactus in traditional religious rituals. |
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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 [[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> |
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LSD was legal in the United States until [[1967]]. The US Federal Government classified it as a Schedule I drug according to the [[Controlled Substances Act]] of [[1970]]. As such, the [[Drug Enforcement Administration]] holds that LSD meets the following three criteria: it is deemed to have a high potential for abuse; it has no legitimate medical use in treatment; and there is a lack of accepted safety for its use under medical supervision. Lysergic acid and lysergic acid amide, LSD precursors, are both classified in Schedule III of the Controlled Substances Act. Ergotamine tartrate, a precursor to lysergic acid, is regulated under the [[Chemical Diversion and Trafficking Act]]. |
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In November 2020, Oregon became the first US state to decriminalize possession of small amounts of LSD after voters approved [[Oregon Ballot Measure 110|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> |
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==LSD in the United States== |
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==Society and culture== |
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Prior to [[1967]], LSD was available legally in the United States as a prescription [[psychiatric]] drug. LSD 'apostle' [[Alfred Matthew Hubbard|Al Hubbard]] actively promoted the drug between the 1950s and the 1970s and introduced thousands of people to it. |
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===Counterculture=== |
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By the mid-1960s, the youth [[counterculture]]s 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] : UNT Digital Library | vauthors = Gilliland J |year=1969 |author-link=John Gilliland |website=[[Pop Chronicles]] |publisher=Digital.library.unt.edu |format=audio |access-date=May 6, 2011 |url-status=live |archive-url=http://archive.wikiwix.com/cache/20110629170356/https://digital.library.unt.edu/ark:/67531/metadc19800/m1/ |archive-date=June 29, 2011}}</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> |
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In San Francisco's Haight-Ashbury neighborhood, the Psychedelic Shop was opened in January 1966 by brothers Ron and Jay Thelin to promote the safe use of LSD. This shop played a significant role in popularizing LSD in the area and establishing [[Haight-Ashbury]] as the epicenter of the hippie counterculture. The Thelins also organized the [[Love Pageant Rally]] in Golden Gate Park in October 1966, protesting against California's ban on LSD.<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> |
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LSD has been manufactured illegally since the 1960s. A limited number of chemists, probably less than a dozen, are believed to have manufactured nearly all of the illicit LSD available in the United States. The best known of these is undoubtedly [[Owsley Stanley|Augustus Owsley Stanley III]], usually known simply as Owsley. The former chemistry student set up a private LSD lab in the mid-Sixties in San Francisco and supplied the LSD consumed at the famous [[Acid Test]] parties held by [[Ken Kesey]] and his [[Merry Pranksters]], and other major events such as the [[Gathering of the Tribes]] in San Francisco in January 1967. He also had close social connections to leading San Francisco bands the [[Grateful Dead]], [[Jefferson Airplane]] and [[Big Brother and The Holding Company]], regularly supplied them with his LSD and also worked as their live sound engineer and made many tapes of these groups in concert. Owsley's LSD activities—immortalized by [[Steely Dan]] in their song "Kid Charlemagne"—ended with his arrest at the end of 1967, but some other manufacturers probably operated continuously for 30 years or more. |
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A similar movement developed in London, led by British academic [[Michael Hollingshead]], who first tried LSD in America in 1961. After experiencing LSD and interacting with notable figures such as [[Aldous Huxley]], [[Timothy Leary]], and [[Richard Alpert]], Hollingshead played a key role in the famous LSD research at Millbrook before moving to New York City for his experiments. In 1965, he returned to the UK and founded the World Psychedelic Center in Chelsea, London.<ref>{{cite book | vauthors = Conners P |title=White Hand Society - The Psychedelic Partnership of Timothy Leary and Allen Ginsberg |publisher=City Lights Books |year=2010 |isbn=9780872865358 |page=[https://archive.org/details/isbn_9780872865358/page/148 148] |url-access=registration |url=https://archive.org/details/isbn_9780872865358/page/148 }}</ref> |
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American LSD usage declined in the [[1970s]] and [[1980s]] — this is often attributed to a large anti-drug program targeted at young people in the U.S. LSD then experienced a mild resurgence in popularity in the [[1990s]]. Although there were many distribution channels during this decade, the U.S. [[Drug Enforcement Administration|DEA]] identified continued tours by the [[psychedelic rock]] band [[Grateful Dead|The Grateful Dead]] and the then-burgeoning [[rave]] scene as primary venues for LSD trafficking and consumption. American LSD usage fell sharply circa [[2000]]. The decline is attributed to the arrest of two chemists whom the DEA claims were manufacturing 95% of the LSD sold in America and much of the European supply. The arrests were a result of the largest LSD manufacturing raid in DEA history. |
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===Music and Art=== |
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[[Image:LSDMissileSilo.jpg|left|thumb|Pickard and Apperson ran an LSD lab in this former missile silo in Kansas.]] |
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[[File:Helix, v.2, no.6, Dec. 1, 1967 - DPLA - 85798bf5973acd2aa823cbc257dfae2a (page 1).jpg|thumb|Psychedelic art for the cover of an issue of underground [[Counterculture of the 1960s|counterculture]] newspaper ''[[Helix (newspaper)|Helix]]'', 1967]] |
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LSD manufacturers and traffickers can be separated into two groups. The first group was based in northern [[California]] and later identified by the DEA as run by chemists (referred to as ''cooks'') [[William Leonard Pickard]] and [[Clyde Apperson]]. Initial distribution points for this group's LSD were usually in the [[San Francisco]] area, or coordinated elsewhere through informal meetings at [[Grateful Dead]] concerts. These men worked in close association with trusted traffickers. The government claims that these two men were responsible for the vast majority of LSD sold illegally in the United States and a significant amount of the LSD sold in [[Europe]], and that black market LSD availability dropped by 95% after the two were arrested in [[2000]]. [http://washingtontimes.com/national/20031126-110958-8471r.htm] |
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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/> |
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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> |
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In [[November]] of [[2003]], Pickard and Apperson were sentenced to two life sentences and two 30 year sentences, respectively, after being convicted in Federal Court of running a large scale LSD manufacturing operation out of several clandestine laboratories, including a former [[missile silo]] near [[Wamego]], [[Kansas]]. |
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Psychedelic music of the 1960s often sought to replicate the LSD experience, incorporating exotic instrumentation, electric guitars with effects pedals, and elaborate studio techniques. Artists and bands utilized instruments like sitars and tablas, and employed studio effects such as backward tapes, panning, and phasing.<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 |author-link=David Sheff |title=All We Are Saying: The Last Major Interview with John Lennon and Yoko Ono |publisher=St. Martin's Press |location=New York |isbn=978-0-312-25464-3 |url=https://archive.org/details/allwearesayingla00lenn |url-access=registration}}</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> |
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The second group of cooks consists of small independent producers who, operating on a comparatively limited scale, can be found throughout the country. As a group, independent producers are of less concern to the [[Drug Enforcement Agency]] than the northern California group, as their production is intended for local consumption only. |
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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 |vauthors=Haring K |page=25 |access-date=December 5, 2023 |archive-date=October 2, 2023 |archive-url=https://web.archive.org/web/20231002134101/https://books.google.com/books?id=PElY27UXXkYC |url-status=live }}</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 |access-date=December 5, 2023 |archive-date=December 5, 2023 |archive-url=https://web.archive.org/web/20231205200458/https://www.vice.com/en/article/newv7g/why-drugs-genres-match-mdma-raves-shrooms-psychedelia-rap-lean |url-status=live }}</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 |access-date=December 5, 2023 |archive-date=September 30, 2023 |archive-url=https://web.archive.org/web/20230930095840/https://liveforlivemusic.com/features/phish-matisyahu-nyc/ |url-status=live }}</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 |archive-date=November 27, 2020 |archive-url=https://web.archive.org/web/20201127003729/https://www.bbc.com/culture/article/20181016-how-lsd-influenced-western-culture |url-status=live }}</ref> |
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==Notable people who have commented on their LSD experiences== |
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''Please add to this list.'' |
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===Legal status=== |
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* [[Paul Allen]] |
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The [[United Nations]] [[Convention on Psychotropic Substances]] of 1971 mandates that signing parties, including the United States, Australia, New Zealand, and most of Europe, prohibit LSD. Enforcement of these laws varies by country. The convention allows medical and scientific research with LSD.<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> |
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* Dr. Richard Alpert (now [[Ram Dass]]), in his book, ''Be Here Now'' |
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* [[Bill Bailey]] |
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* [[J. G. Ballard]] |
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* [[John Perry Barlow]] |
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* [[Syd Barrett]] |
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* [[William Burroughs]], article in ''Journal of Psychoactive Drugs'' |
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* [[John Coltrane]], attributed to the book, ''Chasin' the Trane: The music and mystique of John Coltrane'' |
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* [[Eric Clapton]] |
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* [[Kurt Cobain]] |
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* Dr. [[Sidney Cohen]], who introduced [[Henry Luce]] to LSD |
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* [[Stewart Copeland]] |
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* [[David Crosby]] |
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* [[Robert Crumb]], cartoonist |
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* [http://www.csp.org/chrestomathy/exploring_inner.html Adelle Davis] |
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* [[Philip K. Dick]], in the book ''[[VALIS]]'' |
