Diseases

Tobacco Addiction

Tobacco addiction is a mixture of physical addiction, habit and social pressure. The pharmaceutical industry has made significant progress in the treatment of physical addiction. Further research offers the hope of even better treatments for this disease which by its complications kills millions every year.

What is tobacco addiction? Top

Tobacco addiction includes a habit or a social component and physical addiction that combine to present a formidable challenge to smoking cessation. Many smokers can turn their habit on and off – smoke or not smoke – at will. About 25 per cent of smokers find the addictive powers of nicotine impossible to control. For these people, smoking is not a habit, but a true addiction. Studies have shown that tobacco addiction is more severe than alcohol dependence and at least as binding as addiction to narcotics.

When nerve cells communicate in the brain, impulses jump chemically across a gap called the synapse between two nerve cells or neurons, using the neurotransmitter acetylcholine (ACh). ACh activates specific receptors on the post-synaptic nerve cell. This starts the firing of electrical impulses and, in cells that synthesise dopamine, this pleasure-inducing messenger is released as well. Having completed its task, ACh is rapidly broken down by an enzyme called acetylcholinesterase (AChE). At the synapse, nicotine mimics ACh but it is not broken down by AChE. So it persists there for minutes rather than milliseconds, and excites the post-synaptic neurons for long periods, releasing large amounts of dopamine. Most scientists consider this to be the key reason why nicotine is addictive.

Who does tobacco addiction affect? Top

In the European Union, almost 100 million people or about 30 per cent of the population aged 15 years and above smoke. About 43 per cent of European men and 28 per cent of European women smoke. Among people from 25 to 39 years old, the rate jumps to 55 per cent in men and 40 per cent in women.

Globally, nearly five million premature deaths were caused in 2000 as a result of cigarette smoking. 12 per cent of global deaths among adults were attributable to smoking-related causes. Smoking accounted for 18 per cent of male mortality worldwide and 5 per cent of female mortality. Comparing the number of deaths in developing and industrialised countries, researchers from the Harvard School of Public Health and the University of Queensland, Australia found in 2003 that the numbers were practically identical, as less well-off populations have taken up smoking over the past few decades.

The epidemiologists found that more than 75 per cent of all smoking-related deaths were among men, and this proportion increased to 84 per cent in developing countries, where smoking has historically been more concentrated among men. The main causes of death were cardiovascular disease with 1.7 million deaths, chronic obstructive pulmonary disease (COPD) with just under one million fatal cases, and lung cancer with approximately 850,000 people killed.

While anti-smoking programmes and policies have meanwhile been introduced in industrialised nations, an estimated 930 million of the world’s 1.1 billion smokers live in developing countries. It is estimated that, in the years to come, smoking-related deaths will rise substantially, unless effective intervention and policies to reduce smoking among men and prevent increases among women are implemented. Preliminary numbers released by the World Health Organisation (WHO) predict global deaths due to smoking-related illnesses will nearly double by 2020, to nine million, with more than three-quarters of them in the developing nations.

Country Last available (Male) Last available (Female)
Austria 52.58 (2003) 16.61 (2003)
Belgium 101.97 (1997) 15.20 (1997)
Bulgaria 57.72 (2003) 8.96 (2003)
Czech Republic 81.00 (2003) 18.83 (2003)
Denmark 67.02 (2000) 40.06 (2000)
Estonia 88.70 (2002) 11.36 (2002)
Finland 48.36 (2003) 12.84 (2003)
France 66.00 (2000) 10.50 (2000)
Germany 59.80 (2001) 15.78 (2001)
Greece 72.00 (2001) 10.77 (2001)
Hungary 114.58 (2003) 32.59 (2003)
Ireland 56.20 (2001) 25.37 (2001)
Italy 69.50 (2001) 12.65 (2001)
Latvia 79.80 (2003) 9.72 (2003)
Lithuania 78.82 (2003) 8.99 (2003)
Luxembourg 70.41 (2003) 21.84 (2003)
Malta 55.69 (2003) 8.06 (2003)
Netherlands 71.67 (2003) 27.00 (2003)
Norway 48.87 (2002) 23.40 (2002)
Poland 100.57 (2002) 19.69 (2002)
Portugal 42.10 (2002) 7.76 (2002)
Romania 66.20 (2002) 11.23 (2002)
Slovakia 77.20 (2002) 10.66 (2002)
Slovenia 73.97 (2003) 18.10 (2003)
Spain 69.70 (2001) 6.90 (2001)
Sweden 31.40 (2001) 20.91 (2001)
Switzerland 51.10 (2001) 14.90 (2001)
U. K. 58.02 (2002) 29.84 (2002)

