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Systematic (IUPAC) name
CAS number 125-71-3
ATC code R05DA09
PubChem 5360696
DrugBank APRD00655
Chemical data
Formula C18H25NO 
Mol. mass 271.4 g/mol
Pharmacokinetic data
Bioavailability 11%[1]
Metabolism Hepatic (liver) enzymes: major CYP2D6, minor CYP3A4, and minor CYP3A5
Half life 1.4–3.9 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.


Legal status

Pharmacy Only (S2)(AU) OTC(US)

Routes Oral

Dextromethorphan (sometimes abbreviated as DXM or DM) is an antitussive (cough-suppressant) drug found in many over-the-counter cold and cough medicines. Dextromethorphan has also found other uses in medicine, ranging from pain relief to psychological applications. Pure dextromethorphan occurs as a powder made up of white crystals, but it is generally administered via syrups, tablets, or lozenges manufactured under several different brand names and generic labels.

When taken at doses higher than are medically recommended, dextromethorphan acts as a dissociative hallucinogenic drug. It is classified neurochemically as an NMDA receptor antagonist, producing narcotic effects similar to those of the controlled substances ketamine and phencyclidine (PCP),[2] which affords it a significant potential for abuse.[3]


Dextromethorphan is the dextrorotatory enantiomer of the methyl ether of levorphanol, a narcotic analgesic. It is named according to IUPAC rules as (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan. As the pure free base, dextromethorphan occurs as an odorless, white to slightly yellow crystalline powder. It is freely soluble in chloroform and essentially insoluble in water. Commercially, dextromethorphan is commonly available as the monohydrated hydrobromide salt, although some newer extended-release formulations contain dextromethorphan bound to an ion exchange resin based on polystyrene sulfonic acid. Dextromethophan's specific rotation in water is +27.6° (20°C, Sodium D-line).


The primary use of dextromethorphan is as a cough suppressant, for the temporary relief of cough caused by minor throat and bronchial irritation (as commonly accompanies the common cold), as well as other causes such as inhaled irritants.

Additional uses

  • 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.[4]
  • Dextromethorphan is being investigated as a possible treatment for pain associated with fibromyalgia, a chronic rheumatological organic fatigue disorder.[5]
  • Dextromethorphan is also useful in breaking drug addictions, especially when combined with a CYP2D6 inhibitor, like quinidine.[6]


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 metabolizes within 15 to 60 minutes of ingestion. The average dosage necessary for effective antitussive therapy is between 15 mg and 60 mg, depending on age. The duration of action after oral administration is approximately three to eight hours for dextromethorphan-hydrobromide, and ten to twelve hours for dextromethorphan-polistirex.

Because administration of dextromethorphan can trigger a histamine release (an allergic reaction), its use in atopic children is very limited.


Side-effects of dextromethorphan use can include:[7]

  • body rash/itching
  • dissociation
  • nausea
  • drowsiness
  • dizziness
  • excitation
  • vomiting
  • blurred vision
  • dilated pupils
  • sweating
  • fever
  • hypertension
  • shallow respiration
  • diarrhea
  • urinary retention

Can also cause increases in:

  • heart rate
  • blood pressure

Dextromethorphan can also cause other gastrointestinal disturbances. Some studies suggest that dextromethorphan has the potential to cause Olney's Lesions.[8][9] In some rare documented cases, dextromethorphan has produced psychological dependence in people who abused it. However, it does not produce physical addiction, according to the WHO Committee on Drug Dependence.

