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Joseph Priestley's discovery of nitrous oxide (N2O) was recorded in 1772. In the late 1790's, Humphry Davy experimented with the psychotropic properties of N2O, describing his observations in a book, published in 1800. A dentist, Horace Wells discovered anaesthesia with N2O in 1844. Over a century after Davy, its potential usefulness in psychiatry was first recognised. The seminal researches in neuropsychiatry, between 1920 and 1950, mainly used anaesthetic concentrations of the gas. The psychotropic actions of N2O, at non-anaesthetic doses, were first used by dentists, mainly for its anxiolytic action. In modern dentistry, N2O is always mixed with at least 30% oxygen and titrated to doses rarely exceeding 40% of N2O. At these lower concentrations, untoward effects are almost always avoided, including over-sedation and/or anaesthesia. In the early 1980's, the low-dose dental titration technique was first used to investigate and treat psychiatric conditions, including substance abuse. Until then, most physicians regarded the gas only as an anaesthetic agent. An exception was obstetricians who used a fixed 50% concentration of N2O diluted with oxygen for analgesia during parturition. In 1994, to clearly distinguish between anaesthetic and non-anaesthetic concentrations (as used in dentistry), the term Psychotropic Analgesic Nitrous oxide (PAN) was introduced.

Mini-Review: A Brief History of Nitrous Oxide (N2O) Use in Neuropsychiatry