4. Does development of nicotine addiction depend on the dose?
- 4.1 What happens to nicotine?
- 4.2 How does nicotine exert its effects?
- 4.3 What is the evidence on addictiveness of nicotine?
4.1 What criteria for assessment should be used?
Nicotine inhaled in tobacco smoke is rapidly absorbed through the lungs. An average cigarette contains 6-10 mg of nicotine of which around 1 mg is absorbed. It reaches high levels in the brain within 10-20 seconds of inhalation.
Nicotine in the bloodstream is eventually metabolised in the liver, and its level in the blood falls by half in roughly two hours. It produces a range of breakdown products, most of which have no nicotinic activity. They are excreted via the kidneys, along with around 10 per cent of unchanged nicotine. The precise action of liver enzymes on nicotine varies widely from person to person because of genetic differences in the detoxifying enzyme complex known as cytochrome P450.
4.2 How does nicotine exert its effects?
Nicotine which enters the brain has a wide range of effects on neurotransmitters, the signalling chemicals which carry messages between neurons. This also produces a range of effects elsewhere in the nervous system, ranging from influence on heart rate to intestinal activity and blood glucose levels.
Major effects in the brain arise from nicotine binding to one class of receptors for the neurotransmitter acetylcholine (nicotine acetylcholine receptors, or nAChR). These occur in a range of types, which are widely distributed through the brain and nervous system.
In the brain, nicotine is clearly a stimulant at low doses. It produces a pattern of alertness in the electroencephalogram (EEG), mediates fast synaptic transmission, and positively modulates a range of cognitive functions. As a result, it improves attention, learning, arousal, motor skill, facilitates memory functions and decreases irritability and anxiety,
High doses of nicotine are toxic, mainly due to effects on the nervous system.
4.3 What is the evidence on addictiveness of nicotine?
Nicotine has a range of actions in the body and the mechanisms of addiction are still poorly understood. Individual responses to nicotine vary widely. Addiction to nicotine is difficult to measure directly, and experimental studies usually involve set-ups in which animals can self-administer the drug. Such animal studies indicate that pure nicotine is only weakly addictive. There is little human data on pure nicotine use. However, dependence is strongly linked to the number of cigarettes smoked per day.
Moreover, data on human drug use indicate that the addictive potential of tobacco is very high. More than 30 per cent of those who have ever used tobacco become dependent, a higher figure than for other drugs of dependence such as heroin, cocaine or alcohol.
Animal studies indicate that response to nicotine is dose-dependent, but the relationship is non-linear. Response increases with dose, then falls off again – so the plot of dose-dependence is an inverted U-shape. This resembles results for other drugs of abuse.