Dextrorphan
Dextrorphan (DXO) is the active O-demethylated metabolite of dextromethorphan and a non-competitive NMDA receptor antagonist. It is responsible for much of dextromethorphan's dissociative effects at high doses and was studied as a neuroprotectant, but is not marketed as a drug in its own right.
01 Overview
When dextromethorphan is taken, CYP2D6 converts a large fraction to dextrorphan, which is a more potent NMDA antagonist than the parent. This is why DXM's dissociative 'plateaus' at recreational doses are largely a dextrorphan effect, and why CYP2D6 metaboliser status strongly affects the experience.
Dextrorphan itself was investigated for stroke neuroprotection but development stalled due to psychotomimetic side effects. It has minimal opioid activity compared with levorphanol. It appears occasionally as a research chemical but is mostly encountered as a metabolite rather than a substance people dose directly.
02 Mechanism
Non-competitive NMDA receptor antagonist (plus sigma-1 activity); the principal dissociative metabolite of dextromethorphan.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| No established recreational dose | 0 mg | Oral | Usually encountered as a DXM metabolite, not dosed directly. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| DissociationDrives the higher-plateau dissociative effects of dextromethorphan. | dose-dependent | Observational | |
| Neuroprotection (preclinical)Reduced excitotoxic injury in animal ischaemia models; not proven in humans. | n/a | Preclinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Psychotomimetic effectsConfusion, hallucinations and dissociation at higher exposures, which halted its clinical development. | Moderate | Dose-related | Observational | |
| Serotonin toxicity risk (via parent DXM)Dextromethorphan pathways carry serotonin syndrome risk with serotonergic drugs. | Severe | Uncommon | Observational |