Cited by 258Substance Abuse Treatment and OutcomesStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

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Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders

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Blaine, Sara K., Sinha, Rajita·2017·Neuropharmacology

DOI 10.1016/j.neuropharm.2017.01.037PMC PMC5479733

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Abstract

In this review, we detail the clinical evidence supporting the role of psychological and physiological stress in instrumental motivation for alcohol consumption during the development of mild to moderate alcohol use disorders (AUDs) and in the compulsive, habitual alcohol consumption seen in severe, chronic, relapsing AUDs. Traditionally, the study of AUDs has focused on the direct and indirect effects of alcohol on striatal dopaminergic pathways and their role in the reinforcing effects of alcohol. However, growing evidence also suggests that alcohol directly stimulates the hypothalamic pituitary adrenal (HPA) axis and has effects on glucocorticoid receptors in extrahypothalamic, limbic forebrain, and medial Prefrontal Cortex (PFC) circuits, which contribute to the development of AUDs and their progression in severity, chronicity, and relapse risk. Evidence indicates HPA axis, glucocorticoid, and PFC dysfunction during protracted withdrawal and under high arousal conditions in those with severe AUDs, and novel evidence is also emerging to suggest HPA axis dysfunction with binge/heavy drinking, which is associated with motivation for alcohol in non-dependent individuals. Specifically, alcohol-associated alterations in HPA axis responses to stress and alcohol cues may serve as interoceptive physiological signals and facilitate conditioning mechanisms to influence alcohol motivation. Thus, this dysfunction may serve as a potential biomarker of both risk and of relapse. Based on this emerging data, we conceptualize and present early evidence for treatment targets that may improve PFC function and/or normalize HPA axis functioning and may be beneficial in the treatment and relapse prevention of AUDs. Finally, we suggest that individual differences in alcohol-related pathophysiology in these circuits may modulate treatment and recovery response, thereby supporting the need for building personalized medicine algorithms to understand and treat AUDs. This article is part of the Special Issue entitled "Alcoholism".

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“Consistent with past results (Blaine and Sinha, 2017; Blaine et al., 2019), we found that binge drinkers (BD) had higher cortisol levels than moderate drinkers (MD).”
Influential
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“For example, attenuated cortisol reactivity may have implications for the development of and recovery from substance use disorders (Back et al., 2010; Blaine and Sinha, 2017) and different forms of psychopathology (Petrowski et al.”
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Short and prolonged maternal separation impacts on ethanol-related behaviors in rats: sex and age differences
Leichtweis, K. S., Carvalho, M., Morais‐Silva, G., Marin, M. T., & Amaral, V. C. S. (2019) · Stress · doi:10.1080/10253890.2019.1653847 · Cited by 11
“…increase dopaminergic neurotransmission in reward pathways, thereby modulating behavioral responses to substances of abuse and HPA axis responsiveness in the first days of life (Aisa et al., 2008; Blaine & Sinha, 2017; Montoya, Bos, Terburg, Rosenberger, & van Honk, 2014; Piazza & Le Moal, 1997).”
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Cumulative Risk of Substance Use in Community College Students
García, F. I. S., Bursac, Z., & Derefinko, K. J. (2020) · American Journal on Addictions · doi:10.1111/ajad.12983 · Cited by 12
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“Furthermore, a significant interaction between HPA axis activity and dopaminergic reward circuits [17, 18], which are known to play a major role in development and maintenance of addictive disorders [27–30], has been suggested.”
BackgroundResultInfluential
Sexual trauma history is associated with reduced orbitofrontal network strength in substance-dependent women
Poppa, T., Droutman, V., Amaro, H. D. L. A., Black, D. S., Arnaudova, I., & Monterosso, J. R. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101973 · Cited by 12
“Stress increases the likelihood of relapse in individuals with histories of addiction (Blaine and Sinha, 2017; Sinha, 2008), an effect”
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“Moreover, alterations in different components of the HPA axis facilitate the transition from mild-to-moderate alcohol drinking to excessive alcohol consumption and dependence, and may also contribute to the risk of relapse (Adinoff et al., 2005; Blaine and Sinha, 2017; Galesi et al., 2016; Kiefer et al., 2002a; Koob,…”
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“In parallel, stress is also associated with alcohol consumption, with stress exposure and HPA axis disfunction being an important factor for alcohol intake [280].”
