Mini-Review: A Brief History of Nitrous Oxide (N(2)O) Use in Neuropsychiatry

BACKGROUND: Joseph Priestley’s discovery of nitrous oxide (N(2)O) was recorded in 1772. In the late 1790’s, Humphry Davy experimented with the psychotropic properties of N(2)O, describing his observations in a book, published in 1800. A dentist, Horace Wells discovered anaesthesia with N(2)O 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 concen-trations of the gas. The psychotropic actions of N(2)O, at non-anaesthetic doses, were first used by den-tists, mainly for its anxiolytic action. In modern dentistry, N(2)O is always mixed with at least 30% ox-ygen and titrated to doses rarely exceeding 40% of N(2)O. At these lower concentrations, untoward ef-fects 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, includ-ing substance abuse. Until then, most physicians regarded the gas only as an anaesthetic agent. An ex-ception was obstetricians who used a fixed 50% concentration of N(2)O diluted with oxygen for analge-sia during parturition. In 1994, to clearly distinguish between anaesthetic and non-anaesthetic concen-trations (as used in dentistry), the term Psychotropic Analgesic Nitrous oxide (PAN) was introduced. OBJECTIVE: This paper will give a brief history of the use of the N(2)O in psychiatry since the psycho-tropic actions were first recognised in the 18(th) century until the present. CONCLUSION: The role of other non- opioid systems, and the extent to which they contribute to the psy-chotropic properties of N(2)O, still remains to be established.