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By Expert ID: 10036, M.D.

Smoking is the most common method of consuming tobacco and consequently it is the most common substance smoked. The World Health Organization reports that ongoing tobacco use is the leading preventable cause of death worldwide and causes 5.4 million deaths per year.

Nicotine is an alkaloid found in the “nightshade” family of plants and constitutes 0.6-3.0% of the dry weight of tobacco. In low concentrations nicotine acts as a stimulant and is one of the main factors for the potent habit forming effects of tobacco smoking. An average cigarette yields about 1 mg of absorbed nicotine. The American Heart Association has taken the stance that nicotine has such potent habit forming effects that it is one of the hardest addictions to break.

Free base nicotine will burn at a temperature below its boiling point, therefore when a cigarette is smoked most of the nicotine in it is burned, however enough is inhaled to produce its intended effects. The amount of nicotine inhaled with tobacco smoke is a fraction of the amount contained in the tobacco leaves, but yet it has potent effects.

When nicotine enters the body, it distributes quickly in the bloodstream and readily crosses the blood brain barrier; in fact it takes less than 10 seconds for it to reach the brain once inhaled. Nicotine possesses stimulant like effects, acting on specific nicotinic receptors in the brain. Only a small concentration of nicotine is needed to activate the receptor, which in turn is involved in the release of the neurotransmitter dopamine, the “pleasure” neurotransmitter in the reward center of the brain. It is likely this effect that results in the highly habit forming and addictive properties of nicotine. In actuality, nicotine results in the release of many neurotransmitters, resulting in the myriad of effects that nicotine causes, e.g. relaxation, sharpness, calmness, and alertness.

Most cigarettes contain 0.1 to 2.8 milligrams of nicotine and so it is clear that only a small concentration is needed to produce these effects. At low doses, nicotine potently enhances the actions of norepinephrine and dopamine in the brain, causing a drug effect typical of those of stimulants. At higher doses, nicotine enhances the effect of serotonin and opiate activity, producing a calming, pain-killing effect. Nicotine is unique in comparison to most drugs, as its profile changes from stimulant to sedative/pain killer in increasing dosages and use.

Like other physically addictive drugs, nicotine causes a down-regulation of the production of dopamine and similar neurotransmitters as the brain attempts to compensate for the artificial stimulation. In addition, there is a decreased sensitivity in the nicotinic receptor. To compensate for this compensatory mechanism, the brain then upregulates the number of receptors, convoluting its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. The net effect is an increase in the number of receptors, further increase in release of dopamine and increase in reward pathway sensitivity, an opposite effect of other drugs of abuse such as cocaine and heroin, which reduce reward pathway sensitivity. Nicotine therefore has a high toxicity in comparison to many other alkaloids such as cocaine; however it is uncommon to overdose and die when smoking nicotine alone.

In summary, nicotine is a highly potent drug that crosses into the brain rapidly when absorbed through inhalation resulting in the rapid progression of its effects that ultimately lead to its habit forming properties.

By Expert ID: 10036, M.D.