Since its first discovery Nitrous Oxide effects on the human body have been noticed – these have found uses for medical and nefarious, narcotic purposes
Nitrous oxide is an anaesthetic, this mean that it provokes a loss of sensation when inhaled. The prevailing theory of the molecular mechanism that contributes for the anaesthetic action of nitrous oxide is the non-competitive inhibition of glutamate receivers of the subtype NMDA. This way, the inhibition of the neurotransmission glutamate-induced excitotoxicity is central to the thesis of the anaesthetic effects of nitrous oxide. Other prime target that contributes to the anaesthetic action of the nitrous oxide is potassium channels, like the TREK-1 channel that, when activated, enhances the conductivity of potassium and therefore hyperpolarizes the neurons, changing their firing rates. Even considering the importance of GABAa receptors in anaesthesia through intravenous anaesthetics (propofol, etomidate and pentobarbital) and volatile halogenated anaesthetics is well established, nitrous oxide has an insignificant effect on these antagonist (that inhibit) receptors.
Nitrous oxide has also known analgesic effects; this meaning it can relieve pain. Nitrous oxide induces analgesia by activating opioid neurons in the periaqueductal grey matter and in the adrenergic neurons in locus ceruleus, areas 5 and 7 of the brain (somatosensory cortex). The corticotrophin release factor, released by the hypothalamus, seems to be critical to the activation of the locus ceruleus, a fact that might be provoked the inhibition by NMDA receptors.
Nitrous oxide has widely known anxiolytic effect, meaning that it has a calming effect. For this reason, it is widely used in dentistry to calm the patient before applying local anaesthesia and during the procedure. The patient retains conscience and is relaxed, often reporting a losing track of time. After the procedure, the effects wear off quickly. The anxiolytic effect of nitrous oxide is linked with heightened activity of GABAa receptors.
In studies conducted on mice, it was found nitrous oxide arouses the mesolimbic reward path by the inducement of dopamine and the activation of dopaminergic neurons in the ventral tegmental area and nucleus accumbens. It is theorized that this happens due to the inhibition of NMDA receptors present in the brain. This has been pointed as the reason for the euphoria effects of nitrous oxide, as well as appearing to enhance the analgesic characteristics of nitrous oxide. One interesting result of these studies on mice is nitrous oxide seems to block amphetamine-induced carrier-mediated dopamine release, which blocks addiction to opioids like cocaine or morphine. This might be the reason of its positive effects when dealing with addiction, although studies in humans, through clinical trials, have returned mixed results.