The Contribution of cocoa additive to cigarette smoking addiction
The Contribution of cocoa additive to cigarette smoking addiction The Contribution of cocoa additive to cigarette smoking addiction
Page 198 of 207 RIVM report 650270002 unlikely that cocoa will affect the addiction to cigarette smoking through the psychoactive compound phenylethylamine. Because phenylethylamine exposure through smoking is relatively high compared with the exposure level through food, it is interesting to investigate the contribution of phenylethylamine to the addiction to cigarette smoking. Derivatives of phenylethylamine are stimulant and hallucinogenic substances such as amphetamine, mescaline and some neurotransmitters such as dopamine, adrenaline and noradrenaline. Phenylethylamine is classified as a neuromodulator of dopaminergic and possibly serotinergic and noradrenergic synapses. Phenylethylamine has biphasic effect on guinea pig isolated lung. After an initial relaxation at low concentration (10 -7 – 10 -5 M) it induces contraction at higher concentration (10 -4 – 10 -3 M). When phenylethylamine was perfused in guinea-pig lung, the pulmonary MAO inactivated 95 % of phenylethylamine, indicating a rapid metabolisation by MAO. It is unclear how these results can be extrapolated to the effect of phenylethylamine in cigarette smoke on the bioavailability of nicotine in the pulmonary system. Phenylethylamine has reinforcing properties comparable to amphetamine. Whether phenylethylamine in cigarettes plays a role to the reinforcing effect of cigarette smoking is unknown. Phenylethylamine, like tryptophan, contains reactive groups and forms reaction products during combustion, which have MAO-I properties. Therefore, phenylethylamine may play a role in the cigarette smoking addiction through the MAO-I effects of its reaction products. It can be concluded that phenylethylamine level from added cocoa to cigarette is insufficient to exert any physical effect. However, the phenylethylamine level originating from tobacco may increase the addiction to cigarette smoking by its reinforcing properties or by the MAO-I properties of its reaction products. 4.2.7 Tryptamine Tryptamine occurs naturally in tobacco plant and in cocoa. The estimated tryptamine level in cigarettes originating from tobacco is at least 5000 times higher than from added cocoa. Therefore, it is unlikely that cocoa will affect the addiction to cigarette smoking through its psychoactive compound tryptamine. Because the tryptamine level is relatively high compared with the exposure level through food, it is interesting to investigate the contribution of tryptamine to the addiction to cigarette smoking. There are not enough data on the pulmonary effects of tryptamine through smoking. Although tryptamine does affect the serotonin activity in the brain, it is unknown whether tryptamine plays a role in the tobacco dependency process. Furthermore, tryptamine is a substrate for MAO and will be metabolised rapidly by absorption through the pulmonary system. Tryptamine, like tryptophan and phenylethylamine, contains reactive groups and forms reaction products during combustion, such as beta-carbolines, which has MAO-I properties. Therefore, tryptamine may play a role in the cigarette smoking addiction through the MAO-I effects of its reaction products. 4.2.8 Tyramine Tyramine is a natural compound of tobacco plant and cocoa. The estimated tyramine level in cigarettes originating from tobacco is at least 2700 times higher than from added cocoa. Therefore, it is unlikely that cocoa will affect the addiction to cigarette smoking through the psychoactive compound tyramine. Because tyramine level in cigarettes (10 mg/25 cigarette) is relatively high compared with the exposure level through food (< 10 mg/day), it is interesting to investigate the contribution of tyramine to cigarette smoking addiction. Tyramine is an indirectly acting sympathomimetic substance. Tyramine releases noradrenaline from the sympathetic nervous system and leads to physiological reactions, such as increased blood pressure. Any direct effect of tyramine on the addiction to cigarette
