The Contribution of cocoa additive to cigarette smoking addiction

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