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Dextromethorphan

  • Prescription medicine
  • Prescription only
  • Identity checked
  • Sources last checked 2026-09-04

This page shows what was measured, who it was measured in, and what that does not settle.

What Dextromethorphan does in the body

The liver enzyme CYP2D6 clears it very efficiently, so ordinary doses never build up.

At the dose in a cough syrup, dextromethorphan quietens the cough reflex in the brainstem. At much higher doses, and in people whose CYP2D6 works poorly, enough survives to block the NMDA glutamate receptor, which is what ketamine and PCP do — hence the dissociation. The prescription antidepressant exploits that same bottleneck deliberately: bupropion inhibits CYP2D6, so a modest dose of dextromethorphan reaches concentrations it otherwise could not, and stays there.

Why people take it. Suppressing cough, or paired with bupropion as a prescription antidepressant.

What happened in people

The antidepressant combination improved depression by just under four points beyond inactive treatment over six weeks.

Reviewed first-read answer

Where this came from

A person wrote this and a reviewer approved it against this exact record. It carries no effect size.

A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.

No source is stored against this line.

The limit that matters most

The key study did not compare the combination with bupropion alone, so dextromethorphan’s contribution is unclear.

Where it acts
Medullary cough centre at antitussive doses; NMDA receptors and sigma-1 chaperone sites throughout the central nervous system at the doses used for depression and abused recreationally
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.

What the registries record it as

  • The substance registry classes this as chemical.

    FDA substance registry · 7355X3ROTS · read 2026-08-29

Where each sentence above came from

A person wrote this explanation into the record, with the studies named in the path below.

A reviewer approved this sentence against this exact record and its sources.

The limit a reviewer approved as the one that matters most here.

The four opening statements run to 110 words.

Words this page uses

Four words worth knowing first

Chosen from what this page shows, with each one explained before the word it depends on.

Stand-in result

A stand-in result is a number measured because the real result takes too long.

A picture of it, and where the picture fails

It is like judging a journey by the speedometer rather than by arriving.

Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.

What people get wrong. A stand-in result is often reported as the result itself.

A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.

Randomisation

Randomisation means chance decides who gets which treatment.

A picture of it, and where the picture fails

It is like a coin toss deciding the groups.

Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.

What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.

Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.

Confidence interval

A confidence interval is the range the true answer is likely to sit in.

A picture of it, and where the picture fails

It is like a weather forecast giving a range rather than one number.

Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.

What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.

An interval estimate that would contain the true parameter in a stated proportion of repeated studies.

Pathway

A pathway is a chain of steps inside a cell, each one setting off the next.

A picture of it, and where the picture fails

A pathway is like a row of dominoes.

Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.

What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.

An ordered series of molecular interactions producing a defined cellular change.

What happened in peopleRead from sources, not yet reviewed

What was measured, goal by goal

One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.

Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.

There is no single score. A strong test result and a weak life result are different facts.

Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
GoalLife outcomeWhat a body can doHow a person feelsA test resultA step in the bodyHarmsHow longWho was studied
PainNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Waiting for a reviewer3 registered symptom measure.Nothing in the sources checkedNo registered study lists a test result for this goal.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
MoodNothing in the sources checkedNo registered study lists a life outcome for this goal.Nothing in the sources checkedNo registered study lists a performance measure for this goal.Waiting for a reviewer1 registered symptom measure.Nothing in the sources checkedNo registered study lists a test result for this goal.Nothing in the sources checkedNo registered study lists a body-step measure for this goal.Not recordedHarms were not a registered measure for this goal.Not recordedNo finished study window is recorded.Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Pain
pain tolerance; pain intensity; peak pain intensity
Mood
hamilton depression rating scale

Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.

What each mark on this table means
Nothing in the sources checked
No registered study lists a life outcome for this goal.
Waiting for a reviewer
3 registered symptom measure.
Not recorded
Harms were not a registered measure for this goal.

What happened in peopleRead from sources, not yet reviewed

What happened in people

Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.

Change from baseline to week 6 in MADRS total score

The study showed what it set out to show

Who was studied
GEMINI (AXS-05 dextromethorphan-bupropion in major depressive disorder)
How many people
327
Study design
Phase 3 randomised, double-blind, placebo-controlled
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Least-squares mean difference -3.87, 95% CI -1.39 to -6.36, p = 0.002; remission 39.5% versus 17.3%, p < 0.001
Repeated elsewhere
Partially Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. The comparator was placebo, not bupropion alone, so the trial cannot attribute the effect to the dextromethorphan component. The placebo arm improved by 12.0 MADRS points, which is a large placebo response and compresses the measurable drug effect.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral — syrup, gel capsule, or fixed-dose tablet with a CYP2D6 inhibitor

Interval reported. 95% CI -1

Written into the record, not signed off as a reviewed claim.

Annual rate of single-substance dextromethorphan intentional-abuse exposure calls per million population

The study showed what it set out to show

Who was studied
Karami et al. 2018 National Poison Data System analysis (FDA)
How many people
1761
Study design
National surveillance analysis, 2000-2015
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Rate tripled 2000-2006 then plateaued; adolescents 14-17 fell 56.3% from 143.8 to 80.9 calls per million between 2006 and 2015
Repeated elsewhere
Replicated

What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.

The limits of this study, and where it came from

Main limit. Poison-centre calls measure calls, not exposures. A decline is consistent with reduced abuse, with reduced calling, or with both, and the analysis cannot separate them.

How far it carries. This study is recorded from the curated record, not from the registry match.

Form and route. Oral — syrup, gel capsule, or fixed-dose tablet with a CYP2D6 inhibitor

Interval reported. Not recorded in this summary

Written into the record, not signed off as a reviewed claim.

What we know
RNAWiki holds 2 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.

What happened in peopleRead from sources, not yet reviewed

How close this is to real life

The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.

