A fungus, Cunninghamella elegans, can mimic human drug metabolism and was tested on four tryptamines: DMT, 4-HO-MET, 5-MeO-DALT, and 5-MeO-MiPT. After 72 hours of incubation, the fungus performed key biotransformation steps like hydroxylation, N-oxide formation, carboxylation, deamination, and demethylation. On average, 63% of phase I metabolites previously reported in the literature were also produced by C. elegans, along with some unique metabolites. The findings suggest C. elegans is a useful complementary model for studying the metabolism of natural and synthetic tryptamines, especially given the lack of pharmacological data for new psychoactive substances.
The metabolism of three hallucinogenic phenethylamines—25D-NBOMe, 25E-NBOMe, and 25N-NBOMe—was investigated using pooled human liver microsomes (pHLM) and the fungus Cunninghamella elegans. In pHLM, 36, 26, and 24 phase I metabolites were identified for 25D-NBOMe, 25E-NBOMe, and 25N-NBOMe, respectively; in C. elegans, 14, 11, and 9 metabolites were found. Major biotransformation steps included oxidative deamination, N-dealkylation, O-demethylation, hydroxylation, and oxidation of alcohols. Unique metabolites included N-oxide and hydroxylamine derivatives, reported for the first time for NBOMe compounds. C. elegans produced all main biotransformation steps observed in human microsomes, suggesting its potential as a model for studying new psychoactive substances.