Nitrous Oxide (Dinitrogen Monoxide, Dinitrogen Oxide, Entonox)

Pronunciation: NIGH-truhs OX-eyed
Chemical Abstracts Service Registry Number: 10024-97-2
Formal Names: Dinitrogen Monoxide, Dinitrogen Oxide, Entonox
Informal Names: Fall Down, Gas, Hippie Crack, Hysteria, Laughing Gas, Nitro, Nitrous, Nitrous Acid, Noss, Pan, Shoot the Breeze, Tanks, Thrust, Whippets
Type: Inhalant.  Federal Schedule Listing: Unlisted USA Availability: Nonprescription, but sales and usage are controlled in some  jurisdictions

Uses.
This drug has been known since the 1720s. Some authorities describe nitrous oxide as an opioid; some persons even use the gas to counteract effects from stimulants. Nitrous oxide actions and its recreational use are similar to those of other inhalants. Recreational use is illegal in some jurisdictions but has a venerable history. The writer Samuel Taylor Coleridge, thesaurus compiler Peter Mark Roget, and potter Josiah Wedgwood were all eighteenthcentury notables who relaxed with nitrous oxide.

Although this substance is a pharmaceutical product, it also occurs naturally. For instance, eating lettuce generates enough nitrous oxide that scientists can measure it in a person’s breath. Large quantities are produced by wild prairie grass. Humans do not receive enough nitrous oxide from such natural sources to be affected, however. The substance is also produced by the human body. One study found the amount to increase as oral hygiene declined. As with the amounts produced by grass and lettuce, the level created by the body is too small to have any known effect on a person. From a global environmental perspective, however, nitrous oxide is a gas that promotes the greenhouse effect and ozone layer destruction, and concern exists about medical  usage affecting the world’s climate. Medical sources are estimated to create 2% of the atmosphere’s supply. Such usage may seem insignificant in that regard, but the gas is so durable in the atmosphere that any artificial source has been described as an environmental hazard.

Medically this drug is used as an anesthetic and to relieve pain ranging from dental work to migraine headache and cancer. In a medical context nitrous oxide is considered a reliable sedative. Experimental usage to treat anxiety has been successful, and one authority has noted a therapeutic antidepressant action. The substance has been used to help persons break entazocine addiction. Researchers report success in using the gas to ease alcohol, nicotine, and opioid withdrawal and to reduce craving for alcohol, tobacco, and marijuana among addicts. The latter three substances are so different from one another that nitrous oxide’s ability to reduce craving for all of them is remarkable. Some medical practitioners claim that a single dose of the gas actually eliminates craving for those substances, but that claim sounds much like those made for other “miracle cure” addiction treatments over the years but that turned out to be overly optimistic.

In former times, nitrous oxide was used to fight ear afflictions. For many years the substance was believed to make hearing more acute, but tests of hearing ability while using the compound show no improvement—and volunteers in those tests even felt they had lesser ability to detect soft sounds.

Nitrous oxide can increase pressure in the middle ear, and a case report tells of treatable hearing loss caused by the drug. Hearing defect has been reported from recreational use as well.

Typical nitrous oxide actions are tingling, numbness, dreaminess, euphoria, dysphoria (the opposite of euphoria), altered sensory perceptions, changed awareness of the body, and different experience of time flow. Although nitrous oxide is not classified as a hallucinogen, some descriptions of experiences are indistinguishable from hallucinations, particularly if a user is talented at creating internal imagery. Some persons claim to achieve mystical insight while under the drug’s influence. Intoxication from a dose lasts only a few minutes.

Drawbacks.
The substance disrupts learning ability. That action has been exploited medically to promote amnesia of unpleasant procedures. In a typical experiment volunteers who inhaled a low dose of the drug showed worsened reaction time, worsened ability to do arithmetic, and general sedation accompanied by nervous system depression (as opposed to stimulation). Interference with driving ability has been noted one-half hour after a dose. In another experiment volunteers felt stimulated; in still another experiment some individuals were sedated, and others became stimulated. One group became weary, uneasy, and confused. Short-term exposure can cause dizziness, nausea, vomiting, and breathing difficulty. Some recreational users quickly inhale as much nitrous oxide as possible and hold their breath. This technique causes a sudden change of pressure inside the lungs and can rupture small interior structures needed for breathing. Blood pressure can go up or down, depending on dosage. Users can lose consciousness, which may be hazardous in a recreational context due to falls or inability to shut off the gas source. The substance deactivates vitamin B12, an effect that can cause numbness and difficulty in moving arms and legs. Other results can be impotence and involuntary discharge of urine and feces. Nitrous oxide interferes with blood clotting, and long-term exposure has caused blood abnormalities. Persons with chronic industrial exposure have more kidney and liver disease than usual.

Nitrous oxide can become very cold when released as a gas from a pressurized container, cold enough to cause frostbite upon meeting skin or throat.

Breathing nitrous oxide without an adequate supply of oxygen can be fatal; a little in a closed space or a lot from a face mask can suffocate a user. Although nitrous oxide is called nonflammable, when inhaled it can seep into the abdominal cavity and bowels, mixing with body gases to create a flammable combination. If ignited the result would be like setting off an explosive inside the body; the danger is real enough that surgical personnel administering
nitrous oxide as an anesthetic have been warned about it.

