How Things Work: Laughing gas

In the 1800s, events called “nitrous oxide capers” were held during carnivals or medical shows. During these capers, people were given small doses of nitrous oxide and would end up laughing hysterically and, acting in a very amusing manner until the effects of the gas diminished. Although such recreational use of the gas would be termed as substance abuse today, this anecdote, reported in an article on the website of the University of Bristol, showcases the very interesting effects of nitrous oxide, better known as laughing gas. Discovered in 1775 by Joseph Priestly, nitrous oxide soon became popular for its rather entertaining effects on people. Priestly first synthesized the gas by heating ammonium nitrate over iron filings. This produced the gas nitrous peroxide, which, when passed over water, produced nitrous oxide. The uses of the gas remained largely unknown until British chemist Humphrey Davy administered nitrous oxide on himself. Davy realized that apart from the ability to produce involuntary laughter, the gas also had the effect of dulling pain and physiological sensations. He also coined the term “laughing gas” for nitrous oxide after observing the effects it had on people.

The website explains that Davy, who had been a surgical assistant for some time, realized the potentially positive use of nitrous oxide for surgeries. However, it took nearly 40 years after Davy’s first discovery before nitrous oxide could be formally used as an anesthetic in surgeries. Nitrous oxide is used as an anesthetic even today, and is safer than the traditionally used anesthetic, chloroform. Although the gas does have some beneficial uses, it also has many toxic side effects, and overdoses of the gas can be fatal, causing permanent brain and spinal cord damage. Many substance abuse cases of nitrous oxide have resulted in death, which is why many states in the United States have special laws regarding nitrous oxide sale and possession. Considering these interesting properties of the gas, it is hard not to wonder why the gas causes the effects it does. However, the working of the gas is still largely unclear. An article in Nature Medicine suggests that the mechanism of nitrous oxide may be linked to the N-methyld-aspartate (NMDA) receptors in the brain. NMDA receptors are commonly activated by the neurotransmitter glutamate and are also ion channels, the activation of which causes positively charged ions to move across the cell membrane of neurons. NMDA receptors, thus, help in relaying messages across the neurons in the brain. The research presented in Nature Medicine shows that nitrous oxide may be a possible NMDA receptor antagonist, meaning that it inhibits the activity of the receptors.

This inhibition prevents the formation of ionic currents that NMDA receptor activation normally produces and results in a number of side effects. The neurotoxic effects produced by nitrous oxide are very similar to those produced by other NMDA antagonists, further supporting this theory.
As of now, anesthetics employing nitrous oxide are mixed with less toxic gases like oxygen, or with chemicals that counteract the toxic effects of the gas. Dentists mostly use nitrous oxide as an anesthetic today.

A study reported by ScienceDaily states that the effects of nitrous oxide as an anesthetic can be boosted by hypnotism. In a study conducted by University College London, subjects under the influence of 25 percent nitrous oxide experience a boost in imaginative capabilities.
From these results, the researchers concluded that patients would become more relaxed if spoken to in soft voices. Thus, patients would become sedated faster by nitrous oxide if spoken to in soft, hypnotic voices.