The level of toxins in cigarette smoke is impressive: hydrocyanic acid, benzene and formaldehyde as well as cadmium, lead and around 4,000 other pollutants. Not a mixture people would voluntarily inhale, one would think. However, around 15 million or so smokers in Germany breathe in such a mixture regularly. And most of them are well aware of the toxicity of tobacco smoke. So why do they continue to smoke and run the risk of a smoking-related premature death? In actual fact, smoking is not so voluntary after all; it is in fact an addictive disorder. Does this mean that smokers are helpless and unable to do anything about their addiction, are they controlled by chemical substances against their will?

Prof. Dr. Anil Batra, head of the Section of Addiction Research and Addiction Medicine at the University Hospital of Tübingen knows only too well that this is a complex issue. Even the question of genetically generated tobacco dependence is more complicated than it seems. “In the 1970s and 1980s, epidemiological studies were carried out on twins for example. They indicated that there was a genetic predisposition to tobacco dependence. However, there is no such thing as a 'tobacco gene'. But there are quite a few functional impacts on the genetic level,” says Batra, going on to cite modifications in genes that encode receptors in the membrane of nerve cells in the brain as a prominent example of such influences. Modifications in the gene that encodes the D2 dopamine receptor, to which the neurotransmitter dopamine binds, are associated with the risk of smoking and with the quantity of cigarettes smoked. 

Production of the ‘happiness hormone’ dopamine in the brain increases when nicotine binds to relevant receptors in the membrane of neurons. Many cells react to a large number of molecules that are able to bind to their receptors with the expression of fewer receptors. It is interesting to note that nicotine has a different effect. Batra explains: “alpha-4-beta-2 receptors are nicotinic acetylcholine receptors (i.e. receptors that respond to exposure to nicotine) that are upregulated under the influence of nicotine. This has been demonstrated by histochemical and PET-based studies.” It is assumed that increased receptor production is a kind of compensatory reaction by the cell as nicotine causes the receptors to be less sensitive. 

Varenicline, a prescription medication used to treat nicotine addiction, reduces cravings for and decreases the pleasurable effects of tobacco products. It has a high affinity to the alpha-4-beta-2 receptors and therefore reduces nicotine’s ability to bind and stimulate the dopamine system. As increased smoking does not change the situation because the receptors are already occupied by varenicline and because varenicline binding leads to the weak release of dopamine, varenicline can be used to treat nicotine addiction as it helps reduce cravings and other withdrawal symptoms on the neuronal level.

However, varenicline is not a panacea for tobacco addiction. Rather, it is one of many approaches and medicines used to treat tobacco dependence. Nicotine replacement therapy is one such approach that is based on products that supply low doses of nicotine. This therapy increases the probability of giving up smoking by a factor of 1.7 on average. Another smoking cessation aid is bupropion, an amphetamine derivative that was originally developed for the treatment of depression. According to Batra, an eight-week buproprion treatment is as effective as nicotine replacement therapy. 

Batra believes that behavioural therapy is another effective way of quitting smoking. Batra: “Smoking is primarily a behavioural disorder and not necessarily just a physical addiction. Behavioural therapy seeks to replace the function of the cigarette. However, a person with extensive tobacco dependence might also need to undergo pharmaceutical therapy.” But how does a doctor know if a person’s tobacco dependence is not only behavioural, but also physical? “We can find this out using a questionnaire that helps assess the severity of the dependence. The higher the score, the greater a person’s dependence. From a score of five upwards, we also recommend that the patient undergoes pharmacotherapy,” says Batra. The number of cigarettes per day gives the doctors some idea of a person’s level of addiction. Batra believes that 30 or more cigarettes a day indicates a very high level of addiction. 

Batra believes that the best possible treatment of severe tobacco dependence currently available is the combination of pharmacotherapy and behavioural therapy. This is also reflected in the guidelines for the treatment of tobacco dependence. As a renowned expert on addictive diseases – Batra has been president of the German Society for Addiction Research and Addiction Treatment since 2010, and was formerly head of the Department of Addiction Psychiatry of the German Association for Psychiatry, Psychotherapy and Neurology (DGPPN) – Batra has coordinated the amendment of the German Society for Addiction Research and Addiction Treatment’s tobacco guideline.

The guideline has now reached S3 level, which is the highest possible quality classification for therapy guidelines. Although the guideline does not contain information on groundbreaking drugs or therapies, it pools the results from numerous randomized studies and meta-studies, which confirm the efficacy of previous concepts, and thus reinforce the high quality level of the guideline. A nicotine vaccine is a novel approach in the fight against tobacco dependence. It is a chemical nicotine derivative that induces an immune response, i.e. the production of antibodies against nicotine. The principle: the antibodies capture the nicotine and the antibody-nicotine complexes are structurally too big to cross the blood-brain barrier and are destroyed. This helps to suppress the urge to smoke.

This might sound good but Batra is nevertheless quite sceptical: the initial study has shown that 70 percent of study participants that were vaccinated gave up smoking, whereas 30 percent did not. However, the 30 percent also developed antibodies against nicotine. The long-term effect of this is not yet known. And for me this is a good reason why nicotine vaccines should not be used therapeutically.”

Batra is also critical of e-cigarettes: “It has not yet been demonstrated that people using e-cigarettes find it easier to quit smoking. I see e-cigarettes more as damage limitation exercise. People who use e-cigarettes are smoking in a more environmentally friendly way and are also taking up fewer toxins.” He also envisages the problem that e-cigarettes might actually encourage people to take up smoking because they may feel this makes them look cool.

“There is no such thing as an ‘addictive character’,” says Batra, going on to explain, “the motivation to smoke is different in different people, which is why we have defined addiction types.” One such subtype is the social smoker, the type of person that Batra believes has the greatest possibility of being able to quit smoking. Another subtype is the physically addicted who shows withdrawal symptoms. Around 30 percent of smokers belong to this subtype. Then there is the depressive subtype and the subtype that uses smoking to stimulate mental activity and concentration.

None of these subtypes is entirely safe from the possibility of starting to smoke again. In Batra’s experience, most people start smoking again within the first 100 days of attempting to quit. In Tübingen, standard behavioural therapy lasts for six weeks because “people who have not managed to quit smoking within six weeks, will most likely not manage after ten.” People’s motivation to give up smoking is no longer the primary focus. While a patient previously had to be truly motivated before a therapist would work with him, access to therapy is no longer that difficult. “The picture has changed. Nowadays we believe that it is the therapist’s job to motivate a person to quit smoking,” says Batra.

The latest findings on behavioural therapy and current developments in pharmaceutical therapy are discussed every year at the ‘Tübingen Addiction Therapy Days’, which are organized by the team from Tübingen and aimed at people working in the area of addiction, including medical doctors, pharmacologists as well as professionals from the fields of law, psychology and social affairs.

Further information:
University of Tübingen
Department of Psychiatry and Psychotherapy
Section of Addiction Research and Addiction Medicine
Prof. Dr. Anil Batra
Calwer Str. 14
72076 Tübingen
Tel.: +49 (0)7071-2982685
E-mail: Anil.Batra(at)med.uni-tuebingen.de