Dextromethorphan
Also known asd-Methorphan · delta-Methorphan · Dextromorphan · Dextromethorfan · Dextrometorfano · Dextromethorphane · Albutussin · Destrometerfano
(1S,9S,10S)-4-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene
- PubChem CID
- 5360696
- ChEMBL
- CHEMBL52440
- Measurements
- 25
- InChIKey
- MKXZASYAUGDDCJ-NJAFHUGGSA-N
I · Summary
What is known
Published passages, each quoted whole and attributed to the database that published it. Two blocks are written here rather than quoted, and both say so where they stand: the synthesized summary at the top, which may draw only on the passages beneath it, and the history note, which cites the works it came from. Every claim in either carries a marker to its source.
What it is
Dextromethorphan is a 6-methoxy-11-methyl-1,3,4,9,10,10a-hexahydro-2H-10,4a-(epiminoethano)phenanthrene in which the sterocenters at positions 4a, 10 and 10a have S-configuration. It is a prodrug of dextrorphan and used as an antitussive drug for suppressing cough. It has a role as a oneirogen, a xenobiotic, a prodrug, a neurotoxin, an antitussive, a NMDA receptor antagonist and an environmental contaminant. It is functionally related to a dextrorphan. It is an enantiomer of a levomethorphan.
Dextromethorphan is a levorphanol derivative and codeine analog commonly used as a cough suppressant and also a drug of abuse. Although similar in structure to other opioids, it has minimal interaction with opioid receptors. Dextromethorphan was granted FDA approval before 3 December 1957.
Dextromethorphan is an Uncompetitive N-methyl-D-aspartate Receptor Antagonist and Sigma-1 Agonist. The mechanism of action of dextromethorphan is as an Uncompetitive NMDA Receptor Antagonist and Sigma-1 Receptor Agonist.
Dextromethorphan is a synthetic, methylated dextrorotary analogue of levorphanol, a substance related to codeine and a non-opioid derivate of morphine. Dextromethorphan exhibits antitussive activity and is devoid of analgesic or addictive property. This agent crosses the blood-brain-barrier and activates sigma opioid receptors on the cough center in the central nervous system, thereby suppressing the cough reflex.
Recognized use
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations;…
Therapeutic Uses
Hazardous Substances Data Bank (HSDB)NIH/NLM; ClinicalTrials.Gov. Available from, as of August 30, 2017: https://clinicaltrials.gov/
Dextromethorphan is used for the temporary relief of coughs caused by minor throat and bronchial irritation such as may occur with common colds or with inhaled irritants. Dextromethorphan is most effective in the treatment of chronic, nonproductive cough. The drug is a common ingredient in commercial cough mixtures available without prescription.
Therapeutic Uses
Hazardous Substances Data Bank (HSDB)American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017, p. 2931
Dextromethorphan preparations are administered orally. Lozenges containing dextromethorphan hydrobromide should not be used in children younger than 6 years of age and liquid-filled capsules containing the drug should not be used in children younger than 12 years of age, unless otherwise directed by a clinician.
Therapeutic Uses
Hazardous Substances Data Bank (HSDB)OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 2931
For more Therapeutic Uses (Complete) data for Dextromethorphan (20 total), please visit the HSDB record page.
Therapeutic Uses
Dextromethorphan is indicated in combination with [brompheniramine] and [pseudoephedrine] in the treatment of coughs and upper respiratory symptoms associated with allergies or the common cold. Dextromethorphan is also used in combination with [guaifenesin] as an over-the-counter product to relieve a cough. Dextromethorphan in combination with [quinidine] is indicated in the treatment of pseudobulbar affect.
Drug Indication
Dextromethorphan is a centrally acting antitussive and a nonopioid morphinan derivative. Dextromethorphan also demonstrates additional neurologic and psychotropic applications beyond its role in cough suppression. Since the US Food and Drug Administration (FDA) approved dextromethorphan in 1958, its clinical use has expanded. The expanded therapeutic indications for dextromethorphan now include the treatment of pseudobulbar affect (PBA) when combined with quinidine. Additionally, the medication is used in a fixed-dose combination with bupropion for the treatment of major depressive disorder.
Drug Indication
Dextromethorphan (DXM) is an over-the-counter (OTC) cough suppressant commonly found in cold medications. DXM is often abused in high doses by adolescents to generate euphoria and visual and auditory hallucinations. Illicit use of DXM is referred to on the street as "Robo-tripping" or "skittling." These terms are derived from the most commonly abused products, Robitussin and Coricidin.
Use Classification
Hazardous Substances Data Bank (HSDB)Department of Justice; Drug Enforcement Administration (DEA), Dextromethorphan (July 2012). Available from, as of February 7, 2014: https://www.deadiversion.usdoj.gov/drug_chem_info/dextro_m.pdf
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 those resulting from inhaled irritants. 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.
Use Classification
How it acts
Dextromethorphan is a low-affinity uncompetitive NMDA antagonist and sigma-1 receptor agonist. It is also an antagonist of α3/β4 nicotinic receptors. However, the mechanism by which dextromethorphan's receptor agonism and antagonism translate to a clinical effect is not well understood.
Dextromethorphan (DXM) is the dextro isomer of levomethorphan, a semisynthetic morphine derivative. Although structurally similar to other /CNS depressants/, DXM does not act as a mu receptor opioid (eg, morphine, heroin). DXM and its metabolite, dextrorphan, act as potent blockers of the N-methyl-d-aspartate (NMDA) receptor.
