View source for Dextromethorphan

{{distinguish|Dexamethasone}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 322164571
| IUPAC_name = (+)-3-methoxy-17-methyl-(9α,13α,14α)-morphinan
| image  = Dextromethorphan.svg
| image2 = Dextromethorphan-from-xtal-3D-balls-A.png
| CASNo_Ref = {{cascite}}
| InChI = 1/C18H25NO/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h6-7,12,15,17H,3-5,8-11H2,1-2H3/t15-,17+,18+/m1/s1
| InChIKey = MKXZASYAUGDDCJ-NJAFHUGGBD
| CAS_number = 125-71-3
| ChemSpiderID = 13109865
| MDL_number = MFCD02173901
| ATC_prefix = R05
| ATC_suffix = DA09
| PubChem = 15978238
| smiles = O(c1ccc3c(c1)[C@@]24[C@@H]([C@H](N(CC2)C)C3)CCCC4)C
| DrugBank = APRD00655
| C = 18 | H = 25 | N = 1 | O = 1
| molecular_weight = 271.4 g/mol
| melting_point = 111
| bioavailability = 11%<ref>{{cite web|title=Plasma profile and pharmacokinetics of dextromethorphan after intravenous and oral administration|url=http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2885.2004.00608.x?cookieSet=1&journalCode=jvp|work=Journal of Veterinary Pharmacology and Therapeutics}}</ref>
| metabolism = Hepatic (liver) enzymes: major [[CYP2D6]], minor [[CYP3A4]], and minor [[CYP3A5]]
| elimination_half-life = 1.4–3.9 hours
| excretion = [[Kidney|Renal]]
| pregnancy_AU = A
| pregnancy_US = C
| legal_AU = S2
| legal_US = OTC
| routes_of_administration = Oral
}}

'''Dextromethorphan''' ('''DXM''' or '''DM''') is an [[antitussive]] ([[cough suppressant]]) [[drug]]. It is one of the active ingredients in many [[Over-the-counter drug|over-the-counter]] [[common cold|cold]] and [[cough]] medicines, such as [[Robitussin]], [[NyQuil]], [[Dimetapp]], [[Vicks]], [[Coricidin]], [[Delsym]], and others, including [[generic drug|generic]] labels. Dextromethorphan has also found other uses in medicine, ranging from [[pain relief]] to [[psychological]] applications. It is sold in syrup, tablet, spray, and [[throat lozenge|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 as an [[NMDA receptor antagonist]], producing  effects similar to those of the controlled substances [[ketamine]] and [[phencyclidine]] (PCP).<ref name=dea1>[http://www.deadiversion.usdoj.gov/drugs_concern/dextro_m/dextro_m.htm DEXTROMETHORPHAN (Street Names: DXM, CCC, Triple C, Skittles, Robo, Poor Man’s PCP)<!-- Bot generated title -->]</ref>

== History ==

Dextromethorphan was identified as one of three compounds tested as part of [[US Navy]] and [[CIA]]-funded research that sought a "nonaddictive substitute for [[codeine]]"; it is implied that the compound was first found to have clinical potential in this study<ref>[http://www.dod.mil/pubs/foi/02-A-0846RELEASE.pdf ''Memorandum for the Secretary of Defense"'']</ref>. It was  first patented under {{US patent|2676177}}. The [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) approved dextromethorphan for [[Over-the-counter drug|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.<ref name="cesar">[http://www.cesar.umd.edu/cesar/drugs/dxm.asp Dextromethorphan (DXM) | CESAR<!-- Bot generated title -->]</ref>  In the United States, codeine phosphate syrup is still available in small quantities without a prescription in some states, but requires a signature and ID to purchase, similar to modern rules for sale of [[pseudoephedrine]].  

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 because of frequent abuse, and was replaced by [[cough syrup]] in an attempt to cut down on abuse.<ref name="cesar"/>

More recently (the early 1990s), gel capsule forms began reappearing in the form of Drixoral Cough Liquid Caps and later Robitussin CoughGels as well as several generic forms of that preparation.

== Uses ==

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 [[influenza|flu]] and [[common cold]]), as well as those resulting from inhaled irritants.

