Stress-induced Craving Research Articles

The neurobehavioural effects of cannabidiol in alcohol use disorder: Study protocol for a double-blind, randomised, cross over, placebo-controlled trial

Current treatments for alcohol use disorders (AUD) have limited efficacy. Recently, Cannabidiol (CBD) has been examined in a multitude of clinical settings. Preclinical and clinical results suggest that CBD might be particularly well suited for the treatment of AUD and may reduce alcohol cue and stress-induced craving and alcohol seeking. This study aims to investigate this new pharmacotherapy with a particular focus on neurobiological and physiological indicators of craving. Methods: In this double-blind, within-subject, randomised, placebo-controlled, cross-over study, non-treatment seekers will be randomly allocated to three days of four 200 mg CBD gel capsules (800 mg/day) or placebo, with an 18-day washout period. Cognitive, clinical, and neuroimaging assessments will be completed during these three days. The CBD and placebo assessments will be compared. The primary outcomes are i) BOLD signal as a proxy for regional activity during a cue reactivity and a fear response task measured with functional magnetic resonance imaging (fMRI), ii) heart rate variability and skin conductance levels as a proxy for psychophysiological responses to alcohol stimuli. The secondary outcomes are: i) neurometabolite levels (γ-Aminobutyric acid, ethanol, glutathione, and glutamate + glutamine (combined signal)) using magnetic resonance spectroscopy (MRS); ii) functional connectivity using resting state fMRI (rsfMRI); iii) executive functioning task results; iv) clinical outcomes such as craving, anxiety, and sleep. Discussion: This study will improve the understanding of the mechanisms of action of CBD and provide early signals of efficacy regarding the therapeutic potential of CBD in the treatment of alcohol use disorder.ClinicalTrials.gov Identifier: NCT05387148.

Brain correlates and functional connectivity linking stress, autonomic dysregulation, and alcohol motivation

High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS) disruptions. However, neural mechanisms underlying drinking behaviors associated with stress and ANS disruptions remain unclear. The current study aims to understand neural correlates of stress, ANS disruptions, and subsequent alcohol intake in social drinkers with risky drinking. Using functional magnetic resonance imaging (fMRI), we investigated brain and heart rate (HR) autonomic responses during brief exposure to stress, alcohol, and neutral cues utilizing a well-validated, individualized imagery paradigm in 48 social drinkers of which 26 reported high-risk drinking (HD) while 22 reported low-risk drinking (LD) patterns. Results indicated that HD individuals showed stress and ANS disruptions with increased basal HR, stress-induced craving, and decreased brain response to stress exposure in frontal-striatal regions including the ventromedial prefrontal cortex (VmPFC), anterior cingulate cortex, striatum, insula, and temporal gyrus. Furthermore, whole-brain correlation analysis indicated that greater basal HR was associated with hypoactive VmPFC, but hyperactive medulla oblongata (MOb) responses during stress, with an inverse association between activity in the VmPFC and Mob (whole-brain corrected (WBC), p < 0.05). Functional connectivity with the MOb as a seed to the whole brain indicated that HD versus LD had decreased functional connectivity between the VmPFC and MOb during stress (WBC, p < 0.05). In addition, those with more compromised functional connectivity between the VmPFC and MOb during stress consumed greater amount of alcohol beverage during an experimental alcohol taste test conducted on a separate day, as well as in their self-reported weekly alcohol intake. Together, these results indicate that stress-related, dysfunctional VmPFC control over brain regions of autonomic arousal contributes to greater alcohol motivation and may be a significant risk factor for hazardous alcohol use in non-dependent social drinkers. Findings also suggest that restoring VmPFC integrity in modulating autonomic arousal during stress may be critical for preventing the development of AUD.

