The influence of gender and oxytocin on stress reactivity, cigarette craving, and smoking in a randomized, placebo-controlled laboratory relapse paradigm

Psychopharmacology (Berl). 2020 Feb;237(2):543-555. doi: 10.1007/s00213-019-05392-z. Epub 2019 Dec 3.


Rationale: Female cigarette smokers tend to show greater cessation failure compared with males. Variables that contribute to the maintenance of smoking, including stress and craving, may differentially impact male and female smokers. Novel pharmacotherapies, such as oxytocin, may attenuate stress reactivity and craving in smokers, but work in this area is limited.

Objectives: This study assessed the influence of gender and oxytocin on stress reactivity, craving, and smoking in a randomized, placebo-controlled laboratory relapse paradigm.

Methods: Male and female adult cigarette smokers (ages 18-45) were enrolled (women oversampled 2:1) and completed a laboratory session, in which intranasal oxytocin or placebo was administered followed by a laboratory social stress task. The role of gender and oxytocin were assessed on measures of stress reactivity, cigarette craving, latency to smoke in a resistance task, subjective responses to smoking, and ad-libitum smoking.

Results: Participants (N = 144) had a mean age of 31 were 63% female and 56% White. Following stress induction, female smokers evidenced greater subjective stress than males, though males demonstrated greater neuroendocrine reactivity and smoking intensity than females. No gender differences were demonstrated for craving. Oxytocin did not attenuate any aspect of stress reactivity, craving, smoking, or subjective responses to smoking compared with placebo.

Conclusions: Gender differences in stress reactivity were shown in the hypothesized direction, but oxytocin appeared to exert little impact on subjective or behavioral metrics. Results highlight the complex relationship between gender, stress, and smoking, as well as the implications for oxytocin as a potential pharmacotherapy for smoking cessation.

Keywords: Cortisol; Craving; Cue reactivity; Gender; Oxytocin; Relapse; Sex; Smoking; Stress.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adult
  • Cigarette Smoking / drug therapy
  • Cigarette Smoking / psychology*
  • Craving / drug effects
  • Craving / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxytocin / pharmacology*
  • Oxytocin / therapeutic use
  • Recurrence
  • Research
  • Sex Characteristics*
  • Smoking Cessation / methods
  • Smoking Cessation / psychology
  • Stress, Psychological / drug therapy
  • Stress, Psychological / psychology*
  • Tobacco Products*
  • Young Adult


  • Oxytocin