Dextromethorphan (DXM or DM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms.

The primary use of dextromethorphan is as a cough suppressant, for the temporary relief of cough caused by minor throat and bronchial irritation (such as commonly accompanies the flu and common cold), as well as those resulting from inhaled particle irritants.[8] However, controlled studies have found the symptomatic effectiveness of dextromethorphan similar to placebo.[9]

It’s in clinical trials for major depressive disorder in combination with bupropion, with fast tracked designation by the FDA.[12] It showed positive results on the phase 2 and phase 3 clinical trials.[13][14]

Side Effects

Side effects of dextromethorphan at normal therapeutic doses can include:[2][8][15]

  • body rash/itching (see below)
  • nausea
  • vomiting
  • drowsiness
  • dizziness
  • constipation
  • diarrhea
  • sedation
  • confusion
  • nervousness
  • closed-eye hallucination

A rare side effect is respiratory depression.[8]


Dextromethorphan has been found to possess the following actions (<1 μM) using rat tissues:[24][30]

  • Uncompetitive antagonist of the NMDA receptor via the MK-801/PCP site[30]
  • SERT and NET blocker (cf. serotonin–norepinephrine reuptake inhibitor)
  • Sigma σ1 receptor agonist
  • Negative allosteric modulator of nicotinic acetylcholine receptors
  • Ligand of the serotonin 5-HT1B/1D, histamine H1, α2-adrenergic, and muscarinic acetylcholine receptors

Rather than acting as a direct NMDA receptor antagonist itself, dextromethorphan acts as a prodrug of its much more potent metabolite dextrorphan, and this is the actual mediator of its dissociative effects.[31] What role, if any, (+)-3-methoxymorphinan, dextromethorphan’s other major metabolite, plays in its effects is not entirely clear.[32


Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood–brain barrier.

At therapeutic doses, dextromethorphan acts centrally (meaning that it acts on the brain) as opposed to locally (on the respiratory tract). It elevates the threshold for coughing, without inhibiting ciliary activity. Dextromethorphan is rapidly absorbed from the gastrointestinal tract and converted into the active metabolite dextrorphan in the liver by the cytochrome P450 enzyme CYP2D6. The average dose necessary for effective antitussive therapy is between 10 and 45 mg, depending on the individual. The International Society for the Study of Cough recommends “an adequate first dose of medication is 60 mg in the adult and repeat dosing should be infrequent rather than the qds recommended.”[33]

DXM has an elimination half-life of approximately 4 hours in individuals with an extensive metabolizer phenotype; this is increased to approximately 13 hours when DXM is given in combination with quinidine.[26] The duration of action after oral administration is about three to eight hours for dextromethorphan hydrobromide, and 10 to 12 hours for dextromethorphan polistirex. Around one in 10 of the Caucasian population has little or no CYP2D6 enzyme activity, leading to long-lived high drug levels.


Adverse effects of dextromethorphan in overdose at doses 3 to 10 times the recommended therapeutic dose:[19]

  • mild nausea
  • restlessness
  • insomnia
  • talking fast
  • dilated pupils
  • glassy eyes