The Role of Emotion Dysregulation in Heightened Alcohol Craving Related to Posttraumatic Stress Disorder and Depression Symptoms

Objective: Compared to their male counterparts, women with alcohol use disorders (AUD) alone and those with symptoms of co-occurring emotional disorders (posttraumatic stress disorder, PTSD, and depression) are particularly likely to have increased alcohol craving in response to negative affect and daily stressors. Emotion dysregulation is one transdiagnostic construct that may underlie heightened craving in response to stress within this population. In a secondary data analysis, the current study examined emotion dysregulation as a mediator of the associations of posttraumatic stress symptoms (PTSS) and depression symptoms with heightened stress-induced alcohol craving, as measured in the lab. Given the overlap in symptoms, the relative associations of PTSD and depression symptom clusters with stress-induced craving were explored. Method: 50 women Veterans (84% White, 88% Non-Hispanic, Mage=45.68) attended two in-lab sessions. Self-report measures of emotion dysregulation, PTSD, and depression symptoms were administered at baseline. During session two, participants reported on alcohol craving and negative affect at baseline and again after a personalized stress induction procedure. Results: Emotion dysregulation mediated the association of greater PTSS with heightened stress-induced craving, although emotion dysregulation was not a mediator of the association between depression and stress-induced craving. Greater alcohol craving after the stress induction was positively associated with cognitive-affective symptoms in PTSD and depression (and not with other symptom clusters of these diagnoses, e.g., avoidance, somatic-vegetative symptoms). Conclusions: Emotion dysregulation may be a transdiagnostic factor that helps to explain greater alcohol cravings and drinking in stressful contexts among women Veterans with heightened symptoms of co-occurring emotional disorders.

Progesterone Attenuates the Stress Response in Individuals with Alcohol Dependence and Post-Traumatic Stress Disorder – A Pilot Study

Objective: Evidence from laboratory studies suggests that progesterone may be effective in reducing stress and craving, and may improve cognitive performance in smokers and individuals with cocaine dependence. The objective of this study was to examine if progesterone would attenuate stress-induced craving, anxiety, affect and physiological measures, as well as improve stress-induced cognitive performance (processing speed and selective attention) in individuals diagnosed with alcohol use disorder (AUD) and post traumatic stress disorder (PTSD). Methods: This laboratory study included (n = 13) participants who were diagnosed with current AUD and PTSD who were randomly assigned to recive either progesterone (200mg bid) or placebo in identical looking capsules for 3 days. On the fourth day they completed a laboratory session. In the morning of the test session, they received the last dose of medication and completed the rest of the laboratory procedures. The procedures included presentation in random order of personalized trauma and neutral scripts with relaxation in between. Main outcomes included measure of craving, anxiety, affect and cognitive performance. Results: Consistent with other research, trauma scripts produced significantly greater increases in craving, anxiety and negative affect when compared with neutral scripts. Progesterone significantly reduced stress-induced symptoms of craving, anxiety, fear, anger and sadness but had no effect on positive emotions (joy, relaxation). Progesterone was effective in ameliorating stress-induced decreases in cognitive performance. Conclusions: The findings from this study demonstrate that progesterone can be effective in reducing stress-induced craving, anxiety and negative affect in a laboratory setting in individuals with comorbid AUD and PTSD. Interestingly, progesterone also improved cognitive performance. These findings require replication in a larger clinical trial and may have implications for treatment among individuals with AUD and PTSD. This study was registered as NCT02187224, at www.clinicaltrials.gov

Estrous cycle and hormone regulation of stress-induced reinstatement of reward seeking in female mice

Women are more vulnerable to stress-induced craving, which may be associated with increased vulnerability to relapse. Susceptibility to stress-induced craving also appears to be modulated by the menstrual cycle and is negatively correlated with circulating progesterone levels in women. However, the factors that contribute to relapse vulnerability are poorly characterized in female animals. In this study, we assessed whether chronic ethanol exposure, estrous cycle, or exogenous progesterone administration modulated vulnerability to stress-induced reinstatement. To model ethanol dependence, adult female C57Bl/6J mice underwent chronic intermittent ethanol (CIE) exposure via vapor inhalation. Seventy-two hours after the final ethanol exposure, food-restricted mice began training in a conditioned place preference paradigm (CPP) for a food reward, followed by extinction training. Mice were then subjected to forced swim stress and assessed for reinstatement of their preference for the reward-paired chamber. CIE did not affect stress-induced reinstatement. However, stress-induced reinstatement was attenuated during the diestrus phase, when endogenous levels of progesterone peak in female mice. Further, administration of exogenous progesterone mimicked the attenuated reinstatement observed in diestrus. These findings indicate that circulating hormone levels modulate susceptibility to relapse-like behaviors and implicate progesterone as a potential target for treating stress-induced relapse in women.

