Dextromethorphan (DXM)
Dextromethorphan (DXM) is a morphinan cough suppressant available over the counter in many countries. At therapeutic doses it is antitussive; at much higher recreational doses it acts as a dissociative NMDA antagonist ('robo-tripping'). It carries a significant risk of serotonin syndrome when combined with SSRIs or MAOIs.
01 Overview
DXM is a well-characterised antitussive that has been in clinical use for decades. It is the dextrorotatory morphinan that, unlike its levorotatory counterparts, lacks meaningful opioid analgesic activity at normal doses. Recreational use involves consuming many times the antitussive dose to reach dissociative 'plateaus', each with progressively more intense dissociation, sedation and hallucination.
The main pharmacological hazards are serotonergic: DXM inhibits serotonin reuptake and can precipitate serotonin syndrome when combined with SSRIs, MAOIs or other serotonergic drugs. Many over-the-counter products also combine DXM with acetaminophen (paracetamol), antihistamines or decongestants, adding risk of liver injury and other toxicity at recreational doses.
02 Mechanism
NMDA-receptor antagonist (via itself and its active metabolite dextrorphan) and serotonin/norepinephrine reuptake inhibitor; also a sigma-1 receptor agonist. Antitussive action is central.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Antitussive | 15–30 mg | Oral | Standard cough-suppressant dose. |
| First plateau | 100–200 mg | Oral | Mild stimulation and dissociation. |
| Second plateau | 200–400 mg | Oral | Stronger dissociation. |
| Third/fourth plateau | 400–700 mg | Oral | Intense dissociation; higher toxicity risk. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Cough suppressionEffective central antitussive at therapeutic doses. | Clinical | ||
| DissociationDose-dependent dissociative and hallucinatory effects at recreational doses. | Plateau-dependent | Observational | |
| Euphoria and altered perceptionSought-after effects at higher plateaus. | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Serotonin syndromeAgitation, hyperthermia, rigidity, clonus and autonomic instability when DXM is combined with SSRIs, MAOIs or other serotonergic agents. | Life-threatening | With serotonergic drug combinations | Clinical | |
| Co-ingredient toxicity (acetaminophen etc.)Recreational doses of combination products can deliver hepatotoxic amounts of acetaminophen (paracetamol) or toxic amounts of antihistamines/decongestants. | Severe | With combination products at high doses | Clinical | |
| Dissociative impairment and psychosisConfusion, ataxia, impaired judgement and, at high doses, dissociative psychosis. | Moderate | At higher plateaus | Observational |