Drug interactions

Dextromethorphan should not be taken with either of the following:

CNS depressant drugs and substances, including alcohol, antihistamines, and some psychotropics, will have a cumulative CNS depressant effect if taken with dextromethorphan.[7]


  • Because dextromethorphan can trigger a histamine release (allergic reaction), atopic children, who are especially susceptible to allergic reactions, should be administered dextromethorphan only if absolutely necessary, and only under the strict supervision of a health care professional.[7]

Clinical pharmacology

Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan. The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite. Dextromethorphan is metabolized by various liver enzymes and subsequently undergoes O-demethylation (producing dextrorphan), N-demethylation, and partial conjugation with glucuronic acid and sulfate ions. Hours after dextromethorphan therapy, (in humans) the metabolites (+)-3-hydroxy-N-methylmorphinan, (+)-3-morphinan, and traces of the unchanged drug are detectable in the urine.[7]

A major metabolic catalyst involved is the cytochrome P450 enzyme known as 2D6, or CYP2D6. A significant portion of the population has a functional deficiency in this enzyme and are known as poor CYP2D6 metabolizers. As CYP2D6 is a major metabolic pathway in the inactivation of dextromethorphan, the duration of action and effects of dextromethorphan can be increased by as much as three times in such poor metabolizers.[10]

A large number of medications (including antidepressants) are potent inhibitors of CYP2D6. There exists, therefore, the potential of interactions between dextromethorphan and concomitant medications. There have been reports of fatal consequences arising from such interactions.[11]

Dextromethorphan crosses the blood-brain barrier, and the following pharmacological actions have been reported:

Brand names

Dextromethorphan is an active ingredient in many brand-name cough suppressant preparations, including those manufactured by:


Dextromethorphan was first patented under U.S. Patent 2,676,177 . The FDA approved dextromethorphan for over-the-counter sale as a cough suppressant in 1958. This filled the need for a cough suppressant lacking the sedative side-effects, stronger potential for abuse, and physically addictive properties of codeine phosphate, the most widely-used cough medication at the time (now prescription-only in the United States).[16] As with most cough suppressants, studies show that dextromethorphan's effectiveness is highly debatable,[17] especially in children.[18]

During the 1960s and 1970s, dextromethorphan became available in an over-the-counter tablet form by the brand name Romilar. In 1973, Romilar was taken off the shelves after a burst in sales due to common recreational use, and was replaced by cough syrup in an attempt to cut down on recreational use.[16]

More recently (around 2000) gel capsule forms began reappearing in the form of Robitussin CoughGels as well as several generic forms of that preparation.

Recreational use

Since their introduction, over-the-counter preparations containing the drug dextromethorphan have been used in a manner inconsistent with their labeling, often as a recreational drug, to induce intoxication.[16] Dextromethorphan has little to no psychotropic effect in the doses used medically; however, alteration of consciousness generally occurs following ingestion of approximately 7 to 50 times the therapeutic dose over a relatively short period of time.[16]

Slang terms for dextromethorphan often correlate to the brands of cough medicine used, such as "tussin," "robo," "dex," "Triple C's," and "skittles". Recreational use of dextromethorphan is frequently referred to in verb form as "dexing," "tussing," "roboing," and "robotripping". Due to abuse and theft concerns, many retailers in the US have moved DXM-containing products behind the counter so that one must ask a pharmacist to receive them or be 18 years (19 in NJ) or older to purchase them. Some retailers also give out printed warnings about the potential for abuse with the purchase of products containing DXM.


At high doses, dextromethorphan is classified as a dissociative hallucinogenic drug, like ketamine and phencyclidine (PCP). [19][20] Also like those drugs, dextromethorphan and its metabolite, dextrorphan, act as potent NMDA receptor antagonists. In addition to producing PCP-like behavioral effects, high doses may cause a false-positive result for PCP in some drug tests.[2]

Dextromethorphan generally does not produce withdrawal symptoms characteristic of physically addictive substances, but cases of psychological addiction have been reported.


Antitussive preparations containing dextromethorphan are legal to purchase from most pharmacies worldwide. Since DXM's use as a recreational drug usually involves only the ingestion of large quantities of an over-the-counter medication, no legal distinction currently exists between medical and recreational use, sale, or purchase.