The relationship between craving and insular morphometry in regular cocaine users: Does sex matter?

While it has been suggested that cocaine use and relapse in women is more strongly related to stress‐relief craving, whereas cocaine use in men is more strongly related to reward craving, the neural mechanisms that underlie these differences are poorly understood. The aim of this study was to investigate sex‐dependent differences in insular morphometry and associations with craving, in a sample of regular cocaine users (CUs) and non‐drug using controls (non‐CUs). It was hypothesized that insular volume, thickness and surface area would be lower in CU women, compared with CU men and non‐CUs. It was furthermore hypothesized that insular morphometry, particularly insular thickness, would be negatively associated to reward craving in CU men, while being negatively associated with stress‐relief craving in CU women. In contrast to the hypothesis, we did not find evidence of sex‐specific differences in insular morphometry in CUs. However, sex‐specific association between stress‐relief craving and insular morphometry were found: Right insular volume was negatively associated with stress‐relief craving in CU women, whereas this association was positive in CU men. Additionally, right insular surface area was negatively associated with stress‐relief craving in cocaine‐using men, whereas this association was positive in cocaine‐using women. In conclusion, the current study provides first evidence of sex‐specific differences in the association between craving and insular morphometry in a sample of regular cocaine users. Although speculative, these sex‐specific alterations in insular morphometry may underlie higher stress‐induced craving and relapse in CU women compared with CU men.

Alterations of Stress-Related Glucocorticoids and Endocannabinoids in Hair of Chronic Cocaine Users.

BackgroundPrevious research in animals and humans has demonstrated a potential role of stress regulatory systems, such as the hypothalamic-pituitary-adrenal (HPA) axis and the endocannabinoid (eCB) system, in the development of substance use disorders. We thus investigated alterations of HPA and eCB markers in individuals with chronic cocaine use disorder by using an advanced hair analysis technique.MethodsWe compared hair concentrations of glucocorticoids (cortisone, cortisol) and the eCBs 2-arachidonylglycerol, anandamide (AEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA) between 48 recreational cocaine users (RCU), 25 dependent cocaine users (DCU), and 67 stimulant-naïve controls. Self-reported substance use and hair concentrations of substances were also assessed.ResultsSignificantly higher concentrations of hair cortisone were found in RCU and DCU compared with controls. Hair concentrations of OEA and PEA were significantly lower in DCU compared with RCU and controls. Additionally, within cocaine users, elevated cocaine hair concentration was a significant predictor for increased glucocorticoid and decreased OEA hair levels. Moreover, higher 3,4-methyl​enedioxymethamphetamine hair concentration was correlated with elevated cortisone and AEA, OEA, and PEA levels in hair within cocaine users, whereas more self-reported cannabis use was associated with lower eCBs levels in hair across the total sample.ConclusionOur findings support the hypothesis that the HPA axis and eCB system might be important regulators for substance use disorders. The mechanistic understanding of changes in glucocorticoid and eCB levels in future research might be a promising pharmacological target to reduce stress-induced craving and relapse specifically in cocaine use disorder.

Beyond abstinence and relapse II: momentary relationships between stress, craving, and lapse within clusters of patients with similar patterns of drug use.

Given that many patients being treated for opioid-use disorder continue to use drugs, identifying clusters of patients who share similar patterns of use might provide insight into the disorder, the processes that affect it, and ways that treatment can be personalized. We applied hierarchical clustering to identify patterns of opioid and cocaine use in 309 participants being treated with methadone or buprenorphine (in a buprenorphine-naloxone formulation) for up to 16 weeks. A smartphone app was used to assess stress and craving at three random times per day over the course of the study. Five basic patterns of use were identified: frequent opioid use, frequent cocaine use, frequent dual use (opioids and cocaine), sporadic use, and infrequent use. These patterns were differentially associated with medication (methadone vs. buprenorphine), race, age, drug-use history, drug-related problems prior to the study, stress-coping strategies, specific triggers of use events, and levels of cue exposure, craving, and negative mood. Craving tended to increase before use in all except those who used sporadically. Craving was sharply higher during the 90 min following moderate-to-severe stress in those with frequent use, but only moderately higher in those with infrequent or sporadic use. People who share similar patterns of drug-use during treatment also tend to share similarities with respect to psychological processes that surround instances of use, such as stress-induced craving. Cluster analysis combined with smartphone-based experience sampling provides an effective strategy for studying how drug use is related to personal and environmental factors.

