Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes.

paper Cited Public

Authors: Sinha, Rajita; Fox, Helen C; Hong, Kwang-Ik Adam; Hansen, Julie; Tuit, Keri; Kreek, Mary Jeanne
Year: 2011
Journal: Archives of general psychiatry
PMID: 21536969
DOI: 10.1001/archgenpsychiatry.2011.49
PMCID: PMC3668981

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.

Figure 1

Schedule of procedures is shown for the alcohol-dependent (AD) and healthy control (HC) samples in study 1 and study 2. Alcohol-dependent patients were 1-month abstinent and in inpatient treatment prior to the laboratory sessions, and controls were assessed during a 3-night research hospital stay. Alcohol-dependent patients were prospectively followed up posttreatment and participated in face-to-face interviews at 14, 30, and 90 days after discharge from inpatient treatment to assess alcohol relapse and treatment outcomes.

LLM interpretation

This figure is a schematic timeline diagram illustrating the procedural schedules for healthy controls (HC) and alcohol-dependent (AD) patients across two studies. The HC timeline shows a 3-day hospital admission involving baseline assessments and laboratory testing, while the AD timeline shows a 4-week inpatient treatment period followed by laboratory testing in week 5 and discharge in week 6. A prospective follow-up phase for the AD group is indicated with relapse assessments at 14, 30, and 90 days post-discharge.

Figure 2

Study 1: mean (SEM) anxiety responses (visual analog scale: 0-10 points) to neutral, relaxing; stress; and alcohol cue exposure at baseline, immediately following imagery (0 minutes), and at 5, 15, 30, 45, 60, and 75 minutes in healthy controls (HC) and alcohol-dependent (AD) patients. Alcohol-dependent patients showed higher anxiety in the neutral, relaxing condition (P<.03) and in the alcohol cue condition (P<.001), but not the stress condition, relative to the control group. Both groups showed significant increases in anxiety levels in response to stress relative to the neutral condition (P’s<.001), validating the experimental manipulation, and the AD group showed significantly greater anxiety in the alcohol cue condition relative to the neutral condition (P<.001), but the control group showed no such increases. The AD patients had higher anxiety across conditions relative to controls (P<.03).

LLM interpretation

This figure consists of three line graphs showing mean anxiety ratings (0-5 scale) over time (0 to 75 minutes) for alcohol-dependent (AD) patients and healthy controls (HC) across three conditions: neutral, stress, and alcohol cue. In the stress condition, both groups show a sharp peak in anxiety at 0 minutes followed by a decline. In the alcohol cue condition, the AD group exhibits a significant spike in anxiety at 0 minutes, while the HC group remains baseline. Across all three conditions, the AD group generally maintains higher anxiety ratings than the HC group.

Figure 3

Study 1: mean (SEM) alcohol craving (visual analog scale: 0-10 points) responses to neutral, relaxing; stress; and alcohol cue exposure at baseline, immediately following imagery (0 minutes), and at 5, 15, 30, 45, 60, and 75 minutes in healthy controls (HC) and alcohol-dependent (AD) individuals. The AD group showed higher alcohol craving in the stress (P<.001) and the alcohol cue (P<.001) conditions than the control group. Both groups showed significant increases in alcohol craving in responses to alcohol cues (AD: P<.001; HC: P<.03), but only the AD group showed significantly greater alcohol craving in responses to stress (P<.001) relative to the neutral condition, and the control group showed no such increases.

LLM interpretation

This figure consists of three line graphs showing alcohol craving ratings over 75 minutes for alcohol-dependent (AD) and healthy control (HC) groups across three conditions: neutral, stress, and alcohol cue. In the neutral condition, both groups maintain low, stable craving levels; however, in the stress and alcohol cue conditions, the AD group exhibits significantly higher craving peaks immediately following exposure compared to the HC group. Craving ratings for the AD group peak at 0 minutes and gradually decline over time in both the stress and alcohol cue conditions.

Figure 4

Study 1: baseline-adjusted corticotropin and cortisol mean (SEM) responses to the stress (S), alcohol cue (C), and neutral, relaxing (N) conditions. A, Baseline-adjusted corticotropin responses show an effect of condition, with S greater than N (P<.02) and with group differences in these effects (healthy controls [HC]: S>N [P<.001] and S>C [P<.007]; alcohol-dependent [AD] patients: no differences across conditions; AD>HC in response of N [P<.01]). B, Baseline-adjusted plasma cortisol responses to S, C, and N imagery averaged across time indicated condition effects showing S greater than N (P<.003) and C greater than N (P<.001), but effects varied by group (HC: S>N [P<.001] and C>N [P<.001]; AD patients: C>N [P<.02] and no differences in S vs N). (Controls showed an increased response in S and C relative to N despite the diurnal drop in corticotropin and cortisol levels due to the circadian rhythm.)

LLM interpretation

This figure consists of two bar charts (A and B) comparing baseline-adjusted corticotropin (pg/mL) and cortisol ($\mu$g/dL) responses across three conditions (Neutral, Stress, and Alcohol Cue) for alcohol-dependent (AD) and healthy control (HC) groups. In panel A, the AD group shows relatively stable corticotropin levels across conditions, while the HC group shows a higher response to Stress compared to Neutral and Alcohol Cue. In panel B, the HC group exhibits higher cortisol responses to Stress and Alcohol Cue relative to the Neutral condition, whereas the AD group shows a less pronounced increase.

