Premenstrual symptomatology, alcohol consumption, and family history of alcoholism in women with premenstrual syndrome

OBJECTIVE: The purpose of this study was to examine the relationship among family history of alcoholism (FH), premenstrual syndrome (PMS) symptoms, and alcohol consumption in women with a PMS diagnosis. METHOD: Participants (N = 46) were predominantly white (73%) women, of whom 17 (37%) reported multigenerational alcoholism on the paternal side (FH positive [FH+]) using the Family Alcohol and Drug Survey. Subjects recorded alcohol consumption and PMS symptoms using a daily record form for 3 consecutive months. RESULTS: Demographics and alcohol consumption during the follicular phase (FOL) and premenstrual phase (PREM) of the menstrual cycle did not differ by FH; however, change in drinking from FOL to PREM was greater in FH+ (mean change = 2.78 drinks/week) versus FH negative (FH-; mean change = -0.72 drinks/week) women. During PREM, FH- women reported more PMS symptomatology compared with FH+ women, and alcohol consumption during PREM was positively correlated with ratings of bloating, craving for alcohol, craving for food, and low energy in FH- but not FH+ women. CONCLUSIONS: Although FH+ women increased their drinking premenstrually, such use was unrelated to PMS symptom severity.     

Enhanced sensitivity to stress and drug/alcohol craving in abstinent cocaine-dependent individuals compared to social drinkers.

Chronic exposure to cocaine is associated with neuroadaptions in stress and reward circuits that may increase susceptibility to relapse. We examined whether there are alterations in stress response and craving in abstinent cocaine-dependent individuals compared with a demographically matched group of non-addicted socially drinking community controls. Forty treatment-engaged abstinent cocaine patients (17F/23M) and 40 controls (19F/21M) were exposed to a brief 5 min guided imagery of individually calibrated stressful situations, personal drug/alcohol-related situation and a neutral-relaxing situation, one imagery per session, presented in random order. Craving, anxiety, emotion rating scales, and physiological measures were assessed. Cocaine patients reported significantly higher and more persistent stress- and cue-induced drug/alcohol craving, negative emotions, and physiological responses compared with social drinkers. In cocaine patients, stress- and cue-induced drug craving was accompanied by increased anger, fear, sadness, heart rate, and SBP. Controls reported minimal stress-induced craving and only increases in anxiety and SBP during stress exposure. Cue-induced alcohol craving was accompanied only by an increase in relaxed state. Females reported increased stress-induced anxiety and sadness compared with males, while males were emotionally and physiologically more reactive in the cue condition. These findings are the first to document functional alterations in stress- and reward-related affect and physiology in recently abstinent cocaine patients that is marked by an enhanced sensitivity to stress- and drug-related cue exposure. These data suggest that recovery from chronic cocaine abuse could be hampered by a hyper-responsive stress- and drug-craving state that increases cocaine relapse susceptibility.     

Effect of brief imagery interventions on craving in college student smokers

This study examined the comparative impact of three types of imagery interventions (olfactory, visual, and olfactory-plus-visual imagery) and a distracting cognitive task (serial sevens) on self-reported craving for cigarettes by 54 university students who had been smoking at least a pack of cigarettes per day for the past 3 to 6 months. Using the 10-item, self-report questionnaire of smoking urges, we assessed participants’ experience of craving prior to cue exposure, following 2?min of lab-based cue-exposure, during a 2?min imagery or distraction intervention, and immediately following the intervention. Reported craving during intervention was significantly lower in all three imagery conditions compared to the distracting cognitive task condition, but there was not a significant difference in craving among the imagery conditions. Despite explicit instructions to focus on the designated form(s) of imagery, a majority of participants in each of the imagery conditions also reported experiencing other forms of sensory imagery. Brief imagery interventions hold promise to interrupt, at least temporarily, cue-induced craving in daily smokers.     

The relevance and treatment of cue-induced cravings in tobacco dependence

Craving to smoke is often conceptualized and measured as a tonic, slowly changing state induced by abstinence. In this article, we review the literature on the existence, causes, and treatment of cue-induced cravings: intense, episodic cravings typically provoked by situational cues associated with drug use. In laboratory research, smokers exposed to smoking-related cues demonstrate increased craving as well as distinct patterns of brain activation. Observational field studies indicate that such cue-induced cravings are substantially responsible for relapse to smoking but that smoking can often be averted by coping responses. The effects of pharmacological interventions are mixed. Steady-state medications (bupropion, varenicline, nicotine patch) do not appear to protect smokers from cue-induced cravings. However, acutely administered nicotine medications (such as nicotine gum and lozenge), used after cue exposure as "rescue medications," can help a smoker's recovery from cue-induced cravings. Cue-induced craving plays an important role in smoking and relapse and likely in other addictions as well. Treatments to mitigate the effect of cue-induced craving are both important and needed.     

