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

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

Erin A McClure  1 , Nathaniel L Baker  2 , Kevin M Gray  3 , Caitlyn O Hood  4 , Rachel L Tomko  3 , Matthew J Carpenter  3   5 , Viswanathan R Ramakrishnan  2 , Cole J Buchanan  6 , Michael E Saladin  7
Affiliations
Randomized Controlled Trial

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

Erin A McClure et al. Psychopharmacology (Berl). 2020 Feb.

Abstract

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.

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Figures

Figure 1.
Figure 1.
Timeline of procedures and measures collected during the laboratory session (Day 15). Figure Key: CQ=Craving Questionnaire; TSST=Trier Social Stress Task; SRT=Smoking Resistance Task; ASP=Ad libitum Smoking Period; mCEQ=Modified Cigarette Evaluation Questionnaire. + During the Ad Libitum Smoking Period, assessments were conducted immediately following the first cigarette (typically +5–10 minutes after the start of the ASP).
Figure 2.
Figure 2.
Mean cigarette craving (range of 4–20; shown in Panel A), self-reported stress (range of 1–5; shown in Panel B), and cortisol (ug/dL; shown in Panel C) response shown prior to and following the Trier Social Stress Task (TSST) for male (n=53) and female (n=91) participants. Responses are displayed at baseline (BL), post-medication (PM), which included oxytocin (40 IUs) or matched placebo administration, immediately following the TSST (TSST +0), 20 minutes following the TSST (TSST +20), and 40 minutes following the TSST (TSST +40). Data are shown as the model-based means and standard errors. Data are shown adjusted for A) treatment condition, time, treatment by time interaction, baseline cigarette craving and gender, B) treatment condition, time, treatment by time interaction, baseline stress, gender and gender by time interaction, C) treatment condition, time, treatment by time interaction, baseline cortisol, gender and gender by time interaction. *Indicates p<.05 between males and females at that specific time point.
Figure 3.
Figure 3.
Peak responses (from baseline) are shown for cigarette craving (A), self-reported stress (B), and cortisol (C) to the Trier Social Stress Task (TSST) following oxytocin or placebo administration in male (n=53) and female (n=91) participants. Data are shown as the model-based means and standard errors. Data are shown adjusted for A) treatment condition, baseline craving and gender, B) treatment condition, baseline stress, gender, C) treatment condition, baseline cortisol, gender and gender by treatment interaction. *Indicates p<.05 between male and female participants within a randomized treatment condition.
Figure 4.
Figure 4.
Mean cigarette craving (A), self-reported stress (B), and cortisol (C) response prior to and following the Trier Social Stress Task (TSST) for participants randomized to the oxytocin (n=72) or placebo condition (n=72). Data are shown as the model-based means and standard errors. Data are shown adjusted for A) treatment condition, time, treatment by time interaction, baseline cigarette craving and gender, B) treatment condition, time, treatment by time interaction, baseline stress, gender and gender by time interaction, and C) treatment condition, time, treatment by time interaction, baseline cortisol, gender and gender by time interaction.
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