Subjective, physiological, and cognitive responses to intravenous nicotine: effects of sex and menstrual cycle phase

Neuropsychopharmacology. 2014 May;39(6):1431-40. doi: 10.1038/npp.2013.339. Epub 2013 Dec 18.


Nicotine dependence is a serious public health concern. Optimal treatment of nicotine dependence will require greater understanding of the mechanisms that contribute to the maintenance of smoking behaviors. A growing literature indicates sex and menstrual phase differences in responses to nicotine. The aim of this study was to assess sex and menstrual phase influences on a broad range of measures of nicotine response including subjective drug effects, cognition, physiological responses, and symptoms of withdrawal, craving, and affect. Using a well-established intravenous nicotine paradigm and biochemical confirmation of overnight abstinence and menstrual cycle phase, analyses were performed to compare sex (age 18-50 years; 115 male and 45 female) and menstrual cycle phase (29 follicular and 16 luteal) effects. Females had diminished subjective drug effects of, but greater physiological responses to, nicotine administration. Luteal-phase females showed diminished subjective drug effects and better cognition relative to follicular-phase women. These findings offer candidate mechanisms through which the luteal phase, wherein progesterone is dominant relative to estradiol, may be protective against vulnerability to smoking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Affect / drug effects
  • Affect / physiology
  • Cognition / drug effects*
  • Cognition / physiology
  • Dose-Response Relationship, Drug
  • Drug-Seeking Behavior / drug effects
  • Drug-Seeking Behavior / physiology
  • Female
  • Follicular Phase / physiology*
  • Humans
  • Luteal Phase / physiology*
  • Male
  • Middle Aged
  • Nicotine / administration & dosage
  • Nicotine / pharmacology*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Sex Factors
  • Smoking / physiopathology*
  • Smoking / psychology
  • Substance Withdrawal Syndrome / physiopathology
  • Substance Withdrawal Syndrome / psychology
  • Young Adult


  • Nicotinic Agonists
  • Nicotine