As with most cough suppressants, studies show that dextromethorphan's effectiveness is [[Cough medicine#Effectiveness|unproven]],<ref>[http://news.bbc.co.uk/1/hi/health/3869379.stm ''Cough medicines "have no benefit"''] BBC News: Health,  Tuesday, July 6, 2004.  Accessed July 28, 2007.</ref> especially in children.<ref>[http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2004/07/08/MNGNF7I1G31.DTL ''"Kids' cough medicine no better than placebo"''] San Francisco Chronicle, July 8, 2004</ref> 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]].<ref>Paul IM, Yoder KE, Crowell KR (July 2004). "Effect of Dextromethorphan, Diphenhydramine, and Placebo on Nocturnal Cough and Sleep Quality for Coughing Children and Their Parents." ''Pediatrics'' '''114''' (1):85-90</ref> 

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]].<ref name="D+Q Trial">{{cite journal | author = Brooks B, Thisted R, Appel S, Bradley W, Olney R, Berg J, Pope L, Smith R | title = Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial | journal = Neurology | volume = 63 | issue = 8 | pages = 1364–70 | year = 2004 | pmid = 15505150}}</ref> Dextromethorphan is also being investigated as a possible treatment for [[neuropathic pain]] and pain associated with [[fibromyalgia]].<ref>{{cite web |url=http://www.webmd.com/content/article/106/108142|title=Cough Drug May Help Fibromyalgia Pain|work=WebMD}}</ref>

=== Recreational use===
[[Image:DXM Doses.jpg|thumb|Dextromethorphan gel capsules]]
{{Main|Recreational use of dextromethorphan}}

Since their introduction, [[Over-the-counter substance|over-the-counter]] preparations containing dextromethorphan have been used in manners inconsistent with their labeling, often as a recreational drug.<ref name="cesar" /> At doses higher than medically recommended, dextromethorphan is classified as a [[dissociative drug|dissociative]] [[psychedelic drug]], with visible effects that are similar to those of [[ketamine]] and [[phencyclidine]] (PCP). It can produce distortions of the visual field, feelings of [[dissociation]], distortions of bodily perception, excitement, as well as a loss of comprehension of time.<ref>AJ Giannini. Drugs of Abuse--Second Edition. Los Angeles, Practice Management Information Corp, 1997.</ref><ref>[http://www.erowid.org/chemicals/dxm/dxm.shtml  ]</ref>

== Chemistry ==

Dextromethorphan is the [[Dextrorotation|dextrorotatory]] [[enantiomer]] of the methyl [[ether]] of [[levorphanol]], an [[opioid]] analgesic. It is also a [[stereoisomer]] of [[levomethorphan]], an [[opioid]] [[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 insoluble in [[water]]. Dextromethorphan is commonly available as the monohydrated hydrobromide salt, however some newer extended-release formulations contain dextromethorphan bound to an ion exchange resin based on [[Sodium polystyrene sulfonate|polystyrene sulfonic acid]]. Dextromethorphan's [[specific rotation]] in water is +27.6° (20°C, Sodium D-line).

== Pharmacology ==
=== Pharmacodynamics ===

Dextromethorphan has been shown to possess the following properties, mainly in binding assays to various receptors of animal tissues.
Low K<sub>i</sub> values mean strong binding or high affinity; high K<sub>i</sub> values mean weak binding to the target or low affinity:

