Nor-LSD

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][4] It is the analogue of LSD in which the methyl group at the 6 position of the ergoline ring system has been removed.^[2][3]

Nor-LSD

Clinical data
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; NORLAD; NOR-LAD; 6-Nor-LSD
Drug class	Serotonin receptor modulator; Serotonergic psychedelic; Hallucinogen
ATC code	None
Identifiers
IUPAC name (6aR,9R)-N,N-diethyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide
CAS Number	35779-43-2
PubChem CID	169713
ChemSpider	148419
ChEMBL	ChEMBL21343
CompTox Dashboard (EPA)	DTXSID80189307
ECHA InfoCard	100.164.623
Chemical and physical data
Formula	C19H23N3O
Molar mass	309.413 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCN(CC)C(=O)[C@H]1CN[C@@H]2CC3=CNC4=CC=CC(=C34)C2=C1
InChI InChI=1S/C19H23N3O/c1-3-22(4-2)19(23)13-8-15-14-6-5-7-16-18(14)12(10-20-16)9-17(15)21-11-13/h5-8,10,13,17,20-21H,3-4,9,11H2,1-2H3/t13-,17-/m1/s1 Key:SUXLVXOMPKZBOV-CXAGYDPISA-N

Use and effects

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.^[5][6] Higher doses of nor-LSD do not appear to have been assessed.^[5][6]

Pharmacology

Pharmacodynamics

Nor-LSD showed 5- to 29-fold lower affinity for the serotonin 5-HT₂ receptor compared to LSD (K_i = 30–158 nM vs. 5.4 nM, respectively).^[1][2][4] It also showed affinity for the serotonin 5-HT₁ receptor.^[2] 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.^[7]

Nor-LSD failed to completely substitute for LSD in rodent drug discrimination tests even at very high doses.^[1][2][3] 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).^[2][3] The ED₅₀Tooltip median effective dose was 2,594 nM/kg for nor-LSD and 46 nM/kg for LSD.^[2][3] 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.^[2][3] In another study, nor-LSD failed to produce LSD-like electroencephalogram (EEG) changes in rabbits.^[8]

Pharmacokinetics

Nor-LSD has been reported to occur as a metabolite of LSD in rats and humans.^[9][10][11]

Chemistry

Derivatives

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.^[4][5][6] 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.^[12]

History

Nor-LSD was first described in the scientific literature, by Yuji Nakahara and Tetsukichi Niwaguchi, by at least 1971.^[13][14]

See also

• Substituted lysergamide