A stress-coping profile of opioid dependent individuals entering naltrexone treatment: a comparison with healthy controls.

BACKGROUND: Stress is known to increase addiction vulnerability and risk of relapse to substance use. PURPOSE & METHOD: We compared opioid dependent individuals entering naltrexone treatment (n = 57) with healthy controls (n = 75) on measures of stress, coping, and social support and examined the relative contribution of group membership, coping, and social support to stress within the sample. Analyses of variance (ANOVA) and covariance (ANCOVA), and stepwise multiple regression were conducted. RESULTS: Compared with controls, opioid dependent subjects reported greater stress, less use of adaptive coping, but comparable use of maladaptive/avoidant coping. No group differences were found with respect to social support. Perceived stress was predicted by group membership, low social support, and greater use of maladaptive/avoidant coping, and the prediction by social support and maladaptive/avoidant coping did not differ by group. CONCLUSION: Opioid dependent individuals entering naltrexone treatment experience higher levels of stress and report less use of adaptive coping strategies when compared with controls. Group membership, maladaptive/avoidant coping, and social support independently contribute to perceived stress. Findings suggest that novel treatment approaches that decrease maladaptive/avoidant coping and improve social support are important aspects of decreasing stress during early recovery from opioid addiction.

Sex-specific dissociations in autonomic and HPA responses to stress and cues in alcohol-dependent patients with cocaine abuse.

AIMS: Chronic alcohol and drug dependence leads to neuroadaptations in hypothalamic-pituitary-adrenal (HPA) and sympathetic adrenal medullary (SAM) stress systems, which impact response sensitivity to stress and alcohol cue and facilitates risk of relapse. To date, gender variations in these systems have not been fully assessed in abstinent alcohol-dependent individuals who also met criteria for cocaine abuse. METHODS: Forty-two (21 M/21 F) early abstinent treatment-seeking substance-abusing (SA) men and women and 42 (21 M/21 F) healthy control (HC) volunteers were exposed to three 5-min guided imagery conditions (stress, alcohol/drug cue, neutral relaxing), presented randomly, one per day across three consecutive days. Alcohol craving and anxiety ratings were obtained as well as measures of heart rate (HR), blood pressure, plasma ACTH, cortisol, norepinephrine (NE) and epinephrine (EPI). RESULTS: SA males showed increased ACTH and EPI basal tone compared with HC males and SA females. However, they demonstrated no increase in ACTH and cortisol levels following stress and alcohol cue imagery exposure compared to the neutral condition. SA females demonstrated a typically increased stress response in both measures. In addition, SA males showed no increase in cardiovascular response to either stress or cue, and no increase in catecholamine response to cue compared with their response to neutral imagery. Again, this dampening was not observed in HC males who produced significantly higher levels of cue-related HR and EPI, and significantly higher stress-related DBP. In contrast, SA females showed an enhanced ACTH and cortisol response to stress and cue compared with neutral imagery and this was not observed in the HC females. They also demonstrated a reduced increase in NE and EPI compared with both SA males and HC females as well as reduced HR compared with HC females. CONCLUSIONS: 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.

An endocannabinoid signal associated with desire for alcohol is suppressed in recently abstinent alcoholics.

BACKGROUND: Alcoholics report persistent alcohol craving that is heightened by cognitive cues, stressful situations, and abstinence. The role of endogenous cannabinoids in human alcohol craving--though long suspected--remains elusive. MATERIALS AND METHODS: We employed laboratory exposure to stress, alcohol cue, and neutral relaxed situations through guided imagery procedures to evoke alcohol desire and craving in healthy social drinkers (n = 11) and in treatment-engaged, recently abstinent alcoholic subjects (n = 12) and assessed alcohol craving, heart rate, and changes in circulating endocannabinoid levels. Subjective anxiety was also measured as a manipulation check for the procedures. RESULTS: In healthy social drinkers, alcohol cue imagery increased circulating levels of the endocannabinoid anandamide, whereas neutral and stress-related imagery had no such effect. Notably, baseline and response anandamide levels in these subjects were negatively and positively correlated with self-reported alcohol craving scores, respectively. Cue-induced increases in heart rate were also correlated with anandamide responses. By contrast, no imagery-induced anandamide mobilization was observed in alcoholics, whose baseline anandamide levels were markedly reduced compared to healthy drinkers and were uncorrelated to either alcohol craving or heart rate. CONCLUSIONS: The results suggest that plasma anandamide levels provide a marker of the desire for alcohol in social drinkers, which is suppressed in recently abstinent alcoholics.

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.

Stress and drug-cue-induced craving in opioid-dependent individuals in naltrexone treatment.

BACKGROUND: Naltrexone is a nonaddictive medication that blocks the euphoric effects of opioids. However, naltrexone treatment is associated with high rates of noncompliance and opioid relapse, possibly because it does not reduce stress and protracted withdrawal symptoms during early recovery. Prior clinical and preclinical research has indicated that both stress and drug-cue-related arousal response is associated with craving and vulnerability to relapse in a range of drug-using populations. AIMS: To examine opioid craving and the subjective and cardiovascular response to stress and drug cues in naltrexone-treated opioid abusers. METHOD: Eleven men and three women engaged in naltrexone treatment for opioid dependence. They were exposed to personalized stress, drug-cue, and neutral-relaxing imagery in a single laboratory session. Subjective (craving, emotion) and cardiovascular (heart rate, systolic blood pressure, and diastolic blood pressure) measures were assessed. RESULTS: Stress and drug-cue-related imagery significantly increased opioid craving, anxiety, and negative emotions and significantly decreased positive emotions compared to neutral imagery. Selective emotional responses were greater in the stress condition than in the drug-cue condition. Only stress-related imagery was associated with an increased cardiovascular response. CONCLUSIONS: Naltrexone-treated opioid abusers demonstrate vulnerability to stress and drug-cue-induced craving and arousal responses that may contribute to the high rates of noncompliance and relapse among opioid-dependent individuals undergoing naltrexone treatment. Pharmacological and behavioral interventions that specifically target the negative affectivity that co-occurs with drug-cue and stress-induced craving could be of benefit in improving naltrexone treatment outcomes in opioid dependence.