Figure 5

Study 2: after holding covariates constant, estimated survival risk functions are shown for alcohol craving values for the mean (in red) and at 1, 2, and 3 SDs above the mean and at minimal craving levels (0 and 0.5) for stress-induced alcohol craving (S_CRV) (A) (χ2=4.37; P<.04; hazard ratio=1.15; 95% confidence interval, 1.01-1.31) and alcohol cue-induced craving (C_CRV) (B) (χ2=4.82; P<.03; hazard ratio=1.16, 95% confidence interval, 1.02-1.32). The proportion surviving 90-day relapse is shown on the y-axis and the time during the 90-day period when relapse occurred is shown on the x-axis. Hence, the estimated survival function at day 80 spans a 0.35 (35%) and 0.38 (38%) proportion of surviving relapse for those with an S_CRV and a C_CRV of 0, respectively, while there is only a 0.02 (0.02%) proportional chance of surviving relapse for those at 3 SDs above the mean in S_CRV and C_CRV, respectively. Note: survival functions are cut off at day 80 instead of extending to day 90 because all alcohol-dependent patients with predictor values 3 SDs above the mean had relapsed by day 80.

LLM interpretation

This figure consists of two survival plots (A and B) showing the estimated survival function (proportion surviving relapse) over a period of 80 days. The x-axis represents "Time to Relapse, d" and the y-axis represents the "Estimated Survival Function." In both plots, higher craving values (S_CRV in A and C_CRV in B), indicated by different colored lines, are associated with a steeper decline in survival and a lower overall probability of remaining relapse-free compared to minimal craving levels.

Figure 6

Study 2: after holding covariates constant, estimated survival risk functions are shown for neutral, relaxing-condition cortisol to corticotropin ratio (N_C:C ratio) (adrenal sensitivity) values for the mean (in red) and at 1, 2, and 3 SDs above the mean and at minimal ratio values (0.1 and 0.05) for N_C:C ratio predicting time to alcohol relapse (A) (χ2=7.38; P<.007; hazard ratio=2.12; 95% confidence interval, 1.23-3.63) and time to heavy drinking alcohol relapse (B) (χ2=10.4; P<.001; hazard ratio=2.55; 95% confidence interval, 1.29-4.1). The proportion surviving 90-day relapse is shown on the y-axis and the time during the 90-day period when relapse occurred is shown on the x-axis. Hence, the estimated survival function at day 80 spans a 0.40 (40%) proportion surviving relapse and 0.48 (48%) surviving heavy drinking relapse for cortisol to corticotropin ratios at 0.05, respectively, while there is only a 0.02 (0.02%) proportional chance of surviving relapse and heavy drinking relapse for those at 3 SDs above the mean in N_C:C ratio. Note: survival functions are cut off at day 80 instead of extending to day 90 because all alcohol-dependent patients with predictor values 3 SDs above the mean had relapsed by day 80.

LLM interpretation

This figure consists of two Kaplan-Meier survival plots (A and B) showing the estimated survival function over a 90-day period for different neutral, relaxing-condition cortisol to corticotropin (N_C:C) ratios. The x-axes represent time to relapse (A) and time to heavy relapse (B) in days, while the y-axis represents the estimated survival function (proportion surviving relapse). Higher N_C:C ratios (e.g., 1.7) are associated with a steeper decline in survival probability compared to lower ratios (e.g., 0.05), indicating a higher risk of relapse.

#	Section	Preview
0	METHODS — STUDY 1 — Objective	The objective of study 1 was to examine whether treatment-engaged, 1-month-abstinent,…
1	METHODS — STUDY 1 — Participants	Men and women (aged between 21-50 years) seeking treatment for alcohol dependence and socially…
2	METHODS — STUDY 1 — Participants	currently using opiates or who ever met criteria for opiate dependence and those taking medications…
3	METHODS — STUDY 1 — Procedures	Alcohol-dependent patients were admitted to the Clinical Neuroscience Research Unit, a locked…
4	METHODS — STUDY 1 — Procedures	During the first week of the inpatient stay, subjects underwent an initial medical evaluation and…
5	METHODS — STUDY 1 — Procedures	All subjects participated in an imagery script development session (week 3 of admission for…
6	METHODS — STUDY 1 — Procedures	and taking a bubble bath. Details of each elicited situation were described using the Scene…
7	METHODS — STUDY 1 — Laboratory Sessions	On a day prior to the laboratory sessions, subjects participated in a habituation and imagery…
8	METHODS — STUDY 1 — Laboratory Sessions	a heparin-treated catheter was inserted by the research nurse in the antecubital region of the…
9	METHODS — STUDY 1 — Laboratory Assessments — Subjective Measures	Alcohol craving and anxiety were assessed using a 10-point visual analog scale in which 1 was…
10	METHODS — STUDY 1 — Laboratory Assessments — HPA Axis Measures	To assess plasma levels of corticotropin and cortisol, 4 mL of blood were collected at each point in…
11	METHODS — STUDY 1 — Laboratory Assessments — HPA Axis Measures	released from the pituitary and may vary under rest and challenge conditions,25-27 we also assessed…
12	METHODS — STUDY 1 — Data Analysis	Data were analyzed using mixed-effect models where group (control vs alcohol dependent), condition…
13	METHODS — STUDY 2 — Objective	The objective of study 2 was to assess whether alcohol craving, anxiety, corticotropin level,…
14	METHODS — STUDY 2 — Participants	Ninety-three inpatient treatment-engaged, 1-month-abstinent, recovering alcohol-dependent…
15	METHODS — STUDY 2 — Prospective Follow-up Procedures	On discharge from the inpatient unit, all alcohol-dependent participants were given appointments for…
16	METHODS — STUDY 2 — Prospective Follow-up Procedures	patients who completed the laboratory and follow-up procedures in study 2, 3 attended the 14-day but…
17	METHODS — STUDY 2 — Predictor Measures	Area under the curve for response in each condition, including baseline, was calculated using the…
18	METHODS — STUDY 2 — Primary Outcome Measures	Number of days of aftercare treatment participation (days of any outpatient treatment and self-help…
19	METHODS — STUDY 2 — Data Analysis	Proportional hazards regression models were conducted to evaluate time to any alcohol use (alcohol…

