Editing LSD (section)

==Adverse effects==
[[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>]]
[[File:Possible physical effects of lysergic acid diethylamide (LSD).svg|thumb|Possible physical effects of LSD]]
[[File:Rational harm assessment of drugs radar plot.svg|thumb|upright=1.35|Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in [[Delphi method|delphic analysis]] regarding 20 popular recreational drugs. LSD was ranked 14th in dependence, 15th in physical harm, and 13th in social harm.<ref>{{cite journal |vauthors=Nutt D, King LA, Saulsbury W, Blakemore C |title=Development of a rational scale to assess the harm of drugs of potential misuse |journal=Lancet |volume=369 |issue=9566 |pages=1047–53 |date=March 2007 |pmid=17382831 |doi=10.1016/s0140-6736(07)60464-4 |s2cid=5903121}}</ref>]]

LSD, a classical psychedelic, is deemed physiologically safe at standard dosages (50–200 μg) and its primary risks lie in psychological effects rather than physiological harm.<ref name="pmid14761703">{{cite journal |vauthors=Nichols DE |date=February 2004 |title=Hallucinogens |journal=Pharmacology & Therapeutics |volume=101 |issue=2 |pages=131–181 |doi=10.1016/j.pharmthera.2003.11.002 |issn=1879-016X |pmid=14761703}}</ref><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>

===Psychological effects===
====Mental disorders====
LSD can induce [[panic attacks]] or extreme anxiety, colloquially termed a "[[bad trip]]". Despite lower rates of depression and substance abuse found in psychedelic drug users compared to controls, LSD presents heightened risks for individuals with severe mental illnesses like [[schizophrenia]].<ref>{{cite journal |vauthors=Krebs TS, Johansen PØ |title=Psychedelics and mental health: a population study |journal=PLOS ONE |volume=8 |issue=8 |pages=e63972 |date=2013-08-19 |pmid=23976938 |pmc=3747247 |doi=10.1371/journal.pone.0063972 |bibcode=2013PLoSO...863972K |veditors=Lu L |doi-access=free}}</ref><ref name="Murray">{{citation |title=What can we learn about schizophrenia from studying the human model, drug-induced psychosis?|vauthors=Murray RM, Paparelli A, Morrison PD, Marconi A, Di Forti M |journal=American Journal of Medical Genetics Part B |volume=162 |issue=7 |series=Special Issue: Identifying the Origins of Mental Illness: A Festschrift in Honor of Ming T. Tsuang |pages=661–670 |date=October 2013 |pmid=24132898 |s2cid=205326399 |doi=10.1002/ajmg.b.32177 |doi-access=free}}</ref> These hallucinogens can catalyze psychiatric disorders in predisposed individuals, although they do not tend to induce illness in emotionally healthy people.<ref name="pmid14761703"/> 

====Suggestibility====
While research from the 1960s indicated increased suggestibility under the influence of LSD among both mentally ill and healthy individuals, recent documents suggest that the CIA and Department of Defense have discontinued research into LSD as a means of mind control.<ref>{{cite web |url= http://www.gulfweb.org/bigdoc/rockrep.cfm#hallucinogens |title=Is Military Research Hazardous to Veterans Health? Lessons Spanning Half A Century, part F. HALLUCINOGENS |publisher=103rd Congress, 2nd Session-S. Prt. 103-97; Staff Report prepared for the committee on veterans' affairs |date=December 8, 1994 |vauthors=Rockefeller IV JD |location=West Virginia |archive-url=https://web.archive.org/web/20060813164326/http://gulfweb.org/bigdoc/rockrep.cfm#hallucinogens |archive-date=August 13, 2006 |access-date=December 13, 2018}}</ref><ref>{{cite journal |vauthors=Middlefell R |title=The effects of LSD on body sway suggestibility in a group of hospital patients |journal=The British Journal of Psychiatry |volume=113 |issue=496 |pages=277–280 |date=March 1967 |pmid=6029626 |doi=10.1192/bjp.113.496.277 |s2cid=19439549 |url= http://www.lycaeum.org/research/researchpdfs/1489.pdf |archive-url=https://web.archive.org/web/20110430033215/http://www.lycaeum.org/research/researchpdfs/1489.pdf |archive-date=2011-04-30}}</ref><ref>{{cite journal |vauthors=Sjoberg BM, Hollister LE |title=The effects of psychotomimetic drugs on primary suggestibility |journal=Psychopharmacologia |volume=8 |issue=4 |pages=251–262 |date=November 1965 |pmid=5885648 |doi=10.1007/BF00407857 |s2cid=15249061}}</ref>{{Primary source inline|date=June 2023}}