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* [[Donovan]] |
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* [[Bob Dylan]] (in one of his videos there is a car that has a license-plate = "LSD 25") |
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* [[Dock Ellis]], professional baseball player who pitched a [[no-hitter]] while high on LSD |
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* [[Eminem]] |
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* Dr. [[Douglas Engelbart]], in [[John Markoff]]'s 2005 book, ''What the Dormouse Said'' |
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* [[Peter Fonda]] |
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* [[Michel Foucault]] |
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* [[Jerry Garcia]], numerous interviews. |
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* [[Bill Gates]], interview in the December 1994 ''[[Playboy]]'': [http://beginnersinvest.about.com/library/titans/nbillgatesinterview.htm] |
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* [[William Gibson (novelist)|William Gibson]] |
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* [[Allen Ginsberg]] |
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* [[Philip Glass]] |
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* Dr. [[Sidney Gottlieb]] |
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* [[Cary Grant]], in the September, [[1959]] ''[[Look Magazine]]'', relates how LSD treatment has brought him inner peace. |
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* [[Alex Grey]], in an interview with the ''[http://www.omplace.com/articles/SacredMirrors.html Online Noetic Network]'' and in numerous other interviews and personal writings |
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* [[Alyson Grey]], in many interviews and writings by herself and with her husband [[Alex Grey]] |
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* Dr. [[Stanislav Grof]] |
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* [[Larry Hagman]] in his autobiography, ''[[Hello Darlin']]'' |
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* [[George Harrison]], in his book ''I, Me, Mine'' and in the television/home video production ''[[The Beatles Anthology]]''. |
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* [[Anne Heche]], in her book ''Call Me Crazy'' |
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* [[Mitch Hedberg]], in his comedy act |
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* [[Jimi Hendrix]] |
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* [[Bill Hicks]], in his comedy albums ''Dangerous'' and ''Relentless,'' among others |
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* [[Alex Hixon]] |
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* [[Abbie Hoffman]] |
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* Dr. [[Albert Hofmann]] |
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* [[Aldous Huxley]] |
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* [[Phil Jackson]], in his [[1975]] book ''Maverick'' |
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* Dr. [[Oscar Janiger]] |
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* [[Steve Jobs]] of Apple Computer describes taking LSD as "one of the two or three most important things he has done in his life" in John Markoff's 2005 book, ''What the Dormouse Said''; also in an interview in ''[[Time Magazine]]'' |
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* Dan Joergensen |
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* [[Ernst Junger|Ernst Jünger]] |
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* [[Ken Kesey]] |
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* [[Lemmy Kilmister]] |
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* [[Peter Kuper]], cartoonist |
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* Dr. [[R. D. Laing]] |
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* Dr. [[Timothy Leary]] |
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* [[John Lennon]] |
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* Dr. [[John C. Lilly]] in his book ''Centre of the Cyclone'' and other works |
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* [[Clare Boothe Luce]] |
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* [[Henry Luce]] Founder of Time/Life [http://www.moralgroup.com/NewsItems/Drugs/p10.htm] |
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* [[William H. Macy]], in the July 2001 issue of ''[[Maxim (magazine)|Maxim]]'' |
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* [[Groucho Marx]] |
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* [[Paul McCartney]] |
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* [[Terence McKenna]], interviewed in ''Psychedelic Island Views'' |
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* [[Jim Morrison]] |
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* [[Kary Mullis]], in his essay collection ''Dancing Naked in the Mind Field''. |
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* [[Jack Nicholson]] |
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* [[Anais Nin]], in ''The Diary Of Anais Nin, Volume 5 (1947-1955)'' |
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* [[Frank Olson]] |
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* Dr. [[Humphry Osmond]] |
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* [[John Reynolds (actor)]] |
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* [[Keith Richards]], interviewed in ''[[Rolling Stone magazine|Rolling Stone]]'', October 17, 2002 |
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* [[John Robbins]], Founder of [[EarthSave]], interviewed in ''[[http://www.mavericksofthemind.com/rob-int.htm Mavericks of the Mind]]'' |
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* [[Tawl Ross]] |
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* [[Jean-Paul Sartre]] |
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* [[Michelle Phillips]] |
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* [[Edie Sedgwick]] |
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* [[Grace Slick]] |
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* Dr. [[Huston Smith]], interviewed in Nov/Dec 1997, ''[http://www.motherjones.com/news/qa/1997/11/snell.html MotherJones]'' |
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* [[Owsley Stanley]] |
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* [[Ringo Starr]] |
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* [[Howard Stern]] |
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* [[Oliver Stone]] |
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* [[Keith Thibodeaux]] |
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* [[Hunter S. Thompson]] |
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* [[Bob Wallace]] |
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* [[Alan Watts]] |
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* Dr. [[Andrew Weil]] |
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* [[Brian Wilson]] |
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* [[Robert Anton Wilson]] |
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* [[William Griffith Wilson]], in the Alcoholics Anonymous book, ''[http://www.amazon.com/exec/obidos/tg/detail/-/0916856127/qid=1094541923/sr=1-1/ref=sr_1_1/002-8543800-3240010?v=glance&s=books Pass It on]'' |
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* [[Steven Wright]], in his standup routine. |
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* [[Mark Vonnegut]], in ''The Eden Express'', Bantam Books, 1975 ISBN 0553027557 |
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* [[Adam Yauch]], of [[Beastie Boys]] |
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====Australia==== |
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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> |
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====Canada==== |
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According to [[James Gleick]]'s biography ''Genius,'' [[Richard Feynman]] experimented with LSD during his professorship at [[Caltech]]. Somewhat embarrassed by his actions, Feynman sidestepped the issue when dictating his anecdotes; consequently, the "Altered States" chapter in ''Surely You're Joking, Mr. Feynman!'' only describes [[marijuana]] and [[sensory deprivation]] experiences. |
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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> |
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====United Kingdom==== |
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==LSD-quotes== |
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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> |
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<!-- Please add to this list. --> |
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====United States==== |
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"One world before, many worlds after". (anon.) |
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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| archive-url=https://web.archive.org/web/20160409213251/https://www.law.cornell.edu/supct/html/94-9088.ZO.html| url-status=live}}, originating from U.S. v. Neal, 46 F.3d 1405 (7th Cir. 1995)</ref> |
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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> |
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"Focus on the spaces in between objects and you will find the answers" (L.Miller) |
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====Mexico==== |
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"The seed is as much the point as the flower." (Alan Watts) |
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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> |
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====Czech Republic==== |
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"LSD, 100 µg, i.m." ([[Aldous Huxley]]'s last words, as a written request to his wife from his deathbed) |
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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 |author-link=Supreme Court of the Czech Republic |date=25 February 2012 |title=6 Tdo 156/2010 [NS 7078/2010]}}</ref> |
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== |
===Economics=== |
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====Production==== |
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* [[ALD-52]] |
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[[File:LSDLabGlassware.jpg|thumb|Glassware seized by the DEA]] |
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* [[Hallucinogenic drug]] |
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* [[Psychedelic]] |
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* [[Entheogen]] |
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* [[Psychedelic psychotherapy]] |
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* [[Drug urban legends]] |
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* [[Project MKULTRA|MKULTRA]] - [[CIA]] experiments with LSD |
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* Dr. Richard Alpert (later known as [[Ram Dass]]) |
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* Dr. [[Stanislav Grof]] Czech researcher |
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* Dr. [[Albert Hofmann]] |
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* Dr. [[Timothy Leary]] |
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* Dr. [[John Lilly]] USA researcher |
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* Dr. [[Humphry Osmond]] |
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* [[Owsley Stanley]] Famous LSD chemist of the 1960's |
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* [[Psychedelic rock]] bands associated with LSD use: [[Grateful Dead]], [[Phish]], [[the Beatles]], [[the Doors]], [[Jimi Hendrix]], [[Jefferson Airplane]], [[Smashing Pumpkins]], [[Pink Floyd]] (especially their earlier works and [[Syd Barrett]]'s solo efforts) |
