Dextromethorphan (DXM) is a widely available ingredient in over-the-counter (OTC) cold and cough medications. It is classified as an antitussive, meaning its primary medical purpose is to temporarily relieve coughing caused by minor throat and bronchial irritation, such as that accompanying the common cold or flu. DXM is a synthetic compound approved for medical use since 1958.
The Mechanism of Cough Suppression
Dextromethorphan’s action as a cough suppressant is considered central, meaning it works within the brain rather than directly on the respiratory tract. The drug is a member of the morphinan class of compounds, but it does not exert significant activity on the mu-opioid receptors responsible for the pain relief and dependence associated with traditional opioids like codeine. Instead, DXM elevates the threshold for the cough reflex by decreasing the sensitivity of the brain’s cough center, which is located in the medulla oblongata.
The precise mechanism involves multiple targets within the central nervous system. A significant part of its antitussive effect is thought to be mediated through its role as a sigma-1 receptor agonist. Activation of the sigma-1 receptor modulates neuronal excitability and contributes to the suppression of the cough signal as it passes through the brainstem.
DXM is rapidly metabolized in the liver, primarily by the cytochrome P450 enzyme CYP2D6, into its active metabolite, dextrorphan. The cough-suppressing effect is attributed to the combined activity of both the parent drug and its metabolite. This central action provides symptomatic relief for a dry, non-productive cough without inhibiting the natural ciliary activity in the lungs.
Standard Medical Use and Formulations
The primary medical use of dextromethorphan is the temporary alleviation of a non-productive cough. It is not intended to treat a cough that produces excessive phlegm or mucus, nor is it effective for chronic coughs related to conditions like asthma or emphysema.
DXM is available in numerous over-the-counter formats, either alone or in combination with other ingredients. Common formulations include liquid syrups, liquid-filled capsules, or tablets. There are also extended-release liquid suspensions, often containing DXM polistirex, designed to prolong the duration of the cough-suppressing effect.
Standard therapeutic dosing for adults and children over 12 years old is typically between 10 and 20 milligrams every four hours, or 30 milligrams every six to eight hours. The maximum recommended daily dosage is limited to 120 milligrams in a 24-hour period. Adhering to these guidelines is necessary to ensure the drug functions as an effective antitussive while minimizing adverse effects.
Common Side Effects and Drug Interactions
At recommended therapeutic doses, dextromethorphan generally has a favorable safety profile, with side effects that are usually mild. Common minor effects include gastrointestinal discomfort such as nausea, vomiting, and constipation. Some individuals may also experience central nervous system effects like drowsiness, dizziness, or mild confusion.
The potential for dangerous drug interactions is a significant concern, particularly with medications that affect serotonin levels. DXM possesses mild serotonergic activity, acting as a nonselective serotonin-norepinephrine reuptake inhibitor. When combined with other serotonergic agents, this effect can lead to a condition called Serotonin Syndrome.
This condition results from excessive serotonin activity in the central nervous system. The combination is especially risky when DXM is taken alongside Monoamine Oxidase Inhibitors (MAOIs), Selective Serotonin Reuptake Inhibitors (SSRIs), or Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs). Symptoms include mental status changes, such as agitation or confusion, and autonomic hyperreactivity like a rapid heart rate or high blood pressure. Neuromuscular abnormalities, such as muscle rigidity and tremors, may also occur. Taking DXM with an MAOI is contraindicated, and a person must wait at least 14 days after stopping an MAOI before using DXM.
The Dangers of High-Dose Non-Medical Use
Dextromethorphan is frequently misused at high doses to achieve non-medical psychoactive effects, a practice often called “Robotripping.” At supra-therapeutic concentrations, DXM’s primary mechanism shifts from a cough suppressant to a powerful central nervous system agent. The drug, along with its metabolite dextrorphan, acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor.
Antagonism of the NMDA receptor reduces signaling, which produces a state of dissociation similar to that caused by drugs like ketamine and PCP. Effects include mild euphoria, perceptual distortions, intense visual and auditory hallucinations, loss of motor control, and a profound sense of detachment from reality. High-dose use can lead to extreme agitation, delirium, and violent behavior.
Physiological complications can be severe due to the widespread effects on the body’s systems. High doses can cause cardiovascular issues, such as a rapid heartbeat and high blood pressure, as well as hyperthermia, which is a dangerously elevated body temperature. Central nervous system depression can lead to respiratory depression, and the potential for seizures is also increased.
The risk is compounded when misuse involves products containing DXM mixed with other active ingredients. Acetaminophen (paracetamol) is often included, which can cause fatal liver injury. Combination ingredients like antihistamines or decongestants intensify negative effects, leading to co-toxicity and increasing the risk of over-sedation or severe cardiac events.