13-Hydroxy-LSD

13-Hydroxy-LSD

Clinical data
Other names	13-Hydroxylysergic acid diethylamide; 13-OH-LSD; N,N-Diethyl-13-hydroxy-6-methyl-9,10-didehydroergoline-8β-carboxamide
ATC code	None
Identifiers
IUPAC name (6aR,9R)-N,N-diethyl-2-hydroxy-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
PubChem CID	56634866
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=CC(=CC(=C34)C2=C1)O)C
InChI InChI=1S/C20H25N3O2/c1-4-23(5-2)20(25)13-6-15-16-8-14(24)9-17-19(16)12(10-21-17)7-18(15)22(3)11-13/h6,8-10,13,18,21,24H,4-5,7,11H2,1-3H3/t13-,18-/m1/s1 Key:DZJOIBRTROBFRQ-FZKQIMNGSA-N

13-Hydroxy-LSD is a lysergamide and a metabolite of the psychedelic drug lysergic acid diethylamide (LSD). It is a major metabolite of LSD in rats and guinea pigs but a minor metabolite of LSD in monkeys and humans. Following its formation, 13-hydroxy-LSD undergoes further metabolism via glucuronidation. Little is known about the specific enzymes responsible for generation of LSD metabolites such as 13-hydroxy-LSD in humans.

According to David E. Nichols in 2016, the pharmacology of hydroxylated metabolites of LSD like 13-hydroxy-LSD has not been studied. Nichols has posited that metabolism of LSD into active metabolites with potent dopamine receptor activity may be responsible for the delayed-onset dopaminergic stimulus effects of LSD in rodent drug discrimination tests. Relatedly, lergotrile's corresponding metabolite 13-hydroxylergotrile is 100-fold more potent as a dopamine receptor agonist than lergotrile itself in vitro. However, more research is needed to assess the activity of 13-hydroxy-LSD and its potential involvement in LSD's effects. In any case, 13-hydroxy-LSD has been reported to produce LSD-like electroencephalogram (EEG) changes in rabbits.

Subsequently, 13-hydroxy-LSD was shown by Nichols and colleagues in 2026 to be an extremely potent dopamine D₄ receptor agonist, with an EC₅₀Tooltip half-maximal effective concentration of 36 pM and 380 times greater potency than LSD itself (which had a value of 14 nM). Moreover, 13-hydroxy-LSD is among the most potent dopamine D₄ receptor agonists ever to have been discovered. While 13-hydroxy-LSD is only a minor metabolite of LSD in humans, it is so potent as a dopamine D₄ receptor agonist that it may contribute to LSD's effects and may indeed be responsible for the delayed dopaminergic or "paranoid" phase of LSD's effects.

The 13 position of the ergoline ring system as in LSD and 13-hydroxy-LSD corresponds to the 6 position of the indole ring as in simple tryptamines. 6-Hydroxy-DMT has been found to be active but less potent than dimethyltryptamine (DMT) in animals and to be inactive in humans at the assessed doses. Similarly, it showed very low affinity for the serotonin 5-HT₂ receptors.

13-Hydroxy-LSD was first described in the scientific literature by at least 1963.