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* Related [[chemistry|chemical]] compounds: [[ergoline]]s, [[LSA]], [[psilocybin]], [[Dimethyltryptamine|DMT]], [[serotonin]] |
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* [[Raphael Labro]] LSD Expressionist |
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* [[Bogle-Chandler case]], deaths put down to LSD overdoses |
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An active dose of LSD is very minute, allowing a large number of doses to be synthesized from a comparatively small amount of raw material. Twenty-five kilograms of precursor [[ergotamine]] [[tartrate]] can produce 5–6 kg of pure crystalline LSD; this corresponds to around 50–60 million doses at 100 μg. Because the masses involved are so small, concealing and transporting illicit LSD is much easier than smuggling [[cocaine]], [[cannabis (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> |
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==External links== |
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Manufacturing LSD requires laboratory equipment and experience in the field of [[organic chemistry]]. It takes two to three days to produce 30 to 100 grams of pure compound. It is believed that LSD is not usually produced in large quantities, but rather in a series of small batches. This technique minimizes the loss of precursor chemicals in case a step does not work as expected.<ref name="DEA-pub"/> |
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===Media=== |
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* [http://www.wired.com/news/medtech/0,1286,65025,00.html Wired News: Long Trip for Psychedelics], September 27, 2004 |
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* [http://slate.msn.com/id/2098109 Who's Got the LSD? These Days, Almost Nobody] |
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* [http://www.bayarea.com/mld/mercurynews/news/local/states/california/peninsula/5539149.htm Northern Californian LSD makers found guilty] |
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* [http://www.dea.gov/pubs/states/newsrel/sanfran112403.html Pickard And Apperson Sentenced On LSD Charges] Official DEA press release on the "Largest LSD Lab Seizure In DEA History" |
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* [http://www.lysergicbook.com LYSERGIC] Book Written About Pickard Case |
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=== |
=====Forms===== |
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[[File:5 LSD blotters.png|thumb|Five doses of LSD, often called a "five strip"]] |
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* [http://www.maps.org/research/abrahart.html A Critical Review of Theories and Research Concerning LSD and Mental Health] |
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* [http://www.painmed.org/productpub/statements/pdfs/definition.pdf Definitions of Addiction, Physical Dependence, and Tolerance] |
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* [http://www.flashback.se/archive/my_problem_child/index.html LSD - My Problem Child] online, by LSD inventor Dr. [[Albert Hofmann]] |
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* [http://www.sci-con.org/editorials/20030603.html The Neurochemistry of Psychedelic Experience], ''[[Science & Consciousness Review]]'' |
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* Aldous, F. A. B., Barrass, B. C., Brewster, K., Buxton, D. A., Green, D. M., Finder, R. M., Rich, P., Skeels, M., and Tutt, K. J., [http://www.rhodium.ws/pdf/sar.psychotomimetic.phenylalkylamines.pdf "Structure-Activity Relationships in Psychotomimetic Phenylalkylamines,"] Journal of Medicinal Chemistry, Vol. 17, 1100-1111 (1974) |
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* [http://www.maps.org/research/ Current LSD Research] |
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* [http://www.maps.org/sys/w3pb.pl?face=simple Searchable LSD Bibliography] |
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LSD is produced in crystalline form and is then mixed with [[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{{clarification needed|date=September 2024}} forced a change to [[Tablet (pharmacy)|tablet]] form. Appearing in 1968 as an orange tablet measuring about 6 mm across, "Orange Sunshine" acid was the first largely available form of LSD after its possession was made illegal. [[Tim Scully]], a prominent chemist, made some of these tablets, but said that most "Sunshine" in the USA came by way of Ronald Stark, who imported approximately thirty-five million doses from Europe.<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> |
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===Urban legends=== |
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* [http://nepenthes.lycaeum.org/Tattoo/ Blue Star Tattoo myth] |
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* [http://www.erowid.org/chemicals/lsd/lsd_myth5.shtml Strychnine myth] |
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Over some time, tablet dimensions, weight, shape and concentration of LSD evolved from large (4.5–8.1 mm diameter), heavyweight (≥150 mg), round, high concentration (90–350 μg/tab) dosage units to small (2.0–3.5 mm diameter) lightweight (as low as 4.7 mg/tab), variously shaped, lower concentration (12–85 μg/tab, average range 30–40 μg/tab) dosage units. LSD tablet shapes have included cylinders, cones, stars, spacecraft, and heart shapes. The smallest tablets became known as "Microdots."<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> |
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===General=== |
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* [http://www.erowid.org/chemicals/lsd/lsd.shtml Erowid LSD Vault] |
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* [http://www.thegooddrugsguide.com/lsd/index.htm Good Drugs Guide] |
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* [http://www.cowboybooks.com.au/html/acidtrip1.html LSD Visual experiment] |
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* [http://www.spiritplants.com/ Spirit Plants] |
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* [http://leda.lycaeum.org/?ID=10 The Lycaeum Archive -> LSD] |
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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 [[gelatin]] square a quarter of an inch (6 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 in the Sky with Diamonds|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> |
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{{Hallucinogenic lysergamides}} |
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=====Modern distribution===== |
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<!-- en-US --> |
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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> |
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[[Category:Schedule I controlled substances]] |
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[[Category:Withdrawn drugs]] |
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[[Category:Incapacitating agents]] |
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[[Category:Lysergamides]] |
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As a group, independent producers are of less concern to the [[Drug Enforcement Administration]] than the large-scale groups because their product reaches only local markets.<ref name="LSD: The Drug"/> |
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[[als:LSD]] |
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[[bg:ЛСД]] |
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[[de:Lysergsäurediethylamid]] |
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[[eo:LSD]] |
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[[es:LSD]] |
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[[fr:LSD]] |
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[[ja:LSD]] |
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[[he:LSD]] |
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[[it:LSD]] |
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[[nl:LSD]] |
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[[pl:LSD]] |
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[[ru:ЛСД]] |
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[[fi:LSD]] |
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[[sl:LSD]] |
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[[sv:LSD]] |
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[[zh:LSD]] |
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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> |
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<!-- en-US --> |
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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> |
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====={{anchor|N-Bomb}} Mimics===== |
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[[File:Docpsychadelic.jpg|thumb|LSD blotter acid mimic actually containing DOC]] |
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[[File:Lysergic.JPG|thumb|Different blotters which could possibly be mimics]] |
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Since 2005, law enforcement in the United States and elsewhere has seized several chemicals and combinations of chemicals in blotter paper which were sold as LSD mimics, including [[2,5-dimethoxy-4-bromoamphetamine|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 [[2,5-Dimethoxy-4-chloroamphetamine|DOC]] and [[2,5-dimethoxy-4-iodoamphetamine|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> [[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 [[2,5-Dimethoxy-4-chloroamphetamine|DOC]] and [[2,5-dimethoxy-4-bromoamphetamine|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 [[chromatographic]] analysis of blotter paper containing [[2C-C]] which showed that the paper contained a much greater concentration of the active chemical than typical LSD doses, although the exact quantity was not determined.<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 [[2,5-Dimethoxy-4-chloroamphetamine|DOC]] seized by [[Concord, California]] police had dose markings approximately 6 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> |
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==Research== |
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In the United States, the earliest research began in the 1950s. [[Albert Kurland]] and his colleagues published research on LSD's therapeutic potential to treat schizophrenia. In Canada, [[Humphry Osmond]] and Abram Hoffer completed LSD studies as early as 1952.<ref>{{Cite journal | vauthors = Dyck E |date=1965 |title=Flashback: Psychiatric Experimentation with LSD in Historical Perspective. |journal=Canadian Journal of Psychiatry |volume=50 |issue=7}}</ref> By the 1960s, controversies surrounding "hippie" counterculture began to deplete institutional support for continued studies. |
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Currently, several organizations—including [[Beckley Foundation|the Beckley Foundation]], [[Multidisciplinary Association for Psychedelic Studies|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/> |
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In 2001 the [[United States Drug Enforcement Administration]] stated that LSD "produces no aphrodisiac effects, does not increase creativity, has no lasting positive effect in treating [[alcoholics]] or criminals, does not produce a "[[model psychosis]]", and does not generate immediate personality change."<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/><ref>{{Cite web | vauthors = Jarow O |date=2024-05-15 |title=Psychedelics could treat some of the worst chronic pain in the world |url=https://www.vox.com/future-perfect/2024/5/15/24156372/psychedelics-chronic-pain-cluster-headache-medicine-lsd-psilocybin |access-date=2024-05-25 |website=Vox |language=en-US |archive-date=May 25, 2024 |archive-url=https://web.archive.org/web/20240525084603/https://www.vox.com/future-perfect/2024/5/15/24156372/psychedelics-chronic-pain-cluster-headache-medicine-lsd-psilocybin |url-status=live }}</ref><ref>{{Cite web |title=RFA-AG-25-004: Safety and Early Efficacy Studies of Psychedelic-Assisted Therapy for Chronic Pain in Older Adults (UG3/UH3 Clinical Trial Required) |url=https://grants.nih.gov/grants/guide/rfa-files/RFA-AG-25-004.html |access-date=2024-05-25 |website=grants.nih.gov |archive-date=May 25, 2024 |archive-url=https://web.archive.org/web/20240525084606/https://grants.nih.gov/grants/guide/rfa-files/RFA-AG-25-004.html |url-status=live }}</ref> 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> |
