Tobacco delivered nicotine

Abstract Behavioral discrimination procedures clearly demonstrate that nicotine elicits interoceptive stimulus effects in humans that are malleable by various pharmacological manipulations as well as by some behavioral manipulations. The parameters of nicotine discrimination and both chronic and acute factors that may alter discrimination behavior are addressed in this chapter, which emphasizes research by the author involving nicotine delivered by nasal spray. Human discrimination of nicotine is centrally mediated, as the central and peripheral nicotine antagonist mecamylamine blocks discrimination but the peripheral antagonist trimethaphan does not. The threshold dose for discrimination of nicotine via spray appears to be very low in smokers as well as nonsmokers. Because smoked tobacco delivers nicotine more rapidly than spray, the threshold dose of nicotine via smoking is probably even lower. In terms of individual differences, smokers may become tolerant to the discriminative stimulus effects of higher nicotine doses but not of low doses. 

While nicotine is the primary active pharmacological agent, tobacco has been shown to be a particularly effective vehicle for delivery of nicotine (US Food and Drug Administration 1995 Hurt and Robertson 1998 Slade et al. 1995 World Health Organization 2001). In fact, published research has determined that tobacco-delivered nicotine is not only more toxic, but more addictive than nicotine in a pure form (e.g., nicotine replacement therapy) (Henningfleld et al. 2000 Royal College of Physicians 2000). As noted by a BW scientist in 1990 Nicotine alone in smoke is not practical, nor are extreme tar/nicotine ratios, since nicotine is too irritating -other substances are required for sensoric reasons (Baker 1990). 

The most direct way to help people manage the symptoms of nicotine dependence and withdrawal is therapeutic use of nicotine replacement therapy (NRT) (Fiore et al. 2000 Henningfleld 1995 American Psychiatric Association 1996). Nicotine has been shown to be the main active ingredient in tobacco that causes and sustains addiction to tobacco (US Department of Health and Human Services 1988). Laboratory research has demonstrated that animals (Goldberg et al. 1983) and humans (Henningfleld et al. 1983) who have been chronically exposed to nicotine or tobacco smoke will self-administer nicotine infusions. It should be noted that other constituents in tobacco, such as MAO inhibitors (Fowler et al. 1996a, b), may also play a role in tobacco dependence. The potential role of alkaloids other than nicotine has not been ruled out. This is consistent with the observations that what has been termed tobacco delivered nicotine is more addictive and toxic than formulations provided by nicotine replacement medications (Royal College of Physicians 2000). 

Nicotine replacement medications have been used for over two decades to help smokers quit. However, nicotine delivery from medications could potentially be improved by formulations that better mimic the effects of tobacco-delivered nicotine. Antidepressants such as bupropion have also been shown to aid smoking cessation. Bupropion was initially studied for smoking cessation based upon anecdotal reports... 

Nicotine nasal spray delivers nicotine through the nasal mucosa. One advantage of nicotine nasal spray is that it relieves tobacco cravings quickly. One study found that nicotine nasal spray was 2.6 times more likely to produce smoking cessation, compared with placebo, at 1 year (Sutherland et al. 1992). The active spray was also the most beneficial among highly dependent smokers (Sutherland et al. 1992). 

Evidence from the tobacco industry documents, from research studies that measure free-base directly in tobacco smoke particulate, and from examination of smokeless tobacco products, all show that the level of free-base nicotine as delivered to the tobacco user is a critical variable in the acceptance of tobacco products and their continued use. The physiological impact of the rapid delivery of nicotine in the free-base form is a critical determinant of continued nicotine-seeking behavior, with the unintended consequences of exposure to the other toxic components of tobacco smoke and smokeless tobacco. Evaluating total delivered nicotine alone is not sufficient to characterize product differences. To fully understand the influence nicotine has on the allure of these products, both total and free-nicotine levels must be measured. A comprehensive understanding of nicotine delivery is needed to help find effective means for breaking its addictive nature and, ultimately, in reducing the morbidity and mortality associated with tobacco use. The levels of free-base nicotine must be included as part of any effort to achieve a better understanding of how tobacco products themselves influence their continued use. 

Nicotine is the main psychoactive ingredient of tobacco and is responsible for the stimulant effects and abuse/ addiction that may result form tobacco use. Cigarette smoking rapidly (in about 3 sec ) delivers pulses of nicotine into the bloodstream. Its initial effects are caused by its activation of nicotinic acetylcholine (nACh) receptors. nACh receptors are ligand-gated ion-channels and pre- and postsynaptically located. Reinforcement depends on an intact mesolimbic dopamine system (VTA). nACh receptors on VTA dopamine neurons are normally activated by cholinergic innervation from the laterodorsal tegmental nucleus or the pedunculopontine nucleus. 

Although tobacco Nicotiana tabacum) is widely known for its stimulant and addictive properties, its principal psychoactive constituent, nicotine, has become a candidate drug for improving cognition (Le Houezec 1998 Lawrence and Sahakian 1998 Newhouse et al. 1997). Clearly, the health risks associated with smoking tobacco preclude its clinical use, but nicotine delivered in other forms may be useful. 

The amount of nicotine and nomicotine in Indian bidi tobacco was higher than that in Indian filter-tipped cigarettes (35.2 and 3.4mg g , respectively, versus 14.2 and 1.56mg g respectively). Curiously, the mainstream smoke of Indian bidis delivered less nicotine than Indian cigarettes (1.87 mg per bidi versus 2.58 mg per cigarette) (Pakhale and Maru 1998). 

In 1997, R.J. Reynolds Tobacco Co. introduced Eclipse, a nicotine delivery device purported to deliver lower levels of smoke toxicants than conventional cigarettes. Eclipse uses a carbon fuel element to vaporize nicotine in the rod the user then inhales the nicotine vapor. Venous plasma nicotine boost among ten smokers... 

Abstract Delivery of nicotine in the most desirable form is critical in maintaining people s use of tobacco products. Interpretation of results by tobacco industry scientists, studies that measure free-base nicotine directly in tobacco smoke, and the variability of free-base nicotine in smokeless tobacco products all indicate that the form of nicotine delivered to the tobacco user, in addition to the total amount, is an important factor in whether people continue to use the product following their initial exposure. The physiological impact of nicotine varies with the fraction that is in the free-base form and this leads to continued exposure to other toxic tobacco contents... 

As shown in Fig. 1, the speed of nicotine uptake in venous blood following several forms of nicotine delivery varies widely, from that of the very slow pattern of nicotine appearance in the blood (several hours to peak level) produced by current transdermal nicotine medications to the explosive rise produced by tobacco smoke inhalation. Nicotine gum, lozenge, tablet, and vapor inhaler can provide more rapid delivery of nicotine than the patch, but the speed and amount obtained are constrained by use patterns. Smokeless tobacco products deliver their nicotine more rapidly than nicotine gum and with less physical effort, but are still slower than cigarettes in their nicotine dehvery. 

Nicotine in chewing tobacco is absorbed in the first 10 minutes, with peak levels occurring within 30 minutes. The nicotine from a puff of cigarette reaches the brain within 10 seconds. With approximately 10 puffs per cigarette, a pack per day delivers 200 doses (hits) of this potent drug to the brain. The repeated, frequent... 

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