Progesterone improves cognitive performance and attenuates smoking urges in abstinent smokers

Abstract

Background: Progesterone, a steroid hormone, has been implicated in many CNS functions including reward, cognition, and neuroprotection. The goal of this study was to examine the dose-dependent effects of progesterone on cognitive performance, smoking urges, and smoking behavior in smokers.

Methods: Thirty female and thirty-four male smokers participated in a double-blind, placebo-controlled study. Female smokers were in the early follicular phase of their menstrual cycle during study participation. Smokers were randomly assigned to either 200 or 400mg/day of progesterone or placebo, given in two separate doses, during clinic visit. The first 3 days of the treatment period, smokers abstained from smoking, which was verified with breath CO levels. Smokers attended an experimental session on day 4 where the number of cigarettes smoked were recorded starting 2h after the medication treatment.

Results: Progesterone treatment, 200mg/day, significantly improved cognitive performance in the Stroop and the Digit Symbol Substitution Test. Progesterone at 400mg/day was associated with reduced urges for smoking but did not change ad lib smoking behavior.

Conclusions: These findings suggest a potential therapeutic value of progesterone for smoking cessation.

Figure 1

The average (with standard error of the mean-SEM) plasma progesterone levels (ng/ml) for the 400 mg and 200 mg progesterone and placebo treatments. The measurements were taken just before and 2 hours after administration of progesterone or placebo treatment on day 4. *indicates significant differences from placebo (p<0.05). See text for details.

Figure 2

The average (with SEM) heart rate for the 400 mg or 200 mg progesterone or placebo treatment conditions in male and female smokers. Measurements were taken daily during the 4-day treatment period. *indicates significant differences from placebo (p<0.05). See text for details.

Figure 3

The average (with SEM) throughput score for the Stroop and the DSST correct items for the 400 mg or 200 mg progesterone or placebo conditions. Bars represent the changes from baseline. Measurements were taken at baseline and on day 4 for the Stroop and on days 2, 3, and 4 for the DSST. # indicates significant main effect for treatment and *indicates significant differences from placebo (p<0.05). See text for details.

Figure 4

The average (with SEM) Factor 1 scores of the BQSU for the 400 mg, or 200 mg progesterone, or placebo conditions in males and female smokers. Measurements were taken daily during the 4-day treatment period. # indicates significant treatment-by-time interaction (p<0.05). See text for details.

Figure 5

The average (with SEM) ratings of subjective responses to sample smoking measured with the Drug Effects Questionnaire (DEQ) under 400 mg or 200 mg progesterone or placebo conditions. The measurements were obtained after smoking a cigarette. # indicates significant main effect for treatment (p<0.05). See text for details.