  1. Living longer, or avoiding a major event Evidence recorded. Death, a heart attack, a stroke, a hospital stay.1 registered measure of this kind. No reviewed result.
  2. What a body can do day to day No evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
  3. Measured performance No evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
  4. Symptoms and quality of life Evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.4 registered measures of this kind.
  5. A number that stands in for health Evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.8 registered measures of this kind.
  6. A step measured inside a person Evidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
  7. Animals Evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Mouse. A result in animals says what to test next. It does not say what happens in people.
  8. Cells in a dish Evidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
  9. A guess from software No evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.

Higher on these steps means closer to something a person would feel. It does not mean better done.

What it changes in the bodyRead from sources, not yet reviewed

The path through the body

From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.

  1. Start

    Dextromethorphan

    What a person takes: Oral — syrup, gel capsule, or fixed-dose tablet with a CYP2D6 inhibitor.

    The measurement behind this step

    Over-the-counter delivery is a syrup or capsule, almost always combined with other actives. Prescription delivery is a fixed-dose tablet in which the second ingredient exists to raise dextromethorphan exposure: 10 mg quinidine in Nuedexta, 105 mg bupropion in Auvelity. The combination is the delivery system.

  2. Getting in

    Swallowed, usually as a syrup

    The antitussive dose is tens of milligrams. The prescription antidepressant tablet contains 45 milligrams alongside bupropion.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Oral dextromethorphan hydrobromide. Absorption is rapid, but systemic exposure to the parent compound is low and highly variable because of extensive first-pass metabolism, and varies with CYP2D6 genotype more than with the dose taken.

  3. Reaching the cell

    Destroyed by CYP2D6 — unless something blocks it

    A liver enzyme clears it almost completely on the first pass. Both prescription products include a second drug whose purpose is to stop that enzyme working.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    CYP2D6-mediated O-demethylation to dextrorphan, with minor CYP3A4 N-demethylation to 3-methoxymorphinan. Quinidine at 10 mg in Nuedexta and bupropion at 105 mg in Auvelity are present as CYP2D6 inhibitors. Poor metabolisers and users of paroxetine or fluoxetine reach the same raised concentrations without intending to.

  4. What it acts on

    Quietens the cough reflex at ordinary doses

    In the brainstem it raises the threshold for coughing. That is the whole approved OTC effect.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Central antitussive action at the medullary cough centre, distinct from the opioid antitussive mechanism of codeine, which is why the two sit in the same monograph paragraph with completely different scheduling.

  5. The change it makes

    Blocks the NMDA receptor at high concentrations

    Once enough survives the liver, it plugs the same glutamate receptor channel that ketamine and PCP block, and dissociation follows.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    Non-competitive NMDA-channel block, more potent for dextrorphan than for the parent, with sigma-1 receptor agonism and inhibition of serotonin and norepinephrine transporters. The transporter action is why serotonergic co-medication is the documented interaction hazard.

  6. What that does for a person

    Cough suppression, dissociation, or an antidepressant response

    Which of the three you get is decided by the dose, by your liver genotype, and by whether something else is blocking that enzyme.

    Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.

    The measurement behind this step

    At monograph doses, antitussive effect only. At many times that dose, or in a poor metaboliser, dissociation and the abuse pattern recorded in poison-centre data. At 45 mg with bupropion, a MADRS reduction of 15.9 points against 12.0 on placebo over six weeks. One molecule, three clinical categories, separated by pharmacokinetics rather than pharmacology.

No suggested links are held for this record, so nothing is hidden from this path.

What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.

What it would be like to takeRead from sources, not yet reviewed

Felt, measured, or meaningful

Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.

Felt

Things a person could notice without a test.

  • pain tolerance
  • hamilton depression rating scale
  • pain intensity
  • peak pain intensity

Measured

Things only a test, a scale or a device shows.

  • caffeine urinary molar
  • plasma auc of day 1 and day 8
  • urine tp/cr
  • serum hscrp
  • urine tgf beta/cr level
  • urinary examination
  • maximum plasma concentration
  • area under the plasma concentration curve

Meaningful

Things that change how a life goes, not only a number.

  • national institutes of health stroke severity scale

A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.

Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.

Measured, but not felt. A number moves. The person notices nothing. Both can be true.

Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.

Matters, but takes years. The result that counts may take longer than anyone would keep watching.

Names that fit none of the three (27)
  • efficacy
  • auc0 t simvastatin
  • auc0 t simvastatin acid
  • auc0 t total ezetimibe
  • auc0 t rosuvastatin
  • auc0 t fenofibric acid
  • auc0 t atorvastatin acid
  • auc0 t nicotinic acid
  • auc0 t nicotinuric acid
  • endothelial function
  • pk parameters
  • pharmacokinetic parameters
  • egfr
  • young s mania rating scale
  • anti dac hyp neutralizing antibodies ecl ada assay
  • cmax auc
  • lowest dose of dxm
  • modified rankin
  • glasgow coma scale
  • barthel index

These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.

What is missing or unclearRead from sources, not yet reviewed

Were people like you studied?

RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.

Who was studied

People similar to this profile were included.

  • Almost everyone, at some point, in a cough product. In the depression trials, adults with major depressive disorder. In the poison-centre data, predominantly adolescents aged 14 to 17.

Who is missing from the studies

  • Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

Where the result stopped carrying

  • Dextromethorphan alone has repeatedly failed to reach useful systemic exposure, which is why every approved central indication uses it in a fixed combination with a CYP2D6 inhibitor
  • Attempts to manage abuse without scheduling have relied on retail age restrictions and state law rather than federal control, and the abuse-call rate remained above its 2000 level throughout the surveillance period
  • This is a scope explorer, not a diagnosis engine.
  • It shows who was studied so you can see whether people similar to you were included.

RNAWiki cannot tell whether a study fits you. It can show who was in it.

What it would be like to takeRead from sources, not yet reviewed

Why it might seem to do nothing

A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.

It was studied for a different goal

The studies measured something else entirely.

