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.
Certain ring-substituted phenethylamines produce psychedelic effects mainly through serotonin 5-HT2A receptors. 2C-BI derivatives, a class of 4'-aryl substituted 2,5-dimethoxyphenethylamines, were tested for binding and activity at monoamine receptors and transporters. Several 2C-BI compounds bound strongly to human serotonergic and adrenergic receptors and to rat and mouse trace amine-associated receptor 1. 2C-BI-8 and 2C-BI-12 activated serotonin 5-HT2A and 5-HT2B receptors at submicromolar concentrations, while only 2C-BI-1 and 2C-BI-7 activated human trace amine-associated receptor 1. 2C-BI-3 and 2C-BI-4 interacted weakly with monoamine transporters. The high affinities at the 5-HT2A receptor suggest a sterically tolerant binding pocket, and potent partial activation by 2C-BI-8 and 2C-BI-12 indicates potential psychedelic effects similar to other 2C compounds.