* [[Uncompetitive inhibition|Uncompetitive]] [[NMDA receptor]] (PCP site) [[receptor antagonist|antagonist]] (K<sub>i</sub> = 7,253 nM).<ref name="pmid10064839">{{cite journal | author = Chou YC, Liao JF, Chang WY, Lin MF, Chen CF | title = Binding of dimemorfan to sigma-1 receptor and its anticonvulsant and locomotor effects in mice, compared with dextromethorphan and dextrorphan | journal = Brain Research | volume = 821 | issue = 2 | pages = 516–9 | year = 1999 | month = March | pmid = 10064839 | doi = 10.1016/S0006-8993(99)01125-7| url = http://linkinghub.elsevier.com/retrieve/pii/S0006-8993(99)01125-7}}</ref><ref name="pmid2897648">{{cite journal | author = Wong BY, Coulter DA, Choi DW, Prince DA | title = Dextrorphan and dextromethorphan, common antitussives, are antiepileptic and antagonize N-methyl-D-aspartate in brain slices | journal = Neuroscience Letters | volume = 85 | issue = 2 | pages = 261–6 | year = 1988 | month = February | pmid = 2897648 | doi = 10.1016/0304-3940(88)90362-X| url = }}</ref><ref name="pmid2673498">{{cite journal | author = Church J, Jones MG, Davies SN, Lodge D | title = Antitussive agents as N-methylaspartate antagonists: further studies | journal = Canadian Journal of Physiology and Pharmacology | volume = 67 | issue = 6 | pages = 561–7 | year = 1989 | month = June | pmid = 2673498 | doi = | url = }}</ref><ref name="pmid18812887">{{cite journal | author = Kamel IR, Wendling WW, Chen D, Wendling KS, Harakal C, Carlsson C | title = N-methyl-D-aspartate (NMDA) antagonists--S(+)-ketamine, dextrorphan, and dextromethorphan--act as calcium antagonists on bovine cerebral arteries | journal = Journal of Neurosurgical Anesthesiology | volume = 20 | issue = 4 | pages = 241–8 | year = 2008 | month = October | pmid = 18812887 | doi = 10.1097/ANA.0b013e31817f523f | url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0898-4921&volume=20&issue=4&spage=241}}</ref>
* [[Sigma-1 receptor|σ<sub>1</sub>]] and [[Sigma-2 receptor|σ<sub>2</sub>]] [[sigma receptor]] agonist (K<sub>i</sub> = 205 nM and 11,060 nM, respectively). In a comparative investigation of [[dimemorfan]], dextromethorphan and [[dextrorphan]] in mouse cells, dextromethorpan binds with relatively high affinity to Sigma-1 receptors and with very low affinity to Sigma-2 receptors.<ref name="pmid10064839"/>
* [[alpha3beta4 nicotinic acetylcholine receptor|α<sub>3</sub>β<sub>4</sub>]]-, [[alpha4beta2 nicotinic acetylcholine receptor|α<sub>4</sub>β<sub>2</sub>]]-, and [[alpha7 nicotinic acetylcholine receptor|α<sub>7</sub>]]-[[nicotinic acetylcholine receptor|nACh receptor]] (K<sub>i</sub> = in the μM range) antagonist. Dextromethorphan binds to nicotinic receptors in frog eggs ([[Xenopus]] [[oocytes]]), human embryonic kidney cells and mouse tissue. It inhibits the antinociceptive (pain killing) action of nicotine in the tail-flick test in mice, where mouse tails are exposed to heat, which makes the mouse flick its tail if it feels pain.<ref name="pmid15356218">{{cite journal | author = Damaj MI, Flood P, Ho KK, May EL, Martin BR | title = Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 312 | issue = 2 | pages = 780–5 | year = 2005 | month = February | pmid = 15356218 | doi = 10.1124/jpet.104.075093 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15356218}}</ref><ref name="pmid16563374">{{cite journal | author = Lee JH, Shin EJ, Jeong SM, ''et al.'' | title = Effects of dextrorotatory morphinans on alpha3beta4 nicotinic acetylcholine receptors expressed in Xenopus oocytes | journal = European Journal of Pharmacology | volume = 536 | issue = 1-2 | pages = 85–92 | year = 2006 | month = April | pmid = 16563374 | doi = 10.1016/j.ejphar.2006.02.034 | url = http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00215-9}}</ref><ref name="pmid10869398">{{cite journal |author=Hernandez SC, Bertolino M, Xiao Y, Pringle KE, Caruso FS, Kellar KJ |title=Dextromethorphan and its metabolite dextrorphan block alpha3beta4 neuronal nicotinic receptors |journal=J. Pharmacol. Exp. Ther. |volume=293 |issue=3 |pages=962–7 |year=2000 |pmid=10869398 |doi=}}</ref>
* [[mu-Opioid receptor|μ]]-, [[delta-Opioid receptor|δ]]-, and [[kappa-Opioid receptor|κ]]-[[opioid receptor]] [[agonist]] (K<sub>i</sub> = 1,280 nM, 11,500 nM, and 7,000 nM, respectively).{{Citation needed|date=April 2010}}<ref name="pmid7562497">{{cite journal | author = Codd EE, Shank RP, Schupsky JJ, Raffa RB | title = Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 274 | issue = 3 | pages = 1263–70 | year = 1995 | month = September | pmid = 7562497 | doi = | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7562497}}</ref>
* [[Serotonin transporter|SERT]] and [[norepinephrine transporter|NET]] [[reuptake inhibitor|blocker]] (K<sub>i</sub> = 23 nM and 240 nM, respectively).<ref name="pmid7562497"/><ref name="pmid">{{cite journal | author = Henderson MG, Fuller RW | title = Dextromethorphan antagonizes the acute depletion of brain serotonin by p-chloroamphetamine and H75/12 in rats | journal = Brain Research | volume = 594 | issue = 2 | pages = 323–6 | year = 1992 | month = October | pmid = 1280529| doi = 10.1016/0006-8993(92)91144-4| url = http://linkinghub.elsevier.com/retrieve/pii/0006-8993(92)91144-4}}</ref><ref name="pmid16051647">{{cite journal | author = Gillman PK | title = Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity | journal = British Journal of Anaesthesia | volume = 95 | issue = 4 | pages = 434–41 | year = 2005 | month = October | pmid = 16051647 | doi = 10.1093/bja/aei210 | url = http://bja.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16051647}}</ref><ref name="pmid19238739">{{cite journal | author = Schwartz AR, Pizon AF, Brooks DE | title = Dextromethorphan-induced serotonin syndrome | journal = Clinical Toxicology (Philadelphia, Pa.) | volume = 46 | issue = 8 | pages = 771–3 | year = 2008 | month = September | pmid = 19238739 | doi = | url = }}</ref>
* [[NADPH oxidase]] inhibitor.<ref name="pmid14734632">{{cite journal | author= Zhang W, Wang T, Qin L, Gao HM, Wilson B, Ali SF, Zhang W, Hong JS, Liu B | title=Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase | journal=The FASEB Journal | date=20 January 2004| pmid= 14734632 | doi= 10.1096/fj.03-0983fje | volume= 18 | issue= 3 | pages= 589–91 }}</ref>

