The Contribution of cocoa additive to cigarette smoking addiction

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Page 196 of 207 RIVM report 650270002 The exposure to tyramine and phenylethylamine via smoking and to a lesser extent to tryptamine seems to be relatively high compared with the exposure level via food and also when compared with the plasma reference level. Although the exposure for most of the compounds through food intake is higher than through smoking, the effect of exposure through smoking must not be neglected, because the exposure route is different. The exposure through food intake will exert systemic effects and will be subjected to first-pass effect whereas the exposure through smoking will probably exert only local effects and is not subjected to first-pass effect. Besides, during smoking the compounds are subjected to combustion resulting in compounds with different pharmacological properties. Therefore, it is reasonable to investigate whether the psychoactive cocoa compounds and their combustion products may increase the addictive properties of cigarettes. 4.2 Effects 4.2.1 Theobromine Compared with other methylxanthines such as caffeine or theophylline, the action of theobromine on the central nervous system is considered weak. The central nervous effects of theobromine on human volunteers were investigated in a study, by looking at the subjective effects of theobromine. In that study, Mumford et al. (1994) (3) found that four of their seven volunteers could discriminate theobromine from placebo at an oral dose of 560 mg. The discriminative parameters were changes in mood and behaviour and having motivation to work. Theobromine is assumed to have bronchodilatory effects, thereby increasing the absorption of nicotine. However, the bronchodilatory properties are very weak compared to the bronchodilatory effect of theophylline. A dose of 15 mg theophylline aerosol induced a significant decrease of the airway resistance. This decrease was not observed immediately or within 30 min of theophylline administration. Comparing this information with the amount of theobromine in cigarettes (0.19 mg/cigarette), it can be concluded that the theobromine level in cigarettes is not enough to exert any bronchodilatory effects. Furthermore, the role of theobromine in cocoa craving has been reviewed in the literature and the conclusion was that this agent is not responsible for the craving qualities of chocolate. Based on the evidence discussed above, it can be concluded that theobromine will not affect the cigarette smoking addiction (4, 5). Because no data were available on the combustion products of theobromine, their effect on the cigarette smoking addiction could not be evaluated. Furthermore, the long-term effect on the respiratory system of theobromine is unknown in combination with other methylxanthines or with its combustion products. 4.2.2 Caffeine The physiological effects of caffeine have been extensively investigated. Caffeine is known as a psychostimulant. Caffeine seems to have low addictive properties. Daily caffeine consumption through coffee intake is significantly higher (± 400 times) than the caffeine intake through smoking. Due to the high oral bioavailability, it seems that the caffeine dose (0.02 mg/cigarette) in one cigarette is negligible to exert any effect. Mumford et al. (1994) (3) found subjective effects of caffeine between 10 – 45 min after oral administration of 72 mg caffeine. The bronchodilatory effect of caffeine is interesting because it may increase the bioavailability of nicotine. The bronchodilatory property of caffeine is equipotent or less compared with the methylxanthine theophylline. This means that the caffeine amount (0.02
RIVM report 650270002 Page 197 of 207 mg/cigarette) in one cigarette is not high enough to exert any bronchodilatory effect. In view of the low dose of caffeine in cigarettes, the absence of bronchodilatory effects and the low addictive properties of caffeine, it seems unlikely that caffeine plays a role in addiction to cigarette smoking. Because no data were available on the combustion products of caffeine, their effect on the cigarette smoking addiction could not be evaluated. Furthermore, the longterm effect on the respiratory system of caffeine is unknown in combination with other methylxanthines or with its the combustion products. 4.2.3 Serotonin Serotonin is a neurotransmitter of both the central and the peripheral nervous systems and plays an important role in regulation of mood and behaviour (6). The serotonin intake through smoking (0.6 µg/cigarette) will not exert any systemic effect due to the large endogenous pool (10 mg) and also due to rapid metabolisation by MAO. Therefore, pulmonary intake may probably exert only local effects. Serotonin has bronchoconstrictory effect in animals. In normal human subjects the bronchoconstrictory effect was not observed. It can be concluded that serotonin in cigarette is not likely to increase the addiction to cigarette smoking. 4.2.4 Histamine Histamine has a bronchoconstrictory effect, which means that it may decrease the bioavailablity of nicotine. Histamine is used for diagnostic purposes in asthmatics. Histamine has a bronchoconstrictory effect with a cut-off point for PD20 between 0.7 – 1.2 mg in normal human subjects. These values for histamine are significantly higher than the histamine dose in one cigarette (± 13 ng/cigarette). Thus histamine from added cocoa in cigarettes will probably not exert any bronchoconstrictory effect. 4.2.5 Tryptophan Tryptophan is an essential amino acid and is a precursor for a variety of active compounds including serotonin, melatonin and tryptamine. The level of these active compounds will not be affected by tryptophan exposure through smoking, because the daily intake (250 – 900 mg/day) of tryptophan through food surpassed the exposure through smoking (0.75 mg/day) significantly and there is a large endogenous tryptophan pool present. There are no data available on the respiratory effects of tryptophan through pulmonary exposure. Tryptophan contains reactive groups and forms reaction products with other compounds during combustion, such as beta-carbolines. Beta-carbolines are known inhibitors of MAO. There are indications that cigarette smoke contains MAO-I constituents and smokers have decreased MAO activity (7, 8). Others argue that one smokes for anti-depression properties. The prevalence of cigarette smoking is significantly higher by depressive persons than persons who are not (9). It can be concluded that the MAO-I properties of cigarette smoke may contribute to tobacco dependency. It can be concluded that it is unlikely that tryptophan has any addictive properties but its reaction products formed during combustion may contribute to the addiction to cigarette smoking. 4.2.6 Phenylethylamine Phenylethylamine is a natural compound of the tobacco plant and cocoa. The estimated phenylethylamine level in cigarettes originating from tobacco (12.1 mg/ 25 cigarettes) is about 2200 times higher than from added cocoa (5.5 µg/25 cigarettes). Therefore, it is
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The Contribution of cocoa additive to cigarette smoking addiction

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