From the Guidelines
Codeine can cause a false positive result for morphine on a drug screen due to its metabolism to morphine in the liver. This occurs because codeine is a prodrug that is hepatically metabolized to morphine, among other compounds, through the action of the cytochrome P450 enzyme, CYP2D6, as noted in the study by 1. The metabolism of codeine to morphine can lead to a positive test result for morphine on standard immunoassay drug screens, which often cannot distinguish between the two substances.
Key Points to Consider
- Codeine is metabolized to morphine in the body, which can result in a positive drug test for morphine 1.
- The detection window for codeine/morphine in urine can vary based on factors like dosage, frequency of use, metabolism, and hydration status.
- Confirmatory testing using more specific methods like gas chromatography-mass spectrometry (GC-MS) can differentiate between codeine and morphine, but these tests are not typically performed unless specifically requested after an initial positive screen.
- It is essential to disclose any codeine-containing medications taken, including prescription pain relievers and some over-the-counter cough medicines, if a positive morphine result needs to be explained.
Clinical Implications
The fact that codeine can cause a false positive result for morphine on a drug screen has significant clinical implications. Clinicians should be aware of this possibility when interpreting drug test results, especially in patients who have been prescribed codeine or have taken codeine-containing medications. This knowledge can help prevent misinterpretation of drug test results and ensure that patients are not wrongly accused of taking morphine or other opioids. As noted in 1, urine screening remains the gold standard in drug detection, but it is crucial to understand the limitations and potential for false positives or false negatives.
From the Research
Codeine and Morphine Metabolism
- Codeine is metabolized partly to morphine by the liver enzyme CYP2D6, which is subject to genetic polymorphism 2
- The metabolism of codeine to morphine can lead to positive test results for morphine in individuals who have only taken codeine
False Positive Results for Morphine
- Consumption of codeine can lead to positive urine test for morphine in athletes, and morphine/codeine ratio is used to distinguish the consumption of codeine from abuse of morphine and other narcotics 3
- Codeine can cause a false positive result for morphine on a drug screen, especially if the test is not sensitive enough to distinguish between the two substances 4
Factors Affecting Test Results
- The presence of codeine in morphine preparations as an impurity can also lead to false positive results for codeine in patients who are only prescribed morphine 4
- The cutoff value for opiate screening and confirmation can affect the number of false positive results, with higher cutoff values leading to fewer false positives 5
Clinical Implications
- Clinicians and laboratories testing urine for drugs should be aware of the possibility of codeine causing false positive results for morphine, and consider the morphine/codeine ratio when interpreting test results 3, 4
- The use of codeine can lead to positive test results for morphine, which can have significant clinical implications, especially in athletes and individuals subject to drug testing 3