Notes on the use of Nitrous Oxide

First, there are the dangers which accompany the inhalation of any compressed gas (making sure you get enough air, making sure you don't freeze your lips or inflate your head, making sure you are sitting down and won't hurt yourself if you get dizzy).

Second, there are the health effects specific to nitrous oxide. There have been reports of immunological and reproductive disturbances in professionals who are chronically exposed to nitrous oxide. The immunological disturbances are documented by Peric et al (1991) Anaethesia 46: 531-7. Apparently anaesthetic personnel had been complaining about weakness and recurrent infections and decreased peripheral blood leukocyte counts has been found. The operating rooms were found to be improperly ventilated, causing nitrous oxide and halothane (another anaesthetic) to remain in the air. Even after a 3-4 week holiday, some personnel has decreased B lymphocytes and increased red cell count, haemoglobin concentration and haematocrit and other disturbances. I don't have a reference handy for the reproductive disturbances, but the study basically found that women who were chronically exposed to nitrous had difficulty becoming pregnant. It should be noted that these health effects are the result of chronicexposure; a single balloon at a Dead show (or a single visit to the dentist) is unlikely to be a problem for a healthy individual.

Aside from its psychopharmacological actions, nitrous oxide has one other (known) significant metabolic action: it interacts with vitamin B12. This was first reported in an in vitro study in 1968, but didn't really receive notice from anaesthesiologists until ten years later (because medline didn't exist yet :-) ). In 1978, however, Amess et al showed that 24 h of nitrous oxide administration caused interference with DNA synthesis in humans. Since then, the interaction between nitrous oxide and B12 has been better characterized.

Basically, B12 is a bound coenzyme of methionine synthase and has a tetrapyrrole rings with a monovalent cobalt at the center. The cobalt functions as a methyl carrier in a transmethylation reaction. Nitrous oxide converts the cobalt from the monovalent form to the bivalent form. As a result, methionine synthase activity is inhibited. Recovery is believed to require absorption of new unoxidized B12 (and synthesis of new apoenzyme).

Humans seem to be far more resistant to complications from this than rodents. I don't have the energy to go through the various published studies at this point, so I will quote from Nunn's "Clinical Aspects of the Interaction Between Nitrous Oxide and Vitamin B12" (1987), Br. J. Anaesth. 59: 3-13.

It seems likely that in man, in contrast to the rat, exposure of less than 30 minutes will not cause any measurable change in methionine synthase activity. In combination with a wealth of clinical experience, this suggests that there is no special hazard for short exposures to nitrous oxide. There is a variable response to exposures lasting between 30 minutes and 2 h. However, it now seems likely that exposures of more than 2 h are likely to cause intereference with hepatic methionine synthase activity. The paucity of human data makes it more difficult to say how long an exposure is required to cause significant intereference with DNA synthesis. It is likely that there will be considerable individual variation and results obtained in healthy patients cannot be extrapolated to the patient who is seriously ill. Nevertheless, it seems likely that, once methionine synthase activity is inhibited, it will remain so for days.
With respect to repeated exposures to nitrous, be aware that this effect can build up (Nunn gives "intervals of less than 3 days" as a cut-off). So, go easy on the "hippie crack," people!

Mandatory nitrous horror story: Layzer (in (1978) "Myeloneuropathy after prolonged exposure to nitrous oxide," Lancet 2:1227) reports a case of 15 people who had been inhaling nitrous oxide for long periods of time and developed a condition resembling subacture combined degneration of the cord, whatever that means.

I would suggest that the following types of people in particular avoid exposure to signficant amounts of nitrous:

And BTW I did find a reference on sexual ideation during nitrous oxide, which is a topic that came up some time ago. More on that when I actually get the article.

--Matt Baggott,

From: (Ken Shirriff)
Date: 15 May 1993 01:14:22 GMT
In article <199312.4616.30249@dosgate> "steve szuster"  writes:
>                       Why whipped cream???  (Nitrous in w/c?)

That's an interesting question. The reason why nitrous oxide is used as a propellant is that it dissolves in the liquid cream. When the cream escapes from the can, the gas expands and in doing so whips the cream into a foam. (This explanation is from the book "Food Science".)

Now, the interesting part is that nitrous oxide is an inhalation anesthetic because it dissolves in synaptic lipid membranes. So it's not a coincidence that nitrous oxide is a whipped cream propellant and an inhalation anesthetic: nitrous oxide dissolves in fatty cream and it also dissolves in fatty cell membranes.

Lots of things work as inhalation anesthetics; the better they dissolve in the lipid membranes, the lower the pressure required. This is why spot removers like ether and chloroform work as anesthetics in low concentration. At high enough pressure, even nitrogen will dissolve in membranes; this causes nitrogen narcosis in divers. Even an inert gas like argon will work as an anesthetic since it will dissolve in membranes under enough pressure. This is also why people sniff fat-soluble gases like propane and freon to get high.

Ken Shirriff shirriff@sprite.Berkeley.EDU

Date: 19 Apr 1993 16:21:56 -0500 (EST)

Two references about nitrous oxide that may help:

The Sputnik Nitrous Oxide Pages.

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