Chronic alcohol abuse is associated with changes in stress and reward pathways that could alter vulnerability to emotional stress and alcohol craving. This study examines whether chronic alcohol abuse is associated with altered stress and alcohol craving responses. Treatment-engaged, 28-day abstinent alcohol-dependent individuals (ADs; 6F/22M), and social drinkers (SDs; 10F/18M) were exposed to a brief guided imagery of a personalized stressful, alcohol-related and neutral-relaxing situation, one imagery condition per session, presented in random order across 3 days. Alcohol craving, anxiety and emotion ratings, behavioral distress responses, heart rate, blood pressure, and salivary cortisol measures were assessed. Alcohol patients showed significantly elevated basal heart rate and salivary cortisol levels. Stress and alcohol cue exposure each produced a significantly enhanced and persistent craving state in alcohol patients that was marked by increased anxiety, negative emotion, systolic blood pressure responses, and, in the case of alcohol cue, behavioral distress responses, as compared to SDs. Blunted stress-induced cortisol responses were observed in the AD compared to the SD group. These data are the first to document that stress and cue exposure induce a persistent negative emotion-related alcohol craving state in abstinent alcoholics accompanied by dysregulated HPA and physiological arousal responses. As laboratory models of stress and negative mood-induced alcohol craving are predictive of relapse outcomes, one implication of the current data is that treatments targeting decreases in stress and alcohol cue-induced craving and regulation of stress responses could be of benefit in improving alcohol relapse outcomes.

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.

Background Stress, alcohol cues and dysregulated stress responses increase alcohol craving and relapse susceptibility, but few pharmacologic agents are known to decrease stress and cue-induced alcohol craving and associated stress dysregulation in humans. Here we report findings from a preliminary efficacy study of the alpha1 receptor antagonist, prazosin, in modulating these relapse-relevant factors in alcohol dependent (AD) individuals. Methods Seventeen early abstinent, treatment-seeking alcohol dependent individuals (12 Males /5 Females) were randomly assigned to receive either placebo or 16 mg daily prazosin in a double-blind, placebo controlled manner over four weeks. During week 4, all patients participated in a 3-day laboratory experiment involving 5-min guided imagery exposure to stress, alcohol cue and neutral-relaxing/control conditions, one exposure per day, on consecutive days in a random, counterbalanced order. Alcohol craving, anxiety and negative emotion, cardiovascular measures, plasma hypothalamic-pituitary-adrenal (HPA; cortisol, ACTH) were assessed repeatedly in each session. Results The prazosin group (n=9) versus the placebo group (n=8) showed significantly lower alcohol craving, anxiety and negative emotion following stress exposure. The placebo group also showed significantly increased stress and cue-induced alcohol craving, anxiety, negative emotion and blood pressure as well as a blunted HPA response relative to the neutral condition, while the prazosin group showed no such increases in craving, anxiety, negative emotion and blood pressure, and no blunted HPA response to stress and alcohol cue exposure. Conclusions Prazosin appears efficacious in decreasing stress- and cue-induced alcohol craving and may normalize the stress dysregulation associated with early recovery from alcoholism. Further research to assess the efficacy of prazosin in reducing alcohol craving and stress-related relapse risk is warranted.

Objectives Cocaine dependence is a chronic stress state. Furthermore, both stress and substance abuse have robust and reciprocal effects on immune system cytokines, which are known to be powerful modulators of mood. We therefore examine basal and provoked changes in peripheral cytokines in cocaine dependent individuals to better understand their role in the negative reinforcing effects of cocaine. Methods Twenty-eight (16 F/12 M) treatment-seeking cocaine dependent individuals and 27 (14 F/13 M) social drinkers were exposed to three 5-min guided imagery conditions (stress, drug cue, relaxing) presented randomly across consecutive days. Measures of salivary cortisol, tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1ra) were collected at baseline and various post-imagery time-points. Results Cocaine abusers demonstrated decreased basal IL-10 compared with social drinkers. They also showed significant elevations in pro-inflammatory TNFα when exposed to stress compared with when they were exposed to relaxing imagery. This was not observed in the social drinkers. Conversely, social drinkers demonstrated increases in the anti-inflammatory markers, IL-10 and IL-1ra, following exposure to cue, which were not seen in the dependent individuals. Conclusions Cocaine dependent individuals demonstrate an elevated inflammatory state both at baseline and following exposure to the stress imagery condition. Cytokines may reflect potentially novel biomarkers in addicted populations for treatment development.

