It is produced in the secondary metabolism of the opium poppy Papaver somniferum (Papaveraceae) as an intermediate in the biosynthetic pathway that generates morphine.

[1] As an isoquinoline alkaloid, it is fundamentally derived from tyrosine as part of the shikimate pathway of secondary metabolism.

First, (R)-reticuline undergoes an oxidation at each of its phenol rings mediated by the cytochrome P-450-dependent monooxygenase salutaridine synthase.

The first step is an esterification of the hydroxyl group previously reduced in the conversion of salutaridine to salutaridinol with acetyl-CoA.

Thebaine can then be converted to morphine through two slightly different biosynthetic routes, one of which makes use of the fourth enzyme codeinone reductase.