MadSci Network: Medicine

Re: Why does 'laughing gas' make people laugh?

Date: Sat Dec 20 14:15:10 2003
Posted By: Robin Cooper, Faculty, neurobiology, Univ. of Kentucky
Area of science: Medicine
ID: 1069931442.Me

Hi James,
This is such a good question you ask.

This type of question really makes one scratch their head and wonder “yeah that 
is a real interesting question".

So, lets first try to find out what the mechanism of laughing gas is on the

Laughing gas is mostly made up of a compound called nitrous oxide (N2O).
This has 2 nitrogen molecules and one oxygen molecule.

It is thought that N2O blocks a particular type of receptor in the brain.
The chemical released from one cell in the brain to another cell is called
a neurotransmitter and the type of neurotransmitter that causes excitation
of the target cell is mostly glutamate in our brains. Well most studies in
animals show that N2O blocks that type of receptor (i.e. glutamate
receptors). One of the glutamate receptors in our brain is called a NMDA

Below is some text that I cut and pasted from the following www site:

Nitrous oxide (laughing gas) acts through the NMDA receptor homolog NMR-1.
Laura Metz, Peter Nagele, Mike Crowder. Department of Anesthesiology,
Washington University, St. Louis, MO.
   Nitrous oxide (N2O) produces anesthesia by an unknown mechanism. In the
vertebrate nervous system, N2O has been found to inhibit NMDA and non-NMDA
type glutamate receptors, albeit less effectively. The behavioral and
genetic data implicate NMDA receptors as the molecular target for nitrous

There are also studies that show that N2O might cause some damage in the
brain. This is why when the gas is used on people they mix N2O with some
other gases to try to block the bad effects of N2O. 

Below is an article from a medical journal that discusses some of the toxic
effects and how this is prevented in humans taking N20.

Nat Med. 1998 Apr;4(4):460-3.
Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and
Jevtovic-Todorovic V, Todorovic SM, Mennerick S, Powell S, Dikranian K,
Benshoff N, Zorumski CF, Olney JW.
Department of Anesthesiology, Washington University School of Medicine, St.
Louis, Missouri 63110, USA.
Extensive research has failed to clarify the mechanism of action of nitrous
oxide (N2O, laughing gas), a widely used inhalational anesthetic and drug
of abuse. Other general anesthetics are thought to act by one of two
mechanisms-blockade of NMDA glutamate receptors or enhancement of GABAergic
inhibition. Here we show that N2O, at anesthetically-relevant
concentrations, inhibits both ionic currents and excitotoxic
neurodegeneration mediated through NMDA receptors and, like other NMDA
antagonists, produces neurotoxic side effects which can be prevented by
drugs that enhance GABAergic inhibition. The favorable safety record of N2O
may be explained by the low concentrations typically used and by the fact
that it is usually used in combination with GABAergic anesthetics that
counteract its neurotoxic potential.

Some people are allergic to the compounds in the gases used in the
dentist/medical office. The allergic response can also be due to the other
compounds mixed in with N2O.

People do realize that N20 can be dangerous and can damage brain cells so
it is used with caution in doctors offices with trained people which know
what to do if some one has an allergic reaction.

So to answer your question - it might not be possible since people (i.e.,
scientists) still do not know how N2O fully works in the brain.

I can only guess that N2O blocks some communications in the brain and lets
other areas go unchecked or uncontrolled. Maybe laughing and showing
emotions is controlled in a different part of our brain so when other
places in our brain "go to sleep" by N2O the laughing/emotion center takes

I checked the medical literature and I could not find an article where
someone has monitored brain activity by live imaging, in a scanning
machine, and then given the person laughing gas. I think that would be a
real neat experiment to then find out what centers in the brain are
sleeping and which ones are active when some one is laughing while taking N2O.

I am sorry I do not have a better answer for you. Maybe some other person
can respond to your question on Mad Science Network and help both of us to
better understand N2O's actions with laughing.

All the best,
Robin L. Cooper

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