Addiction as a Coping Response: Hyperkatifeia, Deaths of Despair, and COVID-19.

Addiction as a Coping Response: Hyperkatifeia, Deaths of Despair, and COVID-19.

Effects of Prazosin on Provoked Alcohol Craving and Autonomic and Neuroendocrine Response to Stress in Alcohol Use Disorder.

Chronic alcohol use results in changes to stress biology and autonomic arousal contributing to acute alcohol withdrawal symptoms, neuroendocrine tolerance of the hypothalamic-pituitary-adrenal axis responses, high stress-induced craving, and risk of alcohol relapse. Thus, stress coping and recovery from alcohol during early abstinence may be jeopardized by such stress system dysfunction. Significant preclinical evidence suggests that noradrenergic disruption may contribute to these alcohol-related stress arousal changes and that alpha-1 adrenergic antagonists, such as prazosin, may normalize these stress system adaptations and reduce alcohol intake. Thus, we hypothesized that prazosin would reduce stress-induced craving and improve neuroendocrine and autonomic response to stress and alcohol cue exposure during early abstinence. We secondarily also assessed the role of lifetime anxiety disorders on these prazosin effects. Forty inpatient treatment-seeking alcohol-dependent individuals were randomly assigned to receive placebo (n=18) or 16mg/d, T.I.D., prazosin (n=22) in a double-blind manner, titrated over 2weeks. In weeks 3 to 4 after achieving full dose, patients were exposed to 3 5-minute personalized guided imagery conditions (stress cue, alcohol cue, neutral/relaxing cue), on 3 consecutive days in a random, counterbalanced order. Alcohol craving, anxiety, heart rate, cortisol, and adrenocorticotropic hormone (ACTH) levels were assessed at baseline, following imagery and at repeated recovery timepoints. Prazosin reduced stress cue-induced alcohol craving (p<0.05) and stress- and alcohol cue-induced anxiety (p<0.05) and increased heart rate responses in all imagery conditions (p<0.05). Prazosin lowered basal cortisol and ACTH (p's<0.05) and attenuated stress cue-induced rises in cortisol (p<0.05) versus placebo. Finally, in those without lifetime anxiety disorder, the placebo group showed stress- and alcohol cue-induced increases in cortisol (p's<0.05), while the prazosin group did not. Prazosin may attenuate stress cue-induced alcohol craving and anxiety during early abstinence while improving adrenergic and stress system function, effects which are independent of a history of lifetime anxiety disorders.

Abstract C021: Affective mechanisms of stress-induced cigarette craving: Considerations of sex and ethnicity

Abstract Cigarette smoking continues to be the number one modifiable risk factor for the development of cancer. Among the major impediments to successful smoking cessation are strong cravings to smoke, especially during times of heightened stress. Affective responses to stress (e.g., acute anxious and depressed mood) may serve as important mediators of cigarette cravings that are amenable to intervention. Experimental models have been developed to induce cravings reliably during stress under laboratory conditions, permitting a closer examination of possible changes in affect that may be driving cigarette cravings. The possibility that specific types of affect may be responsible for cigarette cravings, however, has not been investigated. Another key limitation of the extant research is its reliance on samples of predominantly male Caucasian smokers. Although several recent studies suggest possible sex- and ethnicity-based differences in affective responses to acute stress, no studies have explored how such differences may contribute to cigarette cravings. To that end, we conducted an experimental study in which an ethnically diverse sample of healthy volunteer female (n=163) and male (n=139) nicotine-dependent smokers were exposed to a mild stressor (guided imagery of painful dental work). We assessed positive affect (happy, relaxed, energized), negative affect (anxious, depressed, emotionally upset), and cigarette craving immediately before and after the imaginal dental stressor. Mean age of the sample was 38.6 (+ 10.2). Participants reported smoking an average of 19.5 (+ 9.8) cigarettes per day for an average of 18.9 (+ 10.0) years. Path analyses revealed that the acute stressor induced significant increases in negative affect and decreases in positive affect (p's &amp;lt; 0.0001). In turn, increases in anxious, but not depressed mood, mediated effects of the stressor on cigarette craving. Bootstrapped confidence intervals indicated that indirect mediated effects were significant at the 0.05 level. Interestingly, effects were particularly pronounced in women (85% of total effect for women vs. 65% of total effect for men). Among Hispanic (n=81) smokers, elevations in depressed mood mediated increases in cigarette craving (p &amp;lt;0.05), unlike among African American (n=138) and Caucasian (n=62) smokers. Results highlight the importance of considering sex and ethnicity when developing interventions to manage stress-induced cigarette cravings among smokers attempting to quit. Citation Format: Joel Erblich, Guy H. Montgomery, Julie B. Schnur, Camille Ragin. Affective mechanisms of stress-induced cigarette craving: Considerations of sex and ethnicity [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C021.