Acute alcohol intoxication in socially drinking female and male offspring of alcoholic fathers

Alcohol pharmacokinetics, mood-state alterations and psychomotor performance were investigated in women and men at risk for developing alcoholism. Estimated body water was used to calculate the alcohol dose in an effort to eliminate differences in alcohol pharmacokinetics between women and men due to differences in body composition. Differences were not detected between women and men or family history groups (family history positive, FH +, and family history negative, FH-) on absorption time, peak blood alcohol level (BAL), elimination time, or area under the blood alcohol curve (AUC). FH + men reported no central stimulant effects at peak BAL on the Sensation Scale, whereas FH- men and women all reported central stimulant effects. Further, FH + men reported a decrease in anxiety after the ingestion of alcohol. Acute intoxication did not affect performance in the FH + group on a finger-tapping task. In the FH - group, the dominant hand was significantly impaired during the ascending limb of the blood alcohol curve and recovered during the descending limb. Differences between family history groups or sex were not detected on a grooved-pegboard task. Results indicated that FH + men may experience alcohol differently from the FH - group and FH + women. FH + women also showed different reactions to acute alcohol than the FH - group. However, these differences were not as consistent across tasks.     

Reward dependence moderates smoking-cue- and stress-induced cigarette cravings

Background

Cigarette cravings following exposure to smoking cues in a smoker's environment are thought to play an important role in cessation failure. The possibility that dispositional factors may impact cue-induced cravings, though intriguing, has received little attention. According to Cloninger's Tridimensional Personality Theory, factors such as reward dependence (RD), harm avoidance (HA), and novelty seeking (NS) may figure prominently in risk for addiction, as well as relapse, in individuals attempting to abstain from drug and alcohol use. Particularly interesting in this regard is the possibility that smokers with higher levels of RD, who are especially sensitive to reward signals, will have heightened craving reactions to smoking cues.

Methods

To that end, non-treatment-seeking nicotine dependent smokers (n = 96, mean age = 41.1, 47% African American, 17% Caucasian, 22% Hispanic, 19.3 cigs/day, FTND = 7.5) underwent a classic experimental cue-induction, during which they were exposed to imagery of: (1) smoking, (2) neutral, and (3) stress cues, and reported their cigarette cravings (0–100) before and after each exposure. Participants also completed the Tridimensional Personality Questionnaire.

Results

Not surprisingly, smoking and stress cues (but not neutral cues) elicited significant elevations in craving (p's < 0.0001). Consistent with study hypothesis, smokers who scored higher on RD had stronger craving reactions to both smoking cues (p < .02) and stress cues (p < .03).

Conclusions

Findings raise the possibility that dispositional characteristics, in particular, reward dependence, influence smoking by potentiating reactions to environmental smoking cues. Furthermore, the similar effects of RD on stress-induced craving suggest that both cue-and stress-induced cravings may be influenced by a common underlying disposition.     

An acute dose of nicotine enhances cue-induced cocaine craving

The present study examined whether the active component in tobacco, nicotine, can modulate cocaine craving in patients with a history of smoking crack cocaine when exposed to crack cocaine related environmental cues. Twenty patients, all cigarette smokers, were randomly assigned to nicotine (two 22 mg transdermal patches) or placebo in a single-dose, placebo-controlled, crossover, double-blind study. Craving and anxiety were measured before and after cocaine cues with visual analog scales for desire to use cocaine and mood. Skin conductance and skin temperature were recorded before and during cocaine cues. Following exposure to cocaine cues, all patients reported an increase in cocaine craving and anxiety relative to the pre-cue measures. Cue exposure also produced an increase in skin conductance and decrease in skin temperature. The cue-induced increase in cocaine craving was strongly enhanced by nicotine, while the increase in anxiety was slightly augmented. Cue-induced skin conductance and temperature responses were unaffected by nicotine. These findings show that cue-induced cocaine craving is enhanced by nicotine. This occurred in the absence of any tobacco smoking-related cues, suggesting that nicotine may have direct psychopharmacological effects on conditioned cocaine craving.     

