Pharmacodynamic effects of cotinine in abstinent cigarette smokers

Robert M. Keenan, Dorothy K Hatsukami, Paul R Pentel, Timothy N. Thompson, Michael A. Grillo

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


The nicotine metabolite cotinine was administered to abstinent cigarette smokers to determine whether it has pharmacologic activity as assessed by various physiologic and subjective measurements. By means of a randomized, double‐blind, placebo‐controlled counterbalanced‐order design, subjects received cotinine base (30 mg) intravenously after 48 hours of abstinence from cigarette smoking. Serum cotinine concentrations increased to levels commonly achieved during daily cigarette smoking, whereas no change in serum nicotine concentration was observed. Cotinine compared with placebo produced subjective differences in self‐reported ratings of restlessness, anxiety and tension, insomnia, sedation, and pleasantness. Cotinine had minimal effects on cardiovascular measurements. These findings indicate that cotinine is behaviorally active in the setting of cigarette abstinence at blood concentrations similar to those commonly achieved through daily cigarette smoking. Clinical Pharmacology and Therapeutics (1994) 55, 581–590; doi:

Original languageEnglish (US)
Pages (from-to)581-590
Number of pages10
JournalClinical Pharmacology & Therapeutics
Issue number5
StatePublished - May 1994


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