Hazardous Substances Data Bank (HSDB)Department of Justice; Drug Enforcement Administration (DEA), Dextromethorphan (March 2014). Available from, as of August 30, 2017: https://www.deadiversion.usdoj.gov/drug_chem_info/dextro_m.pdf
Behavior carries the pharmacological classes and the acute-effect durations, with plasma half-life kept separate from duration of effect.
In the body
A 30mg oral dose of dextromethorphan reaches a Cmax of 2.9 ng/mL, with a Tmax of 2.86 h, and an AUC of 17.8 ng\*h/mL.
Absorption, Distribution and Excretion
The volume of distribution of dextromethorphan is 5-6.7L/kg.
Absorption, Distribution and Excretion
Dextromethorphan is rapidly absorbed from the GI tract and exerts its antitussive effect in 15-30 minutes after oral administration. The duration of action is approximately 3-6 hours with conventional dosage forms.
Absorption, Distribution and Excretion
Hazardous Substances Data Bank (HSDB)American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017, p. 2932
Dextromethorphan and its metabolites are excreted via the kidney. Depending on the metabolism phenotype up to 11% may be excreted unchanged or up to 100% as demethylated conjugated morphinan compounds. In the first 24 hours after dosing, less than 0.1% is eliminated in the feces.
Absorption, Distribution and Excretion
Hazardous Substances Data Bank (HSDB)International Programme on Chemical Safety; Poisons Information Monograph: Dextromethorphan (PIM 179) (1997). Available from, as of August 30, 2017: https://www.inchem.org/pages/pims.html
Dextromethorphan can be N-demethylated to 3-methoxymorphinan by CYP3A4, CYP2D6, and CYP2C9 or O-demethylated to dextrorphan by CYP2D6 and CYP2C9. Dextrorphan is N-demethylated by CYP3A4 and CYP2D6, while 3-methoxymorphinan is O-demethylated by CYP2D6. Both are metabolized to form 3-hydroxymorphinan. Dextrorphan and 3-hydroxymorphinan are both O-glucuronidated or O-sulfated.
Metabolism/Metabolites
Genetic polymorphism has profound effects on its metabolism. Dextromethorphan undergoes polymorphic metabolism depending on variation in cytochrome P-450 enzyme phenotype. The specific cytochrome P-450 enzyme is P450 2D6(CYP2D6). Fast metabolizers constitute about 84% of the population. After a 30 mg dose plasma levels are less than 5 ng/mL four hours postingestion. Intermediate metabolizers constitute about 6.8% of the population. After an oral dose of 30 mg plasma levels are 10 to 20 ng/mL at 4 hours and less than 5 ng/mL at 24 hours postingestion. Poor metabolizers constitute 5% to 10% of the Caucasian population. The ratio of metabolite to parent drug in 8 hour urine sample is less tha…
Metabolism/Metabolites
Hazardous Substances Data Bank (HSDB)International Programme on Chemical Safety; Poisons Information Monograph: Dextromethorphan (PIM 179) (1997). Available from, as of August 30, 2017: https://www.inchem.org/pages/pims.html
There is a clear first pass metabolism and it is generally assumed that the therapeutic activity is primarily due to its active metabolite, dextrophan.
Metabolism/Metabolites
Hazardous Substances Data Bank (HSDB)International Programme on Chemical Safety; Poisons Information Monograph: Dextromethorphan (PIM 179) (1997). Available from, as of August 30, 2017: https://www.inchem.org/pages/pims.html
It is metabolized in the liver by extensive metabolizers to dextrorphan. Dextrorphan is itself an active antitussive compound. Only small amounts are formed in poor metabolizers. Less than 15% of the dose form minor metabolites including D-methoxymorphinane.
Metabolism/Metabolites
Hazardous Substances Data Bank (HSDB)International Programme on Chemical Safety; Poisons Information Monograph: Dextromethorphan (PIM 179) (1997). Available from, as of August 30, 2017: https://www.inchem.org/pages/pims.html
History, discovery and cultural use
— Not in this archive. PubChem, ChEMBL and the Human Protein Atlas publish pharmacology, regulation and toxicology, and none of them publishes a heading for when Dextromethorphan was first made, by whom, or how it has been used. That is a gap in the databases this site reads and not a gap in the literature — the history of these compounds is written, at length and under peer review, in the works below. This site does not summarize them; it says where they are. Where a published passage above happens to touch origin or traditional use, it appears inside the entry that carries it.
Histories of this field
Scholarship on psychedelics generally, not on Dextromethorphan specifically. Whether any of these treats this compound is a question for the book, not for this page.
Mescaline: A Global History of the First Psychedelic
Traces mescaline and the peyote and San Pedro cacti from pre-Columbian ritual use through nineteenth-century chemistry to twentieth-century psychiatry and the counterculture.
Jay M. Mescaline: A Global History of the First Psychedelic. Yale University Press, New Haven and London; 2019. ISBN 9780300231076.
Expanding Mindscapes: A Global History of Psychedelicsopen access
Essays on the international and cross-cultural history of psychedelic science, deliberately decentring the standard North American and European account.
Dyck E, Elcock C, editors. Expanding Mindscapes: A Global History of Psychedelics. The MIT Press, Cambridge MA; 2023. ISBN 9780262546935 (paper), 9780262376891 (open access). doi:10.7551/mitpress/14417.001.0001.
Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers
Botany, ethnography and chemistry of the principal hallucinogenic plants, by the founder of modern ethnobotany and the chemist who first synthesized LSD.
Schultes RE, Hofmann A, Rätsch C. Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers. 2nd ed. Healing Arts Press, Rochester VT; 2001. ISBN 9780892819799.
Psychonauts: Drugs and the Making of the Modern Mind
The tradition of scientific self-experimentation with psychoactive drugs, and its part in the emergence of psychology and of modernism.
Jay M. Psychonauts: Drugs and the Making of the Modern Mind. Yale University Press, New Haven; 2023. ISBN 9780300257946.
Ancient Psychoactive Substances
Archaeological and bioarchaeological evidence for psychoactive plant use across the ancient world.
Fitzpatrick SM, editor. Ancient Psychoactive Substances. University Press of Florida, Gainesville; 2018. ISBN 9780813056708.
A chapter tracing psychedelic and entactogen research from earlier ritual use through the mid-century research period to current clinical trials.
Stroud C, Posey Norris SM, Matney C, editors. History and Current Status of Psychedelics and Entactogens for the Treatment of Psychiatric Disorders. In: Exploring Psychedelics and Entactogens as Treatments for Psychiatric Disorders: Proceedings of a Workshop. National Academies Press, Washington DC; 2022. NBK587225.
Workshop proceedings record what participants said; they are not a consensus statement of the National Academies.
Peer-reviewed review covering the isolation, synthesis, pharmacology and ritual use of peyote and mescaline.
Dinis-Oliveira RJ, Pereira CL, da Silva DD. Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions. Current Molecular Pharmacology 12(3):184–194; 2019. doi:10.2174/1874467211666181010154139.
Institutional archives
- Heffter Research Institute Funds and coordinates clinical research on psilocybin, and keeps records of the studies it has supported since 1993. Sponsors the research it archives.
- Multidisciplinary Association for Psychedelic Studies (MAPS) Sponsors clinical research, chiefly on MDMA-assisted therapy, and publishes an archive of historical and contemporary documents. A sponsor and an advocacy organization, not a disinterested archive; its clinical programme has a commercial arm.
The rest of this dossier
- Affinity — 25 measurements in this archive, equilibrium constants kept apart from functional readouts.
- Toxicology — 10 published passages, plus any assay in this archive bearing on toxicity.
- Legal — listed by the DEA among its drugs of concern, with no schedule stated in the record held here.
- Systems — where this compound’s targets are transcribed, by brain region and tissue.
Passages via PubChem descriptive sections, aggregating DrugBank, LiverTox, FDA, DEA, HSDB, EPA. Each is quoted whole and attributed to the database that published it. The only prose written here about Dextromethorphan is the history note, which says so on its face and carries a reference for every claim in it.
II · Identity
Structure and descriptors
Descriptors are computed here with RDKit from the structure PubChem returns — not from the archive's stored copy, so an edited local structure cannot reach this table.
- Formula
- C18H25NOR
- Molecular weight
- 271.40g/molR
- Exact mass
- 271.1936DaR
- cLogP
- 3.38R
- TPSA
- 12.5ŲR
- H-bond donors
- 0R
- H-bond acceptors
- 2R
- Rotatable bonds
- 1R
- Aromatic rings
- 1R
- Heavy atoms
- 20R
- Fraction sp³
- 0.667R
- Formal charge
- 0R
Computed with RDKit 2025.09.2 from the SMILES returned by PubChem. Audit run 26/09/2026.
III · Behavior
Behavioral summary
Class, mechanism, and the duration of acute effects — each quoted from the record or trial that publishes it. Duration of effects and plasma half-life are shown separately, because they are different quantities and diverge by a factor of three or four.
Classification
Duration of acute subjective effects
—
No controlled human trial reporting a duration for this compound is cited here. The archive does hold onset and duration ranges for it, inherited from an earlier build, but their source column is empty and so they cannot be shown. A duration is not inferred from a chemical relative.
Plasma elimination half-life
How fast the body clears the drug — not how long the effects last. The two diverge sharply: LSD is cleared with a half-life of about 2.6 h while its subjective effects run 8–12 h.
Dextromethorphan has a half life of 3-30 hours.
DrugBank The half life of /dextromethorphan/ is approximately 2 to 4 hours in people with normal metabolism.
Hazardous Substances Data Bank (HSDB)International Programme on Chemical Safety; Poisons Information Monograph: Dextromethorphan (PIM 179) (1997). Available from, as of August 30, 2017: https://www.inchem.org/pages/pims.html
Primary pharmacological drivers
ChEMBL holds no curated mechanism-of-action record for this compound. The measured affinities below are the evidence this archive has for what it binds.
Mechanism, as published
Quoted verbatim from the database named after each passage, never summarized.
Amantadine and dextromethorphan suppress levodopa (L-DOPA)-induced dyskinesia (LID) in patients with Parkinson's disease (PD) and abnormal involuntary movements (AIMs) in the unilateral 6-hydroxydopamine (6-OHDA) rat model. These effects have been attributed to N-methyl-d-aspartate (NMDA) antagonism. However, amantadine and dextromethorph…
Hazardous Substances Data Bank (HSDB)PMID 22861201Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573705 Dextromethorphan (DM) is a dextrorotatory morphinan and an over-the-counter non-opioid cough suppressant. We have previously shown that DM protects against LPS-induced dopaminergic neurodegeneration through inhibition of microglia activation. Here, we investigated protective effects of DM against endotoxin shock induced by lipopolysacchar…
Hazardous Substances Data Bank (HSDB)PMID 15627475Li G et al; Biochem Pharmacol 69 (2): 233-40 (2005) Dextromethorphan is a low-affinity uncompetitive NMDA antagonist and sigma-1 receptor agonist. It is also an antagonist of α3/β4 nicotinic receptors. However, the mechanism by which dextromethorphan's receptor agonism and antagonism translate to a clinical effect is not well understood.