α2A-adrenergic heteroreceptors are required for stress-induced reinstatement of cocaine conditioned place preference.

The α2a-adrenergic receptor (α2a-AR) agonist guanfacine has been investigated as a potential treatment for substance use disorders. While decreasing stress-induced reinstatement of cocaine seeking in animal models and stress-induced craving in human studies, guanfacine has not been reported to decrease relapse rates. Although guanfacine engages α2a-AR autoreceptors, it also activates excitatory Gi-coupled heteroreceptors in the bed nucleus of the stria terminalis (BNST), a key brain region in driving stress-induced relapse. Thus, BNST α2a-AR heteroreceptor signaling might decrease the beneficial efficacy of guanfacine. We aimed to determine the role of α2a-AR heteroreceptors and BNST Gi-GPCR signaling in stress-induced reinstatement of cocaine conditioned place preference (CPP) and the effects of low dose guanfacine on BNST activity and stress-induced reinstatement. We used a genetic deletion strategy and the cocaine CPP procedure to first define the contributions of α2a-AR heteroreceptors to stress-induced reinstatement. Next, we mimicked BNST Gi-coupled α2a-AR heteroreceptor signaling using a Gi-coupled designer receptor exclusively activated by designer drug (Gi-DREADD) approach. Finally, we evaluated the effects of low-dose guanfacine on BNST cFOS immunoreactivity and stress-induced reinstatement. We show that α2a-AR heteroreceptor deletion disrupts stress-induced reinstatement and that BNST Gi-DREADD activation is sufficient to induce reinstatement. Importantly, we found that low-dose guanfacine does not increase BNST activity, but prevents stress-induced reinstatement. Our findings demonstrate a role for α2a-AR heteroreceptors and BNST Gi-GPCR signaling in stress-induced reinstatement of cocaine CPP and provide insight into the impact of dose on the efficacy of guanfacine as a treatment for stress-induced relapse of cocaine use.

Trauma- and Stress-Induced Craving for Alcohol in Individuals Without PTSD.

The main objective of the study was to compare the differences in craving following trauma and stress scripts in individuals with alcohol dependence (AD) who have experienced trauma but did not meet criteria for post-traumatic stress disorder (PTSD). Twenty-eight men and women who participated in a treatment trial were included in this study before starting treatment. All had to meet criteria for AD and had experienced trauma at some point of their lives but were never diagnosed with PTSD. All participants had one laboratory session and were exposed to stress, trauma and neutral scripts randomly assigned. Main measures of craving, anxiety and mood were administered before, during and after each script. Stress and trauma scripts induced significantly more craving and anxiety than the neutral scripts. Interestingly, stress scripts produced stronger craving and anxiety than the trauma scripts but only with some measures. Stress and trauma scripts produced significantly more fear, anger and sadness and significantly lower ratings of joy and relaxation than the neutral script. Again, there were no differences between stress and trauma scripts for any of the emotional subscales. Trauma scripts did not result in stronger craving than stress scripts. These findings suggest that trauma in the absence of PTSD diagnosis does not lead to stronger craving for alcohol.

