Tobacco and Public Health - TCSC Indonesia

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PHARMACOLOGY OF NICOTINE ADDICTION
a dose-related fashion and that these effects are blocked by centrally but not peripherally
acting nicotinic cholinergic receptor blockers (US DHHS 1988; Henningfield
et al. 1996).
Nicotine can serve as a potent and powerful reinforcer for both humans and animals
as demonstrated by intravenous self-administration studies (Goldberg et al. 1983;
Goldberg and Henningfield 1988; Corrigall 1999), patterns of self-administration are
more similar to those of stimulants than of other drug classes (Griffiths et al. 1980).
However, the range of conditions under which it functions as a reinforcer is smaller
than that under which cocaine serves as a reinforcer.
Intravenous nicotine self-administration is reduced by centrally acting nicotinic
cholinergic receptor blockers, but not by peripherally acting blockers (Corrigall 1999).
Patterns of tobacco product self-administration are influenced by nicotine dose with
manipulations of delivery resulting in changes in behavior that tend to sustain similar
levels of nicotine intake (Gritz 1980; Henningfield 1984; US DHHS 1988). Nicotine
exposure results in a high degree of tolerance, which is mediated by several mechanisms,
and which includes acute and long-term components (Swedberg et al. 1990;
Perkins et al. 1993; Perkins 2002).
Tolerance. Tolerance to some effects may be related to the up-regulation of central
nervous system nicotine receptors, but genetic factors also modulate nicotine effects
including development of tolerance (Collins and Marks 1989). A practical consequence
is that whereas first time tobacco users often become profoundly sick and
intoxicated, these effects generally dissipate within a few hours and are rarely experienced
again due to a combination of learning to avoid overdosing, and tolerance
(US DHHS 1988; Royal College of Physicians 2000). Laboratory studies of intravenous
nicotine (Soria et al. 1996) and nicotine gum administration (Heishman and
Henningfield 2000) have demonstrated greater sensitivity to the mood altering and
behavioral effects of nicotine in subjects who do not use tobacco compared to tobacco
users. The development of snuff products that are marketed as starter products
in which the products delivered lower doses of nicotine more slowly than do the maintenance
products takes advantage of the tolerance phenomenon and minimizes the
likelihood that the initial users experience will be unpleasant (Connolly 1995; FDA
1995, 1996). With respect to cigarettes, because the nicotine dosing is puff by puff, with
the physiologic response occurring quite quickly after each puff, this problem is less
of a barrier to the acquisition of smoking than it is for the acquisition of snuff use
(in which the dose is determined by the amount of snuff put in the mouth) (Connolly
1995; Slade 1995).
Physical dependence and withdrawal. Tobacco withdrawal signs and symptoms,
including changes in brain electrical activity, cognitive performance, anxiety, and
response to stressful stimuli can be altered by administration of pure nicotine in a variety
of forms (e.g. gum, patch, nasal delivery) (Hughes et al. 1990; Heishman et al. 1994;