The sale of dextromethorphan in its pure powder form may incur penalties in the United States, although no explicit law exists prohibiting its sale. There have been cases of individuals incurring time in prison and other penalties for selling pure dextromethorphan in this form, due to the incidental breaking of related drug laws — such as resale of a medication without proper warning labels.[19]

Specifically, the FDA considers the sale of pure dextromethorphan to individuals, or when shipped to residential or post-office boxes, as the sale of a misbranded drug, which is a misdemeanor offense. Often times such distributors place disclaimers on their website or product, to the effect of "not for human consumption," in an effort to evade the regulatory authority of the FDA. This has been viewed by authorities as an "attempt to defraud the FDA," which then raises the offense to a felony with three years' maximum imprisonment. [19]

Dextromethorphan was excluded from the Controlled Substances Act (CSA) of 1970 and was specifically excluded from the Single Convention on Narcotic Drugs. Dextromethorphan is still excluded from the CSA (as of 2007), however officials have warned that it could still be added if increased recreational use warrants its scheduling.[16]

Dextromethorphan is generally available over the counter in most countries, with one exception being Hong Kong. [21]


Dextromethorphan, when consumed in low recreational doses (usually under 200 mg), is described as having a euphoric effect. With higher doses (about 400 mg), intense euphoria (or dysphoria), vivid imagination, and closed-eye hallucinations may occur. With very high doses (600 mg and over), profound alterations in consciousness have been noted, and users often report out-of-body experiences or temporary psychosis.[22][23] Frequent and long-term usage at very high doses can lead to toxic psychosis and other permanent psychological problems.[16] Most users find such high doses to be extremely uncomfortable and are unwilling to repeat them. Flanging (speeding up or slowing down) of sensory input is characteristic at any recreational dosing level.

In 1981, a paper by Gosselin estimated the lethal dose to be between 50 and 500 mg/kg. Doses as high as 15-20 mg/kg are taken by some recreational users. It is suggested by a single case study that the antidote to dextromethorphan overdose is naloxone, administered intravenously.[24]


Dextromethorphan's psychological effects can be attributed largely to dextrorphan (DXO), a metabolite produced when dextromethorphan metabolizes within the body. Both dextrorphan and dextromethorphan are NMDA receptor antagonists,[25] just like the dissociative hallucinogenic drugs ketamine and phencyclidine (PCP); however for that purpose, dextrorphan is more potent than dextromethorphan.[26]

Just like all NMDA receptor antagonists, dextrorphan and dextromethorpan inhibit neurotransmitters (specifically glutamate) from activating neurotransmitter receptors in the brain. This can effectively slow or even shut down certain neural pathways, preventing the brain from "communicating with itself," so to speak, which leaves the user feeling dissociated, "disconnected," or "outside" one's own body.[27][28]

Dextromethorphan's euphoric effects have sometimes been attributed to the triggering of an increase in dopamine levels, since such an increase generally correlates to a pleasurable response to a drug, as is observed with antidepressants. However the effect of dextrorphan and dextromethorphan on dopamine levels is a disputed subject. Studies show that some NMDA receptor antagonists, like ketamine and PCP, do raise dopamine levels.[29][15] Other studies show that dizocilpine, another NMDA receptor antagonist, has no effect on dopamine levels. Some findings even suggest that dextromethorphan actually counters the dopamine increase caused by morphine.[7][30][31][32] Due to these conflicting results, the actual effect of dextromethorphan on dopamine levels is yet to be determined.