Effect of Allopregnanolone on Stress-induced Craving

Effect of Allopregnanolone on Stress-induced Craving

Effects of smoking and paroxetine on stress-induced craving and withdrawal symptoms

ABSTRACTBackground: When smokers relapse, many cite stressful circumstances as the cause. Most smoking cessation medications do not prevent stress-induced increases in craving and withdrawal symptom severity; however, the effect of smoking prior to stress exposure on symptom severity is unclear.Methods: We examined how smoking a cigarette immediately prior to a stressful task affects craving and withdrawal symptom severity by analyzing data from a double-blind, crossover study assessing paroxetine’s effects on the physiological response to the combination of stress and smoking. Measures were obtained prior to and following smoking/stress exposure and following a subsequent 30-min period at two laboratory sessions (i.e., after 1 month each of paroxetine and placebo).Results: Among study completers (n = 63), severity of craving decreased from the beginning of the session to immediately following the smoking/stress exposure (p < 0.01) and severity of smoking urges decreased from the beginning to the end of the laboratory session (p < 0.001). Withdrawal symptoms were less severe while taking paroxetine vs. placebo (p < 0.05) but no treatment × time effects were observed.Conclusions: Additional research is needed to identify interventions that could similarly decrease stress-induced craving in order to determine if smoking cessation rates can be increased.

Income as a moderator of psychological stress and nicotine dependence among adult smokers

BackgroundPerceived stress and psychological distress are associated with more cigarette craving and withdrawal, higher nicotine dependence, and less success during quit attempts. Low income smokers have disproportionately higher rates of smoking and may be particularly vulnerable to the effects of stress on smoking dependence. The aim of the current study was to assess if lower income smokers have a stronger association between stress and nicotine dependence than higher income smokers. MethodsData were obtained from the Pennsylvania Adult Smoking Study, which included 351 daily smokers. Subjects completed PhenX Toolkit and other self-report measures of socioeconomic factors, the 10-item Perceived Stress Scale, Kessler Psychological Distress Scale (K6), Fagerstrom Test for Nicotine Dependence (FTND), and the Hooked on Nicotine Checklist (HONC). Moderation analyses using linear regression examined income-related differences in the association between stress and nicotine dependence. ResultsIncome groups were categorized by an annual household income of $50,000 based on visual-inspection of scatter plots of income by nicotine dependence. Compared to higher income smokers, lower income smokers had significantly higher mean levels of nicotine dependence on the FTND [3.74 vs. 4.79, p < 0.001], perceived stress [15.63 vs. 17.95, p = 0.004], and psychological distress [5.30 vs. 6.86, p = 0.001], respectively. There were interaction effects, such that lower income smokers had a strong, positive associations between FTND and perceived stress (B = −0.11, CI = −0.17 to −0.04, p = 0.002) and psychological distress (B = −0.13, CI = −0.25 to −0.02, p = 0.022) whereas no association was found in higher income smokers. No significant moderation effects were found for the HONC or when income groups were categorized by U.S. federal poverty level. ConclusionsThe results highlight that the relationship between increasing stress and FTND was found in lower but not higher income groups. Future research should examine socioeconomic, environmental and psychosocial factors that may facilitate increased smoking during stress-induced craving.

Trauma‐ and Stress‐Induced Response in Veterans with Alcohol Dependence and Comorbid Post‐Traumatic Stress Disorder

Alcohol dependence (AD) and post-traumatic stress disorder (PTSD) commonly co-occur, and the co-occurrence is associated with worse prognosis than either disorder absent the other. Craving is an important construct related to relapse, but the relationship between PTSD symptoms, craving, and relapse is not well understood. Several studies have documented the relationship between stress and craving in individuals without comorbid PTSD, but the effect on those with comorbid PTSD is not well known. A small literature suggests that trauma imagery affects craving. This is the first study to explore the effects of trauma-induced and stress-induced scripts on alcohol craving, affect, cardiovascular, and cortisol responses in the laboratory. Veterans (n=25) diagnosed with AD and PTSD who were participating in a randomized clinical treatment trial took part in this laboratory study. Baseline assessment included PTSD symptoms and drinking quantity and frequency over 3months before study initiation. In the laboratory, participants were exposed to neutral, stressful, and trauma scripts randomly assigned. Main outcomes included craving, anxiety, mood states, salivary cortisol, and cardiovascular responses. Both stress and trauma scripts produced greater increases in craving, negative affect, and cardiovascular reactivity, compared to neutral scripts. Trauma scripts produced significantly stronger craving for alcohol and greater cardiovascular reactivity than stress scripts. Also, trauma-induced but not stress-induced craving was positively correlated with baseline levels of drinking. There were no changes in cortisol levels from pre- to postexposure of any scripts. The results highlight that trauma cues are more salient in inducing alcohol craving than stress cues and higher reactivity is related to more baseline drinking. This finding is consistent with clinical observations that show an association between PTSD symptoms and alcohol relapse. It also underscores the importance of adequate treatment of PTSD as reactivity related to trauma cues and reminders may be an important factor in craving and relapse.