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Background
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“Clinical studies have shown that stress 1 3 can exacerbate craving for drug seeking (Blaine and Sinha 2017; Preston et al.”
Background
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“Yet, concomitantly assessing the physiological stress response is necessary to better understand alcohol use, as it is the cornerstone of recent models of alcohol use and misuse (Blaine and Sinha, 2017; Koob and Schulkin, 2019).”
BackgroundInfluential
IL-6, but not TNF-α, response to alcohol cues and acute consumption associated with neural cue reactivity, craving, and future drinking in binge drinkers
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“CRH also acts in extrahypothalamic regions by modulating the levels of norepinephrine and dopamine (Bangasser and Kawasumi, 2015; Blaine and Sinha, 2017).”
Background
Sex differences in behavioral, cognitive and voluntary ethanol-intake effects in Dexamethasone-induced depression-like state in Wistar rat
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“Hyper circulating glucocorticoid is a common feature observed in the psychopathology of depression and alcohol use disorders (AUDs).”
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“In addition to stress, other factors that can influence systemic cortisol levels include the glucocorticoid gene [61], inflammation [62], medications use (corticosteroids), food with a high glycemic index [63], chronic pain [64], sleep deprivation [65], alcohol [66], and night-eating syndrome [67].”
Background
Individual stress reactivity predicts alcohol craving and alcohol consumption in alcohol use disorder in experimental and real-life settings
Zaiser, J., Hoffmann, S., Zimmermann, S., Geßner, T., Deck, M., Bekier, N. K., Abel, M., Radler, P., Langejürgen, J., Lenz, B., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03447-8 · Cited by 9
“Further, even though a decreasing EMA compliance rate over time was noted, the response rate was still high considering the time frame of one year.”
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Hemati, H., Blanton, M. B., Koura, J., Khadka, R., Grant, K. A., & Messaoudi, I. (2025) · American Journal Of Pathology · doi:10.1016/j.ajpath.2025.06.010 · Cited by 11
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Gilbertson, R. J., Leff, D. J., & Young, N. A. (2019) · Substance Use & Misuse · doi:10.1080/10826084.2019.1618333 · Cited by 8
“The hypothalamus pituitary adrenal axis (HPA axis) function in individuals with substance use disorders has long been of interest to clinicians and basic scientists (see Blaine & Sinha, 2017 for review).”
Background
Alcohol Use Disorder Masks the Effects of Childhood Adversity, Lifetime Trauma, and Chronic Stress on Hypothalamic–Pituitary–Adrenal Axis Reactivity
Zhang, A., Price, J. L., Leonard, D. S., North, C. S., Surís, A., Javors, M. A., & Adinoff, B. H. (2020) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14334 · Cited by 8
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“In fact, a wealth of studies have reported higher serum cortisol levels in addicts, including substance abusers [41, 65, 66], due to HPA axis sensitization or blunting to stress [64, 65, 67].”
Background
Assessment of early morning serum cortisol levels in adult male patients with alcohol-related disorders
Chakrabarty, B. K., Sud, K., Ganguli, P., & Khan, S. A. (2020) · Medical Journal Armed Forces India · doi:10.1016/j.mjafi.2020.03.001 · Cited by 9
Corticosterone Levels and Glucocorticoid Receptor Gene Expression in High Drinking in the Dark Mice and Their Heterogeneous Stock (HS/NPT) Founder Line
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“Polymorphisms in the gene encoding GR, NR3C1, are associated with both age of onset of drinking and drinking to intoxication in adolescents, factors which are each strong predictors of developing an AUD (Desrivieres et al., 2011).”
