Dextromethorphan, or DXM, is an active ingredient found in over 100 different over-the-counter (OTC) cough and cold preparations. Its primary, approved function is to temporarily relieve coughs caused by minor throat and bronchial irritation from conditions like the common cold or flu. However, its pharmacological profile is complex, involving several receptor systems and potential effects that extend beyond simple cough relief.
The Central Mechanism of Action
For its intended use as a cough suppressant, dextromethorphan works centrally, meaning it acts on the brain. The cough reflex is a complex biological process initiated by nerve endings in the respiratory tract that send signals to a "cough center" in the brainstem, specifically the medulla oblongata.
Dextromethorphan's main mechanism involves disrupting this signaling pathway. It is believed to act directly on the cough center, decreasing its sensitivity and raising the threshold required to trigger a cough reflex. This effectively reduces the frequency and intensity of coughing fits. Its effects begin within 15 to 30 minutes of taking a dose and can last for several hours, especially with extended-release formulations.
Metabolism into Dextrorphan
Dextromethorphan undergoes rapid metabolism in the liver via the enzyme CYP2D6 to its active metabolite, dextrorphan (DX). This metabolite is a powerful N-methyl-D-aspartate (NMDA) receptor antagonist. While this property is largely irrelevant at normal therapeutic use, it is responsible for the dissociative and hallucinogenic effects seen with high concentrations. Dextrorphan is then further metabolized and excreted from the body.
Therapeutic and Approved Uses
- Cough Suppression: The most common and approved use is for short-term relief of a dry, non-productive cough associated with the common cold or flu. It does not treat the underlying cause of the cough or speed up recovery.
- Pseudobulbar Affect (PBA): Since 2010, the FDA has approved a combination product of dextromethorphan and quinidine for the treatment of PBA. This neurological condition causes uncontrollable episodes of crying or laughing. In this application, quinidine is added to inhibit the CYP2D6 enzyme, which increases the bioavailability and concentration of dextromethorphan in the bloodstream.
Comparison: Dextromethorphan vs. Codeine
Historically, codeine was the go-to cough suppressant. However, due to its addictive properties and the potential for serious side effects, dextromethorphan has largely replaced it in OTC products.
| Feature | Dextromethorphan | Codeine |
|---|---|---|
| Availability | Over-the-counter (OTC) | Prescription only |
| Control Status | Unscheduled (not a controlled drug) | Schedule II (high abuse potential) |
| Mechanism | Acts on the cough center in the brainstem. | Mu-opioid receptor agonist. |
| Addiction Potential | Low at therapeutic concentrations, but high-concentration use is a concern. | High addiction potential due to opioid nature. |
| Common Side Effects | Nausea, dizziness, drowsiness (usually mild). | Constipation, nausea, drowsiness. |
| Primary Function | Antitussive (cough suppression). | Analgesic and antitussive. |
Common and Serious Side Effects
At therapeutic concentrations, dextromethorphan is generally well-tolerated, but some side effects can occur.
Common Side Effects include:
- Dizziness or lightheadedness
- Drowsiness
- Nausea and stomach pain
- Nervousness or restlessness
Serious Side Effects and Overuse: Taking larger than recommended amounts can lead to more serious symptoms. Overuse can cause hallucinations, impaired judgment, loss of coordination, seizures, and even coma. These severe effects are often amplified when dextromethorphan is combined with other substances like alcohol.
The Risks of High Concentrations of Dextromethorphan
Due to its dissociative effects at high concentrations, DXM is a drug of abuse, especially among teenagers. This abuse is sometimes called "robotripping" and can lead to a state of intoxication with effects that vary based on the amount consumed:
- Lower concentrations: Can lead to mild stimulation and euphoria.
- Moderate concentrations: May result in euphoria, hallucinations, and impaired motor coordination.
- Higher concentrations: Can cause intense hallucinations, distorted perception, and dissociation.
- Very high concentrations: Can produce a trance-like state, delirium, and loss of motor control, with effects similar to the illegal drug PCP.
Drug Interactions and Safety Warnings
Numerous drug interactions can occur with dextromethorphan, and some are potentially life-threatening.
Monoamine Oxidase Inhibitors (MAOIs): Combining DXM with MAOIs (used for depression or Parkinson's disease) is extremely dangerous and can lead to serotonin syndrome. This condition involves a buildup of high serotonin levels and can cause agitation, confusion, rapid heart rate, and fever. A two-week washout period is required between stopping an MAOI and starting DXM.
Serotonergic Antidepressants: Taking DXM with other serotonergic drugs like SSRIs or SNRIs can also increase the risk of serotonin syndrome and should be done with caution.
Grapefruit: Grapefruit and grapefruit juice can inhibit the CYP3A4 enzyme, slowing DXM's metabolism and potentially causing dangerously high levels of the drug in the system.
For more detailed information on side effects and interactions, the National Institutes of Health provides comprehensive resources.
Conclusion
In summary, what exactly does dextromethorphan do? It is a non-narcotic, centrally-acting antitussive that safely and effectively suppresses coughs at recommended amounts by desensitizing the brain's cough center. It has other specific therapeutic uses, such as treating pseudobulbar affect in combination with quinidine. However, misuse of dextromethorphan, especially in high amounts, can produce dangerous dissociative and hallucinogenic effects. It is critical to use DXM as directed, be aware of its potential for interaction with other medications, and recognize the serious risks associated with its recreational abuse. Always consult a healthcare professional or pharmacist if you have questions or concerns about using any medication.
