Background:
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.
Objective:
This paper will give a brief history of the use of the N2O in psychiatry since the psychotropic
actions were first recognised in the 18th century until the present.
Conclusion:
The role of other non- opioid systems, and the extent to which they contribute to the
psychotropic properties of N2O, still remains to be established.
Pharmacological Evidence for a Motivational Role of κ-Opioid Systems in Ethanol Dependence