On this record: Some registered studies measured things that match no goal on this page.

It was studied in different people

The people in the studies were not much like the reader.

On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

The evidence may simply be wrong

Small early studies often do not hold up.

On this record: RNAWiki has not yet published a reviewed conclusion for this use.

Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.

None of these is a reason to take more. Taking more is not a step this page ever suggests.

What it would be like to takeRead from sources, not yet reviewed

What taking it involves

The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.

How it is supplied

Prescription only

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

Read from the recorded approval status.

No source is stored against this line.

Form and route

Oral — syrup, gel capsule, or fixed-dose tablet with a CYP2D6 inhibitor

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form and route recorded on this substance.

No source is stored against this line.

Who oversees it

RNAWiki has not recorded a supervision or regulatory status for this substance.

Quoted from a source

Where this came from

Copied from a source RNAWiki stored, with the source named.

No register row and no identity class settled the question.

No source is stored against this line.

What is in the pack

Over-the-counter delivery is a syrup or capsule, almost always combined with other actives. Prescription delivery is a fixed-dose tablet in which the second ingredient exists to raise dextromethorphan exposure: 10 mg quinidine in Nuedexta, 105 mg bupropion in Auvelity. The combination is the delivery system.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on how this is sold and what that means for what is in the pack.

No source is stored against this line.

Where it is registered

Regulatory records are listed in the technical disclosure at the foot of this page.

Counted from records

Where this came from

A count of rows RNAWiki holds. It describes our records, not your body.

Register entries are stored per jurisdiction and shown with their dates.

No source is stored against this line.

Why people stop

Not recorded.

Nothing recorded

Where this came from

RNAWiki holds nothing here and says so rather than guessing.

No record of why people stopped taking it is stored for this substance.

No source is stored against this line.

What it would be like to takeRead from sources, not yet reviewed

What can go wrong

Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.

Worth asking a clinician aboutWritten into the record from the studies named on this page

At monograph doses the ingredient is well tolerated. The dose-related hazards are dissociation, agitation, tachycardia, hypertension and, at extreme exposures, respiratory depression. Serotonin toxicity is the documented interaction, through the drug's own serotonin-reuptake inhibition combined with monoamine oxidase inhibitors or serotonergic antidepressants; those same antidepressants may also inhibit CYP2D6 and raise the exposure at the same time. In abuse, the co-formulated ingredients are frequently the greater acute danger, paracetamol above all. CYP2D6 poor metabolisers, roughly a twelfth of people of European ancestry, reach substantially higher parent-drug concentrations from a standard dose. Bupropion carries its own seizure risk, which the combination product inherits.

Nobody counted how many people took this and were fine, so this cannot be turned into a rate.

Where this came from

Reports sent to a regulator

  • These are reports people sent to a regulator. They do not show the medicine caused the reaction.
  • Nobody counted how many people took the medicine and reported nothing.
  • The same event can be reported more than once, and many reports are incomplete.
  • News coverage, lawsuits and new warnings change how often people report.
  • A count is not a rate and not a risk.

Dextromethorphan appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 335 reaction mentions were counted. One report can name several reactions.

The recorded terms (10)
  • serotonin syndrome — 47 reaction mentions
  • drug abuse — 44 reaction mentions
  • agitation — 38 reaction mentions
  • toxicity to various agents — 37 reaction mentions
  • somnolence — 35 reaction mentions
  • confusional state — 30 reaction mentions
  • suicide attempt — 27 reaction mentions
  • vomiting — 27 reaction mentions
  • dizziness — 26 reaction mentions
  • drug interaction — 24 reaction mentions
  • open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot

Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.

Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.

What is missing or unclearRead from sources, not yet reviewed

Does the exact form matter?

Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.

The form that was studied

Oral — syrup, gel capsule, or fixed-dose tablet with a CYP2D6 inhibitor

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

The form used in the studies cited on this page.

No source is stored against this line.

What is sold

Prescription delivery is a fixed-dose tablet in which the second ingredient exists to raise dextromethorphan exposure: 10 mg quinidine in Nuedexta, 105 mg bupropion in Auvelity. The combination is the delivery system.

Source-linked record

Where this came from

A person wrote this into the record with the study named beside it. No reviewer has signed it off.

Recorded notes on which forms are sold and how they compare.

No source is stored against this line.

What is recorded as being sold

  • 2191 products list this as an active ingredient in the United States drug directory. 163 of them contain it and nothing else.

    FDA National Drug Code directory · 72036-138 · read 2026-08-29

  • They are sold as capsule, capsule, coated, capsule, gelatin coated, capsule, liquid filled, chewable gel and crystal, taken oral and topical.

    FDA National Drug Code directory · 72036-138 · read 2026-08-29

  • The regulator's established pharmacologic class for it is sigma-1 agonist [epc], sigma-1 receptor agonists [moa] and uncompetitive n-methyl-d-aspartate receptor antagonist [epc].

    FDA National Drug Code directory · 72036-138 · read 2026-08-29

  • 1972 published labels name it as an active ingredient. 125 of them describe this substance alone, which is where its own label text on this page comes from.

    US prescribing information · da1f1ef9-a974-4998-8e1d-c1d999596943 · read 2026-08-29

  • Those labels are classed as human otc drug and human prescription drug.

    US prescribing information · da1f1ef9-a974-4998-8e1d-c1d999596943 · read 2026-08-29

  • 6 marketed supplement labels list this ingredient, classed as amino acid/protein, botanical with nutrients, non-nutrient/non-botanical and other combinations.

    NIH Dietary Supplement Label Database · 21680 · read 2026-08-29

  • Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.

    NIH Dietary Supplement Label Database · 21680 · read 2026-08-29

  • Recorded price in US: 0.11692 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, for the one priced product, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..

    Recorded source · 2026-08-26 · read 2026-08-28

Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.

What it would be like to takeRead from sources, not yet reviewed

What you could measure

This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.

RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.

