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LSD
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===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>
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