Its [[affinity (pharmacology)|affinities]] for some of the sites listed are relatively very low and are probably insignificant, such as binding to [[NMDA receptor]]s and [[opioid receptor]]s, even at high recreational doses.{{Citation needed|date=April 2010}} Instead of acting as a direct antagonist of the NMDA receptor itself, it is likely that dextromethorphan functions as a prodrug to its nearly 10-fold more potent metabolite dextrorphan, and this is the true mediator of its dissociative effects.<ref name="pmid10064839"/> It is not entirely clear what role, if any, [[(+)-3-methoxymorphinan]], dextromethorphan's other major metabolite, plays in its effects.<ref name="pmid9113345">{{cite journal | author = Schmider J, Greenblatt DJ, Fogelman SM, von Moltke LL, Shader RI | title = Metabolism of dextromethorphan in vitro: involvement of cytochromes P450 2D6 and 3A3/4, with a possible role of 2E1 | journal = Biopharmaceutics & Drug Disposition | volume = 18 | issue = 3 | pages = 227–40 | year = 1997 | month = April | pmid = 9113345| doi = 10.1002/(SICI)1099-081X(199704)18:3<227::AID-BDD18>3.0.CO;2-L}}</ref>

=== Pharmacokinetics ===

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 [[central nervous system|centrally]] (meaning that it acts on the [[brain]]) as opposed to locally (on the [[respiratory tract]]). It elevates the threshold for coughing, without inhibiting [[cilia]]ry 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 dosage necessary for effective antitussive therapy is between 10&nbsp;mg and 45&nbsp;mg, depending on the individual. The International Society for the Study of Cough recommend "an adequate first dose of medication ie 60 mg in the adult and repeat dosing should be infrequent rather than the qds recommended."<ref>Professor Alyn H Morice paper titled 'Cough' par. 'Dextromethorphan' http://www.issc.info/cough.html</ref>