Questions worth asking

  • Which of the trials of Dextromethorphan studied people like me?
  • What was measured, and for how long?
  • Was the result a laboratory value or a health outcome?
  • What would we watch for, and when would we stop?

Tracking can show whether something changed for you. It cannot show what caused it.

RNAWiki records evidence. It does not say whether this substance is right for you.

What is missing or unclearRead from sources, not yet reviewed

Claims that go past the evidence

Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.

Goes past the evidence

That the GEMINI effect is attributable to dextromethorphan rather than to the bupropion in the same tablet, which a placebo-controlled trial cannot establish

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That OTC availability implies low risk at high doses — the poison-centre series measures the opposite

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That the antitussive efficacy of dextromethorphan at monograph doses is itself firmly established; the ingredient predates modern efficacy standards and the cough literature is contested

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

Goes past the evidence

That a routine immunoassay distinguishes dextromethorphan from its scheduled enantiomer; it does not, and a chiral method is required

Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.

The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.

What would change this

A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.

RNAWiki has not yet published a reviewed conclusion for this use.

What is missing or unclearRead from sources, not yet reviewed

What nobody knows yet

Open questions, each with why it is open and what would close it.

How fast does the body clear it?

The sources RNAWiki checked hold nothing for this field.

Why it matters. Without this, nothing on this page can say how long anything lasts.

What would answer it

A stored source that records it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing populations

Which groups were under-represented in the studies has not been recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing long-term data

No completed tested study window is recorded.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

No reviewed conclusion

RNAWiki has not yet published a reviewed conclusion for this use.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Missing interaction studies

No interaction was found in the registers checked. Not finding one is not the same as showing there is none.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Formulation uncertainty

Several salts, forms or products of Dextromethorphan are recorded. Results from one form may not transfer to another.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

Mechanism not reviewed

No reviewed mechanism story exists for this substance.

Why it matters. Recorded by the evidence model as a gap on this record.

What would answer it

A study that measures it, and a reviewer to sign it off.

Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.

What happened in peopleRead from sources, not yet reviewed

Check any of this yourself

Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.

Every line above can be traced to the study named beside it. Follow the link and read it.

