The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 155 of 207
Phenylethylamine
phenylethylamine amount in dried tobacco plant is 70 – 485 µg/g dry weight. The
average amount of phenylethylamine in cocoa varies between 0.22 – 22 µg/g.
The estimated natural phenylethylamine amount from tobacco plant in cigarette is at
least 2200 times higher than phenylethylamine from added cocoa. Therefore, it is
debatable whether phenylethylamine should be considered as an additive to tobacco.
The daily potential intake of phenylethylamine (12.1 mg/25 cigarettes/day) from
cigarettes (from tobacco plant and added cocoa) is higher than phenylethylamine
intake from other sources such as chocolate, sausage and cheese (0.5 – 4 mg/day).
Assuming similar bioavailability and no loss by combustion, the plasma
concentration reached after ingestion of phenylethylamine from chocolate sources or
other food sources is expected to be lower than after exposure from cigarettes. Also
the different route of application via smoking as compared with other sources should
be taken into account. Therefore, the systemic and the local effect of smoking related
exposure to phenylethylamine might be a point of concern. Since nothing is known
about the pyrolysis/combustion products of phenylethylamine, this may also be a
point of concern.
Phenylethylamine is classified as a neuromodulator of dopaminergic and possibly
serotonergic and noradrenergic synapses. At the molecular physiological level,
phenylethylamine potentiates transmission by postsynaptic and possibly presynaptic
action. Phenylethylamine produced a bronchoconstriction of isolated perfused lungs
of guinea-pig. No data are available on phenylethylamine inhalation effects in human.
Therefore, it is unknown whether the phenylethylamine dose in cigarette will exert
bronchoconstrictory effects.
Phenylethylamine exerts both positive inotropic and vasoconstrictory effects in dogs.
Phenylethylamine tended to produce an initial tachycardia followed by a bradycardia
in dogs. Phenylethylamine has amphetamine-like effects in rats including
symphatomimetic effects, increasing nonspecific motoractivity, exploratory behavior,
stereotypic behavior, electrophysiological alerting, reinforcement of complex
behavior and anorectic effects. It is suggested that endogenous phenylethylamine may
contribute to the antidepressant, stimulant, or euphoriant effects of several drugs.
Phenylethylamine exerts its CNS effect at high doses or when the MAO is inhibited.
Based on the current CNS data, it is unknown whether the phenylethylamine dose in
cigarette is enough to exert any CNS effect.
In vitro studies have shown that phenylethylamine is rapidly absorbed by the
pulmonary endothelial tissue and is also rapidly inactivated by pulmonary MAO.
Phenylethylamine is distributed throughout the body. Phenylethylamine crosses the
blood-brain barrier easily and its concentration in the brain after peripheral injection
peaks within 5 minutes and returns to normal level within 30 min. The turnover of
endogenous phenylethylamine in the brain is high with a half-life of 0.4 min.
Phenylethylamine is metabolized by MAO, primarily by type-B (and to a small extent
MAO-A), and aldehyde dehydrogenase to phenylacetic acid, which is the major
metabolite of phenylethylamine in the brain. There are no in vivo pharmacokinetic
data available on respiratory intake of phenylethylamine. Based on the in-vitro kinetic
data of phenylethylamine, the pulmonary MAO will reduce the phenylethylamine
intake through cigarette smoking.