BackgroundInfluential
People who binge drink show neuroendocrine tolerance to alcohol cues that is associated with immediate and future drinking- results from a randomized clinical experiment
Blaine, S. K., Ridner, C. M., Campbell, B., Crone, L., Macatee, R. J., Ansell, E. B., Robinson, J. L., & Claus, E. D. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01735-9 · Cited by 8
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Clay, J. M., Baker, K. A., Mezabrovschi, R., Berti, G., Shields, G. S., Slavich, G. M., Stafford, L. D., & Parker, M. O. (2023) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2023.06.020 · Cited by 8
“The individual contributions of stressor exposure, emotional dysregulation and impulsivity to increased alcohol use are well established (Blaine and Sinha, 2017; Carbia et al., 2021).”
Background
Neuroendocrinology meets addiction: Emerging pharmacotherapies on the horizon
Loftén, A., Farokhnia, M., Vendruscolo, L. F., & Leggio, L. (2025) · Journal of Internal Medicine · doi:10.1111/joim.70021 · Cited by 7
“In humans, acute alcohol intake increases serum cortisol levels, whereas chronic alcohol consumption alters the HPA axis, resulting in higher base-line cortisol levels and blunted cortisol response following alcohol intake [170].”
Sex moderates effects of alcohol and cannabis co‐use on alcohol and stress reactivity
Claus, E. D., Blaine, S. K., Witkiewitz, K. A., & Ansell, E. B. (2022) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14797 · Cited by 7
Body mass index interacts with sex to predict readmission in in‐patients with alcohol use disorder
Hoffmann, S., Gerhardt, S., Koopmann, A., Bach, P., Sommer, W. H., Kiefer, F., Mazza, M., & Lenz, B. (2022) · Addiction Biology · doi:10.1111/adb.13239 · Cited by 7
“oxytocin,(8,9) sex steroids,(10,11) leptin(12) and hormones of the hypothalamus–pituitary–adrenal axis.(13) Nevertheless, due to the low precision and the high costs to measure some of these parameters,”
Background
Sex differences in neural response to an acute stressor in individuals with an alcohol use disorder
Grodin, E. N., Kirsch, D. E., Belnap, M. A., & Ray, L. A. (2024) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.15301 · Cited by 9
An in vivo explorative study to observe the protective effects of Puerariae flos extract on chronic ethanol exposure and withdrawal male mice
Jiang, B., Yang, W.-H., Xiu, Z., Zhang, L., Ren, X., Wang, L., Chen, L., & Asakawa, T. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111306 · Cited by 7
Effect of intravenous ghrelin administration, combined with alcohol, on circulating metabolome in heavy drinking individuals with alcohol use disorder
Kärkkäinen, O. K., Farokhnia, M., Klåvus, A., Auriola, S. O. K., Lehtonen, M., Deschaine, S. L., Piacentino, D., Abshire, K. M., Jackson, S. N., & Leggio, L. (2021) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14719 · Cited by 7
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, T. R., Sklioutovskaya-Lopez, K., Sturgill, T., Fresch, C., Clements, C. W., Lamichhane, R., Egleton, R. D., & Davies, T. H. (2022) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14913 · Cited by 7
Fear of contagion, emotional stress and coping strategies used by adults during the first wave of the COVID-19 pandemic in Nigeria
Foláyan, M. O., Ibigbami, O. I., Brown, B. J., Tantawi, M. E., Aly, N. M., Zúñiga, R. A. A., Abeldaño, G. F., Ara, E., Ellakany, P., Gaffar, B. O., et al. (2022) · BMC Psychiatry · doi:10.1186/s12888-022-04360-w · Cited by 9
“Alcohol consumption is a method that some individuals use for distancing themselves from stressors or challenges [49].”
Background
Preclinical methodological approaches investigating of the effects of alcohol on perinatal and adolescent neurodevelopment
Bailey, C. D. C., Gerlai, R. T., Cameron, N. M., Marcolin, M. L., & McCormick, C. M. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.07.011 · Cited by 7
Dimensions of Craving Interact with COMT Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment
Padula, C. B., Hansen, A. M., Hughes, R. L., & McNerney, M. W. (2021) · Brain Sciences · doi:10.3390/brainsci11010062 · Cited by 6
“and frontal regions of the brain, resulting in increased behavioral disinhibition and overevaluation of alcohol as a reward [24,26].”