Phase 3 in 327 patients: a 3.87-point MADRS advantage
In plain words
Adding dextromethorphan to bupropion beat placebo in a six-week depression trial. The drug group improved by 15.9 MADRS points and the placebo group by 12.0 — a difference of just under four points.
What was measured
Change in MADRS total score from baseline to week 6, n=327
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
GEMINI was a double-blind phase 3 trial run between June and December 2019, randomising 327 patients with DSM-5 major depressive disorder 1:1 to dextromethorphan-bupropion 45 mg/105 mg or placebo, once daily for three days then twice daily, for six weeks. Baseline MADRS was 33.6 and 33.2. Least-squares mean change to week 6 was -15.9 with the combination and -12.0 with placebo: least-squares mean difference -3.87, 95% CI -1.39 to -6.36, p = 0.002. Separation was significant at week 1 (p = 0.007) and week 2 (p < 0.001). Remission (MADRS ≤ 10) reached 39.5% versus 17.3% (difference 22.2 points, 95% CI 11.7 to 32.7, p < 0.001) and response 54.0% versus 34.0% (difference 20.0 points, 95% CI 8.4 to 31.6, p < 0.001). The trial was designed, funded and largely authored by the sponsor. The 3.87-point difference on a 60-point scale is at the low end of what is usually called clinically meaningful, while the remission gap is large — both numbers come from the same trial and this record prints both.
Source
Iosifescu DV et al. J Clin Psychiatry 2022;83:21m14345 (GEMINI)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The approved products work by deliberately blocking the drug's own clearance
In plain words
Dextromethorphan is destroyed so fast by a liver enzyme that on its own it cannot reach useful brain concentrations. Both prescription products solve that by adding a second drug whose job is to block that enzyme.
What was measured
Approved fixed-dose combinations in which the second ingredient is present as a CYP2D6 inhibitor
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
CYP2D6 O-demethylates dextromethorphan to dextrorphan with high efficiency, so oral bioavailability of the parent compound is low and variable and depends on genotype. Nuedexta (NDA 021879, approved 29 October 2010) pairs 20 mg dextromethorphan with 10 mg quinidine, a dose of quinidine far below any antiarrhythmic effect and present solely as a CYP2D6 inhibitor. Auvelity (NDA 215430, approved 18 August 2022) pairs 45 mg dextromethorphan with 105 mg bupropion, which is both an antidepressant in its own right and a CYP2D6 inhibitor. In each case the second ingredient is a pharmacokinetic enabler. The same interaction happens unintentionally: CYP2D6 poor metabolisers, and people taking CYP2D6-inhibiting antidepressants such as paroxetine or fluoxetine, reach far higher dextromethorphan concentrations from an ordinary cough dose than the label anticipates.
Source
Drugs@FDA NDA 021879 (Nuedexta, 29 October 2010) and NDA 215430 (Auvelity, 18 August 2022); Iosifescu DV et al. J Clin Psychiatry 2022;83:21m14345
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Abuse calls tripled to 2006, then fell by more than half
In plain words
FDA researchers counted poison-centre calls for deliberate dextromethorphan abuse from 2000 to 2015. The rate tripled, peaked in 2006 among 14-to-17-year-olds, then dropped 56% over the next decade.
What was measured
Single-substance intentional-abuse exposure calls per million population, by age group, 2000-2015
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Karami et al., working at FDA's Office of Surveillance and Epidemiology, analysed single-substance dextromethorphan intentional-abuse exposure calls in the National Poison Data System from 2000 to 2015. The annual rate tripled between 2000 and 2006 and then plateaued through 2015. The highest rate was among adolescents aged 14 to 17, averaging 1,761 calls per year, or 103.6 calls per million population. Within that group the rate fell 56.3% between 2006 and 2015, from 143.8 to 80.9 calls per million. The authors attribute the decline to public-health efforts to curtail OTC abuse and call for evaluation of state-level sales restrictions. This is exposure-call data, not incidence: it counts calls made, and a fall in calls is consistent with less abuse, with fewer calls per episode, or with both.
Source
Karami S et al. Clin Toxicol 2018;56:656-663
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
It is an over-the-counter monograph ingredient and is not scheduled
In plain words
Dextromethorphan appears in the FDA list of permitted over-the-counter cough suppressants and appears nowhere in the federal drug schedules — unlike codeine, which sits three lines above it in the same regulation.
What was measured
Presence in the OTC antitussive monograph and absence from all federal drug schedules
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
21 CFR 341.14(a) lists the permitted oral antitussive active ingredients: chlophedianol hydrochloride, codeine ingredients, dextromethorphan, dextromethorphan hydrobromide, diphenhydramine citrate and diphenhydramine hydrochloride. The codeine entry carries an explicit cross-reference to 21 CFR 1308.15(c), the Schedule V listing; the dextromethorphan entries carry no such reference, and dextromethorphan appears nowhere in 21 CFR part 1308. The contrast within a single paragraph of one regulation is the cleanest available statement of the drug's legal position: a permitted OTC ingredient, uncontrolled federally, whose abuse is managed through retail-level and state-level measures rather than through scheduling.
Source
21 CFR 341.14(a)(3) and (a)(4), current eCFR text; 21 CFR part 1308, Schedules I-V
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Which ingredient produced the antidepressant effect is not established
In plain words
Auvelity beat placebo. But the comparison was against placebo, not against bupropion alone at the same dose — so how much of the benefit came from the dextromethorphan is a separate question the pivotal trial did not answer.
What was measured
That the 3.87-point MADRS advantage over placebo is attributable to dextromethorphan rather than to the bupropion component of the same tablet
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
GEMINI compared dextromethorphan-bupropion with placebo. Bupropion is itself an approved antidepressant, and at 105 mg twice daily it is at a therapeutic dose. A placebo-controlled result therefore establishes that the combination works, not that adding dextromethorphan to bupropion works. The sponsor ran a separate trial with a bupropion comparator arm, and the regulatory package rests on both; but the trial reported here, which is the one usually cited for the effect size, cannot decompose it. The mechanistic story — NMDA antagonism plus sigma-1 agonism producing rapid glutamatergic antidepressant action — is plausible and is the reason the combination was built, and it is not what a placebo-controlled trial measures.
Source
Iosifescu DV et al. J Clin Psychiatry 2022;83:21m14345, trial design
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Its enantiomer is a Schedule II opioid; this one is not an opioid at all
In plain words
Dextromethorphan is the mirror image of a morphine-like painkiller. The mirror image has no opioid activity, and a routine drug test cannot tell the two apart.
What was measured
Enantiomeric relationship between an uncontrolled antitussive and a scheduled opioid
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Dextromethorphan is the dextrorotatory enantiomer of the methyl ether of levorphanol. Levomethorphan, its mirror image, is a controlled opioid; dextromethorphan has no meaningful mu-opioid activity and no analgesic effect at antitussive doses, and its psychoactivity comes from NMDA-channel block and sigma-1 agonism instead. Because achiral chromatography cannot separate enantiomers, distinguishing the two in a forensic sample requires a chiral method — a practical consequence of a stereochemical fact, and the reason the analytical workflow on this page begins with a chiral separation rather than a mass measurement.
Source
21 CFR part 1308 schedules for levomethorphan and levorphanol; PubChem CID 5360696 stereochemistry
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Fixed-dose combination products are the main acute hazard
In plain words
Most cough syrups contain other drugs alongside dextromethorphan. Taking enough of the syrup to get a dissociative effect means taking many times the safe dose of whatever else is in the bottle.
What was measured
Product-level composition of the cough and cold preparations involved in intentional-abuse exposure calls
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The abuse pattern measured by the National Poison Data System involves cough and cold products, not the isolated ingredient. Those products commonly contain paracetamol, antihistamines such as chlorphenamine or doxylamine, and sympathomimetics such as phenylephrine or pseudoephedrine. A dose of syrup carrying enough dextromethorphan for a dissociative effect carries a correspondingly multiplied dose of every other active ingredient, and for paracetamol that crosses the hepatotoxic threshold well before the dextromethorphan itself becomes life-threatening. The serotonergic interaction is separate and additive: dextromethorphan inhibits serotonin reuptake, so combination with a monoamine oxidase inhibitor or a serotonergic antidepressant is the documented route to serotonin toxicity.
Source
Karami S et al. Clin Toxicol 2018;56:656-663, brand and product analysis of NPDS abuse calls
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim

Where else this substance is registered

FDA substance identifier (UNII)
7355X3ROTS
CAS registry number
125-71-3
PubChem compound
5360696
ChEMBL
CHEMBL52440
ChEBI
4470
WHO international nonproprietary name list entry
166
RxNorm concept
236146
EMA substance identifier
100000092321
European Chemicals Agency number
204-752-2
DrugBank
DB00514

Checks this page had to pass

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  • Not passed

    Trial roles classified for highlighted evidence

    No registered study is classified as testing this substance.

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    enforced by the copy-contract test over the rendered page

  • Not passed

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    No register row and no identity class settled the question.

  • Passed

    Canonical metadata present

    slug and display name present

What is missing or unclearRead from sources, not yet reviewed

How this medicine reached us

Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.

What the approval register records

  • 38 approved applications cover products containing this substance. The earliest was NDA011265, approved 19571203 to ANI PHARMS.

    Drugs@FDA application register · NDA011265 · read 2026-08-29

  • Marketing status on the register: discontinued, none (tentative approval), over-the-counter and prescription.

    Drugs@FDA application register · NDA011265 · read 2026-08-29

  • The earliest marketing start date recorded for a listed product is 19821008.