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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> |
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===Psychedelic therapy=== |
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{{see also|Psychedelic therapy}} |
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In the 1950s and 1960s, LSD was used in psychiatry to enhance psychotherapy, known as [[psychedelic therapy]]. Some psychiatrists, such as [[Ronald A. Sandison]], who pioneered its use at [[Powick Hospital]] in England, believed LSD was especially useful at helping patients to "unblock" repressed subconscious material through other [[psychotherapeutic]] methods,<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=Q. J. Stud. Alcohol |volume=20 |pages=577–590 |vauthors=Chwelos N, Blewett DB, Smith CM, Hoffer A |date=1959 |issue=3 |doi=10.15288/qjsa.1959.20.577 |pmid=13810249 |url=http://www.erowid.org/references/texts/show/1852docid1733 |access-date=June 20, 2012 |archive-url=https://web.archive.org/web/20210224135151/https://www.erowid.org/references/texts/show/1852docid1733 |archive-date=February 24, 2021 |url-status=live}} Via {{cite web |title=Abstract |url=http://www.hofmann.org/papers/blewett_1.html |access-date=February 22, 2012 |url-status=live |archive-url=https://web.archive.org/web/20120203022019/http://www.hofmann.org/papers/blewett_1.html |archive-date=February 3, 2012 |website=Hofmann.org}}</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 [[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. |
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Two recent reviews concluded that conclusions drawn from most of these early trials are unreliable due to serious [[methodological]] flaws. These include the absence of adequate [[control groups]], lack of follow-up, and vague criteria for [[therapeutic]] outcome. In many cases, studies failed to convincingly demonstrate whether the drug or the therapeutic interaction was responsible for any beneficial effects.<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> |
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In recent years, organizations like the [[Multidisciplinary Association for Psychedelic Studies]] (MAPS) have renewed clinical research of LSD.<ref name="new research"/> |
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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|archive-date=June 11, 2021|url-status=live}}</ref> In 2024, the FDA designated a form of LSD as a breakthrough therapy to treat [[generalized anxiety disorder]] which is being developed by [[MindMed Inc.|MindMed]].<ref>{{Cite web | vauthors = Terry K |date=2024-03-26 |title=FDA Opens the Door to Clinical Use of LSD |url=https://www.webmd.com/mental-health/news/20240326/fda-opens-the-door-clinical-use-lsd |access-date=2024-05-25 |website=WebMD |language=en |archive-date=May 25, 2024 |archive-url=https://web.archive.org/web/20240525075810/https://www.webmd.com/mental-health/news/20240326/fda-opens-the-door-clinical-use-lsd |url-status=live }}</ref> |
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===Other uses=== |
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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=[[YouTube]] |date=May 29, 2013 |url=https://www.youtube.com/watch?v=KtL5fafpRKc |access-date=2023-05-02 |language=en |archive-date=September 8, 2019 |archive-url=https://web.archive.org/web/20190908090741/https://www.youtube.com/watch?v=KtL5fafpRKc |url-status=live }}</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> |
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Since 2008 there has been ongoing research into using LSD to alleviate anxiety for [[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> |
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A 2012 meta-analysis found evidence that a single dose of LSD in conjunction with various alcoholism treatment programs was associated with a decrease in alcohol abuse, lasting for several months, but no effect was seen at one year. Adverse events included seizure, moderate [[confusion]] and agitation, nausea, [[vomiting]], and acting in a bizarre fashion.<ref name="Lysergic acid diethylamide LSD fo"/> |
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LSD has been used as a treatment for [[cluster headache]]s with positive results in some small studies.<ref name=Pas2008/> |
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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 |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 [[organoid]]s and improve memory performance in human subjects.<ref>{{Cite news |vauthors=Dolan EW |date=2022-08-11 |title=Neuroscience research suggests LSD might enhance learning and memory by promoting brain plasticity |url=https://www.psypost.org/2022/08/neuroscience-research-suggests-lsd-might-enhance-learning-and-memory-by-promoting-brain-plasticity-63701 |access-date=2022-09-12 |newspaper=Psypost - Psychology News |language=en-US |archive-date=August 26, 2022 |archive-url=https://web.archive.org/web/20220826005449/https://www.psypost.org/2022/08/neuroscience-research-suggests-lsd-might-enhance-learning-and-memory-by-promoting-brain-plasticity-63701 |url-status=live }}</ref> |
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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> |
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==Notable individuals== |
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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. |
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* [[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> |
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* [[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> |
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* [[Richard Feynman]], a notable physicist at [[California Institute of Technology]], tried LSD during his professorship at Caltech. Feynman largely sidestepped the issue when dictating his anecdotes; he mentions it in passing in the "O Americano, Outra Vez" section.<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 |author-link=James Gleick |title=Genius: The Life and Science of Richard Feynman |publisher=[[Pantheon Books]] |year=1992|isbn=978-0-679-40836-9 |oclc=243743850}}</ref> |
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* [[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> |
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* [[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> |
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* [[Aldous Huxley]], author of ''[[Brave New World]]'', became a user of psychedelics after moving to [[Hollywood, Los Angeles|Hollywood]]. He was at the forefront of the counterculture's use of psychedelic drugs, which led to his 1954 work ''[[The Doors of Perception]]''. Dying from cancer, he asked his wife on 22 November 1963 to inject him with 100 μg of LSD. He died later that day.<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> |
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* [[Steve Jobs]], co-founder and former CEO of [[Apple Inc.]], said, "Taking LSD was a profound experience, one of the most important things in my life."<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> |
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* [[Ernst Jünger]], German writer and philosopher, throughout his life had experimented with [[Psychoactive drug|drugs]] such as [[diethyl ether|ether]], [[cocaine]], and [[hashish]]; and later in life he used [[mescaline]] and LSD. These experiments were recorded comprehensively in ''[[Annäherungen]]'' (1970, ''Approaches''). The novel ''[[Besuch auf Godenholm]]'' (1952, ''Visit to Godenholm'') is clearly influenced by his early experiments with mescaline and LSD. He met with LSD inventor [[Albert Hofmann]] and they took LSD together several times. Hofmann's memoir ''LSD, My Problem Child'' describes some of these meetings.<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> |
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* 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, [[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 Lennon|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= |archive-date=December 20, 2021 |archive-url=https://web.archive.org/web/20211220152957/https://www.snopes.com/fact-check/lucy-in-the-sky-with-diamonds/ |url-status=live }}</ref> [[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> |
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*[[Michel Foucault]] had an LSD experience with Simeon Wade in [[Death Valley]] and later wrote "it was the greatest experience of his life, and that it profoundly changed his life and his work."<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 news |url=https://lareviewofbooks.org/article/blowing-the-philosophers-fuses-michel-foucaults-lsd-trip-in-the-valley-of-death/|title=Blowing The Philosopher's Fuses: Michel Foucault's LSD Trip in The Valley of Death|vauthors=Penner J|website=Los Angeles Review of Books|date=June 17, 2019 |language=en-US|access-date=11 April 2021|archive-date=April 11, 2021|archive-url=https://web.archive.org/web/20210411165642/https://lareviewofbooks.org/article/blowing-the-philosophers-fuses-michel-foucaults-lsd-trip-in-the-valley-of-death/#_ftnref4|url-status=live}} Wade: "We fell silent to listen to Stockhausen's ''[[Gesang der Jünglinge|Songs of Youth]]''. Zabriskie Point was filled with the sound of a kindergarten playground overlaid with electric tonalities. ''Kontakte'' followed. [[Glissando]]s 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> |
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* [[Kary Mullis]] is reported to credit LSD with helping him develop [[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> |
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* [[Carlo Rovelli]], an Italian [[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> |
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* [[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 (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> |
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* [[Matt Stone]] and [[Trey Parker]], creators of the TV series ''[[South Park]]'', claimed to have shown up at the [[72nd Academy Awards]], at which they were nominated for Best Original Song, under the influence of LSD.<ref>{{cite web | vauthors = Bose SD |title=When Trey Parker and Matt Stone went to the Oscars on LSD Swapnil Dhruv Bose |date=December 27, 2021 |website=FarOutMagazine.co.uk |url=https://faroutmagazine.co.uk/when-trey-parker-and-matt-stone-went-to-the-oscars-on-lsd/ |access-date=January 20, 2022 |url-status=live |archive-date=January 20, 2022 |archive-url=https://web.archive.org/web/20220120001258/https://faroutmagazine.co.uk/when-trey-parker-and-matt-stone-went-to-the-oscars-on-lsd/}}</ref> |
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== See also == |
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{{portal|1960s}} |
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{{div col |colwidth=15em}} |
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* [[1P-LSD]] |
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* [[1cP-LSD]] |
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* ''[[Claviceps purpurea]]'' (ergot) |
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* [[LSD art]] |
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* [[LSZ]] |
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* [[Psychoplastogen]] |
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{{div col end}} |
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== Notes == |