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In this knowledge base

Title	Year	PMID
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Analyses related to the development of DSM-5 criteria for substance use related disorders: 2. Proposed DSM-5 criteria for alcohol, cannabis, cocaine and heroin disorders in 663 substance abuse patients.	2012	21963333
Stress-related neuropeptides and addictive behaviors: beyond the usual suspects.	2012	23040815

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Testing pharmacotherapies for alcohol use disorder with cue exposure paradigms: A systematic review and quantitative synthesis of human laboratory trial methodology.	Meredith LR et al.	—	2023	→
The Craving-Manager smartphone app designed to diagnose substance use/addictive disorders, and manage craving and individual predictors of relapse: a study protocol for a multicenter randomized controlled trial.	Serre F et al.	—	2023	→
Therapeutics for Substance-Using Women: The Need to Elucidate Sex-Specific Targets for Better-Tailored Treatments.	Fox HC et al.	—	2023	→
Using ecological momentary assessments of negative affect and craving during residential opioid use disorder treatment to predict patients' relapse to substance use.	Cleveland HH et al.	—	2023	→
Alcohol and Prostate Cancer: Time to Draw Conclusions.	Macke AJ et al.	—	2022	→
Alcohol craving and withdrawal at treatment entry prospectively predict alcohol use outcomes during outpatient treatment.	Martins JS et al.	—	2022	→
Clinical Outcomes of Severe Forms of Early Social Stress.	Berhe O et al.	—	2022	→
COVID-19 behavioral health and quality of life.	Hansel TC et al.	—	2022	→
Craving variations in patients with substance use disorder and gambling during COVID-19 lockdown: The Italian experience.	Alessi MC et al.	—	2022	→
Daily stress predicts later drinking initiation via craving in heavier social drinkers: A prospective in-field daily diary study.	Wemm SE et al.	—	2022	→
Exposure to Olfactory Alcohol Cues During Non-rapid Eye Movement Sleep Did Not Decrease Craving in Patients With Alcohol Dependence.	Zhu R et al.	—	2022	→
High-Risk Drinkers Engage Distinct Stress-Predictive Brain Networks.	Goldfarb EV et al.	—	2022	→
How laboratory studies of cigarette craving can inform the experimental alcohol craving literature.	Creswell KG et al.	—	2022	→
Intake assessments of salivary cortisol, survey responses, and adverse childhood experiences are associated with recovery success in an abstinence-based treatment program for substance use disorders.	Maddox-Rooper TR et al.	—	2022	→
ON-ICE trial: Investigation of the combined effects of oxytocin and naltrexone on stress-induced and alcohol cue-induced craving in alcohol use disorder-Study protocol of a phase II randomised double-blind placebo-controlled parallel-group trial.	Zimmermann S et al.	—	2022	→
Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder.	Milivojevic V et al.	—	2022	→
Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice.	Nadia H et al.	—	2022	→
The endocannabinoid system and drug-associated contextual memories.	Asth L et al.	—	2022	→
Anxiety during abstinence from alcohol: A systematic review of rodent and human evidence for the anterior insula's role in the abstinence network.	Flook EA et al.	—	2021	→
A Personalized Approach Bias Modification Smartphone App ("SWiPE") to Reduce Alcohol Use: Open-Label Feasibility, Acceptability, and Preliminary Effectiveness Study.	Manning V et al.	—	2021	→
Association between Alcohol Consumption and Serum Cortisol Levels: a Mendelian Randomization Study.	Yang JH et al.	—	2021	→
Attentional Bias, Alcohol Craving, and Anxiety Implications of the Virtual Reality Cue-Exposure Therapy in Severe Alcohol Use Disorder: A Case Report.	Ghiţă A et al.	—	2021	→
Chronic Ethanol Exposures Leads to a Negative Affective State in Female Rats That Is Accompanied by a Paradoxical Decrease in Ventral Hippocampus Excitability.	Bach EC et al.	—	2021	→
Dimensions of Craving Interact with <i>COMT</i> Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment.	Padula CB et al.	—	2021	→
Effectiveness of an Integrated Intervention Program for Alcoholism: Electrophysiological Findings.	Kumar R et al.	—	2021	→
Effectiveness of drugs acting on adrenergic receptors in the treatment for tobacco or alcohol use disorders: systematic review and meta-analysis.	Vanderkam P et al.	—	2021	→
Examining the Role of Craving, Mindfulness, and Psychological Flexibility in a Sample of Individuals with Substance Use Disorder.	Mallik D et al.	—	2021	→
Mapping data-driven individualized neurobehavioral phenotypes in heavy alcohol drinkers.	DeMartini KS et al.	—	2021	→
Neural correlates of alcohol use disorder severity among nontreatment-seeking heavy drinkers: An examination of the incentive salience and negative emotionality domains of the alcohol and addiction research domain criteria.	Al-Khalil K et al.	—	2021	→
Neurobiology of alcohol seeking behavior.	Domi E et al.	—	2021	→
Neurobiology of peripartum mental illness.	Pawluski JL et al.	—	2021	→
Portuguese validation of the Alcohol Craving Questionnaire-Short Form-Revised.	Rodrigues R et al.	—	2021	→
Reassessing Fitness-to-Drive in Drinker Drivers: The Role of Cognition and Personality.	Tinella L et al.	—	2021	→
Reregulation of cortisol levels and sleep in patients with prescription opioid use disorder during long-term residential treatment.	Mukherjee D et al.	—	2021	→