    FDA National Drug Code directory · 72036-138 · read 2026-08-29

What is missing or unclearRead from sources, not yet reviewed

What to learn next

Ordered by what would most change how you read this page, starting with what is easiest to misunderstand.

This order is fixed in code and does not count clicks or time on the page.

What is not here

4 questions this page could not answer

These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.

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The record as stored

The full record, for auditing

Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.

The older medicine-wide conclusion held in this record

Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.

The same molecule is an unscheduled supermarket cough suppressant, a dissociative whose abuse calls to US poison centres peaked at 143.8 per million adolescents in 2006, and — once a CYP2D6 inhibitor is bolted on to stop the liver destroying it — an FDA-approved antidepressant with a 3.87-point MADRS advantage over placebo.

Recorded evidence blocks (12)

What did Dextromethorphan's largest trial (1500 people) and its longest (11 years) measure?


1500 people in Dextromethorphan's largest registered study, 11 years in its longest registered window, measuring Area Under Concentration-time Curve From 0 to Last Measureable Concentration (AUC0-t) Atorvastatin Acid (Lomitapide 10 mg). ClinicalTrials.gov · 2026-09-01

46 phase1, 23 phase2, 13 phase4, 11 na, 10 phase3, 3 early phase1, 2 na or unstated; NCT00003687; 2009-02-10; no ageing endpoint recorded. Last human test completed 2026, NCT07241065.

Interpretation These counts include studies where Dextromethorphan was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.

Show the evidence
  • phase1
    46
  • phase2
    23
  • phase4
    13
  • na
    11
  • phase3
    10
  • early phase1
    3
2 more recorded rows
  • na or unstated
    2
  • Last recorded human test NCT07241065
    2026-07-20

recorded 2026-09-01 · last checked 2026-09-04

From mouse to human: where has Dextromethorphan shown lifespan?


mouse: lifespan and human: biomarker (104): the rungs where Dextromethorphan has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01

Area Under Concentration-time Curve From 0 to Last Measureable Concentration (AUC0-t) Atorvastatin Acid (Lomitapide 10 mg) — the recorded outcome words.

Yeast C. elegans Drosophila Mouse lifespanRat Dog Non-human primate Human biomarker
Show the evidence
  • mouse
    lifespan
  • human NCT00359281
    biomarker; Area Under Concentration-time Curve From 0 to Last Measureable Concentration (AUC0-t) Atorvastatin Acid (Lomitapide 10 mg); 104

recorded 2026-09-01 · last checked 2026-09-04

11 of Dextromethorphan's trials stopped: safety, accrual/recruitment, funding/business, other?


safety (1), accrual/recruitment (5), funding/business (2) and other (3): Dextromethorphan's stop wording, clustered. ClinicalTrials.gov · 2026-09-01

"slow accrual"; 11 of 104 registered studies

Show the evidence

Trial

  • NCT00176540
    terminated; "slow accrual"
  • NCT00176553
    terminated; "slow accrual"
  • NCT00513864
    withdrawn; "lack of funding"
  • NCT00593957
    terminated; "Study changed to a placebo controlled trial of dextromethorphan"
  • NCT00873366
    terminated; "Funding issues"
  • NCT01257542
    terminated; "See termination reason in detailed description."
5 further recorded trials
  • NCT02271893
    terminated; "Recruitment difficulties"
  • NCT02651116
    terminated; "The study was prematurely discontinued due to slow enrollment during the 2019/2020 cold season. No safety or efficacy concerns led to the decision to terminate"
  • NCT02760615
    withdrawn; "No enrollment"
  • NCT02987920
    terminated; "The surgeon changed pain control protocol for all patients. Continued enrollment impossible under approved protocol."
  • NCT03358706
    terminated; "The study was stopped as all post-marketing commitments had been fulfilled or released"

recorded 2026-09-01 · last checked 2026-09-04

Human studies of Dextromethorphan used Dextromethorphan (30 mg) — over how long?


Human studies of Dextromethorphan used "Dextromethorphan (30 mg)". ClinicalTrials.gov · 2026-09-01

8 recorded entries; human; also "Dextromethorphan 60 mg per day", "Dextromethorphan 30 mg", "dextromethorphan 5 mg"

Show the evidence

human

  • NCT00741468
    Dextromethorphan (30 mg)
  • NCT01188265
    Dextromethorphan 60 mg per day
  • NCT01188265
    Dextromethorphan 30 mg
  • NCT01731067
    dextromethorphan 5 mg
  • NCT02056743
    Dextromethorphan 30mg
  • NCT02438072
    Dextromethorphan (10 mg, R05DA09)
2 more recorded rows
  • human NCT03039842
    30mg dextromethorphan
  • human NCT03054220
    Dextromethorphan 5 MG

recorded 2026-09-01 · last checked 2026-09-04

Could one person measure Dextromethorphan's effect on efficacy?


Efficacy: measured in Dextromethorphan's trials.

Interpretation efficacy is the recorded endpoint.

Show the evidence

biomarkers

  • efficacy; 2026-09-01
  • caffeine urinary molar; 2026-09-01
  • pain tolerance; 2026-09-01
  • auc0 t simvastatin; 2026-09-01
  • auc0 t simvastatin acid; 2026-09-01
  • auc0 t total ezetimibe; 2026-09-01
14 more recorded rows
  • biomarkers
    auc0 t rosuvastatin; 2026-09-01
  • biomarkers
    auc0 t fenofibric acid; 2026-09-01
  • biomarkers
    auc0 t atorvastatin acid; 2026-09-01
  • biomarkers
    auc0 t nicotinic acid; 2026-09-01
  • biomarkers
    auc0 t nicotinuric acid; 2026-09-01
  • biomarkers
    endothelial function; 2026-09-01
  • biomarkers
    plasma auc of day 1 and day 8; 2026-09-01
  • biomarkers
    pk parameters; 2026-09-01
  • biomarkers
    pharmacokinetic parameters; 2026-09-01
  • biomarkers
    egfr; 2026-09-01
  • biomarkers
    urine tp/cr; 2026-09-01
  • biomarkers
    serum hscrp; 2026-09-01
  • biomarkers
    urine tgf beta/cr level; 2026-09-01
  • biomarkers
    young s mania rating scale; 2026-09-01
  • human trials at or under30
    46
  • Not recorded for this substance
    a recorded half-life
  • smallest human trial
    0; NCT00000352; PHASE2; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; COMPLETED