While SA males showed a generalized suppression of HPA, SAM system and cardiovascular markers following both stress and cue, SA women demonstrated a selective sympatho-adrenal suppression to stress only and an enhanced HPA response to both stress and cue. These gender variations are discussed in terms of their potential impact on relapse vulnerability and treatment outcome.

Negative emotional arousal in response to stress and drug cues is known to play a role in the development and continuation of substance use disorders. However, studies have not examined behavioral indicators of such arousal.Objective-The current study examined behavioral and bodily arousal in response to stress and drug cue in individuals with alcohol dependence and cocaine dependence as compared to healthy controls using a new scale.Methods-Fifty-two alcohol dependent (AD group), 45 cocaine dependent (COC group), and 68 healthy controls (HC group) were exposed to individually developed stressful, drug-cue, and neutral-relaxing imagery. Behavioral and bodily responses were assessed with a new scale, the Behavioral Arousal Scale (BAS).Results-The BAS showed acceptable inter-rater reliability and internal consistency and correlated with subjective negative emotion and craving. BAS scores were higher in stress than neutral conditions for all three groups. COC participants showed higher BAS response to stress than AD or HC participants. COC and AD participants showed greater BAS response to drug cue than HC participants.Conclusion-Behavioral arousal is a domain in which stress and drug related arousal is expressed and assessment of this domain could provide unique information about vulnerability to craving and relapse in addicted populations.

Aims Increasing evidence suggests that levels of pro-inflammatory and anti-inflammatory cytokines are dysfunctional in alcohol dependence. Moreover, some initial findings demonstrate that these adaptations in peripheral inflammation may contribute to motivation for alcohol and problem drinking via possible direct effects or the indirect effects of stress responsivity. Importantly, the role of pro-inflammatory and anti-inflammatory cytokines in the progression from healthy to problem drinking is not well understood. The aim of the current study was to assess whether alcohol-related peripheral immune system changes affect stress and alcohol cue-induced craving and anxiety and behavioral alcohol motivation and intake in the laboratory among problem drinkers compared with socially drinking controls. Methods Twenty-six problem drinkers and 38 moderate, social drinkers participated in a laboratory challenge procedure during which they were exposed to 3 personalized 5-minute imagery conditions (stress (S), relaxing (R) and alcohol cue (C), followed by the “alcohol taste test” (ATT) as a measure of implicit alcohol motivation and intake, presented across 3 consecutive days, one per day in a randomized and counterbalanced order. Measures of Tumor Necrosis Factor alpha (TNFα), Interleukin-6 (IL-6), Interleukin-1 receptor antagonist (IL-1ra), alcohol craving and anxiety were assessed at baseline, immediately following imagery exposure and at discreet beer cue presentation in the ATT. Results Compared with moderate drinkers, problem drinkers demonstrated tonic attenuation of IL-6 and IL-1ra. In problem drinkers, these changes also accompanied elevated levels of stress and cue-induced alcohol craving, anxiety, and were predictive of provoked alcohol craving, behavioral alcohol motivation and intake and severity of problem drinking. Conclusions Current findings indicate that selective immunosuppression in problem drinkers may play a key role in motivation for alcohol intake.

Since the emergence of SARS-CoV-2, maintaining healthcare worker (HCW) health and safety has been fundamental to responding to the global pandemic. Vaccination with mRNA-base vaccines targeting SARS-CoV-2 spike protein has emerged as a key strategy in reducing HCW susceptibility to SARS-CoV-2, however, neutralizing antibody responses subside with time and may be influenced by many variables. We sought to understand the dynamics between vaccine products, prior clinical illness from SARS-CoV-2, and incidence of vaccine-associated adverse reactions on antibody decay over time in HCWs at a university medical center. A cohort of 296 HCWs received standard two-dose vaccination with either bnt162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) and were evaluated after two, six, and nine months. Subjects were grouped by antibody decay curve into steep antibody decliners gentle decliners. Vaccination with mRNA-1273 led to more sustained antibody responses compared to bnt162b2. Subjects experiencing vaccine-associated symptoms were more likely to experience a more prolonged neutralizing antibody response. Subjects with clinical SARS-CoV-2 infection prior to vaccination were more likely to experience vaccination-associated symptoms after first vaccination and were more likely to have a more blunted antibody decay. Understanding factors associated with vaccine efficacy may assist clinicians in determining appropriate vaccine strategies in HCWs.