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In article  kkwast@cs.utexas.edu (Kevin Kwast) writes:

>I need to know the bunk on the pros and cons of inhaling nitrous.. I have a
>group of friends who occasionally have some fun with a big tank we get filled
>locally, but there have been a few questions about the health risks involved
>with this...

I've been meaning to write up a FAQ about this and have done some
preparatory reading, so I'll take a shot at a first-pass answer:

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 CHRONIC exposure; 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:

	Pregnant women: since nitrous oxide is a known teratogen in rodents,
	acting by depleting folates and partially reversible by oral
	folinic acid, we can expect a similar syndrome in humans.

	Vegans who don't take B12 supplements: although documented cases of
	vegans with B12 decifiencies are scarce, theories on nutrition
	indicate that vegans are unlikely to get as much B12 as other
	groups of people.

	Individiduals with healing wounds, infections, or immunological
	disorders: I'm throwing this recommendation in based on a "better
	safe than sorry" policy.  Short-term exposure to nitrous oxide
	is unlikely to be a problem, but why not play it safe?

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, bagg@midway.uchicago.edu 

>-- 
>   kkwast@cs.utexas.edu (Kevin A. Kwast)     "The computer is your friend."

============================================================================

From: shirriff@sprite.berkeley.edu (Ken Shirriff)
Newsgroups: alt.drugs
Subject: Re: nitrous oxide
Date: 15 May 1993 01:14:22 GMT
Message-ID: <1t1g5e$ci5@agate.berkeley.edu>

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)
From: Jonathan 
Subject: Re: nitrous oxide
Sender: ALCOHOL & DRUG STUDIES 
To: Multiple recipients of list ALCOHOL 
Message-id: <01GX73PA3MHU8WYFKC@YMIR.CLAREMONT.EDU>

Two references about nitrous oxide that may help:
 
Gillman, M.A. Nitrous oxide abuse in perspective
Clinical Neuropharmacol. 1992, 15:297-306
 
Dohrn, C.S., Lichtor, J.L., Finn, R.S., Uitvlugt, A., Coalson, D.W.,
Rupani, G., de Wit, H. and Zacny, J.P. Subjective and psychomotor
effects of nitrous oxide in healthy volunteers Behavioural Pharmacology
1992,3:19-30