Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use.
Biochemical Pharmacology June 1, 2019 D. Luethi, M. Hoener, S. Krähenbühl et al. 46 citations
LSD is metabolized in the human liver into two main metabolites, nor-LSD and O-H-LSD, but only in small amounts—less than 1% of the parent compound was converted over four hours in laboratory experiments using human liver microsomes. Several cytochrome P450 enzymes contribute to this metabolism: CYP2D6, 2E1, and 3A4 for nor-LSD, and CYP1A2, 2C9, 2E1, and 3A4 for O-H-LSD. Enzyme induction by rifampicin increased metabolite formation, while omeprazole had a minor effect on nor-LSD. LSD and nor-LSD both activate serotonin receptors (5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C), with nor-LSD showing lower affinity at the 5-HT2C receptor. O-H-LSD had much weaker receptor activity, suggesting it is inactive. Genetic variations or drug interactions affecting these enzymes could alter LSD's effects.