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{{notelist}} |
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== References == |
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{{reflist|refs= |
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<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> |
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<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> |
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}} |
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== Further reading == |
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* {{cite book | title = LSD: My Problem Child | author = [[Albert Hofmann]] | url = https://books.google.com/books?id=e5wQAQAAIAAJ | year = 1980| publisher = McGraw-Hill | isbn = 978-0-07-029325-0 }} |
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== External links == |
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{{wikiquote|LSD}} |
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{{commons}} |
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* [http://www.erowid.org/chemicals/lsd/lsd.shtml LSD-25] {{Webarchive|url=https://web.archive.org/web/20081015023231/http://www.erowid.org/chemicals/lsd/lsd.shtml |date=October 15, 2008 }} at [[Erowid]] |
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* [https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml LSD] {{Webarchive|url=https://web.archive.org/web/20151118232537/https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml |date=November 18, 2015 }} at [[TiHKAL]] by [[Alexander Shulgin]] |
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* [https://psychonautwiki.org/wiki/LSD LSD] {{Webarchive|url=https://web.archive.org/web/20220831090729/https://psychonautwiki.org/wiki/LSD |date=August 31, 2022 }} at PsychonautWiki |
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===Documentaries=== |
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* [http://www.nfb.ca/film/hofmanns_potion ''Hofmann's Potion''] {{Webarchive|url=https://web.archive.org/web/20210616120006/http://www.nfb.ca/film/hofmanns_potion/ |date=June 16, 2021 }} a documentary on the origins of LSD, 2002 |
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* [https://web.archive.org/web/20091106130407/http://channel.nationalgeographic.com/series/explorer/4094/Overview ''Inside LSD''] National Geographic Channel, 2009 |
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* ''[https://www.netflix.com/de-en/title/80229847 How to Change Your Mind] {{Webarchive|url=https://web.archive.org/web/20220616180919/https://www.netflix.com/de-en/title/80229847 |date=June 16, 2022 }}'' Netflix docuseries, 2022 |
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Latest revision as of 16:09, 1 January 2025
Clinical data | |
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Pronunciation | /daɪ eθəl ˈæmaɪd/, /æmɪd/, or /eɪmaɪd/[1][2][3] |
Trade names | Delysid |
Other names | LSD, LSD-25, LAD, acid, lucy, among others |
AHFS/Drugs.com | Reference |
Pregnancy category |
|
Dependence liability | Low[4] |
Addiction liability | None[5] |
Routes of administration | By mouth, sublingual |
Drug class | Serotonergic psychedelic (hallucinogen) |
ATC code |
|
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Bioavailability | 71%[6] |
Protein binding | Unknown[7] |
Metabolism | Liver (CYP450)[6] |
Metabolites | 2-Oxo-3-hydroxy-LSD[6] |
Onset of action | 30–40 minutes[8] |
Elimination half-life | 3.6 hours[6][9] |
Duration of action | 8–20 hours[10] |
Excretion | Kidneys[6][9] |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
PDB ligand | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.000.031 |
Chemical and physical data | |
Formula | C20H25N3O |
Molar mass | 323.440 g·mol−1 |
3D model (JSmol) | |
Melting point | 80 to 85 °C (176 to 185 °F) |
Solubility in water | 67.02[11] mg/mL (20 °C) |
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(verify) |
Lysergic acid diethylamide, commonly known as LSD (from German Lysergsäure-diethylamid), is a potent psychedelic drug that intensifies thoughts, emotions, and sensory perception.[12] Often referred to as acid or lucy, LSD can cause mystical, spiritual, or religious experiences.[13][14] At higher doses, it primarily induces visual and auditory hallucinations.[15][16] LSD is not considered addictive, because it does not produce compulsive drug-seeking behavior.[17] Using LSD can lead to adverse psychological reactions, such as anxiety, paranoia, and delusions.[7] Additionally, it may trigger "flashbacks," also known as hallucinogen persisting perception disorder (HPPD), where individuals experience persistent visual distortions after use.[18][19]
The effects of LSD begin within 30 minutes of ingestion and can last up to 20 hours, with most trips averaging 8–12 hours.[20][21] It is synthesized from lysergic acid and commonly administered via tabs of blotter paper.[22] LSD is mainly used recreationally or for spiritual purposes.[20][23] As a serotonin receptor agonist, LSD's precise effects are not fully understood, but it is known to alter the brain’s default mode network, leading to its powerful psychedelic effects.[12][24][25]
The drug was first synthesized by Swiss chemist Albert Hofmann in 1938 and became widely studied in the 1950s and 1960s.[20][18] It was used experimentally in psychiatry for treating alcoholism and schizophrenia.[26] However, its association with the counterculture movement of the 1960s led to its classification as a Schedule I drug in the U.S. in 1968.[27] It was also listed as a Schedule I controlled substance by the United Nations in 1971 and remains without approved medical uses.[20]
Despite its legal restrictions, LSD remains influential in scientific and cultural contexts. Its therapeutic potential has been explored, particularly in treating mental health disorders.[12][28] As of 2017, about 10% of people in the U.S. had used LSD at some point, with 0.7% having used it in the past year.[29] Usage rates have risen, with a 56.4% increase in adult use in the U.S. from 2015 to 2018.[30]
Uses
[edit]Recreational
[edit]LSD is commonly used as a recreational drug.[31]
Spiritual
[edit]LSD can catalyze intense spiritual experiences and is thus considered an entheogen. Some users have reported out of body experiences. In 1966, Timothy Leary established the League for Spiritual Discovery with LSD as its sacrament.[32][33] Stanislav Grof has written that religious and mystical experiences observed during LSD sessions appear to be phenomenologically indistinguishable from similar descriptions in the sacred scriptures of the great religions of the world and the texts of ancient civilizations.[34]
Medical
[edit]LSD currently has no approved uses in medicine.[35][36] A meta analysis concluded that a single dose was shown to be effective at reducing alcohol consumption in people suffering from alcoholism.[37] LSD has also been studied in depression, anxiety,[38][39] and drug dependence, with positive preliminary results.[40][41]
Effects
[edit]LSD is exceptionally potent, with as little as 20 μg capable of producing a noticeable effect.[20]
Physical
[edit]LSD can induce physical effects such as pupil dilation, decreased appetite, increased sweating, and wakefulness. The physical reactions to LSD vary greatly and some may be a result of its psychological effects. Commonly observed symptoms include increased body temperature, blood sugar, and heart rate, as well as goose bumps, jaw clenching, dry mouth, and hyperreflexia. In cases of adverse reactions, users may experience numbness, weakness, nausea, and tremors.[20]
Psychological
[edit]The primary immediate psychological effects of LSD are visual pseudo-hallucinations and altered thought, often referred to as "trips". These sensory alterations are considered pseudohallucinations because the subject does not perceive the patterns seen as being located in three-dimensional space outside the body.[44] LSD is not considered addictive.[45] 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.[46] 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.[47][48]
Negative experiences, commonly known as "bad trips", can induce feelings of fear, agitation, anxiety, panic, and paranoia.[7][49] 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.[50][51]
Sensory
[edit]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 cognitive shifts. Alterations in auditory and visual perception are common.[52][53]
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.[52][54]
There are reports of inanimate objects appearing animated, with static objects seeming to move in additional spatial dimensions.[55] The auditory effects of LSD may include echo-like distortions of sounds, and an intensified experience of music. Basic visual effects often resemble phosphenes and can be influenced by concentration, thoughts, emotions, or music.[56] Higher doses can lead to more intense sensory perception alterations, including synesthesia, perception of additional dimensions, and temporary dissociation.
Adverse effects
[edit]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.[24][59] 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.[60]
Psychological effects
[edit]Mental disorders
[edit]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.[61][62] These hallucinogens can catalyze psychiatric disorders in predisposed individuals, although they do not tend to induce illness in emotionally healthy people.[24]
Suggestibility
[edit]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.[63][64][65][non-primary source needed]
Flashbacks
[edit]Flashbacks are psychological episodes where individuals re-experience some of LSD's subjective effects after the drug has worn off, persisting for days or months post-hallucinogen use.[66][67] These experiences are associated with hallucinogen persisting perception disorder (HPPD), where flashbacks occur intermittently or chronically, causing distress or functional impairment.[19]
The etiology of flashbacks is varied. Some cases are attributed to somatic symptom disorder, where individuals fixate on normal somatic experiences previously unnoticed prior to drug consumption.[68] Other instances are linked to associative reactions to contextual cues, similar to responses observed in individuals with past trauma or emotional experiences.[69] The risk factors for flashbacks remain unclear, but pre-existing psychopathologies may be significant contributors.[70]
Estimating the prevalence of HPPD is challenging. It is considered rare, with occurrences ranging from 1 in 20 users experiencing the transient and less severe type 1 HPPD, to 1 in 50,000 for the more concerning type 2 HPPD.[19] Contrary to internet rumors, LSD is not stored long-term in the spinal cord or other body parts. Pharmacological evidence indicates LSD has a half-life of 175 minutes and is metabolized into water-soluble compounds like 2-oxo-3-hydroxy-LSD, eliminated through urine without evidence of long-term storage.[7] Clinical evidence also suggests that chronic use of SSRIs can potentiate LSD-induced flashbacks, even months after stopping LSD use.[71]: 145
Drug interactions
[edit]Several psychedelics, including LSD, are metabolized by CYP2D6. Concurrent use of SSRIs, potent inhibitors of CYP2D6, with LSD may heighten the risk of serotonin syndrome.[71]: 145 Chronic usage of SSRIs, TCAs, and MAOIs is believed to diminish the subjective effects of psychedelics, likely due to SSRI-induced 5-HT2A receptor downregulation and MAOI-induced 5-HT2A receptor desensitization.[7][71]: 145 Interactions between psychedelics and antipsychotics or anticonvulsants are not well-documented; however, co-use with mood stabilizers like lithium may induce seizures and dissociative effects, particularly in individuals with bipolar disorder.[71]: 146 [72][73] Lithium notably intensifies LSD reactions, potentially leading to acute comatose states when combined.[7]
Lethal dose
[edit]The lethal oral dose of LSD in humans is estimated at 100 mg, based on LD50 and lethal blood concentrations observed in rodent studies.[59]
Tolerance
