PHARMACODYNAMIC EFFECTS OF COTININE IN ABSTINENT CIGARETTE SMOKERS

The nicotine metabolite cotinine was administered to abstinent cigaret te smokers to determine whether it has pharmacologic activity as asses sed by various physiologic and subjective measurements. By means of a randomized, double-blind, placebo-controlled counterbalanced-order des ign, subjects received cotinine base (30 mg) intravenously after 48 ho urs of abstinence from cigarette smoking. Serum cotinine concentration s increased to levels commonly achieved during daily cigarette smoking , whereas no change in serum nicotine concentration was observed. Coti nine compared with placebo produced subjective differences in self-rep orted ratings of restlessness, anxiety and tension, insomnia, sedation , and pleasantness. Cotinine had minimal effects on cardiovascular mea surements. These findings indicate that cotinine is behaviorally activ e in the setting of cigarette abstinence at blood concentrations simil ar to those commonly achieved through daily cigarette smoking.