====Flashbacks====
{{See also|Urban legends about drugs#"Permatripping" and retention of LSD in spinal fluid}}

[[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">{{cite book |title=A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD. |vauthors=Halpern JH, Lerner AG, Passie T |date=2018 |isbn=978-3-662-55878-2 |series=Current Topics in Behavioral Neurosciences |volume=36 |pages=333–360 |doi=10.1007/7854_2016_457 |pmid=27822679}}</ref>

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>

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 [[Urban legends about drugs#"Permatripping" and retention of LSD in spinal fluid|internet rumors]], LSD is not stored long-term in the [[spinal cord]] or other parts of the body. Pharmacological evidence indicates LSD has a half-life of 175 minutes and is metabolized into water-soluble compounds like 2-oxo-3-hydroxy-LSD, eliminated through urine without evidence of long-term storage.<ref name="PassieHalpernStrichtenoth2008" /> 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}}

===Tolerance===
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>

===Addiction and dependence liability===
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-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>

===Cancer and pregnancy===
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="PassieHalpernStrichtenoth2008" />

===Long-term effects===
A potential risk of frequent repeated long-term use of LSD and other serotonergic psychedelics is [[cardiac fibrosis]] and [[cardiac valvulopathy|valvulopathy]] due to [[serotonin]] [[5-HT2B receptor|5-HT<sub>2B</sub> receptor]] [[agonist|agonism]].<ref name="TagenMantuanivanHeerden2023">{{cite journal | vauthors = Tagen M, Mantuani D, van Heerden L, Holstein A, Klumpers LE, Knowles R | title = The risk of chronic psychedelic and MDMA microdosing for valvular heart disease | journal = J Psychopharmacol | volume = 37 | issue = 9 | pages = 876–890 | date = September 2023 | pmid = 37572027 | doi = 10.1177/02698811231190865 | url = }}</ref><ref name="RouaudCalderHasler2024">{{cite journal | vauthors = Rouaud A, Calder AE, Hasler G | title = Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins | journal = J Psychopharmacol | volume = 38 | issue = 3 | pages = 217–224 | date = March 2024 | pmid = 38214279 | pmc = 10944580 | doi = 10.1177/02698811231225609 | url = }}</ref><ref name="NahlawiPtaszekRuskin2025">{{cite journal | vauthors = Nahlawi A, Ptaszek LM, Ruskin JN | title = Cardiovascular effects and safety of classic psychedelics | journal = Nat Cardiovasc Res | volume = 4 | issue = 2 | pages = 131–144 | date = February 2025 | pmid = 39910289 | doi = 10.1038/s44161-025-00608-2 | url = }}</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="McIntyre2023">{{cite journal | vauthors = McIntyre RS | title = Serotonin 5-HT2B receptor agonism and valvular heart disease: implications for the development of psilocybin and related agents | journal = Expert Opin Drug Saf | volume = 22 | issue = 10 | pages = 881–883 | date = 2023 | pmid = 37581427 | doi = 10.1080/14740338.2023.2248883 | url = }}</ref> This may also be the case with [[microdosing]].<ref name="TagenMantuanivanHeerden2023" /><ref name="RouaudCalderHasler2024" /><ref name="NahlawiPtaszekRuskin2025" /> However, the risks are theoretical, and more research is needed to see if these complications can actually occur with psychedelics.<ref name="TagenMantuanivanHeerden2023" /><ref name="Wsół2023" /> A preliminary [[animal study]] found that chronic microdosing of LSD did not result in heart structure changes or valvulopathy in rodents.<ref name="EffingerKingCalderon2024">{{cite journal | vauthors = Effinger D, King J, Calderon J, Strong J, Thompson S | title = ACNP 63rd Annual Meeting: Poster Abstracts P609-P914: P680. Assessing the Potential Cardiovascular Risk of Microdosing Lysergic Acid Diethylamide in Mice | journal = Neuropsychopharmacology | volume = 49 | issue = Suppl 1 | pages = 418–594 (459–459) | date = December 2024 | pmid = 39643635 | doi = 10.1038/s41386-024-02013-y | url = | doi-access = free }}</ref> Research appears to be mixed on whether LSD is a potent serotonin 5-HT<sub>2B</sub> receptor agonist or not, with some studies finding it to be essentially inactive.<ref name="LuethiLiecthi2021">{{cite book | vauthors = Luethi D, Liechti ME | title=5-HT2B Receptors | chapter=Drugs of Abuse Affecting 5-HT2B Receptors | series=The Receptors | publisher=Springer International Publishing | publication-place=Cham | volume=35 | date=2021 | isbn=978-3-030-55919-9 | doi=10.1007/978-3-030-55920-5_16 | pages=277–289}}</ref>