The duration of action after oral administration is approximately three to eight hours for dextromethorphan-hydrobromide, and ten to twelve hours for dextromethorphan-polistirex. Approximately 1 in 10 of the caucasian population has little or no [[CYP2D6]] enzyme activity leading to long lived high drug levels.<ref>Professor Alyn H Morice paper titled 'Cough' http://www.issc.info/cough.html</ref>

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

=== Metabolism ===

The first-pass through the [[hepatic portal vein]] results in some of the drug's being metabolized by O-demethylation into an active [[metabolite]] of dextromethorphan called [[dextrorphan]] (DXO). DXO is the 3-hydroxy derivative of dextromethorphan.  The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite.  Dextromethorphan also undergoes N-demethylation (to 3-methoxymorphinan or MEM),<ref name="DXMdualprobe">{{cite web
|url=http://dmd.aspetjournals.org/cgi/content/full/29/11/1514
|title=Comparative Contribution to Dextromethorphan Metabolism by Cytochrome P450 Isoforms in Vitro: Can Dextromethorphan Be Used as a Dual Probe for Both CYP2D6 and CYP3A Activities?
|accessdate=2008-08-10}}</ref> 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]].<ref name="nhtsa" />

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. O-demethylation of DXM to DXO contributes to 100% of the DXO formed during DXM metabolism.<ref name="DXMdualprobe"/> 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.<ref>{{cite web |url=http://www.nature.com/clpt/journal/v60/n3/abs/clpt1996482a.html |title=Clinical Pharmacology & Therapeutics&nbsp;— Abstract of article: The influence of CYP2D6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans[ast] |accessdate=2007-07-16 |work=}}</ref> In one study on 252 Americans, 84.3% were found to be "fast" (extensive) metabolizers, 6.8% to be "intermediate" metabolizers, and 8.8% were "slow" metabolizers of DXM.<ref name="DXMpolymorphicmetabolism">{{cite web
|url=http://jcp.sagepub.com/cgi/content/abstract/27/2/139
|title=The polymorphic metabolism of dextromethorphan (abstract)
|accessdate=2008-08-10}}</ref>  There are a number of known [[allele]]s for CYP2D6, including several completely inactive variants.  The distribution of alleles is uneven amongst ethnic groups; see also [[CYP2D6#Ethnic_factors_in_variability|CYP2D6 - Ethnic factors in variability]].

A large number of medications are potent inhibitors of [[CYP2D6]]. Some types of medications known to inhibit CYP2D6 include certain [[SSRI]] and [[tricyclic]] [[antidepressant]]s, some antipsychotics, and the commonly-available [[antihistamine]] [[diphenhydramine]] -- also known as Benadryl. There exists, therefore, the potential of interactions between dextromethorphan and medications that inhibit this enzyme, particularly in slow metabolizers.  See also [[CYP2D6#CYP2D6_ligands|CYP2D6 - Ligands]].

DXM is also metabolized by [[CYP3A4]]. N-demethylation is primarily accomplished by CYP3A4, contributing to at least 90% of the MEM formed as a primary metabolite of DXM.<ref name="DXMdualprobe" />

A number of other CYP enzymes are implicated as minor pathways of DXM metabolism.  [[CYP2B6]] is actually more effective than CYP3A4 at N-demethylation of DXM, but, since the average individual has a much lower CYP2B6 content in his/her liver relative to CYP3A4, most N-demethylation of DXM is catalyzed by CYP3A4.<ref name="DXMdualprobe" />