[edit]LSD shows significant tachyphylaxis, with tolerance developing 24 hours after administration. The progression of tolerance at intervals shorter than 24 hours remains largely unknown.[74] Tolerance typically resets to baseline after 3–4 days of abstinence.[75][76] Significant cross-tolerance occurs between LSD, mescaline and psilocybin.[77][78] A slight cross-tolerance to DMT is observed in humans highly tolerant to LSD.[79] Tolerance to LSD also builds up with consistent use,[80] and is believed to result from serotonin 5-HT2A receptor downregulation.[75] Researchers believe that tolerance returns to baseline after two weeks of not using psychedelics.[81]
Addiction and dependence liability
[edit]LSD is widely considered to be non-addictive, despite its potential for abuse.[5][24][82][83] Attempts to train laboratory animals to self-administer LSD have been largely unsuccessful.[24] Although tolerance to LSD builds up rapidly, a withdrawal syndrome does not appear, suggesting that a potential syndrome does not necessarily relate to the possibility of acquiring rapid tolerance to a substance.[84] A report examining substance use disorder for DSM-IV noted that almost no hallucinogens produced dependence, unlike psychoactive drugs of other classes such as stimulants and depressants.[85][86]
Cancer and pregnancy
[edit]The mutagenic potential of LSD is unclear. Overall, the evidence seems to point to limited or no effect at commonly used doses.[87] Studies showed no evidence of teratogenic or mutagenic effects.[7]
Overdose
[edit]There have been no documented fatal human overdoses from LSD,[7][88] although there has been no "comprehensive review since the 1950s" and "almost no legal clinical research since the 1970s".[7] Eight individuals who had accidentally consumed an exceedingly high amount of LSD, mistaking it for cocaine, and had gastric levels of 1000–7000 μg LSD tartrate per 100 mL and blood plasma levels up to 26 μg/ml, had suffered from comatose states, vomiting, respiratory problems, hyperthermia, and light gastrointestinal bleeding; however, all of them survived without residual effects upon hospital intervention.[7][89]
Individuals experiencing a bad trip after LSD intoxication may present with severe anxiety and tachycardia, often accompanied by phases of psychotic agitation and varying degrees of delusions.[59] Cases of death on a bad trip have been reported due to prone maximal restraint (commonly known as a hogtie) and positional asphyxia when the individuals were restrained by law enforcement personnel.[59]
Massive doses are largely managed by symptomatic treatments, and agitation can be addressed with benzodiazepines.[90][91] Reassurance in a calm, safe environment is beneficial.[92] Antipsychotics such as haloperidol are not recommended as they may have adverse psychotomimetic effects.[90] Gastrointestinal decontamination with activated charcoal is of little use due to the rapid absorption of LSD, unless done within 30–60 minutes of ingesting exceedingly huge amounts.[90] Administration of anticoagulants, vasodilators, and sympatholytics may be useful for treating ergotism.[90]
Designer drug overdose
[edit]Many novel psychoactive substances of 25-NB (NBOMe) series, such as 25I-NBOMe and 25B-NBOMe, are regularly sold as LSD in blotter papers.[93][94] NBOMe compounds are often associated with life-threatening toxicity and death.[93][95] Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,[96] and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".[88] Researchers state that the alleged physiological toxicity of LSD is likely due to psychoactive substances other than LSD.[59]
NBOMe compounds are reported to have a bitter taste,[88] are not active orally,[a] and are usually taken sublingually.[98] 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.[99][100][101] Despite its high potency, recreational doses of LSD have only produced low incidents of acute toxicity, but NBOMe compounds have extremely different safety profiles.[88][95] Testing with Ehrlich's reagent gives a positive result for LSD and a negative result for NBOMe compounds.[102][103]
Pharmacology
[edit]Pharmacodynamics
[edit]Target | Affinity (Ki, nM) |
---|---|
5-HT1A | 0.64–7.3 |
5-HT1B | 3.9 |
5-HT1D | 3.9–14 |
5-HT1E | 93 |
5-HT1F | ND |
5-HT2A | 0.48–21 (Ki) 0.24–225 (EC50 ) 23–84% (Emax ) |
5-HT2B | 0.98–30 (Ki) 8.9–12,000 (EC50) 13–71% (Emax) |
5-HT2C | 1.1–48 (Ki) 0.85 (EC50) 26–79% (Emax) |
5-HT3 | >10,000 |
5-HT4 | 1,000 (rat) |
5-HT5A | 9.0 |
5-HT5B | 3.2 (rat) |
5-HT6 | 2.3–6.9 |
5-HT7 | 6.3–6.6 |
α1A | 670–1,128 |
α1B | 8,677 |
α1D | ND |
α2A | 12–46 |
α2B | ND |
α2C | ND |
β1 | 140–1,601 |
β2 | 740–3,461 |
β3 | ND |
D1 | 177–340 |
D2 | 110–126 |
D3 | 27 |
D4 | 56–158 |
D5 | 344 |
H1 | 1,100–1,540 |
H2–H4 | ND |
M1–M5 | ND |
I1 | ND |
σ1 | ND |
σ2 | ND |
TAAR1 | 450 (Ki) (rat) 10,000 (Ki) (mouse) >20,000 (EC50) (human) |
SERT | >30,000 (Ki) >100,000 (IC50 ) |
NET | 5,600–>30,000 (Ki) >100,000 (IC50) |
DAT | >30,000 (Ki) >100,000 (IC50) |
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise noted. Refs: [104][105][106][107][108][109] [110][111][112][113][114][115] |
Most serotonergic psychedelics are not significantly dopaminergic, and LSD is therefore atypical in this regard. The agonism of the D2 receptor by LSD may contribute to its psychoactive effects in humans.[116]
LSD binds to most serotonin receptor subtypes except for the 5-HT3 and 5-HT4 receptors. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM.[24] In humans, recreational doses of LSD can affect 5-HT1A (Ki = 1.1 nM), 5-HT2A (Ki = 2.9 nM), 5-HT2B (Ki = 4.9 nM), 5-HT2C (Ki = 23 nM), 5-HT5A (Ki = 9 nM [in cloned rat tissues]), and 5-HT6 receptors (Ki = 2.3 nM).[117] Although not present in humans, 5-HT5B receptors found in rodents also have a high affinity for LSD.[118] The psychedelic effects of LSD are attributed to cross-activation of 5-HT2A receptor heteromers.[119] Many but not all 5-HT2A agonists are psychedelics and 5-HT2A antagonists block the psychedelic activity of LSD. LSD exhibits functional selectivity at the 5-HT2A and 5-HT2C receptors in that it activates the signal transduction enzyme phospholipase A2 instead of activating the enzyme phospholipase C as the endogenous ligand serotonin does.[120]
Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex[24] and therefore excitation in this area, specifically in layer V.[121] LSD, like many other drugs of recreational use, has been shown to activate DARPP-32-related pathways.[122] The drug enhances dopamine D2 receptor protomer recognition and signaling of D2–5-HT2A receptor complexes,[123] which may contribute to its psychotropic effects.[123] LSD has been shown to have low affinity for H1 receptors, displaying antihistamine effects.[124][125]
LSD is a biased agonist that induces a conformation in serotonin receptors that preferentially recruits β-arrestin over activating G proteins.[126] LSD also has an exceptionally long residence time when bound to serotonin receptors lasting hours, consistent with the long-lasting effects of LSD despite its relatively rapid clearance.[126] A crystal structure of 5-HT2B bound to LSD reveals an extracellular loop that forms a lid over the diethylamide end of the binding cavity which explains the slow rate of LSD unbinding from serotonin receptors.[127] The related lysergamide lysergic acid amide (LSA) that lacks the diethylamide moiety is far less hallucinogenic in comparison.[127]
LSD, like other psychedelics, has been found to increase the expression of genes related to synaptic plasticity.[128] This is in part due to binding to brain-derived neurotrophic factor (BDNF) receptor TrkB.[129]
Mechanisms of action
[edit]Neuroimaging studies using resting state fMRI recently suggested that LSD changes the cortical functional architecture.[131] These modifications spatially overlap with the distribution of serotoninergic receptors. In particular, increased connectivity and activity were observed in regions with high expression of 5-HT2A receptor, while a decrease in activity and connectivity was observed in cortical areas that are dense with 5-HT1A receptor.[132] Experimental data suggest that subcortical structures, particularly the thalamus, play a synergistic role with the cerebral cortex in mediating the psychedelic experience. LSD, through its binding to cortical 5-HT2A receptor, may enhance excitatory neurotransmission along frontostriatal projections and, consequently, reduce thalamic filtering of sensory stimuli towards the cortex.[133] This phenomenon appears to selectively involve ventral, intralaminar, and pulvinar nuclei.[133]
Pharmacokinetics
[edit]The acute effects of LSD normally last between 6 and 10 hours depending on dosage, tolerance, and age.[134][135] Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175 minutes (about 3 hours).[117] However, using more accurate techniques, Papac and Foltz (1990) reported that 1 μg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1 hours, with a peak plasma concentration of 5 ng/mL at 3 hours post-dose.[136]
The pharmacokinetics of LSD were not properly determined until 2015, which is not surprising for a drug with the kind of low-μg potency that LSD possesses.[6][9] In a sample of 16 healthy subjects, a single mid-range 200 μg oral dose of LSD was found to produce mean maximal concentrations of 4.5 ng/mL at a median of 1.5 hours (range 0.5–4 hours) post-administration.[6][9] Concentrations of LSD decreased following first-order kinetics with a half-life of 3.6±0.9 hours and a terminal half-life of 8.9±5.9 hours.[6][9]
The effects of the dose of LSD given lasted for up to 12 hours and were closely correlated with the concentrations of LSD present in circulation over time, with no acute tolerance observed.[6][9] Only 1% of the drug was eliminated in urine unchanged, whereas 13% was eliminated as the major metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) within 24 hours.[6][9] O-H-LSD is formed by cytochrome P450 enzymes, although the specific enzymes involved are unknown, and it does not appear to be known whether O-H-LSD is pharmacologically active or not.[6][9] The oral bioavailability of LSD was crudely estimated as approximately 71% using previous data on intravenous administration of LSD.[6][9] The sample was equally divided between male and female subjects and there were no significant sex differences observed in the pharmacokinetics of LSD.[6][9]
Chemistry
[edit]LSD is a chiral compound with two stereocenters at the carbon atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)-d-LSD,[137] has the absolute configuration (5R,8R). 5S stereoisomers of lysergamides do not exist in nature and are not formed during the synthesis from d-lysergic acid. Retrosynthetically, the C-5 stereocenter could be analysed as having the same configuration of the alpha carbon of the naturally occurring amino acid L-tryptophan, the precursor to all biosynthetic ergoline compounds.
However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of bases, as the alpha proton is acidic and can be deprotonated and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated by chromatography and can be isomerized to LSD.
Pure salts of LSD are triboluminescent, emitting small flashes of white light when shaken in the dark.[134] LSD is strongly fluorescent and will glow bluish-white under UV light.
Synthesis
[edit]LSD is an ergoline derivative. It is commonly synthesized by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride[138] and peptide coupling reagents.[125] Lysergic acid is made by alkaline hydrolysis of lysergamides like ergotamine, a substance usually derived from the ergot fungus on agar plate; or, theoretically possible, but impractical and uncommon, from ergine (lysergic acid amide, LSA) extracted from morning glory seeds.[139] Lysergic acid can also be produced synthetically, although these processes are not used in clandestine manufacture due to their low yields and high complexity.[140][141]
Research
[edit]The precursor for LSD, lysergic acid, has been produced by GMO baker's yeast.[142]
Dosage
[edit]A single dose of LSD is typically 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.[143][144] The practice of using sub-threshold doses is called microdosing.[145] Dosages of LSD are measured in micrograms (μg), or millionths of a gram.