Genetic predictors of cue- and stress-induced cigarette craving: an exploratory study

Cigarette cravings in response to environmental cues and stressors are widely recognized as important predictors of smoking cessation outcomes. Accumulating evidence suggests that genetics plays a role in these craving responses, as well as in smoking cessation more generally. Previous studies of genetic polymorphisms have been limited by examination of single candidate genes and the use of broadly defined phenotypes (e.g., smoking history). In addition, research examining the similarities and differences between cue- and stress-induced cravings has been limited, although some evidence has suggested that they may have common genetic underpinnings. In the current study, we examined associations between a panel of 1,350 candidate genetic polymorphisms and craving responses to laboratory smoking cues and stressors. We hypothesized that common genetic polymorphisms would be predictive of both cue- and stress-induced craving. Nicotine-dependent smokers (n = 210) donated a blood sample, were exposed to neutral, smoking-related, and stress-related stimuli, and completed craving questionnaires immediately prior to and following each stimulus. Findings indicated that craving responses to smoking cues and stressors were moderately correlated (r = .44). However, genetic analysis revealed that cue and stress-induced cigarette craving were predicted by different polymorphisms, such that variants in the glycine and dopamine pathways were predictive of cue-induced craving, whereas variants in the stress-corticotropin pathway predicted stress-induced craving. Conclusions: Study results provide no support for the hypothesis that cue- and stress-induced craving have the same genetic predictors.     

Severity of nicotine dependence modulates cue-induced brain activity in regions involved in motor preparation and imagery

Rationale

In nicotine-dependent subjects, cues related to smoking elicit activity in brain regions linked to attention, memory, emotion and motivation. Cue-induced brain activation is associated with self-reported craving but further correlates are widely unknown.

Objectives

This study was conducted to investigate whether brain activity elicited by smoking cues increases with severity of nicotine dependence and intensity of cue-elicited craving.

Methods

Ten healthy male smokers whose degree of nicotine dependence ranged from absent to severe were investigated. Visual smoking cues and neutral stimuli were presented in a block design during functional magnetic resonance imaging (fMRI). Using multiple linear regression analysis, the blood oxygen level dependent (BOLD) response to smoking cues was correlated with severity of nicotine dependence assessed with the Fagerström Test of Nicotine Dependence (FTND) and with cue-induced craving.

Results

Significant positive correlations between the BOLD activity and FTND scores were found in brain areas related to visuospatial attention (anterior cingulate cortex, parietal cortex, parahippocampal gyrus and cuneus) and in regions involved in motor preparation and imagery (primary and premotor cortex, supplementary motor area). Intensity of cue-induced craving was significantly associated with greater BOLD activation in mesocorticolimbic areas engaged in incentive motivation and in brain regions related to episodic memory.

Conclusions

Our study suggests that severity of nicotine dependence and intensity of craving are independently associated with cue-induced brain activation in separate neuronal networks. The observed association between severity of dependence and brain activity in regions involved in allocation of attention, motor preparation and imagery might reflect preparation of automated drug taking behavior thereby facilitating cue-induced relapse.     

Smoking-related videos for use in cue-induced craving paradigms

Environmental cues (e.g., the sight of a cigarette) have long been recognized as important triggers for craving in smokers. Available imaging technologies (e.g., fMRI) allow investigation of the neural mechanisms for cue-induced craving, but there stands a need for a cue-delivery system compatible with an MRI environment. We developed a standardized set of 24 high-resolution videos, 12 containing cigarette smoking scenes (e.g., lighting up), and 12 containing neutral scenes (e.g., reading a book), each 30 s long, with comparable lighting, visual complexity, and background filmed by a professional cinematographer. Study participants were 20 smokers (mean age=37.7 years, 50% female). Each was exposed to the 24 videos in a random order under laboratory conditions. Dependent measures included heart rate, blood pressure, skin conductance, skin temperature, and self-reported craving (0-100) following each video. Overall findings indicated that smokers had greater reactivity to the smoking videos than to neutral videos (p<.01). Follow-up univariate analyses revealed significant cue effects on self-reported craving, galvanic skin response, and skin temperature. Interestingly, exploratory examination of gender revealed that men had higher blood pressure and skin temperature responses than women, and that women had higher responses when viewing videos of women smoking than when viewing men smoking. Results support this set of videos as an effective tool for investigation of cue-elicited craving, and raise the possibility of unique gender effects in cue reactivity.     