== Side effects ==

Side-effects of dextromethorphan use can include:<ref name="nhtsa">{{cite web|url=http://www.nhtsa.dot.gov/PEOPLE/injury/research/job185drugs/dextromethorphan.htm|title=Dextromethorphan|work=NHTSA}}</ref>
{{col-begin}}
{{col-3}}
* [[Sudden infant death syndrome]] <ref>{{cite news| url=http://edition.cnn.com/2007/HEALTH/10/17/cough.syrup.deaths/index.html | work=CNN | title=Child deaths lead to FDA hearing on cough, cold meds - CNN.com | date=2007-10-17}}</ref>
* body [[rash]]/[[itching]] (see below)
* [[nausea]]
* [[drowsiness]]
* [[dizziness]]
* [[hallucinations]]*
{{col-3}}
* [[vomiting]]*
* blurred vision*
* [[dilated pupils]]*
* [[sweating]]*
* [[fever]]*
{{col-3}}
* [[hypertension]]*
* shallow [[Respiratory system|respiration]]*
* [[diarrhea]]*
* [[urinary retention]]*
* [[Closed-eye hallucination]]
{{col-end}}
* Note: In the article cited, those marked with asterisks are listed not as side effects per se, but , rather as overdose symptoms, occurring at dosages 12.5 to 75 times the recommended therapeutic dose.
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 50mg and up every day up to a month. Small lesions were believed to be found during the autopsy on the brain. However the only side effect the rats showed was a change in personality.<ref>{{cite journal |author=Olney J, Labruyere J, Price M |title=Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs |journal=Science |volume=244 |issue=4910 |pages=1360–2 |year=1989 |pmid=2660263 |doi=10.1126/science.2660263}}</ref><ref>{{cite journal |author=Hargreaves R, Hill R, Iversen L |title=Neuroprotective NMDA antagonists: the controversy over their potential for adverse effects on cortical neuronal morphology |journal=Acta Neurochir Suppl (Wien) |volume=60 |issue= |pages=15–9 |pmid=7976530 |year=1994}}</ref> In some rare documented cases, dextromethorphan has produced [[Substance dependence|psychological dependence]] in some people who used it recreationally. However, it does not produce [[Substance dependence|physical addiction]], according to the [[World Health Organization|WHO]] Committee on Drug Dependence.<ref>{{cite paper | author = WHO Expert Committee on Drug Dependence | title = Seventeenth Report | publisher = World Health Organization | year = 1970 | url = http://whqlibdoc.who.int/trs/WHO_TRS_437.pdf | format = [[Portable Document Format|PDF]] | accessdate = 2008-12-29}}</ref>

== Contraindications ==

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.<ref name="nhtsa" />

=== Drug interactions ===

Dextromethorphan should not be taken with any of the following:

* [[Monoamine oxidase inhibitor]]s (MAOIs)<ref name="nhtsa" />
* [[Serotonin reuptake inhibitor]]s (like SSRIs, SNRis, TCAs, etc.)<ref name="nhtsa" />
* Opiates
* [[CNS depressant]] drugs and substances, including some [[Psychoactive drug|psychotropics]] such as alcohol, will have a cumulative CNS depressant effect if taken with dextromethorphan.<ref name="nhtsa" />

== See also ==
{{Commons category}}
<div style="-moz-column-count:2; column-count:2; -webkit-column-count:2;">
* [[Antitussive]]
* [[Cough syrup]]
* [[Hallucinogen]]
* [[Dissociative]]s
** [[Ketamine]]
** [[Nitrous Oxide]]
** [[Phencyclidine]]
* [[Morphinan]]s
** [[Dextrorphan]]
** [[Dimemorfan]]
** [[Levomethorphan]]
** [[Methorphan]]
</div>

== References ==
{{Reflist|2}}
== External links ==
* [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Dextromethorphan U.S. National Library of Medicine: Drug Information Portal - Dextromethorphan]

{{Drug use}}
{{Antitussives}}
{{Depressants}}
{{Hallucinogens}}
{{Neurotoxins}}
{{Adrenergics}}
{{Cholinergics}}
{{Glutamatergics}}
{{Opioids}}
{{Serotonergics}}

[[Category:Antitussives]]
[[Category:Dissociative drugs]]
[[Category:Dopamine reuptake inhibitors]]
[[Category:Morphinans]]
[[Category:NMDA receptor antagonists]]
[[Category:Sigma agonists]]
[[Category:Serotonin receptor agonists]]
[[Category:Nicotinic antagonists]]
[[Category:Euphoriants]]
[[Category:Phenol ethers]]
[[Category:Enantiopure drugs]]

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