Codeine analgesia is due to codeine-6-glucuronide, not morphine.

Eighty per cent of codeine is conjugated with glucuronic acid to codeine-6-glucuronide. Only 5% of the dose is O-demethylated to morphine, which in turn is immediately glucuronidated at the 3- and 6-position and excreted renally. Based on the structural requirement of the opiate molecule for interaction with the mu-receptor to result in analgesia, codeine-6-glucuronide in analogy to morphine-6-glucuronide must be the active constituent of codeine. Poor metabolisers of codeine, those who lack the CYP450 2D6 isoenzyme for the O-demethylation to morphine, experience analgesia from codeine-6-glucuronide. Analgesia of codeine does not depend on the formation of morphine and the metaboliser phenotype.