Social Learning and Addiction.	Smith MA	—	2021	→
Solitary Nitric Oxide Signaling Mediates Mild Stress-Induced Anxiety and Norepinephrine Release in the Bed Nucleus of the Stria Terminalis during Protracted Ethanol Withdrawal.	Zhao Z et al.	—	2021	→
The Impact of Co-occurring Post-traumatic Stress Disorder and Substance Use Disorders on Craving: A Systematic Review of the Literature.	Renaud F et al.	—	2021	→
The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats.	Makhijani VH et al.	—	2021	→
Translational opportunities in animal and human models to study alcohol use disorder.	Nieto SJ et al.	—	2021	→
Addiction is driven by excessive goal-directed drug choice under negative affect: translational critique of habit and compulsion theory.	Hogarth L	—	2020	→
Alcohol Craving in Heavy and Occasional Alcohol Drinkers After Cue Exposure in a Virtual Environment: The Role of the Sense of Presence.	Simon J et al.	—	2020	→
Alcohol drinking alters stress response to predator odor via BNST kappa opioid receptor signaling in male mice.	Hwa LS et al.	—	2020	→
A Rationale for Allopregnanolone Treatment of Alcohol Use Disorders: Basic and Clinical Studies.	Morrow AL et al.	—	2020	→
Behavioral Health and Response for COVID-19.	Hansel TC et al.	—	2020	→
Behavioral strategies to reduce stress reactivity in opioid use disorder: Study design.	McHugh RK et al.	—	2020	→
Chronic alcohol disrupts hypothalamic responses to stress by modifying CRF and NMDA receptor function.	Marty VN et al.	—	2020	→
Effectiveness of music therapy on improving treatment motivation and emotion in female patients with methamphetamine use disorder: A randomized controlled trial.	Wu Q et al.	—	2020	→
Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes Among Treatment-Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline.	Miranda R et al.	—	2020	→
Effects of Prazosin on Provoked Alcohol Craving and Autonomic and Neuroendocrine Response to Stress in Alcohol Use Disorder.	Milivojevic V et al.	—	2020	→
Evaluating a longitudinal mediation model of perceived stress, depressive symptoms, and substance use treatment outcomes.	Roos CR et al.	—	2020	→
Integrated intervention program for alcoholism improves impulsiveness and disadvantageous reward processing/risk-taking.	Kumar R et al.	—	2020	→
Oxytocin treatment for alcoholism: Potential neurocircuitry targets.	Peris J et al.	—	2020	→
Personalized Approach Bias Modification Smartphone App ("SWIPE") to Reduce Alcohol Use Among People Drinking at Hazardous or Harmful Levels: Protocol for an Open-Label Feasibility Study.	Manning V et al.	—	2020	→
Possible Role of CRF-Hcrt Interaction in the Infralimbic Cortex in the Emergence and Maintenance of Compulsive Alcohol-Seeking Behavior.	Kim JS et al.	—	2020	→
PPARγ activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study.	Schwandt ML et al.	—	2020	→
Regulation of Craving and Negative Emotion in Alcohol Use Disorder.	Suzuki S et al.	—	2020	→
Relative expected value of drugs versus competing rewards underpins vulnerability to and recovery from addiction.	Hogarth L et al.	—	2020	→
Stress Allostasis in Substance Use Disorders: Promise, Progress, and Emerging Priorities in Clinical Research.	Fronk GE et al.	—	2020	→
Stress-related suppression of peripheral cytokines predicts future relapse in alcohol-dependent individuals with and without subclinical depression.	Fox HC et al.	—	2020	→
The physiological responses to acute stress in alcohol-dependent patients: A systematic review.	Chen K et al.	—	2020	→
The recognition and management of protracted alcohol withdrawal may improve and modulate the pharmacological treatment of alcohol use disorder.	Caputo F et al.	—	2020	→
The relationship between perceived stress and depression in substance use disorder treatment.	McHugh RK et al.	—	2020	→
The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats	Makhijani VH et al.	—	2020	—
Trauma- and Stress-Induced Craving for Alcohol in Individuals Without PTSD.	Ralevski E et al.	—	2020	→
Ultra-brief breath counting (mindfulness) training promotes recovery from stress-induced alcohol-seeking in student drinkers.	Shuai R et al.	—	2020	→
A day-by-day prospective analysis of stress, craving and risk of next day alcohol intake during alcohol use disorder treatment.	Wemm SE et al.	—	2019	→
Affective vulnerability in substance use disorders.	McHugh RK et al.	—	2019	→
Alcohol use disorder relapse factors: A systematic review.	Sliedrecht W et al.	—	2019	→
Associations among interpretation bias, craving, and abstinence self-efficacy in adults with substance use disorders.	Beard C et al.	—	2019	→
A transdiagnostic dimensional approach towards a neuropsychological assessment for addiction: an international Delphi consensus study.	Yücel M et al.	—	2019	→
Baclofen but Not Diazepam Alleviates Alcohol-Seeking Behavior and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Stressed Withdrawn Mice.	Rabat Y et al.	—	2019	→
Building better strategies to develop new medications in Alcohol Use Disorder: Learning from past success and failure to shape a brighter future.	Cannella N et al.	—	2019	→
Chronic Intermittent Ethanol Exposure Selectively Increases Synaptic Excitability in the Ventral Domain of the Rat Hippocampus.	Ewin SE et al.	—	2019	→
