The analgesic effect of morphine is dependent on its free phenolic group. Morphine binds to opioid receptors and has an analgesic effect. Even though codeine has a similar structure to morphine, the phenolic group of codeine is masked as methyl ether, and hence it does not bind as strongly to opioid receptors. However, it still shows analgesic activity when administered in vivo.
The analgesic activity of codeine can be explained by examining how it is metabolized by cytochrome P450 enzymes. These enzymes metabolize codeine into a number of metabolites that contribute to the analgesic effect of the drug.
Some prominent examples of analgesic codeine metabolites include morphine itself and codeine-6-glucuronide. The primary cytochrome P450 enzyme responsible for much of the metabolism is CYP2D6, though the enzyme UGT2B7 is what catalyzes the glucuronide conjugation.