Dextromethorphan (DXM) is a common cough suppressant found in many over-the-counter (OTC) cold and flu medications. When taken at therapeutic doses, DXM acts on the central nervous system to suppress coughing. However, the presence of DXM in the body can complicate mandatory drug screenings, such as those required for employment or legal purposes. The primary concern is that the body’s breakdown products of this medication can trigger a positive result for substances considered illicit. This interference stems directly from how the body metabolizes DXM.
The Chemistry of Dextromethorphan Metabolism
DXM is absorbed in the liver and processed by the cytochrome P450 enzyme 2D6 (CYP2D6). This enzyme converts DXM into its main active metabolite, Dextrorphan (DXO). DXO accounts for at least 80% of the metabolized product and is the primary cause of testing issues. DXO is an active substance whose structural makeup closely resembles certain controlled substances. This structural similarity allows DXO to interfere with common immunoassay screening tests designed to detect illicit drugs. Genetic variations in the CYP2D6 enzyme can also affect this process, causing some individuals to metabolize the drug slower, leading to higher concentrations of DXM and DXO for longer periods.
Screening Tests and the Risk of False Positives
Initial drug screenings use immunoassay, a fast and cost-effective method that detects specific drug classes. These tests rely on antibodies designed to bind to a target drug or its metabolites. However, these antibodies are not perfectly specific and can mistakenly bind to structurally similar compounds, causing cross-reactivity.
The most common cross-reactivity involves the illicit drug Phencyclidine (PCP). Antibodies meant to detect PCP can be fooled by the chemical structure of Dextrorphan, resulting in a positive screen for PCP even after a therapeutic dose of cough syrup. While some immunoassay panels may also show cross-reactivity for certain opiates, this is less common with a single, normal dose of DXM.
A positive result on this initial screen is only presumptive and does not confirm the presence of an illicit drug. Screening tests prioritize speed over definitive accuracy, requiring a second, more powerful test to confirm the finding. The likelihood of a cross-reaction increases significantly if the concentration of Dextrorphan is high, such as when a large dose of OTC medication was taken.
Confirmation Testing and How to Prove Legal Use
When an initial immunoassay screen returns a presumptive positive result, the sample undergoes confirmation testing. The gold standard for this process is Gas Chromatography-Mass Spectrometry (GC/MS). Unlike the antibody-based screen, GC/MS separates and identifies compounds based on their unique molecular fingerprints.
GC/MS can accurately differentiate the molecular structure of Dextrorphan from PCP or any other illicit substance. If a presumptive positive for PCP is found, the GC/MS will confirm the presence of Dextrorphan, proving the result was a false positive caused by the cough medicine. The final interpretation is handled by a Medical Review Officer (MRO), a licensed physician specializing in toxicology.
If you receive a presumptive positive result after taking DXM, immediately disclose your use of the OTC medication to the MRO or testing facility. Provide documentation, such as medication receipts or a note from a medical provider, to support the claim of legitimate use. If the MRO verifies the presence of Dextrorphan via the confirmation test, the initial positive screen will be overturned and reported as negative.
Detecting Dextromethorphan Abuse
Standard workplace drug panels do not typically test for DXM, but specialized testing is performed in clinical or forensic settings when abuse is suspected. These specialized tests use highly sensitive methods, such as GC/MS or Liquid Chromatography-Mass Spectrometry (LC-MS-MS), to measure the concentrations of DXM and DXO. This quantification allows toxicologists to determine if the dosage was therapeutic or consistent with high-dose misuse.
Therapeutic doses for cough suppression range from 15 to 30 milligrams every few hours. Recreational misuse, however, often involves much higher doses, sometimes exceeding 500 to 1,500 milligrams. By analyzing the actual concentration of both DXM and DXO, testing can establish a pattern of abuse rather than accidental cross-reactivity from a medicinal dose. The detection window for DXM in urine is typically short, lasting up to two days after the last use.