An aversive tobacco abstinence syndrome, thought to reflect an underlying level of nicotine dependence, contributes to cigarette smokers' failed quit attempts. Nicotine replacement therapy (NRT) suppresses tobacco abstinence, but high relapse rates suggest room for improvement. Improving NRT's efficacy might begin with identifying factors that influence tobacco abstinence symptom suppression. Two such factors are smokers' gender and NRT dose. The purpose of this study was to determine the dose-related effects of transdermal nicotine (TN) on tobacco abstinence symptoms in 75 men and 53 women who regularly smoked cigarettes but who had abstained from smoking for at least 8-12 hr. Participants completed 4 double-blind, randomized 6.5-hr laboratory sessions that differed by TN dose (0, 7, 21, or 42 mg). Each session included blood sampling for plasma nicotine level, measurement of heart rate, participants' ratings of tobacco abstinence symptoms and effects of nicotine, and psychomotor performance. Increases in plasma nicotine level were related to TN dose and were independent of gender. TN-induced abstinence symptom suppression was dose-related for items assessing craving and urge to smoke and largely was independent of gender. TN increased heart rate and ratings of aversive side effects (e.g., nausea, lightheadedness) in a dose-related manner, and women were more sensitive at higher doses. Results from this laboratory study support the continued use of TN as a pharmacotherapy. Higher doses may ameliorate some abstinence symptoms, although the side effect profile, at least in the short term, may limit effectiveness, especially for women.

The tobacco industry markets potential reduced exposure products (PREPs) to smokers, including oral products that are intended to be used in situations where cigarettes cannot. For example, Ariva, marketed by Star Scientific, is a tablet made from compressed tobacco powder and is intended for "adult smokers in situations where they cannot or choose not to smoke." No objective data are available regarding Ariva's effects in smokers, including its nicotine delivery, cardiovascular profile, or subjective effects. In this single-session, clinical laboratory study, 10 overnight-abstinent cigarette smokers were administered one Ariva tablet, followed 90 min later by two Ariva tablets, followed 90 min later by three Ariva tablets. Participants allowed each dose to dissolve in their mouths according to package instructions. Blood was sampled, heart rate monitored, and subjective effects assessed regularly. Ariva delivered nicotine in a dose-dependent manner; mean (SD) nicotine levels increased from 2.4 ng/ml (0.9) at baseline, to 3.4 ng/ml (1.4) 45 min post-1 tablet, 7.3 ng/ml (4.0) 45 min post-2 tablets, and 9.7 ng/ml (4.4) 45 min post-3 tablets. Heart rate increased after tablet administration, independent of dose. The tablets also significantly decreased subjective ratings of craving and urge, and increased ratings of nausea. Based on this short-term laboratory evaluation, Ariva exposes users to nicotine and may suppress some symptoms of tobacco abstinence, though its nausea-inducing characteristics may limit initial acceptability.

Transdermal nicotine (TN) is an efficacious smoking cessation pharmacotherapy thought to work, in part, by attenuating the effects of tobacco/nicotine abstinence and the effects of concurrently smoked cigarettes. Clinical trials suggest that TN may be less efficacious for women. This study explored the possibility of TN-related gender differences in > or = 8 hour abstinent smokers (54 women, 70 men) who completed four within-subject, double-blind, placebo-controlled sessions corresponding to 0, 7, 14, and 21 mg TN. In each approximately 6.5-hr long session participants smoked an own-brand cigarette 4 hours after TN administration and physiological and subjective outcomes were examined throughout each session. Results revealed that TN suppressed some signs and symptoms of tobacco abstinence and attenuated some effects of smoking, and these effects were not dependent on gender. Women were more sensitive to the direct effects of nicotine (e.g., ratings of Nauseous) and, independent of TN dose, self-administered less nicotine when smoking and rated smoking as less rewarding. Thus, although this study does not shed light on clinical observations that TN is less effective for women, results suggest that TN might need to be combined with other interventions to supplement its effects on tobacco/nicotine abstinence and concurrent smoking.

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