Effects of Adrenal Sensitivity, Stress- and Cue-Induced Craving, and Anxiety on Subsequent Alcohol Relapse and Treatment Outcomes

Abstract

Context Alcoholism is a chronic, relapsing illness in which stress and alcohol cues contribute significantly to relapse risk. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increased anxiety, and high alcohol craving have been documented during early alcohol recovery, but their influence on relapse risk has not been well studied. Objectives To investigate these responses in treatment-engaged, 1-month-abstinent, recovering alcohol-dependent patients relative to matched controls (study 1) and to assess whether HPA axis function, anxiety, and craving responses are predictive of subsequent alcohol relapse and treatment outcome (study 2). Design Experimental exposure to stress, alcohol cues, and neutral, relaxing context to provoke alcohol craving, anxiety, and HPA axis responses (corticotropin and cortisol levels and cortisol to corticotropin ratio) and a prospective 90-day follow-up outcome design to assess alcohol relapse and aftercare treatment outcomes. Setting Inpatient treatment in a community mental health center and hospital-based research unit. Participants Treatment-engaged alcohol-dependent individuals and healthy controls. Main Outcome Measures Time to alcohol relapse and to heavy drinking relapse. Results Significant HPA axis dysregulation, marked by higher basal corticotropin level and lack of stress- and cue-induced corticotropin and cortisol responses, higher anxiety, and greater stress- and cue-induced alcohol craving, was seen in the alcohol-dependent patients vs the control group. Stress- and cue-induced anxiety and stress-induced alcohol craving were associated with fewer days in aftercare alcohol treatment. High provoked alcohol craving to both stress and to cues and greater neutral, relaxed-state cortisol to corticotropin ratio (adrenal sensitivity) were each predictive of shorter time to alcohol relapse. Conclusions These results identify a significant effect of high adrenal sensitivity, anxiety, and increased stress- and cue-induced alcohol craving on subsequent alcohol relapse and treatment outcomes. Findings suggest that new treatments that decrease adrenal sensitivity, stress- and cue-induced alcohol craving, and anxiety could be beneficial in improving alcohol relapse outcomes.

The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects

“…Second, we cannot draw definitive conclusions regarding the clinical efficacy of verucerfont in alcoholism based on the current data, as our study measured experimental surrogate markers rather than actual stress-induced relapse to alcohol use. However, the possibility that the outcomes used are not suited to detect CRF1 antagonist activity also appears unlikely: although their properties and predictive power are not fully established, these measures have been shown to predict relapse (Sinha et al, 2011a), and to be sensitive to medications with activity in preclinical models of stress-induced relapse to alcohol seeking (Fox et al, 2012;George et al, 2008).…”

“…The scripts procedure is described in detail elsewhere (Kwako et al, 2014;Sinha et al, 2011a); briefly, it consisted of three sessions that used personalized auditory-guided imagery scripts, each~5 min in duration, to present stress-, alcohol cue-associated or neutral stimuli on days 24-26. The order of the script types was counterbalanced across subjects.…”

Modelos animales de adicción a las drogas

“…Después de la extinción, se da la fase de reinstauración de la conducta donde se mide la capacidad de ciertos estímulos (farmacológicos, físicos o ambientales) llamados "primers" para restablecer de nuevo la respuesta operante aprendida inicialmente (Soria et al, 2008). Actualmente, el modelo de extinción-reinstauración en AA es muy popular para modelar la recaída en la búsqueda de drogas (Bossert, Marchant, Calu y Shaham, 2013;Epstein et al, 2006;Shaham et al, 2003;Sinha et al, 2011;Soria et al, 2008 Recientemente, algunos estudios han evaluado los efectos de desestabilizar el recuerdo de lo que los animales han aprendido durante la adquisición de la AA mediante procedimientos conductuales (extinción) o farmacológicos. En estos estudios, tras conseguir una adquisición estable de la AA, se reactiva la memoria (exponiendo a los animales a la caja de AA durante un breve intervalo de tiempo) y poco tiempo después (de minutos a un par de horas), los animales realizan sesiones de extinción o reciben una inyección de un fármaco amnésico.…”

Dopamine Response to Psychosocial Stress in Chronic Cannabis Users: A PET Study With [11C]-(+)-PHNO

“…Stress is a potent trigger of relapse in addiction (Sinha, 2011;Sinha et al, 2011) and an important risk factor for chronic use of cannabis (see Sinha (2011) for review). Furthermore, cross-sensitization between D 9 -THC and stress have been recently reported in animals (Suplita et al, 2008), suggesting that the putative physiological and psychological effects of cannabis could be potentiated in individuals experiencing adverse environmental stress.…”