By Anthony McDaniel, M.D.
Nitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula N2O. It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic effects. It is known as "laughing gas" due to the euphoric effects of inhaling it, a property that has led to its recreational use as a dissociative anesthetic. It is also used as an oxidizer in rocketry and in motor racing to increase the power output of engines. At elevated temperatures, nitrous oxide is a powerful oxidizer similar to molecular oxygen. Nitrous oxide gives rise to NO on reaction with oxygen atoms, and this NO in turn reacts with ozone. As a result, it is the main naturally occurring regulator of stratospheric ozone. It is also a major greenhouse gas and air pollutant. Considered over a 100 year period, it has 298 times more impact per unit weight than carbon dioxide.
Nitrous oxide can cause analgesia, depersonalization, derealization, dizziness, euphoria, and some sound distortion. Research has also found that it increases suggestibility and imagination. Inhalation of nitrous oxide for recreational use, with the purpose to cause euphoria and slight hallucinations, began as a phenomenon for the British upper class in 1799, known as "laughing gas parties". Until at least 1863, a low availability of equipment to produce the gas, combined with a low usage of the gas for medical purposes, meant it was a relatively rare phenomenon that mainly took place among students at medical universities. When equipment became more widely available for dentistry and hospitals, most countries also restricted the legal access to buy pure nitrous oxide gas cylinders to those sectors. As only medical staff and dentists today are legally allowed to buy the pure gas, the recreational use is also believed to be somewhat limited. The consumers union report from 1972, however found that the use of the gas for recreational purpose still take place in present time, based upon reports of its use in Maryland 1971, Vancouver 1972, and a survey made by Dr.Edward J.Lynn of its nonmedical use in Michigan 1970. Inhaling nitrous oxide from tanks used in automotive systems is unsafe, because the toxic gas sulfur dioxide is mixed in around 100 ppm, specifically to discourage recreational use.
Similarly to other NMDA antagonists like ketamine, N2O has been demonstrated to produce neurotoxicity in the form of Olney's lesions (damage to the posterior cingulate and retrosplenial cortices of the brain) in rodents upon prolonged (e.g., several hour) exposure. However, it also simultaneously exerts widespread neuroprotective effects via inhibiting glutamate-induced excitotoxicity, and it has been argued that on account of its very short duration under normal circumstances, N2O may not share the neurotoxicity of other NMDA antagonists. Indeed, in rodents, short-term exposure results in only mild injury that is rapidly reversible, and permanent neuronal death only occurs after constant and sustained exposure. Moreover, Olney's lesions have never been observed in primates (including humans).
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