DrugBank Dextromethorphan (DXM) is the dextro isomer of levomethorphan, a semisynthetic morphine derivative. Although structurally similar to other /CNS depressants/, DXM does not act as a mu receptor opioid (eg, morphine, heroin). DXM and its metabolite, dextrorphan, act as potent blockers of the N-methyl-d-aspartate (NMDA) receptor.
Hazardous Substances Data Bank (HSDB)Department of Justice; Drug Enforcement Administration (DEA), Dextromethorphan (March 2014). Available from, as of August 30, 2017: https://www.deadiversion.usdoj.gov/drug_chem_info/dextro_m.pdf Dextromethorphan is an opioid-like molecule indicated in combination with other medication in the treatment of coughs and pseudobulbar affect. It has a moderate therapeutic window, as intoxication can occur at higher doses. Dextromethorphan has a moderate duration of action. Patients should be counselled regarding the risk of intoxication…
DrugBank
IV · Clinical
Clinical description
Where this compound's substance class sits in ICD-11 and DSM-5-TR, and how much of the recorded literature speaks to each domain of a mental status examination.
No diagnostic chapter is shown for this compound. Either PubChem records no MeSH pharmacological class for it, or the class it records is not one of the substance classes ICD-11 gives a chapter to. Inferring a chapter from the compound’s name or its binding profile would be a diagnosis this archive is in no position to make.
How much has been written about each domain
The clinical domains, and how many of the records this archive holds for this compound say something under each. What the terms mean, and the word list behind every spoke, are set out in the method.
- Affect 1
- matched on “pseudobulbar affect” · in Pharmacology: Pharmacodynamics
- Mood 2
- matched on “depression”, “panic” · in Toxicology: Hazardous Substances Data Bank (HSDB); PMID 25622122
- Perception 3
- matched on “hallucinat”, “hallucinogen” · in PMID 22526529; PMID 22989498; PMID 25622122
- Cognition 1
- matched on “cognitiv” · in PMID 22989498
- Thought content 1
- matched on “grandios” · in PMID 25622122
- Psychomotor activity 3
- matched on “psychomotor”, “restless”, “sedat” · in Toxicology: Hazardous Substances Data Bank (HSDB); PMID 22526529; PMID 25622122
V · Systems
Systems physiology
Where the targets this compound binds are transcribed — brain regions on the left, peripheral and autonomic tissues on the right. A join of two measurements, not a claim about what the compound does to either.
Brain
basal ganglia: drawn as the caudate nucleus, putamen and globus pallidus.
Measured but not drawn — this anatomogram has no outline for them: retina 0.9, midbrain 0.6, pituitary gland 0.4, spinal cord 0.2.
Body
Square-root ramp · shared scale across both plates
Shading is transcript level — not affinity, and not affinity combined with expression. Outlined but unshaded organs hold none of this compound’s resolved targets above the atlas’s detection threshold. Anatomy from EMBL-EBI Anatomogram (Apache License 2.0); regions identified by Uberon (uberon.org), CC BY 3.0.
Brain regions
Regions where this compound's measured targets are transcribed. Linked from the plate above.
cerebellum
4.4 nTPMbasal ganglia
3.8 nTPMhypothalamus
2.6 nTPMcerebral cortex
2.0 nTPMamygdala
1.9 nTPMretina
0.9 nTPMmidbrain
0.6 nTPMhippocampal formation
0.6 nTPMpituitary gland
0.4 nTPMspinal cord
0.2 nTPM
Peripheral & autonomic
Tissues outside the CNS expressing the same targets — where a compound's bodily effects become possible.
liver
386.2 nTPMsmall intestine
38.0 nTPMlung
27.2 nTPMadrenal gland
9.9 nTPMduodenum
9.7 nTPMpancreas
1.3 nTPMsalivary gland
1.1 nTPMskeletal muscle
1.0 nTPMheart muscle
0.9 nTPMstomach 1
0.8 nTPMcolon
0.5 nTPMthyroid gland
0.4 nTPMspleen
0.4 nTPMkidney
0.3 nTPMsmooth muscle
0.3 nTPMurinary bladder
0.1 nTPM
Each row joins two published measurements and nothing else: the affinity this archive holds for the compound at that target, and the transcript level the Human Protein Atlas reports for that target’s gene in that region. Bars scale with expression only. Expression is not activation — a receptor transcribed in a region is a receptor available to be bound there, which is a weaker and more defensible claim than saying the region is affected.
3 of this compound’s targets could not be resolved to a gene and are absent from both columns: NMDA, Sigma 1, Sodium channel alpha subunits; brain (Types I, II, III).
Expression data from Human Protein Atlas (CC BY-SA 3.0), RNA expression, nTPM (normalized transcripts per million), consensus tissue dataset. Uhlén M, et al. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.
VI · Profile
Affinity rosette
The strongest measurement at each of 8 molecular targets. Cell-line and whole-organism screens are excluded here — they carry no affinity — and appear in the table below.
