Effects of Intranasal Oxytocin on Cigarette Withdrawal and Smoking in the Laboratory: Differences by Sex and Social Functioning Traits

• Published in: Experimental and clinical psychopharmacology 2024-12, Vol.32 (6), p.717-727
• Main Authors: Simpson, Kelsey A., Stone, Matthew D., Leventhal, Adam M., Pang, Raina D., Ray, Lara, Kirkpatrick, Matthew G.
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Adult; Cigarette Smoking - psychology; Female; Hostility; Human; Human Sex Differences; Humans; Male; Nicotine Withdrawal; Oxytocin; Oxytocin - administration & dosage; Oxytocin - pharmacology; Sensitivity (Personality); Sex Factors; Smoking Cessation; Smoking Cessation - methods; Smoking Cessation - psychology; Social Acceptance; Social Functioning; Substance Withdrawal Syndrome - psychology; Tobacco Smoking; Tobacco Use Disorder - drug therapy; Tobacco Use Disorder - psychology; Young Adult
• ISSN: 1064-1297; 1936-2293; 1936-2293
• DOI: 10.1037/pha0000733

Intranasal oxytocin (INOT) has received attention as a treatment for substance use disorders including tobacco dependence. However, it is unclear whether INOT-related effects differ by sex and social functioning traits. This study examined the influence of sex and two trait social functioning measures (hostility and rejection sensitivity) on INOT effects on abstinence-related subjective measures and smoking lapse. Adults who smoked cigarettes daily (N = 64; 21-40 years; 39% female) completed trait hostility and rejection sensitivity surveys at baseline followed by three experimental sessions following 12-hr smoking abstinence. Each session, participants received a single INOT dose (placebo, 20, 40 international units [IU]) in counterbalanced order, completed withdrawal, smoking urges and affect questionnaires, and a smoking lapse analog task. Interactive effects between INOT and sex, hostility, or rejection sensitivity on all outcomes were analyzed. INOT produced differential effects as a function of sex, trait hostility, and rejection sensitivity. The 20 IU dose worsened abstinence-related subjective effects for individuals with high trait hostility. Both INOT doses decreased smoking urges for high rejection sensitivity, and the 20 IU dose increased smoking urges for low rejection sensitivity. INOT increased withdrawal symptoms, smoking urges, and feelings of anger in females but not males. INOT did not improve withdrawal symptoms during abstinence and did not affect smoking lapse. While INOT produced some beneficial effects for a subset of participants with high rejection sensitivity, it worsened abstinence-related symptoms for others. Our results suggest that sex and social functioning should be considered when examining the therapeutic potential of INOT for smoking cessation in future research. Public Health Significance Intranasal oxytocin produced differential abstinence-related subjective effects as a function of dose and individual differences (sex, trait hostility, and rejection sensitivity), with some individuals experiencing benefits and others experiencing greater withdrawal symptoms. Future studies should account for individual differences and dose response when evaluating intranasal oxytocin for smoking cessation or other substance use disorders.