Labetalol treatment enhances the attenuation of tobacco withdrawal symptoms by nicotine in abstinent smokers

The noradrenergic system may mediate some of the acute physiological effects of nicotine and nicotine withdrawal symptoms. This study examined the effects of labetalol, an α- and β-adrenergic receptor blocker, on acute physiological and subjective effects of intravenous nicotine and on tobacco withdrawal symptoms. Five female and four male smokers participated in a double-blind, placebo-controlled, crossover study. Following overnight abstinence from smoking, subjects were treated orally with a single 100- or 200-mg dose of labetalol or placebo in each of three experimental sessions. Two hours after the medication treatment, subjects received an intravenous injection of 15 μg/kg nicotine. The nicotine-induced increases in heart rate were attenuated with the high dose of labetalol. No treatment effects were found for systolic or diastolic blood pressure changes. For the subjective effects of nicotine, treatment with both high and low doses of labetalol enhanced the ratings of "head rush" and "drug strength." The attenuation of tobacco withdrawal symptoms following intravenous nicotine administration was significantly greater with high-dose labetalol treatment, compared with placebo. These results support the proposed role of adrenergic receptors in nicotine withdrawal symptoms. The utility of adrenergic blockers, in combination with nicotine replacement therapies, for smoking cessation needs to be examined further in controlled clinical trials.