Progesterone effects on subjective and physiological responses to intravenous nicotine in male and female smokers

Abstract

Objective Previous studies suggest possible modulatory effects of progesterone on nicotine addiction. The goal of this study was to determine the effects of progesterone, on acute physiological and subjective responses to intravenous (IV) nicotine in overnight abstinent male and female smokers. Methods Twelve smokers, 6 males and 6 females, participated in a double-blind, placebo-controlled, crossover study, which consisted of 2 experimental sessions. Before each session, subjects were treated orally with a single dose of either 200 mg progesterone or placebo. Starting 2 hours following the medication treatment, subjects received an IV saline injection, followed by 0.5 and 1.0 mg/70 kg IV nicotine. Results Progesterone treatment, compared to placebo, enhanced the ratings of “bad effects,” from IV nicotine and attenuated the rating of “drug liking.” Progesterone also enhanced suppression of smoking urges by nicotine as assessed by the Brief Questionnaire on Smoking Urges (BQSU). Conclusions These results suggest that progesterone may alter the subjective effects of nicotine as well as urges to smoke cigarettes. Further studies are warranted to examine the modulation of nicotine’s effects by gonadal hormones.

Association between ovarian hormones and smoking behavior in women.

“…Instead, progesterone appears to reduce smoking behavior only when it is not opposed by estradiol. These findings are consistent with animal and human studies demonstrating diminished interest in nicotine following progesterone administration in the context of low levels of estradiol (Lynch, 2009;Sofuoglu & Mooney, 2009) and diminished relapse rates among female smokers who quit during the luteal phase compared to the follicular phase (Allen, et al., 2008). In this study, the P:E ratio was more strongly correlated with smoking behavior than the E:P ratio, which suggests that the level of progesterone relative to estradiol rather than the reverse should be examined in future studies of smoking behavior.…”

“…Estradiol is thought to enhance women's sensitivity to nicotine, whereas progesterone is thought to be protective (Lynch & Sofuoglu, 2010). Tonic progesterone administration in the context of relatively low estradiol levels increases the subjective negative effects of nicotine, decreases the subjective positive effects of nicotine, and reduces the urge to smoke in women (Sofuoglu & Mooney, 2009). These findings are supported by experimental animal studies, which have demonstrated decreased motivation for nicotine when progesterone levels are high (Lynch, 2009).…”

Systematic and Meta-Analytic Review of Research Examining the Impact of Menstrual Cycle Phase and Ovarian Hormones on Smoking and Cessation

“…43,50,55 There were insufficient data for meta-analysis so the individual studies are reviewed below. The first study 38 found lower reported positive subjective effects in response to intravenous (IV) nicotine (e.g., "high," "feel good," "want more") for women in the luteal phase compared to women in the follicular phase.…”

“…Ratings for "strength" and "head rush" were lower in the progesterone condition as well but these differences did not reach significance. In the third study, 50 six women in the early follicular phase and six men participated in two laboratory sessions, each following overnight abstinence from smoking, during which they received either 200 mg progesterone or placebo. Across the full sample, the rating of the "bad effects" was greater and "like drug" was lower in the progesterone condition than the placebo condition in response to IV nicotine.…”

Cigarette Consumption and Related Factors in Schizophrenia, Schizoaffective Disorder and Delusional Disorder

“…There is no such difference between smoker and non-smoker women. It is thought that female sex hormones particularly progesterone, which has an inhibitory effect on β2*-nAChRs may have role in this difference (42,43).…”