What is better for psychiatry: Titrated or fixed concentrations of nitrous oxide?

Medication dosages are crucial-no single dose fits all. My paper compares the safety, scientific and practical applicability of fixed 25-50% concentrations of nitrous oxide (N2O) with the variable titrated concentrations of Psychotropic Analgesic N2O (PAN), as used in dentistry, and neuropsychiatry. A crucial difference is that PAN is always titrated, via an open circuit (nasal mask), to the minimum concentration (dose), which ensures full consciousness, cooperation, comfort and relaxation. With PAN, the goal is subject comfort, not dose. In contrast, fixed goal concentrations are usually given via relatively closed circuits (full facial mask/similar) without account for individual patient's dose-response. Hence, fixed concentrations, in N2O sensitive subjects, could result in unconsciousness and other adverse effects (nausea, vomiting, anxiety, aspiration, might occur; requiring an anaesthesiologist for patient safety. PAN is titrated using each subject's subjective and objective responses as the guide to the ideal concentration. Thus, when PAN is used, there is no fixed concentration even for a single subject, nor is an anaesthesiologist required. Furthermore, there is a greater scientific rationale for using PAN, because the receptor systems involved are better known, whilst those for fixed concentrations are not. The PAN or dental titration method has been safely used in general dentistry for over 70 years and as an investigative, diagnostic and therapeutic tool for neuropsychiatry for over 40 years. Clinical applications include substance abuse detoxification, ameliorating depression, and investigations of schizophrenia, human orgasm, pain perception and basic neuroscience. By contrast, the experience with fixed doses in psychiatry is limited.

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

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.

Psychotropic analgesic nitrous oxide for acute cocaine withdrawal in man.

This article reports the first single-blind study using psychotropic analgesic nitrous oxide (PAN) for treating acute withdrawal states following cocaine abuse. Thirty-one of the 33 cases responded by a reduction of symptom scores of 50% or more, which clinical experience has shown to be synonymous with observed recovery. Five subjects were placebo responders without further improvement following PAN. Eleven subjects were not improved by placebo but responded positively to PAN. Fifteen responded to both the O2 with a further improvement following PAN. Aggregate scores of symptoms such as craving, anxiety, and dysphoria were greatly decreased by O2. These improvements were even greater following PAN as compared to post O2 scores. Two patients failed to respond to any treatment condition. Thus 93.9% of the subjects were improved by the use of PAN and/or O2 alone.

Combined cannabis/methaqualone withdrawal treated with psychotropic analgesic nitrous oxide.

This article reports the first single-blind study using psychotropic analgesic nitrous oxide (PAN) for treating acute withdrawal states following the abuse of methaqualone combined and smoked with cannabis. Smoked methaqualone combined with cannabis is called "white pipe" (WP). South Africa is the only country in the world where WP is a major form of substance abuse. This article demonstrates in 101 consecutively treated patients given placebo (100% oxygen) followed by PAN that this therapy produced a measurable therapeutic effect (more than 50% improvement) in 87 patients. This study confirms that WP is a form of substance abuse confined mainly to young adult male subjects.

Enlarged double-blind randomised trial of benzodiazepines against psychotropic analgesic nitrous oxide for alcohol withdrawal.

We report a randomised double-blind controlled study with an enlarged cohort of participants (N = 51) using psychotropic analgesic nitrous oxide (PAN) versus benzodiazepines (BZs) for treating acute alcoholic withdrawal states. An additional 28 participants having received a BZ the night previous to the study were pooled with the previously analysed 23 (with no additional BZ). These pooled results showed that PAN is superior to a BZ regimen at P = .05 level, despite additional BZs. Our work provides further support for previous findings that show that PAN is a safe, rapid, and effective therapy for acute mild to moderately severe withdrawal states.

Randomized double-blind trial of psychotropic analgesic nitrous oxide compared with diazepam for alcohol withdrawal state.

In this article, we report the first randomized double-blind controlled study of the use of psychotropic analgesic nitrous oxide (PAN) vs. a single dose of benzodiazepine (diazepam) for treating acute alcoholic withdrawal states. In previous studies, it was demonstrated that a single treatment of PAN was sufficient to reverse 90% of acute alcoholic withdrawal states within the first 60 minutes of administration with lasting effect in a single-blind manner. Despite the small sample used (n = 23), the gas was significantly more effective than the benzodiazepine at the P = 0.05 level when compared at 120 minutes. This study provides further support for previous findings that show PAN is a safe, rapid and effective therapy for acute mild to moderately severe withdrawal states.