  1. ^ Plasma profile and pharmacokinetics of dextromethorphan after intravenous and oral administration. Journal of Veterinary Pharmacology and Therapeutics.
  2. ^ a b
  3. ^
  4. ^ Brooks B, Thisted R, Appel S, Bradley W, Olney R, Berg J, Pope L, Smith R (2004). "Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial.". Neurology 63 (8): 1364-70. PMID 15505150.
  5. ^ Cough Drug May Help Fibromyalgia Pain. WebMD.
  6. ^ Patent application.
  7. ^ a b c d e f g h Dextromethorphan. NHTSA.
  8. ^ Olney J, Labruyere J, Price M (1989). "Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs". Science 244 (4910): 1360-2. PMID 2660263.
  9. ^ Hargreaves R, Hill R, Iversen L. "Neuroprotective NMDA antagonists: the controversy over their potential for adverse effects on cortical neuronal morphology". Acta Neurochir Suppl (Wien) 60: 15-9. PMID 7976530.
  10. ^ Clinical Pharmacology & Therapeutics - Abstract of article: The influence of CYP2D6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans[ast]. Retrieved on 2007-07-16.
  11. ^ Jones K, Taranto M (2006). "Illicit Drug Manual: Dextromethorphan ("Robo-tripping")". collegehealth-e 1 (4): 13–17.
  12. ^ British Journal of Pharmacology - The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via [sigma1 receptor activation: comparison with the effects of dextromethorphan]. Retrieved on 2007-07-16.
  13. ^ Hernandez SC, Bertolino M, Xiao Y, Pringle KE, Caruso FS, Kellar KJ (2000). "Dextromethorphan and its metabolite dextrorphan block alpha3beta4 neuronal nicotinic receptors". J. Pharmacol. Exp. Ther. 293 (3): 962-7. PMID 10869398.
  14. ^ Kamei J, Mori T, Igarashi H, Kasuya Y (1992). "Serotonin release in nucleus of the solitary tract and its modulation by antitussive drugs". Res. Commun. Chem. Pathol. Pharmacol. 76 (3): 371-4. PMID 1636059.
  15. ^ a b Verma A, Moghaddam B (Jan 1996). "NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine". Journal of Neuroscience 1: 373-9.
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  17. ^ Cough medicines "have no benefit" BBC News: Health, Tuesday, July 6, 2004. Accessed July 28 2007.
  18. ^ [1] "Kids' cough medicine no better than placebo" San Francisco Chronicle, July 8, 2004
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  22. ^ Bornstein, S; Czermak, M; Postel, J., (1968). "Apropos of a case of voluntary medicinal intoxication with dextromethorphan hydrobromide". Annales Medico-Psychologiques 1 (3): 447-451.
  23. ^ Dodds A, Revai E (1967). "Toxic psychosis due to dextromethorphan.". Med J Aust 2: 231.
  24. ^ Schneider SM, Michelson EA, et al. (1991). "Dextromethorphan poisoning reversed by naloxone.". Am. J. Emerg. Med. 9: 237-238.
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  27. ^ Muir, KW; Lees KR (1995). "Clinical experience with excitatory amino acid antagonist drugs". Stroke 26 (3): 503-513. Retrieved on 2007-01-17.
  28. ^ Kristensen, JD; Svensson B, and Gordh T Jr (1992). "The NMDA-receptor antagonist CPP abolishes neurogenic 'wind-up pain' after intrathecal administration in humans". Pain 51 (2): 249-253. PMID 1484720. Retrieved on 2007-01-17.
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  30. ^ Steinmiller, CL; Maisonneuve IM, Glick SD. (2003). "Effects of dextromethorphan on dopamine release in the nucleus accumbens: Interactions with morphine.". Pharmacol Biochem Behav. 74 (4): 803-10. Center for Neuropharmacology and Neuroscience (MC-136). PMID 12667894. Retrieved on 2007-05-18.
  31. ^ Carrozza, DP; Ferraro TN, Golden GT, Reyes PF, Hare TA. (1992). "In vivo modulation of excitatory amino acid receptors: microdialysis studies on N-methyl-D-aspartate-evoked striatal dopamine release and effects of antagonists.". Brain Res. 74 (4): 803-10. PMID 1353403. Retrieved on 2007-05-18.
  32. ^ Huang, EY; Liu TC, Tao PL. (2003). "Co-administration of dextromethorphan with morphine attenuates morphine rewarding effect and related dopamine releases at the nucleus accumbens.". Brain Res. 368 (5): 386-92. PMID 14564449. Retrieved on 2007-05-18.

See also

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Dextromethorphan". A list of authors is available in Wikipedia.
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