Recommendation (from TRS)
Substance identification
Nitrous oxide (IUPAC name: Nitrous oxide, N 2O) is an inhalational anaesthetic marketed under a range
of trade names as both a single ingredient gas and in multi-ingredient preparations. It is also
manufactured for industrial use, including in food production, as small metal canisters, bulbs and
larger cylinders. It is described as a colourless gas.
WHO review history
Nitrous oxide is not currently under international control and has never been reviewed by the ECDD.
Information was brought to WHO’s attention by a Member State of increased nonmedical use, such
that it presented a risk to public health.
Similarity to known substances and effects on the central nervous system
Nitrous oxide appears to have multiple mechanisms of action that are not entirely understood. There
is some evidence for effects on opioid, GABAergic, glutamatergic and other neurotransmitter systems.
Nitrous oxide produces anaesthesia, analgesia and, in laboratory studies with humans, subjective
effects such as perceptual distortion, paranoia, delusions, anhedonia and cognitive disorganization.
Dependence potential
Acute and chronic tolerance to the effects of nitrous oxide have been documented in experimental
animals, with signs of withdrawal when exposure was ended abruptly. Animals that were tolerant to
nitrous oxide were partially cross-tolerant to ethanol but not to barbiturates or morphine.
Laboratory studies in humans provide evidence of tolerance to some effects of nitrous oxide, but the
degree of tolerance varied according to the effect and between individuals. Epidemiological and
clinical studies provide evidence of dependence.
Actual abuse and/or evidence of likelihood of abuse
The evidence from studies in experimental animals on the likelihood of abuse of nitrous oxide is
inconsistent.The abuse potential of nitrous oxide has been reported since the 19th century, including its euphoric
effects and ability to cause auditory and visual distortions. Nitrous oxide was originally promoted for
recreational use as “laughing gas”; however, laboratory studies with humans have produced
inconsistent results on abuse liability.
The global prevalence of non-medical use of nitrous oxide is unknown. Reports from several countries
indicate that nonmedical use is highest among adolescents and young adults, and evidence from
some countries indicates an increase in use in recent years. Nitrous oxide used nonmedically is
typically obtained from legal manufacturers, with no evidence of illicit manufacture and minimal
evidence of cross-border trading.
Nitrous oxide use has been implicated in cases of impaired driving. Deaths directly related to
nonmedical use of nitrous oxide appear to be rare and to be due to intended or unintended asphyxia.
Long-term exposure can result in neurological and haematological toxicity.
Therapeutic use
Nitrous oxide is widely used globally for analgesia and sedation during childbirth and in painful short
procedures in dentistry and emergency medicine. It is used commonly as a supplementary agent in
anaesthesia. Nitrous oxide is listed on the 2023 WHO Model List of Essential Medicines and the
Essential Medicines List for Children as an inhalational anaesthetic. Clinical trials of nitrous oxide are
being conducted to explore its value as a medication for other indications such as treatment-resistant
depression and management of alcohol withdrawal symptoms.
Rationale and recommendation
Nitrous oxide is a widely used inhalation anaesthetic and is listed on the 2023 WHO Model List of
Essential Medicines and Essential Medicines List for Children. While the Committee acknowledged the
concerns raised by some countries, it recommended that nitrous oxide not proceed to critical review
because of the absence of evidence of illicit manufacture and of common trading across borders, and
in recognition of its global therapeutic value.
The Committee recommended that nitrous oxide not proceed to critical review but be kept under
surveillance by the WHO Secretariat.
ECDD Recommendation
Added to surveillance list at 46th ECDD (2023)
Nitrous oxide is a widely used inhalation anaesthetic listed on the 2023 WHO Model List of Essential Medicines and the Essential Medicines List for Children. When pre-reviewed by the ECDD, the Committee acknowledged the concerns raised by some countries with respect to its nonmedical use. However, the Committee recommended that nitrous oxide not proceed to critical review because of the absence of evidence of illicit manufacture and of common trading across borders, and in recognition of its global therapeutic value. For these reasons the Committee recommended that nitrous oxide not proceed to critical review but be kept under surveillance by the WHO secretariat.