Among these is the release of neurotransmitter and hormones but especially catecholamines. The release of epinephrine by nicotine especially from adrenal medulla, causes an increase in free fatty acids, glycerol, and lactate concentrations in the blood. All nicotinic effects appear to be blocked by drugs such as mecamylamine, a non-competitive blocker that occupies the ion channel and not the nicotinic binding site. A lethal dose in adults is estimated to be approximately 60 mg. A few drops of pure nicotine on the tongue would quickly kill a healthy adult.
Tolerance is regarded as a clinical manifestation of neuronal adaptation to nicotine.
Nicotine receptors are upregulated in the brains of smokers. In humans, the syndrome may begin within a few hours after the last dose and may continue for several weeks. Tobacco withdrawal, although distressing, is not life-threatening. Signs include craving for nicotine, irritability, frustration, anxiety, depression and increase in appetite. Relief of withdrawal is the most recognized negative reinforcement.