Nor-LSD
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| Other names | norLSD; N,N-Diethyl-6-norlysergamide; N-Desmethyllysergic acid diethylamide; N-Desmethyl-LSD; Norlysergic acid diethylamide; N-Demethyl-LSD; 9,10-Didehydro-N,N-diethylergoline-8β-carboxamide; H-LAD; 6-Nor-LSD |
| Drug class | Serotonin receptor modulator; Serotonergic psychedelic; Hallucinogen |
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| ECHA InfoCard | 100.164.623 |
| Chemical and physical data | |
| Formula | C19H23N3O |
| Molar mass | 309.413 g·mol−1 |
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Nor-LSD, or norLSD, also known as N,N-diethyl-6-norlysergamide or as N-desmethyllysergic acid diethylamide (N-desmethyl-LSD), is a serotonin receptor modulator and putative psychedelic of the lysergamide family related to lysergic acid diethylamide (LSD).[1][2][3] It is the analogue of LSD in which the methyl group at the 6 position of the ergoline ring system has been removed.[1][2]
Use and effects
[edit]According to Alexander Shulgin, nor-LSD showed no psychedelic effects at assessed doses of up to 500 μg in humans, whereas LSD was active at doses as low as 50 μg.[4][5] Higher doses of nor-LSD do not appear to have been assessed.[4][5]
Pharmacology
[edit]Pharmacodynamics
[edit]The drug showed 5- to 29-fold lower affinity for the serotonin 5-HT2 receptor compared to LSD (Ki = 30–158 nM vs. 5.4 nM, respectively).[1][3] It also showed affinity for the serotonin 5-HT1 receptor.[1] In another more recent study however, nor-LSD showed similar or even higher affinities, activational potencies, and/or efficacies at the serotonin 5-HT1A, 5-HT2A, and 5-HT2B receptors as LSD, whereas it showed 36-fold lower affinity for the serotonin 5-HT2C receptor compared to LSD.[6]
Nor-LSD failed to completely substitute for LSD in rodent drug discrimination tests even at very high doses.[1][2] The greatest degree of substitution with nor-LSD was 75% at a dose of 7,420 nM/kg, whereas 100% substitution occurred with LSD at a dose of 186 nM/kg (a 40-fold lower dose).[1][2] The ED50 was 2,594 nM/kg for nor-LSD and 46 nM/kg for LSD.[1][2] 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.[1][2]
Pharmacokinetics
[edit]Nor-LSD has been reported to occur as a metabolite of LSD in rats and humans.[7][8][9]
Chemistry
[edit]Derivatives
[edit]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.[3][4][5] There appears to be a length of about 3 carbon atoms that can be tolerated at the 6 position before potent psychedelic activity is lost.[10]
History
[edit]Nor-LSD was first described in the scientific literature, by Yuji Nakahara and Tetsukichi Niwaguchi, by at least 1971.[11][12]
See also
[edit]References
[edit]- ^ a b c d e f g h Hoffman AJ (August 1987). Synthesis and pharmacological evaluation of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives (Ph.D. thesis). Purdue University.
Table 7. 5-HT2 binding affinity of N(6)-alkyl norLSD derivatives. [...]
- ^ a b c d e f Hoffman AJ, Nichols DE (September 1985). "Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives". Journal of Medicinal Chemistry. 28 (9): 1252–1255. doi:10.1021/jm00147a022. PMID 4032428.
- ^ a b c Pfaff RC, Huang X, Marona-Lewicka D, Oberlender R, Nichols DE (1994). "Lysergamides revisited". NIDA Research Monograph. 146: 52–73. PMID 8742794.
TABLE 1. Drug discrimination ED50 values and receptor affinities of N(6)-alkyl-nor-LSD derivatives [...]
- ^ a b c Jacob P, Shulgin AT (1994). "Structure-activity relationships of the classic hallucinogens and their analogs" (PDF). NIDA Research Monograph. 146: 74–91. PMID 8742795.
- ^ a b c Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4.
- ^ Luethi D, Hoener MC, Krähenbühl S, Liechti ME, Duthaler U (June 2019). "Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use". Biochem Pharmacol. 164: 129–138. doi:10.1016/j.bcp.2019.04.013. PMID 30981875.
- ^ Nichols DE (October 2018). "Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)" (PDF). ACS Chemical Neuroscience. 9 (10): 2331–2343. doi:10.1021/acschemneuro.8b00043. PMID 29461039.
- ^ Dolder P (2017). The Pharmacology of d-Lysergic Acid Diethylamide (LSD) (PDF) (Thesis). University of Basel. p. 112. doi:10.5451/UNIBAS-006786123. Retrieved 3 June 2025.
- ^ Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A (2008). "The pharmacology of lysergic acid diethylamide: a review". CNS Neuroscience & Therapeutics. 14 (4): 295–314. doi:10.1111/j.1755-5949.2008.00059.x. PMC 6494066. PMID 19040555.
- ^ Gumpper RH, Nichols DE (October 2024). "Chemistry/structural biology of psychedelic drugs and their receptor(s)". British Journal of Pharmacology. doi:10.1111/bph.17361. PMID 39354889.
- ^ Niwaguchi T, Nakahara Y (1971). "Studies on Lysergic Acid Diethylamide and Related Compounds. I. Synthesis of d-N6-Demethyl-lysergic Acid Diethylamide". Chemical and Pharmaceutical Bulletin. 19 (11): 2337–2341. doi:10.1248/cpb.19.2337. ISSN 0009-2363. Retrieved 3 June 2025.
- ^ Niwaguchi T, Inoue T, Nakahara Y (March 1974). "Studies on enzymatic dealkylation of D-lysergic acid diethylamide (LSD)". Biochemical Pharmacology. 23 (6): 1073–1078. doi:10.1016/0006-2952(74)90007-0. PMID 4151050.
External links
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