VII · Toxicology
Toxicological profile
What has been measured, and what has been published — kept apart, and neither scored. There is no risk rating on this page; the archive once carried one, identical for every compound, produced by a stub.
Measured in this archive
Assays that bear on toxicity, drawn from the same ChEMBL records as everything else on this page. They are measurements of what a compound binds or does to cells — not verdicts about what it does to a person.
Cytochrome P450 inhibition 4
Inhibition of a drug-metabolising enzyme, which is how interactions arise — the harmala alkaloids' MAO inhibition is the same kind of fact, and appears with the measurements above.
- Cytochrome P450 2D6IC5043.00nMCHEMBL5117646
- Cytochrome P450 2D6IC5052.00nMCHEMBL5332454
- Cytochrome P450 2D6IC50242nMCHEMBL5609488
- Cytochrome P450 2D6Potency2,512nMCHEMBL1614110
Lethal-dose values — animal studies
These are not human doses. An LD50 is the dose killing half of a group of animals of one species by one route, and it is a poor predictor of human risk for these compounds. Each value is printed whole, with the species and route it was measured in, because a lethal dose separated from those two facts is worse than no figure at all. Nothing here supports inferring a safe dose for anyone.
LD50 Mouse sc 112 mg/kg
Hazardous Substances Data Bank (HSDB)Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1101
LD50 Mouse oral 201 mg/kg
Hazardous Substances Data Bank (HSDB)Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1101
As published
Quoted verbatim from the database named after each passage, never summarized — a summary of a toxicology statement is a new claim.
Toxicity Summary
IDENTIFICATION AND USE: Dextromethorphan is a white odorless solid crystal or powder. It is an opium alkaloid derivative, which is found in cough and cold preparations. HUMAN STUDIES: Dextromethorphan is a drug of abuse. The main risks associated with dextromethorphan are ataxia, central nervous system (CNS) stimulation, dizziness, lethargy and psychotic behavior. Less frequently with large doses seizures and respira…
Signs and Symptoms of Overdose
Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The firs…
Human Toxicity Excerpts
/HUMAN EXPOSURE STUDIES/ Dextromethorphan (DXM) is abused most commonly among adolescents as a recreational drug to generate a dissociative experience. The objective of the study was to assess driving with and without DXM ingestion. The effects of one-time maximum daily doses of DXM 120 mg versus a guaifenesin 400 mg dose were compared among 40 healthy subjects using a crossover design. Subjects' ability to drive was…
Hazardous Substances Data Bank (HSDB)PMID 26294136Perry PJ et al; J Forensic Sci 60 (5): 1258-62 (2015)
/HUMAN EXPOSURE STUDIES/ This study in humans evaluated the effects of supratherapeutic doses of dextromethorphan (DXM) and triazolam. Single, acute oral doses of DXM (100, 200, 300, 400, 500, 600, 700, and 800 mg/70 kg), triazolam (0.25 and 0.5 mg/70 kg), and placebo were administered to 12 healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Su…
Hazardous Substances Data Bank (HSDB)PMID 22526529Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652430
/HUMAN EXPOSURE STUDIES/ Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5mg/70 kg), and pla…
Hazardous Substances Data Bank (HSDB)PMID 22989498Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562553
/SIGNS AND SYMPTOMS/ Dextromethorphan (DXM) in combination with antihistamines and/or pseudoephedrine is widely available as an over-the-counter remedy commonly used for relief of colds and cough. In supratherapeutic amounts, DXM can be extremely activating. These cough preparations have been adopted by many young users of recreational drugs for their psychoactive effects. When used in amounts exceeding those recomme…
Hazardous Substances Data Bank (HSDB)PMID 25622122Stanciu CN, Penders TM; J Addict Med 9 (2): 159-60 (2015)
For more Human Toxicity Excerpts (Complete) data for Dextromethorphan (23 total), please visit the HSDB record page.
Published passages via PubChem toxicology sections, aggregating Hazardous Substances Data Bank (HSDB), RTECS, LiverTox. No figure on this page is scored, ranked or combined into a risk level.
VIII · Evidence
Every measurement
One row per published value. The identifier in the last column resolves to the ChEMBL assay record it was read from.
Equilibrium binding constants 13
Ki and Kd — a concentration at equilibrium. Directly comparable across rows at the same target.
| Target | Class | Type | Value (nM) | pX | Organism | Assay |
|---|---|---|---|---|---|---|
| SERT | Monoamine transporters | Ki | 1.44 | 8.84 | Homo sapiens | CHEMBL1909109 |
| Sigma 1 | Sigma receptors | Ki | 10.00 | 8.00 | Cavia porcellus | CHEMBL4775642 |
| SERT | Monoamine transporters | Ki | 23.00 | 7.64 | RAT | PMID 7562497 |
| Sigma 1 | Sigma receptors | Ki | 63.00 | 7.20 | Cavia porcellus | CHEMBL4775632 |
| NET | Monoamine transporters | Ki | 240 | 6.62 | RAT | PMID 7562497 |
| Sigma 1 | Sigma receptors | Ki | 348 | 6.46 | Homo sapiens | CHEMBL808203 |
| MOR | Opioid receptors | Ki | 1,280 | 5.89 | RAT | PMID 7562497 |
| Unchecked | Unclassified | Ki | 1,636 | 5.79 | — organism not recorded | CHEMBL1909154 |
| NMDA | Glutamate receptors | Ki | 1,680 | 5.77 | Homo sapiens | CHEMBL761030 |
| NMDA | Glutamate receptors | Ki | 2,246 | 5.65 | Rattus norvegicus | CHEMBL764638 |
| NMDA | Glutamate receptors | Ki | 4,540 | 5.34 | Rattus norvegicus | CHEMBL978910 |
| Sigma 1 | Sigma receptors | Ki | 5,070 | 5.29 | Rattus norvegicus | CHEMBL807413 |
| KOR | Opioid receptors | Ki | 7,000 | 5.15 | RAT | PMID 7562497 |
Functional readouts 12
IC₅₀, EC₅₀, AC₅₀ and potency. Assay-dependent, and not interchangeable with a binding constant.
