Dextromethorphan

(9S,13S,14S)-3-methoxy-17-methylmorphinan

Overview

Dextromethorphan belongs to Dissociatives.

Key safety note: At the low doses in cough medicine DXM is safe for most people, but recreational high-dose use ('robotripping') is risky.[2]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • At antitussive doses DXM simply suppresses coughing, with little or no psychoactive effect.
  • Recreationally the effects rise through four dose-dependent 'plateaus': the first (~1.5–2.5 mg/kg) feels like mild stimulation, a 'drunk' euphoria and enhanced music. The second (~2.5–7.5 mg/kg) adds stronger euphoria, sedation, spatial disorientation and mild hallucinations.
  • Higher plateaus are intensely dissociative: the third (~7.5–15 mg/kg) brings memory suppression, ego-loss, hallucinations and profound disconnection, and the fourth (~15+ mg/kg) a near-anaesthetic, fully dissociated state with a high risk of injury, vomiting, blackouts and overdose. Throughout, common bodily effects include ataxia (the characteristic 'robo-walk'), nausea, sweating, itching and a raised heart rate.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral (syrup, gel-caps, extended-release suspension). The recreational figures below are the commonly cited dissociative 'plateaus', not safe or recommended doses (the antitussive dose is only ~10–30 mg). The single most important harm-reduction point: use ONLY single-ingredient dextromethorphan. Most cough products also contain paracetamol/acetaminophen, chlorphenamine, pseudoephedrine or guaifenesin, and a plateau dose of those co-formulated drugs can cause liver failure, anticholinergic delirium, seizures or cardiac harm well before the DXM. Because response depends on CYP2D6 genetics it is unpredictable. Onset is slow, so redosing early risks a much heavier trip than intended.

Dose ranges

Antitussive (medical)

10–30 mg per dose

1st plateau

~1.5–2.5 mg/kg (≈100–200 mg)

2nd plateau

~2.5–7.5 mg/kg (≈200–400 mg)

3rd plateau

~7.5–15 mg/kg (≈300–600 mg)

4th plateau

~15–20 mg/kg (≈600 mg +): near-anaesthetic, dangerous

Duration

onset

30–120 minutes

peak

3–6 hours

total

8–12 hours

after effects

4–24 hours

Chemical & Physical Properties
FormulaC18H25NO
Molar mass271.4 g/mol
StateSolid
Melting point109–111 °C
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP3.4 (predicted, XLogP3)
Solubility1.5 g/100 mL, Practically insoluble in water, Freely soluble in chloroform
Refractive indexNot reported
Identifiers & Synonyms
CAS125-71-3
CAS (enantiomer)
PubChem CID5360696
InChIKeyMKXZASYAUGDDCJ-NJAFHUGGSA-N
InChIInChI=1S/C18H25NO/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h6-7,12,15,17H,3-5,8-11H2,1-2H3/t15-,17+,18+/m1/s1
SMILESCN1[C@H]2CC3=CC=C(OC)C=C3[C@@]4(CC1)C2CCCC4

Synonyms

  • DXM
  • Robitussin (component)
  • Dextromethorphan
  • Delsym
  • Robo
Pharmacodynamics & Biochemistry

Dextromethorphan (DXM) is the dextrorotatory morphinan cough suppressant found in many over-the-counter cold and cough products. Unusually for a morphinan it has essentially no classical opioid (μ-receptor) activity at normal doses, so it produces neither opioid analgesia nor a typical opioid high. DXM itself acts mainly as a sigma-1 receptor agonist and a serotonin–noradrenaline reuptake inhibitor, with only weak NMDA activity. Its antitussive effect comes from a central action that raises the cough threshold. The dissociative, 'robotripping' effects come mostly from its metabolite: the liver enzyme CYP2D6 O-demethylates DXM to dextrorphan, a considerably more potent non-competitive NMDA-receptor antagonist (the same channel-blocking mechanism as ketamine and PCP). Because dextrorphan formation depends on CYP2D6, a highly variable enzyme, the experience is unpredictable: extensive metabolizers convert quickly and reach dissociation, while poor metabolizers (or people taking CYP2D6 inhibitors such as quinidine, fluoxetine, paroxetine or bupropion, or drinking grapefruit juice) accumulate the parent drug, prolonging its effects and raising the serotonin-related risk.

Biological targets

  • NMDA
  • Sigma-1
  • SERT

Binding & functional measurements

TargetMeasurementSpecies
sigma non-opioid intracellular receptor 1pKi 6.3Human
NMDA receptorKi 3,400 ± 800 nMPig
Pharmacokinetics
Bioavailability≈11% (oral, extensive first-pass)
Tmax≈2–2.5 h
Half-life≈2–4 h (CYP2D6-dependent, longer in poor metabolizers)
VdNot reported
Protein bindingNot reported
MetabolismHepatic CYP2D6 to active dextrorphan
ExcretionRenal
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

At the low doses in cough medicine DXM is safe for most people, but recreational high-dose use ('robotripping') is risky. By far the biggest hazard is combination products: DXM is usually sold mixed with paracetamol/acetaminophen (liver failure), antihistamines such as chlorphenamine (anticholinergic delirium and seizures), pseudoephedrine (dangerous blood-pressure and heart effects) or guaifenesin (heavy vomiting): taking a 'recreational' dose of a multi-ingredient product can be lethal from those other drugs long before the DXM does harm. Only single-ingredient DXM avoids this. DXM is also serotonergic, so combining it with MAOIs, SSRIs, SNRIs, tramadol or MDMA can cause serotonin syndrome. High doses cause marked dissociation, ataxia, a fast heart rate, raised blood pressure, hyperthermia and, occasionally, psychosis or seizures, because effects hinge on CYP2D6 genetics they are hard to predict, and mixing with alcohol or other depressants sharply increases the danger.[2]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

MAOIs, SSRIs, SNRIs, Tramadol, Triptans, Other serotonergic drugs Risk of serotonin syndrome. MAOIs are contraindicated, and MDMA or other serotonergic drugs add to the risk.[2]
Strong CYP2D6 inhibitors (e.g. paroxetine, fluoxetine) Quinidine, fluoxetine, paroxetine, bupropion or grapefruit juice raise DXM levels, intensifying and prolonging effects.[2]
Alcohol, Benzodiazepines Additive sedation and impairment.[2]
Co-formulated cough/cold ingredients (paracetamol, antihistamines, pseudoephedrine) Paracetamol, antihistamines and pseudoephedrine in combination cough/cold products carry their own overdose ceilings and toxicities.[2]

Contraindications

Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent or recent (within 14 days) MAOI use, or any serotonergic medication.[2]
Concurrent ritonavir or other strong CYP2D6 inhibitor CYP2D6 poor metabolisers or concurrent CYP2D6 inhibitors.[2]
Usage & Context
  • The active ingredient in most non-prescription cough suppressants (Robitussin, Delsym and many combination cold-and-flu products), taken to relieve dry cough.
  • In prescription medicine it is combined with quinidine (Nuedexta) for pseudobulbar affect and, since 2022, with bupropion (Auvelity) as a rapid-acting antidepressant: both pairings use a CYP2D6 inhibitor to raise and stabilise DXM levels.
  • It is widely misused recreationally, especially by adolescents ('robotripping', 'skittling'), for its dissociative high, which is why several US states restrict over-the-counter sales to adults.
Sources & Evidence

Further Information