As with many other drugs, effects of nitrous oxide can be influenced by changes in setting. For example, volunteers who knew what to expect performed better on tests than persons who had no information about what nitrous oxide would do to them.

Abuse factors.
In tests of the drug’s appeal, people in general chose nitrous oxide no more often than placebo; such lack of preference is a classic sign of low addictive potential. One experiment revealed a catch to such findings, however: Volunteers who enjoyed nitrous oxide effects chose it more often than placebo, and volunteers who disliked the drug actions chose it less often
than placebo. Thus, overall in the general population the drug might be no more attractive than placebo, but nonetheless some persons may find it captivating.

Such a finding is consistent with drugs having high abuse potential, such as heroin; so the fact that persons typically find no attraction in nitrous oxide does not prove low abuse potential for nitrous oxide. Its nickname “hippie crack” suggests that users have recognized an abuse potential. Nonetheless, a medical practitioner who administered the gas as a drug addiction
treatment said that in 15,000 cases not a single addict indicated subsequent craving for nitrous oxide; such a patient population would be expected to show particular susceptibility if given a substance with abuse potential. The same practitioner notes that regardless of theoretical possibilities, 200 years of experience demonstrate that nitrous oxide is among the least abused drugs.

Tolerance develops in rats. Human experimentation documents tolerance developing to some effects (such as euphoria and pain relief) but not necessarily to all.

Drug interactions.
In an experiment comparing light drinkers of alcohol to moderate drinkers, the moderate drinkers found nitrous oxide more appealing. One group of researchers found that alcohol boosts nitrous oxide effects and that the drug combination creates effects produced by neither substance alone. Those researchers concluded, however, that the combination was not
potent enough to have more appeal than nitrous oxide alone. That conclusion assumes, of course, that drug abusers base their conduct on rational analysis of scientific findings. In a similar experiment comparing users and nonusers of marijuana, when given a choice neither group preferred nitrous oxide more than a placebo, but nitrous oxide effects felt stronger to marijuana users. In rats ketamine boosts effects from nitrous oxide. In a human medical context
that combination is routine and appears safe, but the combination causes brain damage in rats. Persons using morphine or other opiates can experience muscle rigidity when inhaling nitrous oxide, a situation that can interfere with breathing.

Cancer.
Studies do not indicate that nitrous oxide causes cancer in animals. Whether the drug causes cancer in humans is unknown. Genetic damage similar to the amount from daily smoking 10 to 20 cigarettes has been found in health care workers routinely exposed to minuscule amounts of nitrous oxide; such damage might have a potential for causing cancer.

Pregnancy.
Fertility is lower in female rats exposed to nitrous oxide than in rats having no exposure. Lower fertility has also been observed among female health care workers with occupational exposure to the gas, and reduced fertility is also reported for males. Offspring of male mice exposed to nitrous oxide have weighed less than normal and have not matured as fast as normal.

Birth defects resulted from an experiment exposing pregnant rats to the gas for 24 hours. When given to pregnant women during childbirth the drug builds up in the fetal blood and brain; one authority recommends administering oxygen to any newborn whose mother received nitrous oxide while giving birth. As the twenty-first century began researchers reported that the gas might cause permanent fetal and newborn brain damage, a finding in contrast to previous understanding of the drug. Occupational exposure to nitrous oxide is associated with smaller infants and lower birth weight and may increase likelihood of spontaneous abortion. Pregnant and breast-feeding health workers are advised to avoid rooms where nitrous oxide residues may contaminate the air. Sperm abnormalities and lower fertility have been noted in male rats exposed to nitrous oxide. Wives of men exposed to the gas have shown a higher spontaneous abortion rate, compared to wives of men with no exposure. The compound is not detected in milk of nursing mothers.

Additional information.
“Nitrous acid” is an unstable nitrite substance. The nickname “nitrous acid” is sometimes used for nitrous oxide, but they are different substances.

Additional scientific information may be found in:
Block, R.I., et al. “Psychedelic Effects of a Subanesthetic Concentration of Nitrous Oxide.” Anesthesia Progress 37 (1990): 271–76.

Danto, B.L. “A Bag Full of Laughs.” American Journal of Psychiatry 121 (1964): 612–13.

Dohrn, C.S., et al. “Subjective and Psychomotor Effects of Nitrous Oxide in Healthy Volunteers.” Behavioural Pharmacology 3 (1992): 19–30.

Linden, C.H. “Volatile Substances of Abuse.” Emergency Medicine Clinics of North America 8 (1990): 559–78.

Temple, W.A., D.M. Beasley, and D.J. Baker. “Nitrous Oxide Abuse from Whipped Cream Dispenser Chargers.” New Zealand Medical Journal 110 (1997): 322–23.

Yagiela, J.A. “Health Hazards and Nitrous Oxide: A Time for Reappraisal.” Anesthesia Progress 38 (1991): 1–11.

Zacny, J.P., et al. “Examining the Subjective, Psychomotor and Reinforcing Effects of Nitrous Oxide in Healthy Volunteers: A Dose-Response Analysis.” Behavioural Pharmacology 7 (1996): 194–99. (drugsencyclopedia.blogspot.com)