In the mid-1960s, the most important black market LSD manufacturer (Owsley Stanley) distributed LSD at a standard concentration of 270 μg,[146] while street samples of the 1970s contained 30 to 300 μg. By the 1980s, the amount had reduced to between 100 and 125 μg, dropping more in the 1990s to the 20–80 μg range,[147] and even more in the 2000s (decade).[146][148]
Reactivity and degradation
[edit]"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."[134]
LSD has two labile protons at the tertiary stereogenic C5 and C8 positions, rendering these centers prone to epimerisation. The C8 proton is more labile due to the electron-withdrawing carboxamide attachment, but the removal of the chiral proton at the C5 position (which was once also an alpha proton of the parent molecule tryptophan) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with the indole ring.[citation needed]
LSD also has enamine-type reactivity because of the electron-donating effects of the indole ring. Because of this, chlorine destroys LSD molecules on contact; even though chlorinated tap water contains only a slight amount of chlorine, the small quantity of compound typical to an LSD solution will likely be eliminated when dissolved in tap water.[134] The double bond between the 8-position and the aromatic ring, being conjugated with the indole ring, is susceptible to nucleophilic attacks by water or alcohol, especially in the presence of UV or other kinds of light. LSD often converts to "lumi-LSD," which is inactive in human beings.[134]
A controlled study was undertaken to determine the stability of LSD in pooled urine samples.[149] The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. These studies demonstrated no significant loss in LSD concentration at 25 °C for up to four weeks. After four weeks of incubation, a 30% loss in LSD concentration at 37 °C and up to a 40% at 45 °C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. The stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. It was also demonstrated that trace amounts of metal ions in the buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of EDTA.
Detection
[edit]LSD can be detected in concentrations larger than approximately 10% in a sample using Ehrlich's reagent and Hofmann's reagent. However, detecting LSD in human tissues is more challenging due to its active dosage being significantly lower (in micrograms) compared to most other drugs (in milligrams).[151]
LSD may be quantified in urine for drug testing programs, in plasma or serum to confirm poisoning in hospitalized victims, or in whole blood for forensic investigations. The parent drug and its major metabolite are unstable in biofluids when exposed to light, heat, or alkaline conditions, necessitating protection from light, low-temperature storage, and quick analysis to minimize losses.[152] Maximum plasma concentrations are typically observed 1.4 to 1.5 hours after oral administration of 100 μg and 200 μg, respectively, with a plasma half-life of approximately 2.6 hours (ranging from 2.2 to 3.4 hours among test subjects).[153]
Due to its potency in microgram quantities, LSD is often not included in standard pre-employment urine or hair analyses.[151][154] However, advanced liquid chromatography–mass spectrometry methods can detect LSD in biological samples even after a single use.[154]
History
[edit]... affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away.
Swiss chemist Albert Hofmann first synthesized LSD in 1938 from lysergic acid, a chemical derived from the hydrolysis of ergotamine, an alkaloid found in ergot, a fungus that infects grain.[20][18] LSD was the 25th of various lysergamides Hofmann synthesized from lysergic acid while trying to develop a new analeptic, hence the alternate name LSD-25. Hofmann discovered its effects in humans in 1943, after unintentionally ingesting an unknown amount, possibly absorbing it through his skin.[156][157][158] LSD was subject to exceptional interest within the field of psychiatry in the 1950s and early 1960s, with Sandoz distributing LSD to researchers under the trademark name Delysid in an attempt to find a marketable use for it.[157] During this period, LSD was controversially administered to hospitalised schizophrenic autistic children, with varying degrees of therapeutic success.[159][160][161][162]
LSD-assisted psychotherapy was used in the 1950s and early 1960s by psychiatrists such as Humphry Osmond, who pioneered the application of LSD to the treatment of alcoholism, with promising results.[157][163][26][37] Osmond coined the term "psychedelic" (lit. mind manifesting) as a term for LSD and related hallucinogens, superseding the previously held "psychotomimetic" model in which LSD was believed to mimic schizophrenia. In contrast to schizophrenia, LSD can induce transcendent experiences, or mental states that transcend the experience of everyday consciousness, with lasting psychological benefit.[12][157] During this time, the Central Intelligence Agency (CIA) began using LSD in the research project Project MKUltra, which used psychoactive substances to aid interrogation. The CIA administered LSD to unwitting test subjects to observe how they would react, the most well-known example of this being Operation Midnight Climax.[157] LSD was one of several psychoactive substances evaluated by the U.S. Army Chemical Corps as possible non-lethal incapacitants in the Edgewood Arsenal human experiments.[157]
In the 1960s, LSD and other psychedelics were adopted by and became synonymous with, the counterculture movement due to their perceived ability to expand consciousness. This resulted in LSD being viewed as a cultural threat to American values and the Vietnam war effort, and it was designated as a Schedule I (illegal for medical as well as recreational use) substance in 1968.[164] It was listed as a Schedule I controlled substance by the United Nations in 1971 and currently has no approved medical uses.[20] As of 2017[update], about 10% of people in the United States have used LSD at some point in their lives, while 0.7% have used it in the last year.[29] It was most popular in the 1960s to 1980s.[20] The use of LSD among US adults increased by 56.4% from 2015 to 2018.[165]
LSD was first synthesized on November 16, 1938[166] by Swiss chemist Albert Hofmann at the Sandoz Laboratories in Basel, Switzerland as part of a large research program searching for medically useful ergot alkaloid derivatives. The abbreviation "LSD" is from the German "Lysergsäurediethylamid".[167]
LSD's psychedelic properties were discovered 5 years later when Hofmann himself accidentally ingested an unknown quantity of the chemical.[168] The first intentional ingestion of LSD occurred on April 19, 1943,[155] 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.[169] 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."[170] Sandoz would send the drug for free to researchers investigating its effects.[156]
Beginning in the 1950s, the US Central Intelligence Agency (CIA) began a research program code-named Project MKUltra. The CIA introduced LSD to the United States, purchasing the entire world's supply for $240,000 and propagating the LSD through CIA front organizations to American hospitals, clinics, prisons, and research centers.[171] Experiments included administering LSD to CIA employees, military personnel, doctors, other government agents, prostitutes, mentally ill patients, and members of the general public to study their reactions, usually without the subjects' knowledge. The project was revealed in the US congressional Rockefeller Commission report in 1975.
In 1963, the Sandoz patents on LSD expired[147] and the Czech company Spofa began to produce the substance.[156] Sandoz stopped the production and distribution in 1965.[156]
Several figures, including Aldous Huxley, Timothy Leary, and Al Hubbard, had begun to advocate the consumption of LSD. LSD became central to the counterculture of the 1960s.[172] In the early 1960s the use of LSD and other hallucinogens was advocated by new proponents of consciousness expansion such as Leary, Huxley, Alan Watts and Arthur Koestler,[173][174] and according to L. R. Veysey they profoundly influenced the thinking of the new generation of youth.[175]
On October 24, 1968, possession of LSD was made illegal in the United States.[176] The last FDA approved study of LSD in patients ended in 1980, while a study in healthy volunteers was made in the late 1980s. Legally approved and regulated psychiatric use of LSD continued in Switzerland until 1993.[177]
In November 2020, Oregon became the first US state to decriminalize possession of small amounts of LSD after voters approved Ballot Measure 110.[178]
Society and culture
[edit]Counterculture
[edit]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.[179] 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.[180][181] 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).[182]
In San Francisco's Haight-Ashbury neighborhood, the Psychedelic Shop was opened in January 1966 by brothers Ron and Jay Thelin to promote the safe use of LSD. This shop played a significant role in popularizing LSD in the area and establishing Haight-Ashbury as the epicenter of the hippie counterculture. The Thelins also organized the Love Pageant Rally in Golden Gate Park in October 1966, protesting against California's ban on LSD.[183][184]
A similar movement developed in London, led by British academic Michael Hollingshead, who first tried LSD in America in 1961. After experiencing LSD and interacting with notable figures such as Aldous Huxley, Timothy Leary, and Richard Alpert, Hollingshead played a key role in the famous LSD research at Millbrook before moving to New York City for his experiments. In 1965, he returned to the UK and founded the World Psychedelic Center in Chelsea, London.[185]
Music and Art
[edit]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.[186]
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.[187]
Psychedelic music of the 1960s often sought to replicate the LSD experience, incorporating exotic instrumentation, electric guitars with effects pedals, and elaborate studio techniques. Artists and bands utilized instruments like sitars and tablas, and employed studio effects such as backward tapes, panning, and phasing.[188][189] 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.[190][page needed][191]
Contemporary artists influenced by LSD include Keith Haring in the visual arts,[192] various electronic dance music creators,[193] and the jam band Phish.[194] The 2018 Leo Butler play All You Need is LSD is inspired by the author's interest in the history of LSD.[195]
Legal status
[edit]The United Nations Convention on Psychotropic Substances of 1971 mandates that signing parties, including the United States, Australia, New Zealand, and most of Europe, prohibit LSD. Enforcement of these laws varies by country. The convention allows medical and scientific research with LSD.[196]
Australia
[edit]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.[197] In Western Australia, the Misuse of Drugs Act 1981 provides guidelines for possession and trafficking of substances like LSD.[198]
Canada
[edit]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.[199]
United Kingdom
[edit]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.[200][201]
United States
[edit]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.[202]
Oregon decriminalized personal possession of small amounts of drugs, including LSD, in February 2021, and California has seen legislative efforts to decriminalize psychedelics.[203]
Mexico
[edit]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.[204]
Czech Republic
[edit]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.[205][206]
Economics
[edit]Production
[edit]An active dose of LSD is very minute, allowing a large number of doses to be synthesized from a comparatively small amount of raw material. Twenty-five kilograms of precursor ergotamine tartrate can produce 5–6 kg of pure crystalline LSD; this corresponds to around 50–60 million doses at 100 μg. Because the masses involved are so small, concealing and transporting illicit LSD is much easier than smuggling cocaine, cannabis, or other illegal drugs.[207]
Manufacturing LSD requires laboratory equipment and experience in the field of organic chemistry. It takes two to three days to produce 30 to 100 grams of pure compound. It is believed that LSD is not usually produced in large quantities, but rather in a series of small batches. This technique minimizes the loss of precursor chemicals in case a step does not work as expected.[207]
Forms
[edit]LSD is produced in crystalline form and is then mixed with excipients or redissolved for production in ingestible forms. Liquid solution is either distributed in small vials or, more commonly, sprayed onto or soaked into a distribution medium. Historically, LSD solutions were first sold on sugar cubes, but practical considerations[clarification needed] forced a change to tablet form. Appearing in 1968 as an orange tablet measuring about 6 mm across, "Orange Sunshine" acid was the first largely available form of LSD after its possession was made illegal. Tim Scully, a prominent chemist, made some of these tablets, but said that most "Sunshine" in the USA came by way of Ronald Stark, who imported approximately thirty-five million doses from Europe.[208]
Over some time, tablet dimensions, weight, shape and concentration of LSD evolved from large (4.5–8.1 mm diameter), heavyweight (≥150 mg), round, high concentration (90–350 μg/tab) dosage units to small (2.0–3.5 mm diameter) lightweight (as low as 4.7 mg/tab), variously shaped, lower concentration (12–85 μg/tab, average range 30–40 μg/tab) dosage units. LSD tablet shapes have included cylinders, cones, stars, spacecraft, and heart shapes. The smallest tablets became known as "Microdots."[209]
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.[208][209] More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975.[209] About the same time as blotter paper LSD came "Windowpane" (AKA "Clearlight"), which contained LSD inside a thin gelatin square a quarter of an inch (6 mm) across.[208] 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.[47][210] Authorities have encountered the drug in other forms—including powder or crystal, and capsule.[211]
Modern distribution
[edit]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.[212][213]
As a group, independent producers are of less concern to the Drug Enforcement Administration than the large-scale groups because their product reaches only local markets.[170]
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.[214]
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.[186]
Mimics
[edit]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,[215][216] a mixture of DOC and DOI,[217] 25I-NBOMe,[218] and a mixture of DOC and DOB.[219] Many mimics are toxic in comparatively small doses, or have extremely different safety profiles. Many street users of LSD are often under the impression that blotter paper which is actively hallucinogenic can only be LSD because that is the only chemical with low enough doses to fit on a small square of blotter paper. While it is true that LSD requires lower doses than most other hallucinogens, blotter paper is capable of absorbing a much larger amount of material. The DEA performed a chromatographic analysis of blotter paper containing 2C-C which showed that the paper contained a much greater concentration of the active chemical than typical LSD doses, although the exact quantity was not determined.[220] Blotter LSD mimics can have relatively small dose squares; a sample of blotter paper containing DOC seized by Concord, California police had dose markings approximately 6 mm apart.[221] Several deaths have been attributed to 25I-NBOMe.[222][223][224][225]
Research
[edit]In the United States, the earliest research began in the 1950s. Albert Kurland and his colleagues published research on LSD's therapeutic potential to treat schizophrenia. In Canada, Humphry Osmond and Abram Hoffer completed LSD studies as early as 1952.[226] By the 1960s, controversies surrounding "hippie" counterculture began to deplete institutional support for continued studies.
