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Codeine is an alkaloid found in opium in concentrations ranging from 0.7 to 2.5 percent. While codeine can be extracted from opium, most codeine used in the United States is synthesized from morphine through the process of O-methylation.

In the United States, codeine is regulated by the Controlled Substances Act. It is a Schedule II controlled substance for pain-relief products containing codeine alone. In combination with aspirin or acetaminophen (paracetamol) it is listed as Schedule III. Codeine is also available outside the United States as an over-the-counter medication (Schedule V) in liquid cough-relief formulations. Internationally, codeine is a Schedule II drug under the Single Convention on Narcotic Drugs.

In the United Kingdom, codeine is regulated by the Misuse of Drugs Act 1971; it is a Class B Drug.

In Australia and Canada, codeine is regulated, however it is available without prescription in combination preparations from licensed pharmacists in doses up to 12.5 mg/tablets.

Codeine is considered a prodrug, since it is metabolised in vivo to the principal active analgesic agent morphine. It is, however, less potent than morphine since only about 10% of the codeine is converted. It also has a correspondingly lower dependence-liability than morphine.

Theoretically, a dose of approximately 200 mg (oral) of codeine must be administered to give equivalent analgesia to 30 mg (oral) of morphine (Rossi, 2004). It is not used, however, in single doses of greater than 60mg (and no more than 240 mg in 24 hours) since there is a ceiling effect.

The conversion of codeine to morphine occurs in the liver and is catalysed by the cytochrome P450 enzyme CYP2D6. Approximately 6–10% of the Caucasian population have poorly functional CYP2D6 and codeine is virtually ineffective for analgesia in these patients (Rossi, 2004). Many of the adverse effects, however, are still experienced. Also, some medications are CYP2D6 inhibitors and reduce or even completely eliminate the efficacy of codeine. The most notorious of these are the selective serotonin reuptake inhibitors, such as fluoxetine (Prozac) and citalopram (Celexa).