Dextromethorphan (DXM or DM) is an antitussive (cough suppressant) drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, including generic labels and store brands, Benylin DM, Mucinex DM, Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, TheraFlu, and others. Dextromethorphan has also found other uses in medicine, ranging from pain relief to psychological applications. It is sold in syrup, tablet, spray, and lozenge forms. In its pure form, dextromethorphan occurs as a white powder.
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. The major metabolite of DXM, dextrorphan, also acts as an NMDA receptor antagonist. In high doses this produces effects similar to, yet distinct from, the dissociative states created by other dissociative anaesthetic such as ketamine and phencyclidine. As well, the metabolite 3-methoxymorphinan of dextrorphan (thus a second-level metabolite of DXM) produces local anesthetic effects in rats with potency above dextrorphan, but below that of DXM.
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.
A 2004 study showed that dextromethorphan was no more effective for children than a placebo. 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.
A combination of dextromethorphan and quinidine, a CYP2D6 inhibitor, has been shown to alleviate symptoms of easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis. Dextromethorphan is also being investigated as a possible treatment for neuropathic pain and pain associated with fibromyalgia.In 2010, the FDA approved the combination product dextromethorphan/quinidine (Nuedexta) for the treatment of pseudobulbar affect (PBA).
Dextromethorphan has been shown to be effective in treating opioid withdrawal. At doses of 2mg/kg in rats all signs of opioid withdrawal were eliminated.
Since their introduction, over-the-counter preparations containing dextromethorphan have been used in manners inconsistent with their labeling, often as a recreational drug.At doses much higher than medically recommended, dextromethorphan is classified as a dissociative hallucinogen, possessing certain effects that are somewhat similar to the dissociative agents ketamine and phencyclidine. It may produce distortions of the visual field – feelings of dissociation, distorted bodily perception, and excitement, as well as a loss of sense of time. Some users report stimulant-like euphoria, particularly in response to music. Dextromethorphan usually provides its recreational effects in a non-linear fashion, so that they are experienced in significantly varied stages. These 5 stages are commonly referred to as “plateaus”.
Side-effects of dextromethorphan use can include:
At normal doses:
- Body rash/itching
- Closed-eye hallucination
- Difficulty breathingAt dosages 12.5 to 75 times the recommended therapeutic dose:
- Blurred vision and/or double vision
- Bloodshot eyes
- Dilated pupils
- Shallow respiration
- Urinary retention
- muscle spasms
- Sight loss
- Unable to focus eyes
- Skin rash
Dextromethorphan can also cause other gastrointestinal disturbances. Dextromethorphan had been thought to cause Olney’s Lesions when administered intravenously; however, this was later proven inconclusive, due to lack of research on humans. Tests were performed on rats, giving them 50 mg and up every day up to a month.
Neurotoxic changes, including vacuolation, have been observed in posterior cingulate and retrosplenial cortices of rats administered other NMDA antagonists such as PCP, but not with dextromethorphan.In many documented cases, dextromethorphan has produced psychological dependence in people who used it recreationally. However, it does not produce physical addiction, according to the WHO Committee on Drug Dependence.