Inhalation provides the quickest and most efficient route to the brain and is therefore the most addictive. Some of the free nicotine and most of the cotinine and other metabolites are excreted by the kidney. Cigarette smoking is known to enhance the metabolism of a wide variety of drugs. This effect is not due to nicotine, but is produced by the constituents of tar. Tolerance is seen with nicotine use.
Smokers actually develop an increased number of nicotine receptors in the brain.
Signs and symptoms of withdrawal from nicotine include craving for nicotine, irritability, frustration, fatigue, increased peripheral circulation, anxiety, depression and increased appetite which results in weight gain. Decreased heart rate and EEG changes are also prominent signs of nicotine withdrawal. Nicotine has both negative and positive reinforcing effects. Relief of withdrawal symptoms is the most recognized negative reinforcer. Its reinforcing actions are thought to be related to the central stimulation of nicotinic cholinergic receptors which eventually lead to dopamine release.