| Target | Class | Type | Value (nM) | pX | Organism | Assay |
|---|---|---|---|---|---|---|
| SERT | Monoamine transporters | IC50 | 2.71 | 8.57 | Homo sapiens | CHEMBL1909109 |
| Sigma 1 | Sigma receptors | IC50 | 15.20 | 7.82 | Cavia porcellus | CHEMBL946010 |
| Cytochrome P450 2D6 | Enzymes | IC50 | 43.00 | 7.37 | Homo sapiens | CHEMBL5117646 |
| Cytochrome P450 2D6 | Enzymes | IC50 | 52.00 | 7.28 | Homo sapiens | CHEMBL5332454 |
| Sigma 1 | Sigma receptors | IC50 | 232 | 6.63 | Cavia porcellus | CHEMBL946009 |
| Cytochrome P450 2D6 | Enzymes | IC50 | 242 | 6.62 | Homo sapiens | CHEMBL5609488 |
| Sodium channel alpha subunits; brain (Types I, II, III) | Ion channels | IC50 | 1,300 | 5.89 | Rattus norvegicus | CHEMBL804528 |
| NMDA | Glutamate receptors | IC50 | 1,320 | 5.88 | Rattus norvegicus | CHEMBL3619813 |
| Unchecked | Unclassified | IC50 | 2,415 | 5.62 | — organism not recorded | CHEMBL1909154 |
| Cytochrome P450 2D6 | Enzymes | Potency | 2,512 | 5.60 | Homo sapiens | CHEMBL1614110 |
| NET | Monoamine transporters | IC50 | 16,540 | 4.78 | Homo sapiens | CHEMBL6117149 |
| SERT | Monoamine transporters | IC50 | 33,000 | 4.48 | Homo sapiens | CHEMBL6117148 |
- P
- PubChem
- C
- ChEMBL
- R
- Computed here with RDKit
- D
- Derived here from the stored measurement
IX · Trials
Registered clinical trials
Studies filed with ClinicalTrials.gov that name this compound as an intervention. A registered trial is a protocol, not a result — status and enrollment are printed beside every row, and withdrawn studies are counted rather than hidden.
129T
Registered studies
13T
Open or ongoing
125T
With a phase recorded
By phase
A study may carry two phase codes at once, so these count studies bearing each phase and do not sum to the total.
- Early phase 13
- Phase 152
- Phase 231
- Phase 317
- Phase 415
- Not applicable13
By status
The registry’s own status for each record. Withdrawn and terminated studies are counted here rather than hidden — a stopped trial is part of what is known.
- Completed92
- Terminated11
- Recruiting10
- Unknown status10
- Active, not recruiting2
- Withdrawn2
- Not yet recruiting1
- No longer available1
The 25 most recently started, of 129
Newest first by start date. Each identifier opens the registry record it came from; the title is the sponsor’s own, quoted.
- NCT07766655Recruiting · Phase 3
Studying NMDA and Sigma-1 in Smoking Cessation Treatment (SUMMIT)
- Enrollment
- 705Testimated
- Started
- 2026-08-27
- Sponsor
- Axsome Therapeutics, Inc.
Conditions Smoking Cessation
Matched “Dextromethorphan” in the study’s intervention “AXS-05 (dextromethorphan-bupropion)”
- NCT07665723Recruiting · Phase 1
An Early-Stage Study in Multiple Clinics of How Afimkibart May Affect the Body's Processing of Medicines That Rely on Cytochrome P450 Enzymes in Participants With Ulcerative Colitis
- Enrollment
- 25Testimated
- Started
- 2026-06-29
- Sponsor
- Hoffmann-La Roche
Conditions Active Ulcerative Colitis
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT07386730Recruiting · Phase 1
A Study of Psychedelics in Healthy Older Adults With Low Well-being
- Enrollment
- 80Testimated
- Started
- 2026-06-01
- Sponsor
- Jennifer Mitchell
Conditions Anhedonia in Healthy Volunteers · Older Adults (50-90 Years)
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan (DXM)”
- NCT07583589Not yet recruiting · Phase 2
Nintedanib With or Without Dextromethorphan in Patients With Idiopathic Pulmonary Fibrosis (IPF)
- Enrollment
- 60Testimated
- Started
- 2026-05-12
- Sponsor
- First Affiliated Hospital of Wenzhou Medical University
Conditions Idiopathic Pulmonary Fibrosis (IPF)
Matched “Dextromethorphan” in the study’s intervention “Nintedanib,Dextromethorphan”
- NCT07241065Completed · Phase 1
A Study to Investigate the Effect of Capivasertib on the Pharmacokinetics of Oral Dextromethorphan (CYP2D6 Substrate) in Healthy Participants
- Enrollment
- 42Tactual
- Started
- 2026-03-19
- Sponsor
- AstraZeneca
Conditions Healthy Participants
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT07523048Recruiting · Phase 2
Dextromethorphan-Bupropion on Striatal Activity in Adults With Major Depressive Disorder
- Enrollment
- 30Testimated
- Started
- 2025-11-21
- Sponsor
- Roger McIntyre
Conditions Major Depressive Disorder (MDD)
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan-Bupropion”
- NCT06383338Recruiting · Phase 1
A Study Investigating the Change in Metabolism Phenotype in Paediatric, Adolescent & Young Adults With Hodgkin or Non-Hodgkin Lymphoma.
