Nitrous Oxide
Nitrous oxide (N2O, laughing gas) is an inhaled gas used for over a century as an analgesic and anaesthetic adjunct in medicine and dentistry. It acts largely as an NMDA receptor antagonist, producing brief euphoria, analgesia and dissociation. Recreational use from cream chargers is widespread, and repeated heavy use causes serious vitamin B12-related neuropathy.
01 Overview
Nitrous oxide has extensive clinical use in dentistry, obstetrics (Entonox, a 50:50 mix with oxygen) and procedural sedation. Onset and offset are very rapid because of its low blood solubility. At sub-anaesthetic concentrations it produces analgesia, giddiness and mild dissociation.
Recreationally it is inhaled from small chargers or larger tanks, giving a 30-90 second rush. The main harms are hypoxia if inhaled without oxygen, and functional B12 inactivation with heavy or chronic use, which can cause subacute combined degeneration of the spinal cord and peripheral neuropathy. Dependence with very heavy daily use is increasingly reported.
02 Mechanism
Primarily non-competitive NMDA receptor antagonism, with additional opioid and GABA-A/two-pore potassium channel actions contributing to analgesia and anxiolysis; irreversibly oxidises the cobalt in vitamin B12, inactivating methionine synthase.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Recreational (single charger) | 1 charger (~8 g) | Inhaled | Balloon inhalation; effect lasts under a minute. |
| Medical/dental analgesia | 30–70 % in oxygen | Inhaled | Titrated mix with oxygen; never pure N2O for sustained use. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Euphoria and analgesiaBrief giddy euphoria with strong analgesia and altered perception. | 30-90 s | Clinical | |
| DissociationDetachment, auditory distortion and a sense of pressure or waves at higher concentrations. | brief | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Hypoxia / asphyxiationInhaling pure N2O without oxygen, or in a confined space/bag, can cause fatal oxygen deprivation. | Life-threatening | Uncommon but serious | Observational | |
| B12 deficiency neuropathyRepeated or heavy use inactivates vitamin B12, causing numbness, tingling, weakness and, in severe cases, subacute combined degeneration of the spinal cord. | Severe | Common with heavy use | Observational | |
| Frostbite injuryDirect inhalation from a charger or tank valve can freeze lips, mouth and airway. | Moderate | Uncommon | Observational |