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

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.     

Verbal and nonverbal abstracting--problem-solving abilities and familial alcoholism in female alcoholics

Women alcoholics (N = 54) had significantly worse performance on clusters of verbal and nonverbal abstracting - problem-solving tasks than peer nonalcoholic controls (N = 48). On the nonverbal cluster, alcoholic women with an alcoholic parent or sibling (FH+) performed significantly poorer than peer alcoholics without such a family history (FH-) and nonalcoholic FH+ and FH- groups. On the verbal cluster, FH+ alcoholics performed significantly worse than the nonalcoholic groups. FH- alcoholics did not differ significantly from the nonalcoholic groups on either of the clusters. There were no differences between FH+ and FH- nonalcoholics on the two types of tasks. The results suggest that female alcoholics have a generalized deficit on cognitive tasks involving abstracting and problem-solving, and that these deficits tend to be more pronounced in alcoholic women with a positive family history of alcohol abuse. Whether these deficits are due to a premorbid lowering of abstracting - problem-solving abilities in the FH+ individuals who subsequently become alcoholics, or are the result of a selective vulnerability of these cognitive processes to the effects of alcohol abuse in such subjects, or some combination of these factors, remains to be investigated.     

Effects of d-amphetamine and smoking abstinence on cue-induced cigarette craving

In this study, the authors investigated the effects of the indirect dopamine agonist d-amphetamine (AMPH) on cue-induced cigarette craving in smokers. Abstinent or nonabstinent cigarette smokers (N=21) rated their cravings for cigarettes and for food (control) after pretreatment with AMPH (15 mg) or placebo and before and after viewing blocks of smoking-related, food-related, and neutral pictures. Before the cues were presented, AMPH increased cigarette craving and decreased food craving. Smoking and food cues increased craving for cigarettes and for food, respectively. AMPH also further increased cigarette craving (and decreased food craving) after cue presentation, but it did so regardless of cue type (food or smoking). Smoking abstinence markedly increased craving regardless of cue presentation or drug condition. These results suggest that both AMPH and smoking abstinence can increase cigarette craving, but they do not appear to specifically affect responses to conditioned smoking-related cues.     

Comparison of nicotine oral soluble film and nicotine lozenge on efficacy in relief of smoking cue-provoked acute craving after a single dose of treatment in low dependence smokers

Rationale

Pilot study results suggested that a new form of nicotine oral soluble film relieved smoking cue-provoked acute craving faster than nicotine lozenge or gum. The new nicotine film may provide smokers another choice to relieve acute craving.

Objectives

This study compared the efficacy of the 2.5 mg nicotine oral soluble film to 2 mg nicotine lozenge for acute relief of smoking cue-provoked craving.

Methods

A randomized, open label, active comparator controlled, parallel group study was conducted with 322 smokers enrolled. After 4 h of abstinence from smoking, eligible subjects were exposed to smoking cues as provocation. Immediately after the post-provocation baseline craving assessment using a 0–100 mm visual analogue scale (VAS), subjects took a randomized single dose of either the 2.5 mg nicotine film or the 2 mg nicotine lozenge. Craving assessments were completed at 50 s, 3 min, 5 min, 7 min, 15 min, 20 min, 25 min and 30 min after drug administration.

Results

Both treatments reduced cue-induced craving and had similar maximum effects on craving relief. However, the 2.5 mg nicotine film relieved cue-induced craving to a greater degree than the 2 mg nicotine lozenge at 50 s (mean difference: ?4.9, p?=?0.014), 3 min (mean difference: ?6.7, p?=?0.011), and 5 min (mean difference: ?5.6, p?=?0.049) post-treatment.

Conclusions

The study confirmed the results from the pilot study. The 2.5 mg nicotine film relieved cue-provoked craving much quicker than the 2 mg nicotine lozenge while both having similar maximum effects. Nicotine film could be useful to provide quick craving relief for low dependence smokers.     