Which of anti dac hyp neutralizing antibodies ecl ada assay, area under the curve 0 24h of caffeine and area under the plasma concentration curve did Dextromethorphan's trials measure?


anti dac hyp neutralizing antibodies ecl ada assay, area under the curve 0 24h of caffeine and area under the plasma concentration curve lead 40 outcome terms across Dextromethorphan's trials. ClinicalTrials.gov · 2026-09-01

auc0 t simvastatin, auc0 t simvastatin acid, auc0 t total ezetimibe, auc0 t rosuvastatin, auc0 t fenofibric acid and auc0 t atorvastatin acid follow.

Show the evidence
  • efficacy
    1
  • caffeine urinary molar
    1
  • pain tolerance
    1
  • auc0 t simvastatin
    1
  • auc0 t simvastatin acid
    1
  • auc0 t total ezetimibe
    1
14 more recorded rows
  • auc0 t rosuvastatin
    1
  • auc0 t fenofibric acid
    1
  • auc0 t atorvastatin acid
    1
  • auc0 t nicotinic acid
    1
  • auc0 t nicotinuric acid
    1
  • endothelial function
    1
  • plasma auc of day 1 and day 8
    1
  • pk parameters
    1
  • pharmacokinetic parameters
    1
  • egfr
    1
  • urine tp/cr
    1
  • serum hscrp
    1
  • urine tgf beta/cr level
    1
  • young s mania rating scale
    1

recorded 2026-09-01 · last checked 2026-09-04

Which of Dextromethorphan's 9 ongoing trials reports first?


9 registered trials of Dextromethorphan are open; earliest completion 2025-10-15. ClinicalTrials.gov · 2026-09-01

Improvement in OCD or related disorder symptoms as measured by the Y-BOCS; Motor Evoked Potential; latest 2030-12-31

Show the evidence

Trial

  • NCT04899687
    "Study of Dextromethorphan in OCD and Related Disorders"; n 60; "Improvement in OCD or related disorder symptoms as measured by the Y-BOCS"; 2028-12-01
  • NCT04923659
    "Pharmacological Mechanisms of Low-intensity Focused Ultrasound for Motor Cortex Neuroplasticity"; n 20; "Motor Evoked Potential"; 2026-05
  • NCT05068791
    "Psilocybin-facilitated Treatment for Chronic Pain"; n 30; "Change in daily self-reported pain severity"; 2026-12-31
  • NCT05278494
    "Dextromethorphan for Treatment of Postoperative Pain"; n 160; "Post-op opioid use"; 2026-12-31
  • NCT06383338
    "A Study Investigating the Change in Metabolism Phenotype in Paediatric, Adolescent & Young Adults With Hodgkin or Non-Hodgkin Lymphoma."; n 10; "Proportion of patients who consent to study and complete baseline and at least two longitudinal timepoints with successful measurement of probe drug MR (Metabolic ratio)"; 2026-11
  • NCT06632990
    "A Study Evaluating the Potential of BMS-984923 to Alter the Systemic Exposure of Three Orally Administered Probe Substrates"; n 36; "Area under the curve for the first and last 96 hours of dosing (AUC96h) as determined by PK modeling"; 2025-10-15
3 further recorded trials
  • NCT06772753
    "Investigation of Psychedelic Effects in Psychoactive Substances"; n 50; "Mystical Experience Questionnaire (MEQ-30)"; 2027-12
  • NCT07386730
    "A Study of Psychedelics in Healthy Older Adults With Low Well-being"; n 80; "Acute changes in EEG-based ESBA"; 2030-02
  • NCT07665723
    "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"; n 25; "Area Under the Plasma Concentration-time Curve Up to Time t (AUC0-t [AUC last]) of CYP Probe Substrates (Midazolam, 1-OH-Midazolam, Omeprazole, 5-OH-Omeprazole, Dextromethorphan, Dextrorphan, R-Warfarin, S-Warfarin, Caffeine, and…"; 2030-12-31

recorded 2026-09-01 · last checked 2026-09-04

Which 45 trials of Dextromethorphan posted no result?


Posted no result
45 of 45 completed trials
Registrations
NCT00000352, NCT00001344, NCT00001365, NCT00001725, NCT00605605 and NCT00310323, and 39 more
Completion dates
oldest 1998-04; newest 2023-11-30
Show the evidence

Trial

  • NCT00000352
    1998-04
  • NCT00001344
    2001-02
  • NCT00001365
    2001-06
  • NCT00001725
    2002-01
  • NCT00605605
    2005-12
  • NCT00310323
    2006-02
14 further recorded trials
  • NCT00108446
    2006-03
  • NCT00127686
    2006-12
  • NCT01189006
    2008-12
  • NCT00788047
    2009-01
  • NCT00003687
    2009-02-10
  • NCT00920088
    2009-11
  • NCT00055549
    2009-11-13
  • NCT00950586
    2009-12-24
  • NCT01570569
    2011-03
  • NCT01188265
    2011-06
  • NCT00964106
    2011-08-29
  • NCT01017939
    2012-04
  • NCT01441986
    2012-05
  • NCT01651325
    2012-05

At the median, Dextromethorphan's trials enrolled 35 people — anything larger?


Median enrolment
35
Largest enrolment
1500
Registered trials counted
102

What do 335 spontaneous reports say about Dextromethorphan — and not say?


These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.

