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Threshold Dose for Nicotine Discrimination in Cigarettes

Principal Investigator: Kenneth Perkins

Funding Mechanism: National Institutes of Health- Grant

ID number: 1R21DA035968-01

Award Date: 8/15/2013

Institution: University of Pittsburgh

Despite extensive animal research on nicotine discrimination and human studies of threshold dose for discriminating drugs other than nicotine, no studies have clearly assessed the nicotine discrimination threshold in humans because of the difficulty in controlling nicotine dosing with tobacco intake. Investigators will employ a well-validated behavioral discrimination methodology to identify the cigarette nicotine threshold dose for discrimination using a nicotine research cigarette from the National Institute on Drug Abuse (NIDA) Drug Supply Program; the study will assess threshold doses in a diverse sample of 100 healthy male and female smokers (aged 18-65) who vary in dependence level and menthol preference. This study will also separately assess self-administration of nicotine to determine the relationship between nicotine discrimination threshold dose and reinforcement threshold dose. The primary aim is to reliably assess the threshold dose for nicotine discrimination via cigarettes; hypotheses investigated will include the following: (1) the threshold dose will be 0.4 mg or lower (below the yield of most commercial brands) for greater than 95% of the study population; (2) the threshold dose will be lower in nondependent vs. dependent smokers and in men vs. women, consistent with research on subgroup differences in nicotine sensitivity; (3) a significant association will exist between discrimination threshold and self-administration threshold; and (4) the threshold dose will vary by menthol preference. Identification of the lowest dose of nicotine that reinforces tobacco use and promotes nicotine dependence will have implications for understanding the onset and maintenance of dependence.

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