RIVM report 650270002 Page 199 of 207 smoking is unknown. Tyramine, like tryptophan and tryptamine, contains reactive groups and forms reaction products during combustion, which have MAO-I properties. Therefore, tyramine may play a role in the cigarette smoking addiction through the MAO-I effects of its reaction products. 4.2.9 Octopamine The level of octopamine in cocoa is unknown and therefore the level in cigarettes could not be calculated. Octopamine is an endogenous compound in the human body and is metabolised by MAO. When octopamine was perfused in guinea-pig lung, the pulmonary MAO inactivated 35 % of octopamine. The activity data of octopamine and noradrenaline on ß-adrenoreceptors indicate that the activity of octopamine is too low to have any significant physiological effect on the respiratory system. No data are available on possible dependency properties of octopamine. 4.2.10 Anandamide Anandamide activates cannabinoid receptors in humans. Anandamide seems to control the tonus of the bronchus but compared with the dosis in cigarettes (12.5 ng/25 cigarettes) large doses (± 5 mg/kg i.v.) are needed to affect the respiratory system. Therefore, it seems that anandamide will not affect the nicotine bioavailability through a bronchodilatory effect. Due to recent discovery of anandamide in cocoa, it was suggested that anandamide may attribute to the craving quality of cocoa. However, others have calculated that large quantities of cocoa have to be ingested in order to show cannabimimetic effects (e.g. 25 kg chocolate has to be ingested) (10). It is obvious that the anandamide quantity present in cigarette will not induce such an effect. Although, it is tempting to link anandamide with craving and the endogenous cannabinoid system, it seems unlikely that anandamide will contribute to the addiction to cigarette smoking. 4.3 Combined effects In this review we discussed the ten best known pharmacologically active constituents found in cocoa and their effect on the addiction to cigarette smoking. The effect on the addiction to cigarette smoking was evaluated by considering the effect on the pulmonary bioavailability of nicotine and the addictive properties of those compounds. The body is exposed to the psychoactive compounds via food and drinks or is synthesized by the body itself. The exposure to the psychoactive cocoa compounds via cigarette smoking is negligible compared with the exposure to the psychoactive compounds via food and drinks or compared with the endogenous production of those compounds. Furthermore, the compounds, especially the bioamines, are degraded rapidly when consumed. Some compounds do have addictive properties or affect the activity of compounds in the brain. However, based on the evidence discussed above, it is unlikely that the psychoactive compounds in tobacco originating cocoa exert any systemic pharmacological effects or increase the addiction to cigarette smoking. Compounds, such as phenylethylamine, tryptamine and tyramine, are naturally occurring in tobacco. The intake of those compounds through cigarette smoking is comparable to or higher than the intake through food. The relatively higher exposure to these compounds via cigarette smoking compared with exposure via food and drinks is mainly attributed by the natural occurrence of these compounds in tobacco rather than by addition of cocoa to cigarettes. Therefore, it is unlikely that cocoa will affect the cigarette smoking addiction via
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unlikely that <strong>cocoa</strong> will affect the <strong>addiction</strong> <strong>to</strong> <strong>cigarette</strong> <strong>smoking</strong> through the psychoactive<br />
compound phenylethylamine. Because phenylethylamine exposure through <strong>smoking</strong> is<br />
relatively high compared with the exposure level through food, it is interesting <strong>to</strong> investigate<br />
the contribution <strong>of</strong> phenylethylamine <strong>to</strong> the <strong>addiction</strong> <strong>to</strong> <strong>cigarette</strong> <strong>smoking</strong>.<br />
Derivatives <strong>of</strong> phenylethylamine are stimulant and hallucinogenic substances such as<br />
amphetamine, mescaline and some neurotransmitters such as dopamine, adrenaline and<br />
noradrenaline. Phenylethylamine is classified as a neuromodula<strong>to</strong>r <strong>of</strong> dopaminergic and<br />
possibly serotinergic and noradrenergic synapses. Phenylethylamine has biphasic effect on<br />
guinea pig isolated lung. After an initial relaxation at low concentration (10 -7 – 10 -5 M) it<br />
induces contraction at higher concentration (10 -4 – 10 -3 M). When phenylethylamine was<br />
perfused in guinea-pig lung, the pulmonary MAO inactivated 95 % <strong>of</strong> phenylethylamine,<br />
