A team led by Nadja Grobe from the Donald Danforth Plant Science Center and Marc Lamshöft from the Institute of Environmental Research, University of Technology Dortmund have now shown conclusively for the first time that mammals are able to synthesise morphine. When either unlabelled or deuterated THP, a potential precursor of morphine, was administered to mice, analysis of their urine showed that the compound had been extensively metabolised. Salutaridine, a known biosynthetic precursor of morphine in the opium poppy, was found amongst the metabolites and when deuterated salutaridinol, the biosynthetic reduction product of salutaridine, was administered to the mice, it was shown to be converted to deuterated thebaine, which was excreted in their urine. Deuterated thebaine was also administered and deuterated morphine together with the related compounds, codeine and oripavine, was recovered in urine.
The study, which is published in the journal PNAS, provides the first evidence that mammals have the capacity to convert THP, known to be present in the brain, into morphine. Although the pathway has now been shown to exist, it is still not clear whether mammals naturally produce morphine as an analgesic.