title: Marihuana smoking suppresses luteinizing hormone in women. Effects of progesterone stimulated allopregnanolone on craving and stress response in cocaine dependent men and women
abstract: Smoking a single 1-g marihuana cigarette containing 1.8 % delta 9-tetrahydrocannabinol induced a 30 % suppression of plasma luteinizing hormone levels ( P less than .02 ) in women during the luteal phase of the menstrual cycle . After marihuana placebo cigarette smoking , no luteinizing hormone suppression was observed in the same women under double-blind conditions . Marihuana may have adverse effects upon reproductive function during the luteal phase of the menstrual cycle as a consequence of gonadotropin inhibition OBJECTIVES Fluctuations in progesterone levels during the menstrual cycle have been shown to affect physiological and subjective effects of cocaine . Furthermore , our laboratory has demonstrated that following drug-cue exposure , cocaine dependent women with high levels of circulating progesterone display lower diastolic and systolic blood pressure responses and report lower levels of anxiety and drug craving compared to cocaine dependent women with low levels of progesterone . In the current study we examined the role of the progesterone derived neuroactive steroid allopregnanolone ( ALLO ) on stress arousal , inhibitory control and drug craving in cocaine dependent subjects . METHODS Plasma levels of ALLO were measured using GC/MS in 46 treatment-seeking cocaine dependent men and women on day 5 of a 7-day treatment regimen of micronized progesterone ( 15M/8F ) ( 400mg/day ) or placebo ( 14M/9F ) administered in a double blind , r and omized manner . As a control , levels of the testosterone derived neurosteroid and rostanediol ( ADIOL ) were also measured . All subjects participated in laboratory sessions on days 5 - 7 of progesterone/placebo administration in which they were exposed to a series of 5-min personalized guided imagery of either a stressful situation , cocaine use or of a neutral setting and dependent variables including subjective craving , mood , Stroop task as a measure of inhibitory control performance and plasma cortisol were assessed . Participants were grouped by high or low ALLO level and levels of dependent variables compared between ALLO groups . RESULTS Progesterone relative to placebo significantly increased ALLO levels with no sex differences . There were no effects of micronized progesterone on the testosterone derived ADIOL . Individuals in the high versus the low ALLO group showed decreased levels of cortisol at baseline , and a higher cortisol response to stress ; higher positive mood scores at baseline and improved Stroop performance in the drug-cue and stress conditions , and reduced cocaine craving across all imagery conditions . CONCLUSIONS As expected , cocaine dependent individuals administered progesterone showed significantly higher ALLO plasma levels . High levels of ALLO appeared to normalize basal and stress response levels of cortisol , decrease cocaine craving and also contribute to improvements in positive emotion and Stroop performance in response to stress and drug-cue exposures . These findings suggest that the neuroactive steroid ALLO plays a significant role in mediating the positive effects of progesterone on stress arousal , cognitive performance and drug craving in cocaine dependence
target: Such prevalence rates have not been observed in adolescents .
  Differences between men and women involve : ( i ) the biological response to the drug , ( ii ) the progression to drug dependence , and ( iii ) the comorbid psychiatric diagnoses , which may be due to both sociocultural factors and innate biological differences .
  The introduction of gender into forensic toxicological evaluations may help eluci date the relationship between the body 's absorption of abused drugs ( alone or in combination ) and the onset of intoxications , both lethal and none
background: Gender differences in substance use/abuse have been the focus of research in the last 15 years .
  Initiation , use patterns , acceleration of disease course , and help-seeking patterns are known to be influenced by gender differences with regard to biological , psychological , cultural and socioeconomic factors .
  This paper presents a systematic review of published data on gender differences in the use/abuse of psychoactive and psychotic drugs , focusing on the importance of a multidisciplinary approach .
  A crucial role played by ovarian hormones ( oestrogens and progesterone ) has been documented in both human and animal model studies .