- Enrollment
- 10Testimated
- Started
- 2025-07-22
- Sponsor
- Murdoch Childrens Research Institute
Conditions Hodgkin Lymphoma · Non Hodgkin Lymphoma
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT06957223Completed · Not applicable
Efficacy of Dextromethorphan-Bupropion Versus SSRIs in the Treatment of Major Depressive Disorder
- Enrollment
- 80Tactual
- Started
- 2025-05-06
- Sponsor
- Asad Ullah Jan
Conditions Major Depressive Disorder (MDD)
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan-Bupropion”
- NCT06958692Recruiting · Phase 3
A Trial of Dextromethorphan and Bupropion Sustained-Release Tablets in Patients With Major Depressive Disorder
- Enrollment
- 388Testimated
- Started
- 2025-04-11
- Sponsor
- CSPC Ouyi Pharmaceutical Co., Ltd.
Conditions Major Depressive Disorder (MDD)
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan and Bupropion Sustained-Release Tablets”
- NCT06772753Recruiting · Phase 1
Investigation of Psychedelic Effects in Psychoactive Substances
- Enrollment
- 50Testimated
- Started
- 2025-02-05
- Sponsor
- Johns Hopkins University
Conditions Psychedelic Effects in Healthy Volunteers
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan (DXM)”
- NCT06736509Terminated · Phase 3
An Open-Label Study to Assess the Long-term Safety of AXS-05 in Subjects With Dementia of the Alzheimer's Type, ADVANCE-2 and ACCORD-2 Extension Study
- Enrollment
- 139Tactual
- Started
- 2024-11-21
- Sponsor
- Axsome Therapeutics, Inc.
Conditions Agitation in Patients With Dementia of the Alzheimer's Type · Alzheimer Disease · Agitation, Psychomotor
Matched “Dextromethorphan” in the study’s intervention “AXS-05 (dextromethorphan-bupropion)”
- NCT06632990Active, not recruiting · Phase 1
A Study Evaluating the Potential of BMS-984923 to Alter the Systemic Exposure of Three Orally Administered Probe Substrates
- Enrollment
- 36Testimated
- Started
- 2024-11-04
- Sponsor
- Allyx Therapeutics
Conditions Drug Drug Interaction (DDI)
Matched “Dextromethorphan” in the study’s intervention “dextromethorphan”
- NCT06566794Completed · Not applicable
KF2022#4-trial: Effects of a Beta Blocker and NSAID on CYP Mediated Drug Metabolism
- Enrollment
- 12Tactual
- Started
- 2024-08-22
- Sponsor
- Helsinki University Central Hospital
Conditions Drug Interaction
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan Oral Solution”
- NCT06348290Unknown status · Phase 1
Study to Evaluate the Drug-drug Interaction of JMKX001899 in Healthy Subjects
- Enrollment
- 72Testimated
- Started
- 2024-04-01
- Sponsor
- Jemincare
Conditions Solid Tumor, Adult
Matched “Dextromethorphan” in the study’s intervention “dextromethorphan”
- NCT05068791Recruiting · Early phase 1
Psilocybin-facilitated Treatment for Chronic Pain
- Enrollment
- 30Testimated
- Started
- 2023-11-01
- Sponsor
- University of Alabama at Birmingham
Conditions Fibromyalgia, Primary
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT05944510Completed · Phase 4
Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia
- Enrollment
- 40Tactual
- Started
- 2023-08-31
- Sponsor
- All India Institute of Medical Sciences, Bhubaneswar
Conditions Treatment Resistant Schizophrenia
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT05699993Completed · Phase 1
A Study of IBI351 in Healthy Subjects
- Enrollment
- 24Tactual
- Started
- 2023-03-10
- Sponsor
- Innovent Biologics (Suzhou) Co. Ltd.