Compulsivity in Alcohol Use Disorder and Obsessive Compulsive Disorder: Implications for Neuromodulation.	Burchi E et al.	—	2019	→
Craving, cortisol and behavioral alcohol motivation responses to stress and alcohol cue contexts and discrete cues in binge and non-binge drinkers.	Blaine SK et al.	—	2019	→
Cued for risk: Evidence for an incentive sensitization framework to explain the interplay between stress and anxiety, substance abuse, and reward uncertainty in disordered gambling behavior.	Hellberg SN et al.	—	2019	→
Cue-Elicited Anxiety and Alcohol Craving as Indicators of the Validity of ALCO-VR Software: A Virtual Reality Study.	Ghiţă A et al.	—	2019	→
Differences in pituitary-adrenal reactivity in Black and White men with and without alcohol use disorder.	Price JL et al.	—	2019	→
Early postpartum resting-state functional connectivity for mothers receiving buprenorphine treatment for opioid use disorder: A pilot study.	Swain JE et al.	—	2019	→
[Effect of clinical characteristics on relapse of alcohol dependence: a prospective cohort study].	Zhu R et al.	—	2019	→
Effects of opioids on the parental brain in health and disease.	Swain JE et al.	—	2019	→
Examining Perceived Stress, Childhood Trauma and Interpersonal Trauma in Individuals With Drug Addiction.	Garami J et al.	—	2019	→
Hypermethylation of Proopiomelanocortin and Period 2 Genes in Blood Are Associated with Greater Subjective and Behavioral Motivation for Alcohol in Humans.	Gangisetty O et al.	—	2019	→
Negative Mood Induction Increases Choice of Heroin Versus Food Pictures in Opiate-Dependent Individuals: Correlation With Self-Medication Coping Motives and Subjective Reactivity.	Hogarth L et al.	—	2019	→
Neurofunctional Domains Derived From Deep Behavioral Phenotyping in Alcohol Use Disorder.	Kwako LE et al.	—	2019	→
Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence.	Sebold M et al.	—	2019	→
Stress System Response and Decision Making in Heavy Episodic Users of Alcohol and Online Video Games.	Gilbertson RJ et al.	—	2019	→
Targeting the Glucocorticoid Receptors During Alcohol Withdrawal to Reduce Protracted Neurocognitive Disorders.	Béracochéa D et al.	—	2019	→
A paradigm for examining stress effects on alcohol-motivated behaviors in participants with alcohol use disorder.	McCaul ME et al.	—	2018	→
Cardiac vagal dysfunction moderates patterns of craving across the day in moderate to heavy consumers of alcohol.	Mayhugh RE et al.	—	2018	→
Central and Peripheral Biomarkers of Stress Response for Addiction Risk and Relapse Vulnerability.	Milivojevic V et al.	—	2018	→
Depressive statements prime goal-directed alcohol-seeking in individuals who report drinking to cope with negative affect.	Hogarth L et al.	—	2018	→
Medications for alcohol use disorders: An overview.	Akbar M et al.	—	2018	→
Negative mood-induced alcohol-seeking is greater in young adults who report depression symptoms, drinking to cope, and subjective reactivity.	Hogarth L et al.	—	2018	→
Prazosin for the Treatment of Alcohol Use Disorders.	Sinha R	—	2018	→
Psychosocial stress increases craving for alcohol in social drinkers: Effects of risk-taking.	Clay JM et al.	—	2018	→
Repeated restraint stress reduces the acquisition and relapse of methamphetamine-conditioned place preference but not behavioral sensitization.	Seo JY et al.	—	2018	→
Sexual dimorphism in the neural impact of stress and alcohol.	Logrip ML et al.	—	2018	→
Stress Promotes Drug Seeking Through Glucocorticoid-Dependent Endocannabinoid Mobilization in the Prelimbic Cortex.	McReynolds JR et al.	—	2018	→
Stress vulnerability and alcohol use and consequences: From human laboratory studies to clinical outcomes.	Ramchandani VA et al.	—	2018	→
Text Messaging to Reduce Alcohol Relapse in Prelisting Liver Transplant Candidates: A Pilot Feasibility Study.	DeMartini KS et al.	—	2018	→
The role of stress-reactivity, stress-recovery and risky decision-making in psychosocial stress-induced alcohol consumption in social drinkers.	Clay JM et al.	—	2018	→
Under the influence: Effects of adolescent ethanol exposure and anxiety on motivation for uncertain gambling-like cues in male and female rats.	Hellberg SN et al.	—	2018	→
A Decade of Orexin/Hypocretin and Addiction: Where Are We Now?	James MH et al.	—	2017	→
Adrenocortical sensitivity, moderated by ongoing stress, predicts drinking intensity in alcohol-dependent men.	Adinoff B et al.	—	2017	→
Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders.	Blaine SK et al.	—	2017	→
A Qualitative Exploration of Social Support during Treatment for Severe Alcohol Use Disorder and Recovery.	Brooks AT et al.	—	2017	→
A role for the peripheral immune system in the development of alcohol use disorders?	de Timary P et al.	—	2017	→
Biochemical Diagnosis in Substance and Non-substance Addiction.	Shen W et al.	—	2017	→
Cingulate cortex functional connectivity predicts future relapse in alcohol dependent individuals.	Zakiniaeiz Y et al.	—	2017	→
Current major depression is associated with greater sensitivity to the motivational effect of both negative mood induction and abstinence on tobacco-seeking behavior.	Hogarth L et al.	—	2017	→
Daily stressors as antecedents, correlates, and consequences of alcohol and drug use and cravings in community-based offenders.	Neupert SD et al.	—	2017	→
Development of an integrated cognitive behavioral therapy for anxiety and opioid use disorder: Study protocol and methods.	McHugh RK et al.	—	2017	→
