DXM is also used recreationally. When exceeding label-specified maximum dosages, dextromethorphan acts as a dissociative hallucinogen. Its mechanism of action is via multiple effects, including actions as a nonselective serotonin reuptake inhibitor and a sigma-1 receptor agonist and the action of its major metabolite dextrorphan as an NMDA receptor antagonist, producing effects similar to those of the controlled substances ketamine and phencyclidine (PCP), as well as the active metabolite 3-methoxymorphinan, which produces local anesthetic effects in rats with a potency above dextrorphan but below dextromethorphan itself.

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 irritants.^{[citation needed]}

A 2004 study showed that dextromethorphan was no more effective for children than a placebo.^[8] Studies conducted by the American Academy of Pediatrics show that dextromethorphan is not superior to a placebo in providing nocturnal symptom relief for children with cough and sleep difficulty due to upper respiratory infections.^[9]

In addition, a combination of dextromethorphan and quinidine has been shown to alleviate symptoms of easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis.^[10] Dextromethorphan is also being investigated as a possible treatment for neuropathic pain and pain associated with fibromyalgia.^[11] On October 29, 2010 The FDA approved the combination product (Nuedexta) manufactured by Avanir pharmaceutical corporation for the treatment of pseudobulbar affect (PBA).