Changes in Stress Reactivity among Stimulant Dependent Adults After Treatment with Mindfulness Based Relapse Prevention: Results from a Pilot Randomized Clinical Trial

Background: In light of recent evidence suggesting the presence of stress processing deficits in stimulant users, coupled with laboratory studies demonstrating an association between stress reactivity and relapse to stimulant use, interventions that target stress-induced craving and stress reactivity may reduce relapse risk in this population. Objective: This study examines changes in stress reactivity among adults with stimulant use disorders (N=22) in response to an 8 week Mindfulness Based Relapse Prevention (MBRP) intervention. Methods: Study participants were enrolled in a in a pilot randomized clinical trial, evaluating the efficacy of MBRP, relative to a health education control condition (HE). At baseline and treatment-end, biological and subjective responses to a laboratory psychosocial stress task (i.e., the Trier Social Stress Task) were measured. Results: MBRP participants evidenced significantly lower levels of salivary cortisol in response to the posttreatment laboratory stress provocation, relative to those in the HE condition. Likewise, HE participants evidenced disproportionately greater increases in subjective stress, anxiety and stimulant cravings in response to the posttreatment stress provocation, relative to those who received MBRP. Conclusion: Results of this pilot investigation suggest that MBRP effectively attenuates stress reactivity among adults with stimulant use disorders. This approach may have utility as an adjunct to comprehensive programs treating stimulant addiction. Future research evaluating the impact of changes in stress reactivity on post-treatment relapse to stimulant use and the long-term effects of MBRP on stress reactivity is warranted.

Effects of stress and dietary tryptophan enhancement on craving for alcohol in binge and non-binge heavy drinkers.

Stress is known to play an important role in alcohol abuse, whereas binge drinking may increase individuals' susceptibility to the development of alcohol dependence. We set out to investigate whether binge drinkers (BDs) or non-BDs (NBDs) are at a greater risk of an increase in their desire for alcohol following experimental stress induction (modified Trier Social Stress Test; Experiment 1) and to explore the biological mechanisms underlying such an effect (Experiment 2). Preclinical evidence suggests that serotonin may mediate stress-induced reinstatement of alcohol intake. We therefore tested whether dietary tryptophan (TRP) enhancement would modulate stress-induced desire for alcohol and whether it would affect the two populations (BD/NBD) differently. In Experiment 1 (14 NBDs, 10 BDs; mean weekly alcohol intake 50.64 U), stress induction selectively increased strong desire for alcohol compared with the nonstressful condition in BDs. Throughout the experiment, BDs reported greater negative reinforcement type of craving than NBDs, but also a higher expectancy of alcohol-induced negative effects. In Experiment 2, 41 participants (22 NBDs, 19 BDs; mean alcohol intake 38.81 U) were given either the TRP-rich (TRP+; 9 BDs, 11 NBD) or the control (CTR; 10 BD, 11 NBD) diet before undergoing stress induction. In BDs, the TRP+ diet prevented the stress-induced increase in strong desire that was observed in individuals receiving the CTR diet. In NBDs, the TRP+ diet appeared to facilitate an increase in strong desire. These findings suggest that BDs may indeed be at a greater risk than NBDs of an increase in their craving for alcohol when stressed. Furthermore, whereas enhancement of 5-hydroxytryptamine function may moderate the impact of stress on craving in BDs, it seems to facilitate stress-induced craving in NBDs, suggesting that the serotonergic system may be differentially involved depending on individual binge drinking status.

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

BackgroundCigarette 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. MethodsTo that end, non-treatment-seeking nicotine dependent smokers (n=96, mean age=41.1, 47% African American, 17% Caucasian, 22% Hispanic, 19.3cigs/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. ResultsNot 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). ConclusionsFindings 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.