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Nicotine intake and dose response when smoking reduced–nicotine content cigarettes
Author(s) -
Benowitz Neal L.,
Jacob Peyton,
Herrera Brenda
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2006.09.007
Subject(s) - nicotine , carboxyhemoglobin , medicine , smoke , crossover study , pack year , confidence interval , blood pressure , cigarette smoke , population , physiology , cigarette smoking , anesthesia , zoology , chemistry , environmental health , carbon monoxide , placebo , biochemistry , alternative medicine , organic chemistry , pathology , biology , catalysis
Objectives The progressive reduction of the nicotine content of cigarettes has been suggested as a way to wean smokers from nicotine and tobacco. As a first step in evaluating this strategy, we studied smokers smoking cigarettes containing tobacco with differing nicotine content. Methods Twelve healthy smokers participated in a semiblinded, within‐subject, crossover study. Subjects were asked to smoke 1 of their usual brand of cigarette and then on 5 subsequent occasions to smoke a research cigarette, each with differing nicotine content. The research cigarettes contained 0.6 to 10.1 mg nicotine per cigarette. Plasma nicotine and blood carboxyhemoglobin levels, as well as subjective and cardiovascular responses, were measured after smoking. Systemic nicotine intake per cigarette was estimated by use of plasma nicotine concentrations over time and clearance data from the general population. Results Systemic nicotine intake (0.26‐1.47 mg per cigarette) varied with nicotine content of the cigarette ( r = 0.82, P < .001). Compensation when smoking single low–nicotine content cigarettes ranged from −1% (95% confidence interval, −23% to 21%) to 34% (95% confidence interval, −39% to 107%) for 1‐mg to 8‐mg research cigarettes. Carbon monoxide intake and estimated tar exposure were similar across cigarettes. Low–nicotine content cigarettes were rated as being of lower quality and less satisfying than the 12‐mg research cigarette or the usual brand ( P < .05 for both comparisons). Cigarette smoking increased heart rate and decreased skin temperature, but the nicotine dose‐response curve flattened at higher doses, with a maximal response being observed in cigarettes at a nicotine content level of about 8 mg. Conclusions Our study suggests that reduced–nicotine content cigarettes are reasonable candidates for trying to reduce the level of nicotine addiction in smokers. The flat nicotine dose–cardiovascular response curve is consistent with other studies demonstrating tolerance to the cardiovascular effects of nicotine. Clinical Pharmacology & Therapeutics (2006) 80 , 703–714; doi: 10.1016/j.clpt.2006.09.007