Background
Differences in pituitary-adrenal reactivity in Black and White men with and without alcohol use disorder
Price, J. L., Frazier, I. R., Lewis, B., Walker, R., Javors, M. A., Nixon, S. J., & Adinoff, B. H. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.10.004 · Cited by 7
Established and Nascent Entrepreneurs: Comparing the Mental Health, Self-Care Behaviours and Wellbeing in Singapore
Gong, J., Xu, Z., Wang, S. X., Gu, M., Ong, P., & Li, Y. (2022) · Frontiers in Sociology · doi:10.3389/fsoc.2022.843101 · Cited by 6
Effects of moderate alcohol consumption on behavior and neural systems of Wistar rats
Conte, R., Zangirolame, C. M. S., Gobbo, D. R., Pereira, L. D. S., Panfílio, C. E., Reginato, R. D., Sueur, L. D. P. L., SCERNI, D. A., & Céspedes, I. C. (2022) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765202220210673 · Cited by 6
“Generally, alcohol seeking behaviors are induced, partly, by the activity of CRF system in specific regions of the brain involved in cognition and emotional control (Anthenelli 2012, Blaine & Sinha 2017).”
Background
Hypothalamic‐pituitary‐adrenal and autonomic response to psychological stress in abstinent alcohol use disorder individuals with and without depressive symptomatology
Syed, S. A., Sinha, R., Milivojevic, V., MacDougall, A., LaVallee, H., Angarita, G. A., & Fox, H. C. (2023) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2867 · Cited by 6
“Numerous studies have found that alcohol use globally perturbs stress system sensitivity at baseline and resting state (Blaine & Sinha, 2017; Gilpin & Weiner, 2017; Lu & Richardson, 2014; Muehlhan et al., 2017; Seo et al., 2013).”
Background
Early Screening for Posttraumatic Stress Disorder in Inpatient Detoxification and Motivation Treatment: Results and Consequences
Proescholdt, M. G., Müller, S. E., Vogel, M., Lang, U. E., Wiesbeck, G. A., Breit, W., Linde, A., Walter, M., & Odenwald, M. G. (2018) · European Addiction Research · doi:10.1159/000490382 · Cited by 6
Dissociative Tendencies and Alcohol Use Disorder
Noël, X., Saeremans, M., Kornreich, C., & Jaafari, N. (2018) · Current Addiction Reports · doi:10.1007/s40429-018-0225-8 · Cited by 6
Modeling neurocognitive and neurobiological recovery in addiction
Meyerhoff, D. J., & Durazzo, T. C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815298-0.00028-9 · Cited by 6
“The same factors as well as stress and stress response (Blaine and Sinha, 2017) also modulate metabolic and functional brain injury and recovery in AUD.”
Background
Clinical Outcomes of Severe Forms of Early Social Stress
Berhe, O., Gerhardt, S., & Schmahl, C. G. (2021) · Current topics in behavioral neurosciences · doi:10.1007/7854_2021_261 · Cited by 7
HPA activity mediates the link between trait impulsivity and boredom
Clay, J. M., Badariotti, J. I., Kozhushko, N., & Parker, M. O. (2024) · Physiology & Behavior · doi:10.1016/j.physbeh.2024.114637 · Cited by 5
“For example, individuals who are dependent on drugs, such as alcohol, show hypercortisolism and a blunted stress response (for reviews, see: Blaine & Sinha, 2017; Sinha, 2001) [26,27].”
Background
Risk of major depressive increases with increasing frequency of alcohol drinking: a bidirectional two-sample Mendelian randomization analysis
Feng, W., Zhang, B., Duan, P., Bi, Y.-H., Jin, Z., Li, X., Zhao, X., & Zuo, K. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1372758 · Cited by 7
Risky online buying-shopping behavior: The role of stress responsivity on the transfer from goal-directed behavior to stimulus-response habits
Thomas, T. A., Schmid, A. M., Erdal, N. K., Blümel, S., Müller, S. M., Merz, C. J., Wolf, O. T., Brand, M., Steins‐Loeber, S., & Müller, A. (2025) · Journal of Behavioral Addictions · doi:10.1556/2006.2025.00062 · Cited by 5
“A blunted biological stress reaction was found in individuals with alcohol use disorder (Blaine & Sinha, 2017) and this stress reaction has been linked to the risk of relapse (Mil-ivojevic & Sinha, 2018).”