Laboratory-based,cue-elicited craving and cue reactivity as predictors of naturally occurring smoking behavior

Cigarette craving, one hallmark sign of nicotine dependence, is often measured in laboratory settings using cue reactivity methods. How lab measures of cue reactivity relate to real world smoking behavior is unclear, particularly among non-treatment seeking smokers. Within a larger study of hormonal effects on cue reactivity (N = 78), we examined the predictive relationship of cue reactivity to smoking, each measured in several ways. Results indicated that cue-evoked craving in response to stressful imagery, and to a lesser extent, in vivo smoking cues, significantly predicted smoking behavior during the week following testing. However, this predictive relationship was absent upon controlling for reactivity to neutral cues. Nicotine dependence may moderate the relationship between cue reactivity and actual smoking, such that this predictive relationship is less robust among highly dependent smokers than among smokers low in nicotine dependence. The question of whether cue-elicited craving predicts smoking among smokers not in treatment is best answered with a qualified yes, depending on how craving is manipulated and measured. Our findings highlight important methodological and theoretical considerations for cue reactivity research.     

Guanfacine effects on stress, drug craving and prefrontal activation in cocaine dependent individuals: preliminary findings

Cocaine dependence is associated with increased stress and drug cue-induced craving and physiological arousal but decreased prefrontal activity to emotional and cognitive challenge. As these changes are associated with relapse risk, we investigated the effects of α2 receptor agonist guanfacine on these processes. Twenty-nine early abstinent treatment-seeking cocaine dependent individuals were randomly assigned to either daily placebo or guanfacine (up to 3 mg) for four weeks. In a laboratory experiment, all patients were exposed to three 10-min guided imagery conditions (stress/stress, drug cue/drug cue, stress/drug cue), one per day, consecutively in a random, counterbalanced order. Subjective craving, anxiety and arousal as well as cardiovascular output were assessed repeatedly. Brain response to stress, drug cue and relaxing imagery was also assessed during a functional magnetic resonance (fMRI) imaging session. In the current study, guanfacine was found to be safe and well-tolerated. Lower basal heart rate and blood pressure was observed in the guanfacine versus placebo group. Guanfacine lowered stress and cue-induced nicotine craving and cue-induced cocaine craving, anxiety and arousal. The guanfacine group also showed increased medial and lateral prefrontal activity following stress and drug cue exposure compared with placebo. Data suggest further exploration of guanfacine is warranted in terms of its potential for reducing stress-induced and cue-induced drug craving and arousal.     

Effect of impulsivity on cardiovascular and subjective reactivity to smoking cues

Individuals with high levels of impulsivity are more likely to smoke and may have greater difficulty quitting than other smokers. Although the specific mechanisms mediating this relationship are not explicitly known, one candidate is disproportionate cigarette craving in response to environmental smoking cues. We assessed the effect of impulsivity on three measures of cue reactivity. Regular smokers (n=75) were exposed to a smoking cue and a neutral cue in 2 counterbalanced experimental sessions. Cigarette craving, heart rate (HR), and mean arterial pressure (MAP) were used to index cue reactivity. More impulsive smokers exhibited a disproportionate response to the smoking cue in terms of MAP (p=.009) but not HR or craving. Impulsive smokers may experience disproportionate cigarette craving in response to environmental smoking cues that are not reflected in self-report measures due to a relative lack of conscious awareness of the urge to smoke.     

Sex Differences in Guanfacine Effects on Drug Craving and Stress Arousal in Cocaine-Dependent Individuals

Currently, no FDA-approved medication exists for the treatment of cocaine use disorder. Furthermore, as women become increasingly more at risk for the consequences of cocaine addiction, the need to establish better-tailored treatment medications is paramount. We examine the effects of the alpha2 adrenergic agonist, guanfacine HCl, on responses to stress and drug cue in a group of cocaine-dependent men and women who also abuse alcohol and nicotine. Forty early abstinent treatment-seeking cocaine-dependent males and females were randomly assigned to receive either daily placebo (12 M/7 F) or guanfacine (2 or 3 mg) (15 M/6 F) for 3 weeks. In week 4, they participated in a laboratory experiment and were exposed to three 10-min guided imagery conditions (stress/stress, cue/cue, and stress/cue), one per day, consecutively in a random, counterbalanced order. Craving, negative emotion, anxiety, and cardiovascular function were assessed at baseline, immediately following imagery exposure, and at various recovery time points. Guanfacine significantly attenuated cocaine craving, alcohol craving, anxiety, and negative emotion following exposure to all three imagery conditions in females, but not males. Guanfacine did, however, reduce sympathetic tone as well as stress and cue-induced nicotine craving and systolic blood pressure (SBP) in both males and females. These findings highlight sex-specific effects of guanfacine on drug craving, anxiety, and negative mood with significant effects in women and not men. The findings suggest further evaluation of guanfacine in the treatment of cocaine use disorder with a specific focus on sex differences in treatment response.