nor-LSD

According to Alexander Shulgin, nor-LSD showed no psychedelic effects at assessed doses of up to 500{{nbsp}}μg in humans, whereas LSD was active at doses as low as 50{{nbsp}}μg.{{cite journal | vauthors = Jacob P, Shulgin AT | title = Structure-activity relationships of the classic hallucinogens and their analogs | journal = NIDA Research Monograph | volume = 146 | pages = 74–91 | date = 1994 | pmid = 8742795 | url = https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 }}{{cite book | vauthors = Shulgin AT | veditors = Laing RR | chapter = Basic Pharmacology and Effects | title = Hallucinogens: A Forensic Drug Handbook | pages = 67–137 | year = 2003 | publisher = Elsevier Science | series = Forensic Drug Handbook Series | isbn = 978-0-12-433951-4 | url = https://books.google.com/books?id=l1DrqgobbcwC | chapter-url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 }} Higher doses of nor-LSD do not appear to have been assessed.

The drug showed 5- to 29-fold lower affinity for the serotonin 5-HT₂ receptor compared to LSD (K_i = 30–158{{nbsp}}nM vs. 5.4{{nbsp}}nM, respectively).{{cite thesis | vauthors = Hoffman AJ | degree = Ph.D. | title = Synthesis and pharmacological evaluation of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives | date = August 1987 | publisher = Purdue University | url = https://bitnest.netfirms.com/external/Theses/Hoffman1987 | quote = Table 7. 5-HT2 binding affinity of N(6)-alkyl norLSD derivatives. [...] }} It also showed affinity for the serotonin 5-HT₁ receptor. In another more recent study however, nor-LSD showed similar or even higher affinities, activational potencies, and/or efficacies at the serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2B receptors as LSD, whereas it showed 36-fold lower affinity for the serotonin 5-HT_2C receptor compared to LSD.{{cite journal | vauthors = Luethi D, Hoener MC, Krähenbühl S, Liechti ME, Duthaler U | title = Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use | journal = Biochem Pharmacol | volume = 164 | issue = | pages = 129–138 | date = June 2019 | pmid = 30981875 | doi = 10.1016/j.bcp.2019.04.013 | url = }}

Nor-LSD failed to completely substitute for LSD in rodent drug discrimination tests even at very high doses. The greatest degree of substitution with nor-LSD was 75% at a dose of 7,420{{nbsp}}nM/kg, whereas 100% substitution occurred with LSD at a dose of 186{{nbsp}}nM/kg (a 40-fold lower dose). The {{Abbrlink|ED₅₀|median effective dose}} was 2,594{{nbsp}}nM/kg for nor-LSD and 46{{nbsp}}nM/kg for LSD. Hence, nor-LSD was approximately 56-fold less potent than LSD in terms of producing LSD-like effects in rodents and failed to produce full LSD-like effects even at the highest assessed dose.

Nor-LSD has been reported to occur as a metabolite of LSD in rats and humans.{{cite journal | vauthors = Nichols DE | title = Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD) | journal = ACS Chemical Neuroscience | volume = 9 | issue = 10 | pages = 2331–2343 | date = October 2018 | pmid = 29461039 | doi = 10.1021/acschemneuro.8b00043 | url = https://shaunlacob.com/wp-content/uploads/2020/12/DC-LSD.pdf }}{{cite thesis | vauthors = Dolder P | title = The Pharmacology of d-Lysergic Acid Diethylamide (LSD) | pages = 112 | date = 2017 | doi = 10.5451/UNIBAS-006786123 | publisher = University of Basel | url = https://core.ac.uk/download/pdf/154350706.pdf#page=112 | access-date = 3 June 2025 }}{{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 | pmid = 19040555 | pmc = 6494066 | doi = 10.1111/j.1755-5949.2008.00059.x }}

Derivatives of nor-LSD substituted at the 6 position include LSD (METH-LAD; 6-methyl), ETH-LAD (6-ethyl), PRO-LAD (6-propyl), BU-LAD (6-butyl), AL-LAD (6-allyl), and PARGY-LAD (6-propynyl), among others. There appears to be a length of about 3{{nbsp}}carbon atoms that can be tolerated at the 6 position before potent psychedelic activity is lost.{{cite journal | vauthors = Gumpper RH, Nichols DE | title = Chemistry/structural biology of psychedelic drugs and their receptor(s) | journal = British Journal of Pharmacology | date = October 2024 | pmid = 39354889 | doi = 10.1111/bph.17361 }}

Nor-LSD was first described in the scientific literature, by Yuji Nakahara and Tetsukichi Niwaguchi, by at least 1971.{{cite journal | vauthors = Niwaguchi T, Nakahara Y | title = Studies on Lysergic Acid Diethylamide and Related Compounds. I. Synthesis of d-N6-Demethyl-lysergic Acid Diethylamide | journal = Chemical and Pharmaceutical Bulletin | volume = 19 | issue = 11 | pages = 2337–2341 | date = 1971 | doi = 10.1248/cpb.19.2337 | issn = 0009-2363 | doi-access = free | url = https://www.jstage.jst.go.jp/article/cpb1958/19/11/19_11_2337/_pdf | access-date = 3 June 2025 }}{{cite journal | vauthors = Niwaguchi T, Inoue T, Nakahara Y | title = Studies on enzymatic dealkylation of D-lysergic acid diethylamide (LSD) | journal = Biochemical Pharmacology | volume = 23 | issue = 6 | pages = 1073–1078 | date = March 1974 | pmid = 4151050 | doi = 10.1016/0006-2952(74)90007-0 }}

• Substituted lysergamide

{{Reflist}}

• [https://isomerdesign.com/pihkal/explore/5346 Nor-LSD - Isomer Design]

{{Psychedelics}}

{{Serotonin receptor modulators}}

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Category:5-HT2A agonists

Category:5-HT2B agonists

Category:Diethylamino compounds

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Category:Lysergic acid diethylamide

Category:Psychedelic lysergamides

Category:Serotonin receptor modulators