Dextromethorphan appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 335 reaction mentions were counted: serotonin syndrome 47; drug abuse 44; agitation 38; toxicity to various agents 37. open-targets-adr · CHEMBL1201461 · 2026-06-24

Show the evidence
  • serotonin syndrome
    47
  • drug abuse
    44
  • agitation
    38
  • toxicity to various agents
    37
  • somnolence
    35
  • confusional state
    30
4 more recorded rows
  • suicide attempt
    27
  • vomiting
    27
  • dizziness
    26
  • drug interaction
    24

recorded 2026-06-24 · last checked 2026-09-04

Was Dextromethorphan studied with fasting and exercise?


fasting and exercise are named in Dextromethorphan's label sentences: "Compared to placebo, dextromethorphan 30 mg significantly increased the distension-evoked sensation scores for nausea (P=0.004) and satiation (P=0.004) during fasting; and for bloating (P= 0.001), nausea (P=0.000) and satiation (P=0.01) 30 min postprandially." openfda-label+europepmc · 2021-01-01

2 recorded statements; fasting, exercise

Show the evidence
  • fasting
    Compared to placebo, dextromethorphan 30 mg significantly increased the distension-evoked sensation scores for nausea (P=0.004) and satiation (P=0.004) during fasting; and for bloating (P= 0.001), nausea (P=0.000) and satiation (P=0.01) 30 min postprandially.
  • exercise
    The strongest (controlled trial) evidence suggests beneficial effects of risperidone, propranolol, fluvoxamine, vigorous aerobic exercise, and dextromethorphan/quinidine for treating aggression in adults with ASD, with lower levels of evidence supporting behavioral interventions, multisensory environments, yokukansan, and other treatments.

recorded 2021-01-01 · last checked 2026-09-04

What is recorded about Dextromethorphan and senolytic?


"Human studies establish that CYP2D6 phenotype and inhibition materially alter dextromethorphan exposure; NAC has heterogeneous adjunctive psychiatric evidence; NMN has human NAD-related target-engagement data without established antidepressant efficacy; and senolytics have limited early human data outside TRD." — where Dextromethorphan and senolytic appear together. Europe PMC · pathway abstract search · 2026-08-24

senolytic, NAD+, mTOR; PMID 42670437, 42688195

Show the evidence
  • senolytic PMID 42670437
    "Human studies establish that CYP2D6 phenotype and inhibition materially alter dextromethorphan exposure; NAC has heterogeneous adjunctive psychiatric evidence; NMN has human NAD-related target-engagement data without established antidepressant efficacy; and senolytics have limited early human data outside TRD."
  • NAD+ PMID 42670437
    "Human studies establish that CYP2D6 phenotype and inhibition materially alter dextromethorphan exposure; NAC has heterogeneous adjunctive psychiatric evidence; NMN has human NAD-related target-engagement data without established antidepressant efficacy; and senolytics have limited early human data outside TRD."
  • senolytic PMID 42688195
    "Building on those directional findings, this short communication proposes a minimal three-arm oral regimen with unequal evidentiary weight: first, the Cheung Glutamatergic Regimen, consisting of low-dose dextromethorphan potentiated by a CYP2D6 inhibitor together with piracetam and L-glutamine, as an exploratory adjunct aimed at preserving residual functional connectivity; second, daily…"
  • NAD+ PMID 42688195
    "Building on those directional findings, this short communication proposes a minimal three-arm oral regimen with unequal evidentiary weight: first, the Cheung Glutamatergic Regimen, consisting of low-dose dextromethorphan potentiated by a CYP2D6 inhibitor together with piracetam and L-glutamine, as an exploratory adjunct aimed at preserving residual functional connectivity; second, daily…"
  • mTOR
    "We propose a fully oral, low-cost, four-component regimen designed to replicate ketamine's entire plasticity cascade: (1) dextromethorphan (DXM) supplies fast NMDA antagonism; (2) a strong CYP2D6 inhibitor (fluoxetine, paroxetine, or high-dose duloxetine) prolongs DXM exposure without relying on bupropion; (3) the AMPA positive allosteric modulator piracetam amplifies the downstream glutamate…"

recorded 2026-08-24 · last checked 2026-09-04

Where it is registered
Identifiers, relations and other names

The exact record

ChEMBL id
CHEMBL1201461
PubChem CID
5360696
CAS number
125-71-3
RxCUI
236146
InChIKey
MKXZASYAUGDDCJ-NJAFHUGGSA-N
Also called
DEXTROMETHORPHAN POLISTIREX, DEXTROMETHORPHAN HYDROBROMIDE, dm, dxm, Dextromethorphane, Dextrometorfano, Dimetane-dx, axs-05
Trade name
Delsym, Beecham coughcaps, Brontyl, Contac coughcaps, Franolyn dry, Franolyn sed, St. joseph cough syrup, Tussabron, Tuxium, Cough Dm, Robitussin 12 Hour Cough Relief, Cough Relief
Development code
NSC-751452, NSC-756723
Salt form
Dextromethorphan hydrobromide component of auvelity, Dextromethorphan hydrobromide component of avp-923, Dextromethorphan hydrobromide component of bromanate dm, Dextromethorphan hydrobromide component of bromfed-dm, Dextromethorphan hydrobromide component of dimetane-dx, Dextromethorphan hydrobromide component of mucinex dm, Dextromethorphan hydrobromide component of nuedexta, Dextromethorphan hydrobromide component of pherazine dm, Dextromethorphan hydrobromide component of promethazine dm, Dextromethorphan Hydrochloride
Sources (9)

Sources

3 more sources

ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work

How these records are assembled · Which registers were checked

Index-quality checks
  • identity passed: no open identity hold
  • required summary fields resolved: 5 required field(s) not terminal: Why people use it, Best-supported result, Most important common problem, Biggest unanswered question, Human evidence
  • public claims reviewed: 0 reviewed claim(s); drafts are never rendered
  • source coverage passed: 9 source rows
  • no critical contamination: no quarantine open
  • canonical metadata passed: slug and display name present
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