Don't stress about CRF: assessing the translational failures of CRF<sub>1</sub>antagonists.	Spierling SR et al.	—	2017	→
Effects of Acute Stress on Decision Making.	Wemm SE et al.	—	2017	→
Gender differences in neural correlates of stress-induced anxiety.	Seo D et al.	—	2017	→
Khat Use is Associated with Tobacco, Alcohol, and Illicit Drug Use: A Cross-Sectional Examination in the United States.	Nakajima M et al.	—	2017	→
Medications for substance use disorders (SUD): emerging approaches.	Butelman ER et al.	—	2017	→
Neural stress reactivity relates to smoking outcomes and differentiates between mindfulness and cognitive-behavioral treatments.	Kober H et al.	—	2017	→
Peripheral and prefrontal stress system markers and risk of relapse in alcoholism.	Blaine SK et al.	—	2017	→
Peripheral Immune System Adaptations and Motivation for Alcohol in Non-Dependent Problem Drinkers.	Milivojevic V et al.	—	2017	→
Peripheral immune system suppression in early abstinent alcohol-dependent individuals: Links to stress and cue-related craving.	Fox HC et al.	—	2017	→
Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence.	Kaye JT et al.	—	2017	→
Reduction of smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial.	Hamidovic A et al.	—	2017	→
Stress-related salivary alpha-amylase (sAA) activity in alcohol dependent patients with and without a history of childhood maltreatment.	Muehlhan M et al.	—	2017	→
Studies using macaque monkeys to address excessive alcohol drinking and stress interactions.	Jimenez VA et al.	—	2017	→
Targeted intervention: Computational approaches to elucidate and predict relapse in alcoholism.	Heinz A et al.	—	2017	→
Targeting Stress Pathophysiology to Improve Alcoholism Relapse Outcomes.	Milivojevic V et al.	—	2017	→
The Corticotropin Releasing Factor Receptor 1 in Alcohol Use Disorder: Still a Valid Drug Target?	Pomrenze MB et al.	—	2017	→
11β-hydroxysteroid dehydrogenase inhibition as a new potential therapeutic target for alcohol abuse.	Sanna PP et al.	—	2016	→
Accelerated HF-rTMS Protocol has a Rate-Dependent Effect on dACC Activation in Alcohol-Dependent Patients: An Open-Label Feasibility Study.	Herremans SC et al.	—	2016	→
Acute effects of resistance exercise on affect, arousal, and urge to drink in temporarily abstinent young adult hazardous drinkers.	Ciccolo JT et al.	—	2016	→
Addictions Neuroclinical Assessment: A Neuroscience-Based Framework for Addictive Disorders.	Kwako LE et al.	—	2016	→
Alcohol Effects on Stress Pathways: Impact on Craving and Relapse Risk.	Blaine SK et al.	—	2016	→
Association between a brief alcohol craving measure and drinking in the following week.	McHugh RK et al.	—	2016	→
Association Splitting: A randomized controlled trial of a new method to reduce craving among inpatients with alcohol dependence.	Schneider BC et al.	—	2016	→
Behavioral Neuroadaptation to Alcohol: From Glucocorticoids to Histone Acetylation.	Mons N et al.	—	2016	→
Blunted cardiac stress reactors exhibit relatively high levels of behavioural impulsivity.	Bibbey A et al.	—	2016	→
Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders.	Sofuoglu M et al.	—	2016	→
Craving Mediates Stress in Predicting Lapse During Alcohol Dependence Treatment.	Law B et al.	—	2016	→
Cue-induced craving to paraphernalia and drug images in opioid dependence.	McHugh RK et al.	—	2016	→
Differential Impact of Depressive and Manic Mood States on Alcohol Craving in Comorbid Bipolar Alcoholism: Preliminary Findings.	Balsamo DN et al.	—	2016	→
FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence.	Spagnolo PA et al.	—	2016	→
Gender-specific effects of comorbid depression and anxiety on the propensity to drink in negative emotional states.	Karpyak VM et al.	—	2016	→
Neural Correlates and Connectivity Underlying Stress-Related Impulse Control Difficulties in Alcoholism.	Seo D et al.	—	2016	→
Neuroimmune Interface in the Comorbidity between Alcohol Use Disorder and Major Depression.	Neupane SP	—	2016	→
Oxytocin for the treatment of drug and alcohol use disorders.	Lee MR et al.	—	2016	→
Persistent adaptation by chronic alcohol is facilitated by neuroimmune activation linked to stress and CRF.	Breese GR et al.	—	2016	→
Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites.	Knapp DJ et al.	—	2016	→
Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress.	Mantsch JR et al.	—	2016	→
Substance use modulates stress reactivity: Behavioral and physiological outcomes.	Fosnocht AQ et al.	—	2016	→
The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects.	Schwandt ML et al.	—	2016	→
Trauma- and Stress-Induced Response in Veterans with Alcohol Dependence and Comorbid Post-Traumatic Stress Disorder.	Ralevski E et al.	—	2016	→
A Preliminary Examination of Negative Affect, Emotion Dysregulation, and Risky Behaviors among Military Veterans in Residential Substance Abuse Treatment.	Weiss NH et al.	—	2015	→
Cardiac stress reactions and perseverance: Diminished reactivity is associated with study non-completion.	Ginty AT et al.	—	2015	→
Chronic alcohol exposure differentially affects activation of female locus coeruleus neurons and the subcellular distribution of corticotropin releasing factor receptors.	Retson TA et al.	—	2015	→
Cigarettes and alcohol: The influence of nicotine on operant alcohol self-administration and the mesolimbic dopamine system.	Ostroumov A et al.	—	2015	→
Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G.	Lovallo WR et al.	—	2015	→
Craving and substance use among patients with alcohol, tobacco, cannabis or heroin addiction: a comparison of substance- and person-specific cues.	Fatseas M et al.	—	2015	→
Deep TMS on alcoholics: effects on cortisolemia and dopamine pathway modulation. A pilot study.	Ceccanti M et al.	—	2015	→
Gender Considerations in Addiction: Implications for Treatment.	Polak K et al.	—	2015	→
Guanfacine enhances inhibitory control and attentional shifting in early abstinent cocaine-dependent individuals.	Fox H et al.	—	2015	→
Importance of sex differences in impulse control and addictions.	Mitchell MR et al.	—	2015	→
Methods for inducing alcohol craving in individuals with co-morbid alcohol dependence and posttraumatic stress disorder: behavioral and physiological outcomes.	Kwako LE et al.	—	2015	→
Neuroplasticity and Predictors of Alcohol Recovery.	Seo D et al.	—	2015	→
Noninvasive brain stimulation to suppress craving in substance use disorders: Review of human evidence and methodological considerations for future work.	Hone-Blanchet A et al.	—	2015	→
Problematic Internet use, excessive alcohol consumption, their comorbidity and cardiovascular and cortisol reactions to acute psychological stress in a student population.	Bibbey A et al.	—	2015	→
Psychological changes in alcohol-dependent patients during a residential rehabilitation program.	Giorgi I et al.	—	2015	→
Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase.	Roche DJ et al.	—	2015	→
The corticotropin releasing hormone-1 (CRH1) receptor antagonist pexacerfont in alcohol dependence: a randomized controlled experimental medicine study.	Kwako LE et al.	—	2015	→
The neurokinin-1 receptor antagonist aprepitant in co-morbid alcohol dependence and posttraumatic stress disorder: a human experimental study.	Kwako LE et al.	—	2015	→
Treatment of co-occurring anxiety disorders and substance use disorders.	McHugh RK	—	2015	→
Alcohol, stress hormones, and the prefrontal cortex: a proposed pathway to the dark side of addiction.	Lu YL et al.	—	2014	→
Assessing craving and its relationship to subsequent prescription opioid use among treatment-seeking prescription opioid dependent patients.	McHugh RK et al.	—	2014	→
Characterizing subjective responses to alcohol among adolescent problem drinkers.	Miranda R et al.	—	2014	→
Chronic treatment with prazosin or duloxetine lessens concurrent anxiety-like behavior and alcohol intake: evidence of disrupted noradrenergic signaling in anxiety-related alcohol use.	Skelly MJ et al.	—	2014	→
Cocaine self-administration and extinction alter medullary noradrenergic and limbic forebrain cFos responses to acute, noncontingent cocaine injections in adult rats.	Buffalari DM et al.	—	2014	→
Computer-aided diagnosis of alcoholism-related EEG signals.	Acharya UR et al.	—	2014	→
Epigenetics and the regulation of stress vulnerability and resilience.	Zannas AS et al.	—	2014	→
Framing ethnic variations in alcohol outcomes from biological pathways to neighborhood context.	Chartier KG et al.	—	2014	→
Future pharmacological treatments for substance use disorders.	Forray A et al.	—	2014	→
Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine.	Schwager AL et al.	—	2014	→
New view on treatment of drug dependence.	Ranjbaran M et al.	—	2014	→
Oral self-administration of EtOH: sex-dependent modulation by running wheel access in C57BL/6J mice.	Piza-Palma C et al.	—	2014	→
Preventive Effects of Forced Exercise against Alcohol-induced Physical Dependency and Reduction of Pain Perception Threshold.	Motaghinejad M et al.	—	2014	→
Restraint stress attenuates nicotine's locomotor stimulant but not discriminative stimulus effects in rats.	Harris AC et al.	—	2014	→
Stress and alcohol interactions: animal studies and clinical significance.	Spanagel R et al.	—	2014	→
Stress moderates the effect of childhood trauma and adversity on recent drinking in treatment-seeking alcohol-dependent men.	Eames SF et al.	—	2014	→
Stress modulates illness-course of substance use disorders: a translational review.	Lijffijt M et al.	—	2014	→
Stress-related alcohol consumption in heavy drinkers correlates with expression of miR-10a, miR-21, and components of the TAR-RNA-binding protein-associated complex.	Beech RD et al.	—	2014	→
Stress, substance abuse, and addiction.	Duffing TM et al.	—	2014	→
The impact of atrial natriuretic peptide on anxiety, stress and craving in patients with alcohol dependence.	Koopmann A et al.	—	2014	→
The neurobiology of alcohol craving and relapse.	Seo D et al.	—	2014	→
The role of guanfacine as a therapeutic agent to address stress-related pathophysiology in cocaine-dependent individuals.	Fox H et al.	—	2014	→
Acquisition of Rater Agreement for the Stressful Life Events Schedule.	James LM et al.	—	2013	→
Addiction and corticotropin-releasing hormone type 1 receptor antagonist medications.	Contoreggi C et al.	—	2013	→
Alcohol administration attenuates hypothalamic-pituitary-adrenal (HPA) activity in healthy men at low genetic risk for alcoholism, but not in high-risk subjects.	Mick I et al.	—	2013	→
Alcohol stress response dampening during imminent versus distal, uncertain threat.	Hefner KR et al.	—	2013	→
Altered neural processing of threat in alcohol-dependent men.	Yang H et al.	—	2013	→
