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Alexander Shulgin -- Memorial Gathering
August 2nd, 1pm-6pm, Berkeley CA
Nitrous Pharmacology Notes
In article <1992Oct5.135942.23068@linus.mitre.org> lewis@aera8700.mitre.org (Keith Lewis) writes:
>I've seen the claim that N2O does not react chemically more than once on
>this network, yet nobody seems to be able to explain why it gives you a
>buzz. This sounds a bit fishy to me.

According to _Introduction to Anesthesia_, Dripps, Eckenhoff, Vandam, the action of inhalation anesthetics is still not totally understood, but there are several theories and possible explanations:

"The basic principle that lipid solubility of anesthetics governs anesthetic action remains viable. Specifically, the narcotic action of a drug correlates strongly with its solubility in biologic membranes. Interactions of anesthetics with biologic membranes cause expansion of the membrane. Membrane expansion by a critical volume of 0.4 per cent results in anesthesia. Evidence is available to show that anesthetics selectively combine with hydrophobic groups in biologic proteins, whether purified or membrane-associated. Perhaps these alterations in membrane structure affect synaptic transmission in the brain, giving rise to anesthesia." Another possible method is changes in membrane protein structure altering ion flow. Action on membranes in mitochondria and endoplasmic reticulum might also be responsible.

The primary anesthetic action seems to be the synapse. Anesthetics may alter the binding of neurotransmitter to specific receptor proteins. The section concludes that the mechanisms are not necessarily exclusive of one another. Multiple mechanisms may be responsible for anesthesia.

Ken Shirriff




A FEW WORDS ON METHOD OF ACTION...

N20 is a weak anaesthetic gas that has been in use since the late 18th century both in surgery and at parties. It is also used in the dairy industry as a mixing and foaming agent as it is non-flammable, bacteriostatic (stops bacteria from growing) and leaves no taste or odour on the food.

N2O does not combine with haemoglobin, but is carried free in the blood and excreted unchanged through the lungs. The risk of hypoxia comes not from any interaction between N2O and O2 in the blood or brain, but from simply not inhaling oxygen often enough. The vast majority of deaths from N2O abuse have been through stupidity (tying a plastic bag full of N2O round the head, letting off a tank in a airtight place, that sort of thing). There have been a few cases of malignant hyperthermia (raised body temperature),and this is considered a potentially serious threat to those with the genetic requirement (check out your family history - look for deaths during surgery, both minor and major).

There are 4 stages of general anaesthesia. The first is drowsiness, confusion and analgesia. The second stage involves excitement, euphoria, spontaneous muscle movements, hallucinations (auditory and visual). The third stage is loss of consciousness, and the fourth stage is heading into coma, where the patient stops breathing. Anaesthetists generally aim for the upper levels of stage three, which is why some people 'wake up' during the operation - they've drifted up into stage two. From personal experience, I think that recreational use of inhalational anaesthetics (N2O and ether) induce stage 2 and sometimes stage 3, depending on the pattern of use.

General Anaesthetics can give nausea and vomiting as a side effect, the risk of this is increased if you have been drinking alcohol. Not only is this a bit unpleasant but there is a risk of inhaling your own vomit if you are a bit confused or temporarily unconscious.

Reverse tolerance has been reported in the literature, and this seems to be confirmed by my own personal experiences. Reverse tolerance is getting more intense or prolonged feelings with the same or lower quantities of a drug. Most psychoactive substances don't work this way, I don't know why N2O does. As all traces of the gas are excreted from the body within an hour after cessation of use, it's not due to fat stores being reintroduced to the blood (as can happen with marijuana).

Be very careful of home made N2O. In some states of the US, there is a leaflet floating around with instructions on how to make your own, but you are almost guaranteed to end up with a lungful of assorted rubbish like NO2, H2NO3, and other yummy toxic things. REF: Annals of Internal Medicine, Vol 96, 3,Mar 1982,pp333-334:Home made Nitrous Oxide: No laughing matter.

Nitrous oxide will dissolve out of blood into air filled spaces eg the intestines, the middle ear. N2O in the gut will just give you a gut pain, but if you have ever had middle ear disease, or damaged ear drums, you could be in for permanent hearing loss. There are also some cases of transient hearing loss, but I don't know much about this.

There isn't very much in the medical literature about recreational use of N2O, which is a different pattern to surgical use. Next time I get a tank, I'll run a few tests and observations on my friends just to see what's really happening.

Karen