12-Hydroxy-LSD

12-Hydroxy-LSD is a drug of the ergoline and lysergamide families and a derivative of lysergic acid diethylamide (LSD).^[1][2][3][4] In terms of chemical structure, 12-hydroxy-LSD is to LSD as bufotenin (5-HO-DMT) is to dimethyltryptamine (DMT), with 12-hydroxy-LSD notably containing bufotenin within its rigidified structure.^[5] 12-Hydroxy-LSD produces psychedelic-like effects in animals,^[6] whereas reports on its activities in humans are very limited and have been conflicting.^{[1][4][2][7][3]}

12-Hydroxy-LSD

Clinical data
Other names	12-Hydroxylysergic acid diethylamide; 12-OH-LSD; 12-HO-LSD; "5-OH-LSD"; "5-HO-LSD"; "5-Hydroxy-LSD"; 9,10-Didehydro-N,N-diethyl-6-methyl-12-hydroxyergoline-8β-carboxamide
Drug class	Serotonin receptor modulator
Identifiers
IUPAC name (6aR,9R)-N,N-diethyl-1-hydroxy-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
CAS Number	60573-89-9
PubChem CID	3042820
ChemSpider	2305940
CompTox Dashboard (EPA)	DTXSID00209374
Chemical and physical data
Formula	C20H25N3O2
Molar mass	339.439 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCN(CC)C(=O)[C@H]1CN([C@@H]2CC3=CNC4=C3C(=C(C=C4)O)C2=C1)C
InChI InChI=1S/C20H25N3O2/c1-4-23(5-2)20(25)13-8-14-16(22(3)11-13)9-12-10-21-15-6-7-17(24)19(14)18(12)15/h6-8,10,13,16,21,24H,4-5,9,11H2,1-3H3/t13-,16-/m1/s1 Key:SJBIVHSZSSHVGK-CZUORRHYSA-N

Pharmacology

12-Hydroxy-LSD is known to be pharmacologically active in animal studies.^[1] The drug's effects in rabbits include antiserotonergic activity (25% of that of LSD) and hyperthermia (dose ratio relative to LD₅₀Tooltip median lethal dose of 1:44 for 12-hydroxy-LSD and 1:725 for LSD).^[1] In addition, like LSD, it is highly potent in terms of lethality, with a median lethal dose (LD₅₀) of 0.3 mg/kg i.v.Tooltip intravenous administration in rabbits (relative to 0.1 mg/kg for LSD).^[1][2] 12-Hydroxy-LSD also produces LSD-like electroencephalogram (EEG) changes in rabbits.^[8]

According to Robert C. Pfaff and David E. Nichols and colleagues, 12-hydroxy-LSD substitutes for LSD in rodent drug discrimination tests.^[6] Hence, it appears to show psychedelic-like effects in animals.^[6] However, 12-hydroxy-LSD was described as having unremarkable properties in this assay and only having about 20% of the potency of LSD.^[6] It was reported in the 1960s that 12-hydroxy-LSD does not produce hallucinogenic effects in humans.^[1][4][2][7] On the other hand however, Michael Valentine Smith claimed in his 1981 book Psychedelic Chemistry that 12-hydroxy-LSD has "about the same activity as LSD".^[3]

Presumably 12-hydroxy-LSD acts as an agonist of serotonin and dopamine receptors, as with LSD and other related lysergamides, but its pharmacology has not been studied with modern techniques.^[1][2]

Chemistry

Synthesis

The chemical synthesis of 12-hydroxy-LSD is described as being very difficult.^[6]

Analogues

An analogue of 12-hydroxy-LSD is 12-methoxy-LSD, which would be structurally akin to 5-MeO-DMT.^[1][2][3] As with 12-hydroxy-LSD, it has been reported that 12-methoxy-LSD is inactive as a psychedelic in humans.^[1]

History

12-Hydroxy-LSD was first described in the scientific literature by 1962.^{[9][10][11][1]} Subsequently, it was further described in the 1970s and 1980s.^{[2][7][8][3][4]} David E. Nichols and colleagues reported that 12-hydroxy-LSD produces psychedelic-like effects in animals in 1994.^[6] It was initially thought that 12-hydroxy-LSD might be a metabolite of LSD,^[9][12] but this proved not to be the case.^[11][13][14]

See also

• 12-Methoxy-LSD
• 13-Hydroxy-LSD
• 2-Bromo-LSD
• Bufotenin (5-HO-DMT)