Interesting studies, these two studies were the first two I pulled up when searching nicotine and glutamate toxicity.
http://www.jneurosci.../10093.full.pdf
http://jpet.aspetjou.../2/772.full.pdf
Both show that nicotine is neuroprotective via agonising the alpha7 nAChR's which reduces the calcium influx associated with glutamate toxicity.
Nicotine is certainly not the scourge it is demonized as within the context of smoking itself is the real addiction. The total action of smoking, the manner and contexts in which it is generally engaged, and in that it has such potent relaxant and anti-depressant effects makes it so prone to abuse and so difficult to quit. The toxins within smoking are not of course the nicotine itself. Nicotine is actually a superior therapeutic for neurodegenerative diseases.
With smoking, prior to chronic use it is stimulating due to the initial glutamate enhancement, which quickly develops a tolerance due to downregulation. This severe downregulation then requires the smoker to become highly addicted as they need to right their now highly dysregulated Achnicotinergic/glutaminergic dynamics, as well as resulting dopaminergic dysregulation.
Inhalation itself likely causes such rapid and profound tolerance and downregulation (desensitization) of course; this is otherwise than if supplemented orally, as a therapeutic. The proper level for a therapeutic benefit is likely one that would also maintain a modest degree of the stimulant effect.
The 'abuse' upon these receptors caused by smoking so chrnically may even corrupt the receptor due to such overstimulation, as perhaps is the case with overstimulation by beta-amyloid. Delicate balances can of course not tolerate such 'abuse' without severe negative impact.
Smoking is obviously highly addictive and cessation is incredibly difficult. I have not really seen this the case with those who engaged nicotine orally. I have seen this be the case with oral users, even ones that use it fairly frequently. It is the while of smoking that is trends to abuse and addiction, as well as all related health consequences, likely primarily due to other toxins, though perhaps as well to the severity of nicotine overstimulation itself as well.
To come a bit full circle here, when respected, one might have the most effective and readily available neuroprectant/neuroenhancer within nicotine itself; administration via pure oral route may be superior for the desired effects (above buccal such as with gums and lozenges as that may be too rapid as well, though acceptable over inhalation of course). No abuse of these forms is seen at all commonly.
Partial agonists specific for alpha7 should be a highly desirable pathway, but may or may not be superior for intended goals as that in which may even simply be derived by nicotine used in a therapeutic manner.
Smoking = BAD!!!
Nicotine = GREAT?!!? (used orally and responsibly)
LongeCity
