Sex steroid hormones, stress response, and drug craving in cocaine-dependent women: Implications for relapse susceptibility

Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
Experimental and Clinical Psychopharmacology (Impact Factor: 2.63). 10/2007; 15(5):445-52. DOI: 10.1037/1064-1297.15.5.445
Source: PubMed

ABSTRACT Cocaine dependence is associated with an enhanced sensitivity to stress and drug craving. Increases in stress-induced craving and hypothalamic-pituitary-adrenal reactivity are also predictive of cocaine relapse outcomes. More important, sex differences in these responses have also been reported. To further understand the basis of the sex differences, the authors examined the influence of sex steroid hormones on subjective and physiological stress responses and drug craving in cocaine-dependent women. Women who had low progesterone levels (n=5) were compared with those with high progesterone levels (n=5) and with those with moderate levels of estradiol and progesterone (n=9) in their responses during exposure to stress, cocaine cues, and neutral imagery conditions. The high progesterone group showed significantly lower stress-induced and drug cue-induced cocaine craving ( p<.05) and reduced drug cue-induced anxiety levels ( p<.08) and lower drug cue-induced systolic and diastolic blood pressure levels compared with the low progesterone group. These data suggest that there are significant effects of sex steroid hormones on stress and drug cue-induced cocaine craving, anxiety, and cardiovascular responses. In particular, high progesterone during the midluteal phase of the cycle was associated with decreased stress-induced and drug cue-induced craving and decreased cue-induced anxiety and blood pressure responses. These findings are consistent with previous preclinical and clinical studies of progesterone's effects on the behavioral responses to cocaine and warrant further research to examine the effects of progesterone on stress-induced cocaine craving, stress arousal, and cocaine relapse susceptibility in women.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective As sex differences in substance dependence may impinge upon the perception and regulation of emotion, we assess emotional intelligence (EI) as a function of gender, menstrual cycle (MC) phase and hormonal changes in early abstinent cocaine-dependent individuals who abuse alcohol (CDA).Methods Study 1: The Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT) was administered to 98 CDA (55 M/43 F) and 56 healthy (28 M/28 F) individuals. Performance in women was also assessed by MC phase. Study 2: The MSCEIT was administered to 28 CDA (19 M/9 F) who received exogenous progesterone (400 mg/day) versus placebo for 7 days (study 2).ResultsStudy 1: Healthy females were better than healthy males at facilitating thought and managing emotions. This gender discrepancy was not observed in the CDA group. Additionally, all women in the high compared with the low progesterone phase of their MC were better at managing their emotions. Study 2: Exogenous progesterone improved ability to facilitate thought in both males and females.ConclusionsCDA women may be vulnerable to difficulties managing and regulating emotions. Gonadal hormones may contribute to this gender effect, as increases in both endogenous and exogenous progesterone improved selective aspects of EI. Copyright © 2014 John Wiley & Sons, Ltd.
    Human Psychopharmacology Clinical and Experimental 11/2014; 29(6). DOI:10.1002/hup.2446 · 1.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Progesterone modulates multiple brain functions implicated in the pathogenesis ofdrug addiction. During high endogenous progesterone states, women reduce use of cocaine. We sought to test whether progesterone replacement reduces cocaine use in postpartum women with a cocaine use disorder (CUD).
    The Lancet Psychiatry 10/2014; 1(5):360-367. DOI:10.1016/S2215-0366(14)70333-5
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite extensive research on gender differences in addiction, there are relatively few published reports comparing treatment outcomes for women versus men based on evidence-based treatments evaluated in randomized clinical trials. An aggregate sample comprised of data from five randomized clinical trials of treatment for cocaine dependence (N=434) was evaluated for gender differences in clinical outcomes. Secondary analyses compared gender differences in outcome by medication condition (disulfiram versus no medication) and across multiple behavioral treatment conditions. Women, compared with men, had poorer treatment outcomes on multiple measures of cocaine use during treatment and at post-treatment follow-up. These results appear to be primarily accounted for by disulfiram being less effective in women compared with men. There was no evidence of meaningful gender differences in outcome as a function of the behavioral therapies evaluated. These findings suggest that women and men may benefit to similar degrees from some empirically validated behavioral treatments for addiction. Conversely, some addiction pharmacotherapies, such as disulfiram, may be associated with poorer outcomes among women relative to men and point to the need for careful assessment of pharmacological treatments in both sexes prior to widespread clinical implementation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Drug and Alcohol Dependence 10/2014; 145C:156-167. DOI:10.1016/j.drugalcdep.2014.10.007 · 3.28 Impact Factor