indicating a rapid metabolisation by MAO. It is unclear how these results can be extrapolated<br />
<strong>to</strong> the effect <strong>of</strong> phenylethylamine in <strong>cigarette</strong> smoke on the bioavailability <strong>of</strong> nicotine in the<br />
pulmonary system. Phenylethylamine has reinforcing properties comparable <strong>to</strong> amphetamine.<br />
Whether phenylethylamine in <strong>cigarette</strong>s plays a role <strong>to</strong> the reinforcing effect <strong>of</strong> <strong>cigarette</strong><br />
<strong>smoking</strong> is unknown. Phenylethylamine, like tryp<strong>to</strong>phan, contains reactive groups and forms<br />
reaction products during combustion, which have MAO-I properties. <strong>The</strong>refore,<br />
phenylethylamine may play a role in the <strong>cigarette</strong> <strong>smoking</strong> <strong>addiction</strong> through the MAO-I<br />
effects <strong>of</strong> its reaction products.<br />
It can be concluded that phenylethylamine level from added <strong>cocoa</strong> <strong>to</strong> <strong>cigarette</strong> is insufficient<br />
<strong>to</strong> exert any physical effect. However, the phenylethylamine level originating from <strong>to</strong>bacco<br />
may increase the <strong>addiction</strong> <strong>to</strong> <strong>cigarette</strong> <strong>smoking</strong> by its reinforcing properties or by the MAO-I<br />
properties <strong>of</strong> its reaction products.<br />
4.2.7 Tryptamine<br />
Tryptamine occurs naturally in <strong>to</strong>bacco plant and in <strong>cocoa</strong>. <strong>The</strong> estimated tryptamine level in<br />
<strong>cigarette</strong>s originating from <strong>to</strong>bacco is at least 5000 times higher than from added <strong>cocoa</strong>.<br />
<strong>The</strong>refore, it is unlikely that <strong>cocoa</strong> will affect the <strong>addiction</strong> <strong>to</strong> <strong>cigarette</strong> <strong>smoking</strong> through its<br />
psychoactive compound tryptamine. Because the tryptamine level is relatively high compared<br />
with the exposure level through food, it is interesting <strong>to</strong> investigate the contribution <strong>of</strong><br />
tryptamine <strong>to</strong> the <strong>addiction</strong> <strong>to</strong> <strong>cigarette</strong> <strong>smoking</strong>. <strong>The</strong>re are not enough data on the pulmonary<br />
effects <strong>of</strong> tryptamine through <strong>smoking</strong>. Although tryptamine does affect the sero<strong>to</strong>nin activity<br />
in the brain, it is unknown whether tryptamine plays a role in the <strong>to</strong>bacco dependency<br />
process. Furthermore, tryptamine is a substrate for MAO and will be metabolised rapidly by<br />
absorption through the pulmonary system. Tryptamine, like tryp<strong>to</strong>phan and<br />
phenylethylamine, contains reactive groups and forms reaction products during combustion,<br />
such as beta-carbolines, which has MAO-I properties. <strong>The</strong>refore, tryptamine may play a role<br />
in the <strong>cigarette</strong> <strong>smoking</strong> <strong>addiction</strong> through the MAO-I effects <strong>of</strong> its reaction products.<br />
4.2.8 Tyramine<br />
Tyramine is a natural compound <strong>of</strong> <strong>to</strong>bacco plant and <strong>cocoa</strong>. <strong>The</strong> estimated tyramine level in<br />
<strong>cigarette</strong>s originating from <strong>to</strong>bacco is at least 2700 times higher than from added <strong>cocoa</strong>.<br />
<strong>The</strong>refore, it is unlikely that <strong>cocoa</strong> will affect the <strong>addiction</strong> <strong>to</strong> <strong>cigarette</strong> <strong>smoking</strong> through the<br />
psychoactive compound tyramine. Because tyramine level in <strong>cigarette</strong>s (10 mg/25 <strong>cigarette</strong>)<br />
is relatively high compared with the exposure level through food (< 10 mg/day), it is<br />
interesting <strong>to</strong> investigate the contribution <strong>of</strong> tyramine <strong>to</strong> <strong>cigarette</strong> <strong>smoking</strong> <strong>addiction</strong>.<br />
Tyramine is an indirectly acting sympathomimetic substance. Tyramine releases<br />
noradrenaline from the sympathetic nervous system and leads <strong>to</strong> physiological reactions, such<br />
as increased blood pressure. Any direct effect <strong>of</strong> tyramine on the <strong>addiction</strong> <strong>to</strong> <strong>cigarette</strong>