Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing 11C-nicotine.

Tobacco smoking is a chronic, relapsing disorder that constitutes one of the primary preventable causes of death in developed countries. Two of the popular hypotheses to explain the development and maintenance of strong nicotine dependence in cigarette smokers posit (i) a rapid brain nicotine accumulation during cigarette smoking and/or (ii) puff-associated spikes in brain nicotine concentration. To address these hypotheses, we investigated the dynamics of nicotine accumulation in the smoker's brain during actual cigarette smoking using PET with 3-s temporal resolution and (11)C-nicotine loaded into cigarettes. The results of the study, performed in 13 dependent smokers (DS) and 10 nondependent smokers (NDS), suggest that puff-associated spikes in the brain nicotine concentration do not occur during habitual cigarette smoking. Despite the presence of a puff-associated oscillation in the rate of nicotine accumulation, brain nicotine concentration gradually increases during cigarette smoking. The results further suggest that DS have a slower process of brain nicotine accumulation than NDS because they have slower nicotine washout from the lungs and that DS have a tendency to compensate for their slower rate of brain nicotine accumulation compared with NDS by inhaling a larger volume of smoke. For these reasons, smokers' dependence on cigarette smoking, or the resistance of NDS to becoming dependent, cannot be explained solely by a faster brain nicotine accumulation.

Precessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment.

INTRODUCTION: Previous studies have reported that smoking abstinence rates are increased when nicotine skin patch treatment is initiated prior to the target quit smoking date, as compared with conventional treatment beginning on the quit date. We hypothesized that smoking in the presence of continuous levels of nicotine would attenuate the reinforcing effects of cigarette smoking and lead to a decline in dependence on inhaled nicotine, thus facilitating cessation. METHODS: This study involved four groups of smokers (n = 100 per group) who received either nicotine patch (21 mg/24 hr) or placebo patch treatment for 2 weeks before the quit smoking date, and during this period, smoked their usual brands of cigarettes or switched to low-tar and nicotine cigarettes: a 2 (nicotine patch) x 2 (cigarette type) factorial design. From the quit date on, all groups received standard nicotine patch treatment, consisting of 6 weeks of 21 mg/24 hr, 2 weeks of 14 mg/24 hr, and 2 weeks of 7 mg/24 hr. Abstinence was defined as self-report of no smoking from the quit date on, confirmed by expired-air carbon monoxide. RESULTS: Continuous abstinence rates were approximately doubled by precessation nicotine patch treatment. The treatment mainly benefited smokers with lower levels of dependence, based on Fagerström Test for Nicotine Dependence score. All treatments were well tolerated. DISCUSSION: In view of these findings and similar results from previous studies, current labeling of the nicotine patch, which recommends using nicotine replacement therapy only after the quit date, should be reexamined.