Conditions Healthy Subjects
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT05947604Completed · Phase 1
DDI Study of Single Oral Dose of Acoziborole With Sequential Co-administration of Midazolam and Dextromethorphan
- Enrollment
- 20Tactual
- Started
- 2023-02-09
- Sponsor
- Drugs for Neglected Diseases
Conditions Trypanosomiasis, African
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT05602675Completed · Phase 1
A Drug Interaction Study of LY3871801 in Healthy Participants
- Enrollment
- 39Tactual
- Started
- 2022-11-02
- Sponsor
- Eli Lilly and Company
Conditions Healthy
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT05278494Recruiting · Not applicable
Dextromethorphan for Treatment of Postoperative Pain
- Enrollment
- 160Testimated
- Started
- 2022-09-15
- Sponsor
- Nathanael Heckmann
Conditions Post-operative Pain
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan Hydrobromide”
- NCT05444556Completed · Phase 1
A Study of Imlunestrant (LY3484356) in Female Healthy Participants
- Enrollment
- 113Tactual
- Started
- 2022-07-07
- Sponsor
- Eli Lilly and Company
Conditions Healthy
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT05236530Completed · Phase 1
Drug-drug Interaction Study of Ganaplacide and Lumefantrine With Midazolam, Repaglinide, Dextromethorphan, Metformin, Rosuvastatin and Dolutegravir
- Enrollment
- 48Tactual
- Started
- 2022-03-09
- Sponsor
- Novartis Pharmaceuticals
Conditions Malaria
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT05181527Completed · Phase 4
Repurposing of Dextromethorphan as an Adjunct Therapy in Patients With Major Depressive Disorder
- Enrollment
- 60Tactual
- Started
- 2022-02-10
- Sponsor
- All India Institute of Medical Sciences, Bhubaneswar
Conditions Major Depressive Disorder
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT04899687Recruiting · Phase 2
Study of Dextromethorphan in OCD and Related Disorders
- Enrollment
- 60Testimated
- Started
- 2022-01-20
- Sponsor
- Stanford University
Conditions Obsessive-Compulsive Disorder · Illness Anxiety Disorder · Body Dysmorphic Disorders · Somatic Symptom Disorder
Matched “Dextromethorphan” in the study’s intervention “Dextromethorphan”
- NCT04947553Completed · Phase 3
A Study to Assess the Long-term Safety and Efficacy of AXS-05 in Subjects With Alzheimer's Disease Agitation
- Enrollment
- 456Tactual
- Started
- 2021-06-17
- Sponsor
- Axsome Therapeutics, Inc.
Conditions Agitation in Patients With Dementia of the Alzheimer's Type · Alzheimer Disease · Agitation, Psychomotor
Matched “Dextromethorphan” in the study’s intervention “AXS-05 (dextromethorphan-bupropion)”
Records from ClinicalTrials.gov (U.S. National Library of Medicine, NIH), API v2. A study is listed against a compound only when a verified name for that compound appears as a whole word in one of the study's own intervention names. A short code must appear as written, and a name the registry uses for something else (Aleph, a vaccine maker) is not matched. Title matches are not accepted. The matched name and the intervention text it matched are shown with every row.
Searched as Dextromethorphan · d-Methorphan · delta-Methorphan. Run this search at the registry — it returns the unfiltered result, including studies this page rejected as belonging to a different molecule.
A registered trial is a protocol somebody filed with the registry. It is not a result, and nothing on this plate says whether Dextromethorphan worked.
X · Legal
Controlled-substance status
United States federal scheduling, read from the DEA records this archive holds and shown with the passage each was read from. Not legal advice, and not necessarily current.
- DEA class
- Other Substances
- Added
- October 1998
As the DEA states it
Quoted whole. The badge above is a reading of these passages and adds nothing to them.
Dextromethorphan (Class: Other Substances, Added Date: 10-1998)
Other regulatory records
Registers outside the DEA that hold an entry for Dextromethorphan — chemical-safety and national inventories, each naming itself. They are not scheduling decisions.
Antitussive active ingredients. The active ingredients of the product consist of the following when used within the dosage limits and in the dosage forms established for each ingredient in section 341.74(d): Dextromethorphan and dextromethorphan hydrobromide are included on this list.
Hazardous Substances Data Bank (HSDB)21 CFR 341.14 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of October 18, 2017: https://www.ecfr.gov
The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including dextromethorphan hydrobromide, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Dextromethorphan hydrobromide/
Hazardous Substances Data Bank (HSDB)DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of October 18, 2017: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed over-the-counter drug products, including dextromethorphan hydrobromide, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Dextromethorphan hydrobromide/
Hazardous Substances Data Bank (HSDB)DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of October 18, 2017: https://www.fda.gov/cder/ob/
United States federal status only. State law differs, and so does the law of every other country — none of it is represented here. Scheduling changes, and this reflects the DEA records held by PubChem descriptive sections when the monograph was last harvested, not necessarily today. This is a record of what a database publishes, not legal advice.
XI · Literature
Sources behind this dossier
The papers this compound's values were read from, ranked by what each contributed. Not a review of the field.
Every paper below is one some value on this page came from — a binding constant, a passage of pharmacology or toxicology, or a measured duration. Each entry says what this archive took from it. Nothing else is claimed about any of them: the title is the study’s own account of itself, and a summary written here would be an assertion with no source behind it.
- 01
Codd EE, Shank RP, Schupsky JJ et al. · The Journal of pharmacology and experimental therapeutics 1995
- · 4 measurements at 4 targets (Ki), strongest SERT at 7.64 pX
- 02
Mania after misuse of dextromethorphan: a case report and brief review of "robotripping"
Stanciu CN, Penders TM · Journal of addiction medicine 2015
- · Human Toxicity Excerpts
- 03
The Effects of Dextromethorphan on Driving Performance and the Standardized Field Sobriety Test
Perry PJ, Fredriksen K, Chew S et al. · Journal of forensic sciences 2015
- · Human Toxicity Excerpts
- 04
Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans
Carter LP, Reissig CJ, Johnson MW et al. · Drug and alcohol dependence 2013
- · Human Toxicity Excerpts
- 05
Paquette MA, Martinez AA, Macheda T et al. · The European journal of neuroscience 2012
- · Mechanism of Action
- 06
High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens
Reissig CJ, Carter LP, Johnson MW et al. · Psychopharmacology 2012
- · Human Toxicity Excerpts
- 07
Protective effect of dextromethorphan against endotoxic shock in mice
Li G, Liu Y, Tzeng NS et al. · Biochemical pharmacology 2005
- · Mechanism of Action