Currently, several organizations—including the Beckley Foundation, MAPS, Heffter Research Institute and the Albert Hofmann Foundation—exist to fund, encourage and coordinate research into the medicinal and spiritual uses of LSD and related psychedelics.[227] New clinical LSD experiments in humans started in 2009 for the first time in 35 years.[228] As it is illegal in many areas of the world, potential medical uses are difficult to study.[35]
In 2001 the United States Drug Enforcement Administration stated that LSD "produces no aphrodisiac effects, does not increase creativity, has no lasting positive effect in treating alcoholics or criminals, does not produce a "model psychosis", and does not generate immediate personality change."[170] More recently, experimental uses of LSD have included the treatment of alcoholism,[229] pain and cluster headache relief,[7][230][231] and prospective studies on depression.[232]
A 2020 meta-review indicated possible positive effects of LSD in reducing psychiatric symptoms, mainly in cases of alcoholism.[233] There is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits.[234][235]
Psychedelic therapy
[edit]In the 1950s and 1960s, LSD was used in psychiatry to enhance psychotherapy, known as psychedelic therapy. Some psychiatrists, such as Ronald A. Sandison, who pioneered its use at Powick Hospital in England, believed LSD was especially useful at helping patients to "unblock" repressed subconscious material through other psychotherapeutic methods,[236] and also for treating alcoholism.[237][238] One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender,"[26] presumably by forcing the user to face issues and problems in that individual's psyche.
Two recent reviews concluded that conclusions drawn from most of these early trials are unreliable due to serious methodological flaws. These include the absence of adequate control groups, lack of follow-up, and vague criteria for therapeutic outcome. In many cases, studies failed to convincingly demonstrate whether the drug or the therapeutic interaction was responsible for any beneficial effects.[239][240]
In recent years, organizations like the Multidisciplinary Association for Psychedelic Studies (MAPS) have renewed clinical research of LSD.[228]
It has been proposed that LSD be studied for use in the therapeutic setting, particularly in anxiety.[38][39][83][241] In 2024, the FDA designated a form of LSD as a breakthrough therapy to treat generalized anxiety disorder which is being developed by MindMed.[242]
Other uses
[edit]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.[48][243][244][245] 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.[246][247]
Since 2008 there has been ongoing research into using LSD to alleviate anxiety for terminally ill cancer patients coping with their impending deaths.[38][228][248]
A 2012 meta-analysis found evidence that a single dose of LSD in conjunction with various alcoholism treatment programs was associated with a decrease in alcohol abuse, lasting for several months, but no effect was seen at one year. Adverse events included seizure, moderate confusion and agitation, nausea, vomiting, and acting in a bizarre fashion.[37]
LSD has been used as a treatment for cluster headaches with positive results in some small studies.[7]
LSD is a potent psychoplastogen, a compound capable of promoting rapid and sustained neural plasticity that may have wide-ranging therapeutic benefit.[249] LSD has been shown to increase markers of neuroplasticity in human brain organoids and improve memory performance in human subjects.[250]
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.[251]
Notable individuals
[edit]Some notable individuals have commented publicly on their experiences with LSD.[252][253] 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."[254] 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."[255] He also said, "Nothing much happened but I did get the distinct impression that some birds were trying to communicate with me."[256]
- Daniel Ellsberg, an American peace activist, says he has had several hundred experiences with psychedelics.[257]
- Richard Feynman, a notable physicist at California Institute of Technology, tried LSD during his professorship at Caltech. Feynman largely sidestepped the issue when dictating his anecdotes; he mentions it in passing in the "O Americano, Outra Vez" section.[258][259]
- 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."[260]
- Bill Gates implied in an interview with Playboy that he tried LSD during his youth.[261]
- Aldous Huxley, author of Brave New World, became a user of psychedelics after moving to Hollywood. He was at the forefront of the counterculture's use of psychedelic drugs, which led to his 1954 work The Doors of Perception. Dying from cancer, he asked his wife on 22 November 1963 to inject him with 100 μg of LSD. He died later that day.[262]
- Steve Jobs, co-founder and former CEO of Apple Inc., said, "Taking LSD was a profound experience, one of the most important things in my life."[263]
- Ernst Jünger, German writer and philosopher, throughout his life had experimented with drugs such as ether, cocaine, and hashish; and later in life he used mescaline and LSD. These experiments were recorded comprehensively in Annäherungen (1970, Approaches). The novel Besuch auf Godenholm (1952, Visit to Godenholm) is clearly influenced by his early experiments with mescaline and LSD. He met with LSD inventor Albert Hofmann and they took LSD together several times. Hofmann's memoir LSD, My Problem Child describes some of these meetings.[264]
- 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.[190]: 182 Nonetheless, John Lennon consistently stated over the course of many years that the fact that the initials of "Lucy in the Sky with Diamonds" spelled out L-S-D was a coincidence (he stated that the title came from a picture drawn by his son Julian) and that the band members did not notice until after the song had been released, and Paul McCartney corroborated that story.[265] 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."[266]
- Michel Foucault had an LSD experience with Simeon Wade in Death Valley and later wrote "it was the greatest experience of his life, and that it profoundly changed his life and his work."[267][268] 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.[269]
- Kary Mullis is reported to credit LSD with helping him develop DNA amplification technology, for which he received the Nobel Prize in Chemistry in 1993.[270]
- Carlo Rovelli, an Italian theoretical physicist and writer, has credited his use of LSD with sparking his interest in theoretical physics.[271]
- 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.[272]
- Matt Stone and Trey Parker, creators of the TV series South Park, claimed to have shown up at the 72nd Academy Awards, at which they were nominated for Best Original Song, under the influence of LSD.[273]
See also
[edit]Notes
[edit]- ^ The potency of N-benzylphenethylamines via buccal, sublingual, or nasal absorption is 50–100 greater (by weight) than oral route compared to the parent 2C-x compounds.[97] 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.[97]
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Further reading
[edit]- Albert Hofmann (1980). LSD: My Problem Child. McGraw-Hill. ISBN 978-0-07-029325-0.
External links
[edit]- LSD-25 Archived October 15, 2008, at the Wayback Machine at Erowid
- LSD Archived November 18, 2015, at the Wayback Machine at TiHKAL by Alexander Shulgin
- LSD Archived August 31, 2022, at the Wayback Machine at PsychonautWiki
Documentaries
[edit]- Hofmann's Potion Archived June 16, 2021, at the Wayback Machine a documentary on the origins of LSD, 2002
- Inside LSD National Geographic Channel, 2009
- How to Change Your Mind Archived June 16, 2022, at the Wayback Machine Netflix docuseries, 2022
- Drugs not assigned an ATC code
- Lysergic acid diethylamide
- 1938 introductions
- 1938 in science
- 1938 in Switzerland
- Counterculture of the 1960s
- Dopamine agonists
- Drugs developed by Novartis
- Entheogens
- Experimental hallucinogens
- Incapacitating agents
- Light-sensitive chemicals
- Mind control
- Serotonin receptor agonists
- Swiss inventions
- Withdrawn drugs