Cortisol as a risk biomarker to guide recovery from substance use disorders
Fitzpatrick‐Schmidt, T., & Edwards, S. (2023) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.15018 · Cited by 5
Early Life Stress and Substance Use Disorders: Underlying Neurobiology and Pathways to Adverse Outcomes
Kirsch, D. E., Nemeroff, C. B., & Lippard, E. (2025) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.25023013 · Cited by 6
Plasma corticosterone, epinephrine, and norepinephrine levels increase during administration of nitrous oxide in rats
Al‐Noori, S., Cimpan, A., Maltzer, Z., Kaiyala, K. J., & Ramsay, D. S. (2017) · Stress · doi:10.1080/10253890.2017.1402175 · Cited by 5
“Glucocorticoids have been specifically implicated as an important factor influencing addictive vulnerability (Blaine & Sinha, 2017; Piazza & Deroche-Gamonet, 2013; Picetti et al., 2013; Stephens & Wand, 2012).”
Background
Genetic association of FKBP5 with trait resilience in Korean male patients with alcohol use disorder
Park, C. I., Kim, H. W., Hwang, S. S., Kang, J. I., & Kim, S. J. (2021) · Scientific Reports · doi:10.1038/s41598-021-98032-6 · Cited by 7
Randomized Placebo-Controlled Clinical Trial of Dutasteride for Reducing Heavy Drinking in Men
Covault, J., Tennen, H. A., & Feinn, R. (2024) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001849 · Cited by 4
Post-Traumatic Bio-Behavioral Rehabilitation of Adult Female Victims
Brewer‐Smyth, K., Koenig, H. G., Kafonek, K., Adams, T., Raine, A., Phil, D. L. E., & Granger, D. A. (2021) · Delaware Journal of Public Health · doi:10.32481/djph.2021.021 · Cited by 4
Association between weekly working hours and risky alcohol use: A 12-year longitudinal, nationwide study from South Korea
Baek, S., Won, J., & Yoon, J. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115325 · Cited by 4
Adolescent alcohol disrupts development of noradrenergic neurons in the nucleus of the tractus solitarius and enhances stress behaviors in adulthood in mice in a sex specific manner
Aguilar, L. A., Coker, C. R., McCullers, Z., Evans, A., Showemimo, O., Melkumyan, M., Keller, B. N., Snyder, A. E., Bingaman, S. S., Randall, P. A., et al. (2023) · Addiction Neuroscience · doi:10.1016/j.addicn.2023.100132 · Cited by 4
“…the current work may have numerous implications as stress is known to be a major factor in relapse to AUDs in treatment seeking individuals [4], although there is very little data on differences in stress-induced relapse rates in adult AUD patients with and without a history of adolescent…”
Background
Characterization in the rat of the individual tendency to rely on alcohol to cope with distress and the ensuing vulnerability to drink compulsively
Martí‐Prats, L., & Belin, D. (2024) · Brain Communications · doi:10.1093/braincomms/fcae169 · Cited by 4
“18.”
