What is Doxylamine Succinate?
Doxylamine succinate is a first-generation antihistamine that is a primary active ingredient in many over-the-counter (OTC) sleep aids, such as Unisom, and is also found in nighttime cold and flu remedies like NyQuil [1.5.2, 1.6.2]. Its primary mechanism of action involves blocking the histamine H1 receptor in the brain, which leads to sedative and hypnotic effects [1.5.2]. It also has potent anticholinergic properties, which contribute to side effects like dry mouth and drowsiness but can cause delirium at toxic doses [1.5.2, 1.5.3]. Because of its effectiveness as a sleep aid and its use in treating nausea and vomiting during pregnancy, it is one of the most widely used sleep medications globally [1.5.2, 1.5.5]. The typical half-life of doxylamine is about 10 hours in adults, meaning it can take over two days for the body to eliminate it completely [1.4.1, 1.4.4].
How Drug Tests Can Produce False Positives
Drug testing is a common procedure in many workplaces and medical settings. The process usually begins with an initial screening test, most often a urine immunoassay [1.10.2]. Immunoassays are designed to be fast and efficient for large-scale screening [1.10.2]. They use antibodies to detect the presence of specific drugs or their metabolites. However, a significant drawback of these screening tests is the potential for cross-reactivity. This occurs when the test's antibodies mistakenly recognize a structurally similar, but different, compound as the targeted drug, leading to a false-positive result [1.10.2].
Research indicates that false positives may occur in 5% to 10% of cases, often due to common OTC medications [1.8.2, 1.6.4]. When an initial immunoassay screen is positive, a more accurate and specific confirmatory test, such as Gas Chromatography-Mass Spectrometry (GC-MS), is typically performed [1.10.2]. GC-MS is considered the gold standard for confirmation because it separates and identifies the specific molecules in the sample, virtually eliminating the risk of a false positive [1.2.4, 1.10.2]. Hair testing, for instance, almost exclusively uses these sophisticated confirmatory methods, making false positives extremely rare [1.2.4].
Doxylamine's Cross-Reactivity on Drug Screens
Due to its chemical structure, doxylamine is a known culprit for causing false positives on initial immunoassay drug screens. The FDA label for the combination drug containing doxylamine succinate explicitly warns that false positives for methadone, opiates, and Phencyclidine (PCP) can occur [1.11.1].
Which Substances Can Doxylamine Be Mistaken For?
- Methadone: Numerous case studies and reports confirm that doxylamine's molecular structure bears a resemblance to methadone, causing it to trigger false positives for this opioid on immunoassay tests [1.2.1, 1.11.2, 1.3.1].
- Phencyclidine (PCP): There is also evidence that doxylamine, particularly at toxic levels, can lead to false-positive results for PCP in immunoassay-based urine drug screens [1.2.3, 1.7.4].
- Opiates: The FDA has also noted the potential for false positives for opiates in general [1.11.1].
- Benzodiazepines: Some sources suggest that doxylamine may also trigger false positives for benzodiazepines [1.3.4].
These false positives primarily occur with urine immunoassay tests, which are the most common type of initial screening [1.2.3]. Confirmatory tests like GC-MS will correctly identify the substance as doxylamine and rule out the presence of illicit drugs [1.2.4, 1.11.3].
Comparison of Common OTC Antihistamines and False Positives
| Medication | Common Brand Name(s) | Potential False Positive For | Notes |
|---|---|---|---|
| Doxylamine Succinate | Unisom, NyQuil | Methadone, PCP, Opiates, Benzodiazepines [1.7.4, 1.11.1, 1.3.4] | Cross-reactivity is well-documented, especially with methadone. |
| Diphenhydramine | Benadryl, ZzzQuil | Methadone, PCP [1.6.3, 1.6.5] | Similar to doxylamine, it can cause false positives for methadone and, more rarely, PCP. |
| Pseudoephedrine | Sudafed | Amphetamine, Methamphetamine [1.6.4] | Its chemical structure is very similar to amphetamines. |
What to Do If You Suspect a False Positive
If you receive a positive drug test result that you believe is false due to taking doxylamine or another medication, it's important to act promptly.
- Be Transparent: Before the test, if possible, disclose any OTC or prescription medications you are taking to the test administrator [1.9.1].
- Request a Confirmatory Test: Immediately request a more specific, confirmatory test, such as GC-MS or High-Performance Liquid Chromatography (HPLC) [1.9.2]. The initial screening result should always be considered presumptive until confirmed [1.10.2].
- Gather Documentation: Collect any evidence related to your medication use, such as the original packaging or a note from a doctor or pharmacist, to support your case [1.9.4].
- Consult with Professionals: Speak with the testing lab, your employer's medical review officer (MRO), or an attorney to understand your rights and the next steps in the dispute process [1.9.3, 1.9.2].
Conclusion
Yes, the common OTC sleep aid doxylamine succinate can indeed cause a positive drug test. This happens because its chemical structure is similar enough to other substances—most notably methadone, PCP, and other opiates—to trigger a false positive on initial immunoassay screening tests [1.11.1, 1.11.3]. This highlights the critical importance of confirmatory testing, like GC-MS, which can accurately distinguish between doxylamine and the illicit substances being screened for [1.2.4]. By being aware of this potential interaction, disclosing medication use, and insisting on confirmatory analysis, individuals can effectively challenge and resolve a false-positive result.
For more information on the appropriate use and risks of doxylamine, consult authoritative sources such as the National Institutes of Health's MedlinePlus. MedlinePlus [1.5.5]