Cross country profile: Standardized death rate from trachea, bronchus and lung cancer (per 100,000 population)

Sources: “European Health for All” database, WHO Regional Office for Europe, Copenhagen, Denmark, © 2003 World Health Organization

Present treatments Top

An estimated 70 per cent of smokers want to quit smoking, but only 2.5 per cent per year succeed in doing so permanently. Effective strategies for treating tobacco addiction include advice by medical providers, counselling on behaviour modification, and pharmacotherapy. Pharmacotherapy is a vital element of this multi-component approach.

There are several first-line medications for treating tobacco use. Nicotine chewing gum is approved as an over-the-counter nicotine replacement product. Chewing the gum releases nicotine, which is absorbed through the mouth and mucous membranes. Nicotine gum is available in different dosages. The higher dose may be a better aid for those highly dependent on nicotine. Nicotine patches contain a reservoir of nicotine that diffuses through the skin and into the smoker’s bloodstream at a constant rate. Patches are available both as over-the-counter and prescription medications. Additionally, nicotine nasal spray for prescription use and a nicotine inhaler as a prescription medication have been made available to treat tobacco dependence.

The first non-nicotine medical smoking cessation aid is an antidepressant prescription medication. The compound functions as a neurotransmitter modifier, which has dopaminergic properties. It may also be used in conjunction with nicotine replacement therapy.

What’s in the development pipeline? Top

Other antidepressant medications are in Phase 3 clinical trials for smoking cessation. The discovery that dopaminergic antidepressive therapy in non-depressed individuals is an effective treatment has triggered a rapid increase in development of potential new non-nicotine pharmacotherapies, including a prolactin-inhibitor, a selective noradrenalin-reuptake-inhibitor (NARI), a selective CB1 endocannabinoid receptor antagonist, a medicine originally developed to treat Parkinson’s disease and a partial agonist that is specific to the alpha4/beta2 (nicotinic) receptor. The availability of medications that do not contain nicotine will provide patients and physicians with new choices and decisions on the optimal approach to smoking cessation in their practices. The best hope of improved treatment comes from combining existing and new medicines with effective behavioural therapy.

New pharmacological interventions will most probably have utility in reducing use, ameliorating withdrawal symptoms or attenuating cravings in tobacco users. Several neurochemical systems such as glutamatergic, noradrenergic and the involvement of gamma-amino butyric acid (GABA) have been identified as playing a role in the reinforcement of nicotine self-administration in animals and/or in neuronal and synaptic processes associated with nicotine addiction.

The longer-term future: Top

Significant progress has been made in the treatment of tobacco addiction, and as a result, there are safe and reliable medications available as the first-line treatments of choice. Similarly, behavioural approaches have been shown to produce a treatment response. However, a significant number of tobacco users remain addicted, many of whom are unable to quit their use of tobacco products even when assisted by current treatment approaches.

Knowing specifically which receptor molecules are activated by nicotine in the dopamine-releasing cells would be a promising first step in developing a medicine to help people give up the habit. Another recent investigation using sophisticated brain imaging technology suggests that, in addition to nicotine, some unknown compound in cigarette smoke also raises dopamine levels in smokers' brains by inhibiting an enzyme that breaks down dopamine. If further research confirms that smoking alters dopamine levels through multiple mechanisms, it would open the door to new approaches to developing effective smoking treatment medications.

That is a challenging goal, since there are many cell receptor proteins, each in turn comprising a set of “subunit proteins” that may respond to nicotine, or instead, to a completely different chemical signal. Previous work in several laboratories in the 1990s had suggested that, of the many so-called nicotinic ACh receptors, one consisting of subunits called alpha4 and beta2, was important for nicotine addiction.

Recently, research groups have determined that when receptors with the specific subunit alpha4 are activated by nicotine, it is sufficient for some addiction-related events to occur, such as pleasure response, sensitisation, and tolerance to repeated doses of nicotine. This research suggests that alpha4, and the molecules that are triggered in turn by alpha4, may prove to be useful targets for addiction therapies. The eventual hope is that one of those signals might provide a molecular target which can be specifically blocked, providing a therapy against addiction. This strategy would resemble modern cancer drugs, which block only specific signalling molecules needed by proliferating cancer cells.