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The Contribution of cocoa additive to cigarette smoking addiction

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RIVM report 650270002 Page 111 <strong>of</strong> 207<br />

Tryptamine<br />

Conclusion<br />

<strong>The</strong> estimated natural tryptamine amount in <strong>to</strong>bacco leaves is at least 5000 times<br />

higher than the tryptamine amount from added <strong>cocoa</strong>. <strong>The</strong>refore, it is debatable<br />

whether tryptamine should be considered as an <strong>additive</strong> <strong>to</strong> <strong>to</strong>bacco. <strong>The</strong> daily<br />

potential intake <strong>of</strong> tryptamine from <strong>cigarette</strong>s (from <strong>to</strong>bacco leaves and from <strong>cocoa</strong>)<br />

is higher than tryptamine intake from other sources such as chocolate or <strong>to</strong>ma<strong>to</strong>, and<br />

is comparable with Italian dry sausages. Assuming similar bioavailability and no loss<br />

by combustion, the plasma concentration reached after ingestion <strong>of</strong> tryptamine from<br />

chocolate sources or other food sources is expected <strong>to</strong> be lower than after exposure<br />

from <strong>cigarette</strong>s. Also the different route <strong>of</strong> application via <strong>smoking</strong> as compared <strong>to</strong><br />

other sources should be taken in<strong>to</strong> account. <strong>The</strong>refore, the systemic and the local<br />

effect <strong>of</strong> <strong>smoking</strong> related exposure <strong>to</strong> tryptamine might be a point <strong>of</strong> concern. Since<br />

nothing is known about tryptamine’s pyrolysis/combustion products, this may also be<br />

a point <strong>of</strong> concern.<br />

PHARMACODYNAMICS<br />

Mechanism <strong>of</strong> action<br />

Tryptamine is a neurotransmitter (12) or a modula<strong>to</strong>r <strong>of</strong> neurotransmission (12, 16,<br />

17). Studies with [ 3 H]-tryptamine have shown [ 3 H]-tryptamine-binding sites in<br />

various brain regions and in several visceral organs. Three active classes <strong>of</strong><br />

compounds, tryptamine analogues, ß-carbolines and substituted phenylethylamines,<br />

were shown <strong>to</strong> displace [ 3 H]-tryptamine binding (12, 18). Tryptamine evokes<br />

physiological effects through interaction with the large family <strong>of</strong> sero<strong>to</strong>nin recep<strong>to</strong>r<br />

by means <strong>of</strong> modulation. It is suggested that synthesis <strong>of</strong> tryptamine occurs in<br />

terminals <strong>of</strong> dopaminergic neurons and these neurons are seen as allosteric regula<strong>to</strong>r<br />

<strong>of</strong> sero<strong>to</strong>nin recep<strong>to</strong>rs. <strong>The</strong> modula<strong>to</strong>ry effects <strong>of</strong> tryptamine are mediated either<br />

directly at presynaptic and/or postsynaptic tryptamine binding sites <strong>of</strong> sero<strong>to</strong>nergic<br />

neurons or by inducing allosteric changes at sero<strong>to</strong>nin recep<strong>to</strong>r (12).<br />

Furthermore, tryptamine derivatives, such as ß-carbolines, inhibit monoamine oxidase<br />

and the monoamine uptake and bind <strong>to</strong> benzodiazepine recep<strong>to</strong>r (7).<br />

Pulmonary system<br />

breathing frequency: Tryptamine produces pharmacological effects in man<br />

which are similar <strong>to</strong> those produced by LSD and other tryptamine derivatives.<br />

One <strong>of</strong> these effects is tachypnea. No details were available on tryptamine data<br />

(19).<br />

tidal volume: no data available<br />

lung compliance: no data available<br />

airway resistance: no data available<br />

Cardiovascular system<br />

blood pressure: see below<br />

heart rate:<br />

Tryptamine has a biphasic effect on the sero<strong>to</strong>nin recep<strong>to</strong>rs, regulating the arterial<br />

<strong>to</strong>ne (12). Tryptamine (2-20 µg/dose), administered in<strong>to</strong> the lateral cerebral ventricle<br />

<strong>of</strong> the rat, evoked a pressor response, which was sometimes followed by a prolonged<br />

depressor response. <strong>The</strong> intracisternal administration <strong>of</strong> tryptamine (7-20 µg/dose)<br />

caused a slow progressive and long-lasting depressor effect without or with an initial<br />

pressor effect. <strong>The</strong> pressor response was accompanied by variable changes in heart

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