A variant on the kappa opioid receptor gene (OPRK1) is associated with stress response and related drug craving, limbic brain activation and cocaine relapse risk.	Xu K et al.	—	2013	→
Brain imaging biomarkers to predict relapse in alcohol addiction.	Volkow ND et al.	—	2013	→
Chronic childhood adversity and stages of substance use involvement in adolescents.	Benjet C et al.	—	2013	→
Corticosterone acts in the nucleus accumbens to enhance dopamine signaling and potentiate reinstatement of cocaine seeking.	Graf EN et al.	—	2013	→
Deficient plasticity in the hippocampus and the spiral of addiction: focus on adult neurogenesis.	Canales JJ	—	2013	→
Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk.	Seo D et al.	—	2013	→
Dopamine response to psychosocial stress in chronic cannabis users: a PET study with [11C]-+-PHNO.	Mizrahi R et al.	—	2013	→
Genetic influences on craving for alcohol.	Agrawal A et al.	—	2013	→
Hybrid cognitive behavioral therapy versus relaxation training for co-occurring anxiety and alcohol disorder: a randomized clinical trial.	Kushner MG et al.	—	2013	→
Long-term ethanol and corticosterone co-exposure sensitize the hippocampal ca1 region pyramidal cells to insult during ethanol withdrawal in an NMDA GluN2B subunit-dependent manner.	Butler TR et al.	—	2013	→
Modeling relapse situations in the human laboratory.	Sinha R	—	2013	→
Neural correlates of stress and favorite-food cue exposure in adolescents: a functional magnetic resonance imaging study.	Hommer RE et al.	—	2013	→
Nicotine decreases ethanol-induced dopamine signaling and increases self-administration via stress hormones.	Doyon WM et al.	—	2013	→
Pain and suicidality: insights from reward and addiction neuroscience.	Elman I et al.	—	2013	→
Physiological and endocrine reactions to psychosocial stress in alcohol use disorders: duration of abstinence matters.	Starcke K et al.	—	2013	→
Positive affect and stress reactivity in alcohol-dependent outpatients.	McHugh RK et al.	—	2013	→
Repetitive Transcranial Magnetic Stimulation (rTMS) in the Management of Alcohol Dependence and other Substance Abuse Disorders - Emerging Data and Clinical Relevance.	Sousa AD	—	2013	→
Resting state synchrony in anxiety-related circuits of abstinent alcohol-dependent patients.	Orban C et al.	—	2013	→
Stress system changes associated with marijuana dependence may increase craving for alcohol and cocaine.	Fox HC et al.	—	2013	→
Temptation to drink as a predictor of drinking outcomes following psychosocial treatment for alcohol dependence.	Witkiewitz K	—	2013	→
The effects of exogenous progesterone on drug craving and stress arousal in cocaine dependence: impact of gender and cue type.	Fox HC et al.	—	2013	→
The relationship between impulsivity and craving in alcohol dependent patients.	Joos L et al.	—	2013	→
The role of the neuropeptide S system in addiction: focus on its interaction with the CRF and hypocretin/orexin neurotransmission.	Cannella N et al.	—	2013	→
Analyses related to the development of DSM-5 criteria for substance use related disorders: 2. Proposed DSM-5 criteria for alcohol, cannabis, cocaine and heroin disorders in 663 substance abuse patients.	Hasin DS et al.	—	2012	→
Association of V89L SRD5A2 polymorphism with craving and serum leptin levels in male alcohol addicts.	Lenz B et al.	—	2012	→
Brief case finding tools for anxiety disorders: validation of GAD-7 and GAD-2 in addictions treatment.	Delgadillo J et al.	—	2012	→
Clinical laboratory stressors used to study alcohol-stress relationships.	Thomas S et al.	—	2012	→
Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats.	Vendruscolo LF et al.	—	2012	→
Cue-induced craving and physiological reactions in recently and long-abstinent heroin-dependent patients.	Zhao M et al.	—	2012	→
Effects of alcohol dependence and withdrawal on stress responsiveness and alcohol consumption.	Becker HC	—	2012	→
How does stress lead to risk of alcohol relapse?	Sinha R	—	2012	→
Immune system inflammation in cocaine dependent individuals: implications for medications development.	Fox HC et al.	—	2012	→
Multiple roles for orexin/hypocretin in addiction.	Mahler SV et al.	—	2012	→
Naltrexone effects on cortisol secretion in women and men in relation to a family history of alcoholism: studies from the Oklahoma Family Health Patterns Project.	Lovallo WR et al.	—	2012	→
Prazosin effects on stress- and cue-induced craving and stress response in alcohol-dependent individuals: preliminary findings.	Fox HC et al.	—	2012	→
Resilience to meet the challenge of addiction: psychobiology and clinical considerations.	Alim TN et al.	—	2012	→
Sex, stress, and drug cues in addiction.	Moeller FG	—	2012	→
Stress-related neuropeptides and addictive behaviors: beyond the usual suspects.	Schank JR et al.	—	2012	→
Yohimbine-induced amygdala activation in pathological gamblers: a pilot study.	Elman I et al.	—	2012	→
Effects of stress on alcohol drinking: a review of animal studies.	Becker HC et al.	—	2011	→
New findings on biological factors predicting addiction relapse vulnerability.	Sinha R	—	2011	→
Translational and reverse translational research on the role of stress in drug craving and relapse.	Sinha R et al.	—	2011	→
Vulnerability to the rapid ("telescoped") development of alcohol dependence in individuals with anxiety disorder.	Kushner MG et al.	—	2011	→