Sex differences in binge drinking-related higher morning cortisol levels and in prospective association with future alcohol intake
McGowan, C. R., Krah, M., Fogelman, N., Seo, D., & Sinha, R. (2024) · Alcohol and Alcoholism · doi:10.1093/alcalc/agae047 · Cited by 4
Alcohol and Immunity
Газатова, Н. Д., Yurova, K. A., Gavrilov, D. V., & Litvinova, L. S. (2018) · Genes and Cells · doi:10.23868/201805005 · Cited by 4
Stress and alcohol use: An experimental investigation of cognitive mechanisms
Buckheit, K. A., & Maisto, S. A. (2023) · Addiction Neuroscience · doi:10.1016/j.addicn.2023.100078 · Cited by 5
Is There an Association Between Salivary Cortisol and Dropping Out of Inpatient Substance Addiction Treatments? A Prospective Repeated Measures Study
Bøhle, K., Otterholt, E., & Bjørkly, S. K. (2022) · Substance Abuse Research and Treatment · doi:10.1177/11782218221106797 · Cited by 4
HPA-Axis Activity and Nutritional Status Correlation in Individuals with Alcohol Use Disorder
Georgakouli, K., Manthou, E., Fatouros, I. G., Deli, C. K., Koutedakis, Y., Theodorakis, Y., & Jamurtas, A. Z. (2022) · Nutrients · doi:10.3390/nu14234978 · Cited by 4
Measuring the Intensity of Stress Experienced and Its Impact on Life in Patients with Diagnosed Alcohol Use Disorder
Curyło, M., Czerw, A. I., Rynkiewicz-Andryśkiewicz, M., Andryśkiewicz, P., Mikos, M., Partyka, O., Pajewska, M., Świtalski, J., Sygit, K., Sygit, M., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13020572 · Cited by 4
Impacts of maternal separation stress on ethanol intake and endocannabinoid system in adolescent mice
Favoretto, C. A., Bertagna, N. B., Anjos-Santos, A., Loss, C. M., Rodolpho, B. T., Righi, T., Bezerra, F. R., Bianchi, P., & Cruz, F. C. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.11.037 · Cited by 5
Atrial natriuretic peptide (ANP): A novel mechanism for reducing ethanol consumption and seeking behaviors in female alcohol preferring (P) rats
Hauser, S. R., Waeiss, R. A., Molosh, A. I., Deehan, G. A., Bell, R. L., McBride, W. J., & Rodd, Z. A. (2020) · Peptides · doi:10.1016/j.peptides.2020.170403 · Cited by 4
The link between early-life adversity and later alcohol use disorder: A role for microglia?
Lichtenstein, H. D., Sequeira, M. K., & Bolton, J. L. (2025) · Neurobiology of Stress · doi:10.1016/j.ynstr.2025.100714 · Cited by 3
“Both ELA and AUD have been found to impact the activity of the body ’ s hormonal stress-response system, the HPA axis, in both humans and rodents (Allen et al., 2011; Blaine and Sinha, 2017; Frias et al., 2000; Raymond et al., 2021; Rice et al., 2008; Richardson et al., 2008).”
PT150 blocks the rewarding properties of ethanol and attenuates ethanol-induced reduction of egg laying in Coturnix quail
Radevski, M. E., Prendergast, M., Bardo, M. T., & Akins, C. K. (2023) · Psychopharmacology · doi:10.1007/s00213-022-06299-y · Cited by 3
“Increased CORT has been linked to the sensitization of the dopaminergic reward pathways and the increased reward of ethanol in preclinical models (Bjork and Gilman 2014; Blaine and Sinha 2017; Levita et al.”
Background
Global DNA methylation patterns in Alcohol Use Disorder
Schuch, J. B., Bandeira, C. E., Jorge, L. S., Müller, D., Charão, M. F., da Silva, B. S., Grevet, E. H., Kessler, F. H. P., DIEMEN, L. V., Rovaris, D. L., et al. (2023) · Genetics and Molecular Biology · doi:10.1590/1678-4685-gmb-2023-0139 · Cited by 3
“This scenario could be related to the development and severity of AUD (Blaine and Sinha, 2017).”
Background
Emotional difficulties among individuals with alcohol use disorder: the mediating role of psychological mechanisms linked to mindfulness
Cavicchioli, M., Ramella, P., Simone, G., Vassena, G., Movalli, M., & Maffei, C. (2020) · Journal of Substance Use · doi:10.1080/14659891.2020.1745310 · Cited by 3
Hypothalamic-pituitary-adrenal axis dysregulation initiated by a binge drinking pattern, but not by acute alcohol intake, in female and male adolescents
Pina, M. R. R., Monleón, S., & Vinader‐Caerols, C. (2021) · Adicciones · doi:10.20882/adicciones.1665 · Cited by 3
The association between mental health symptoms and alcohol use among Chinese psychiatrists during the early stage of the COVID-19 pandemic
Mo, D., Gluck, R. L., Jiang, F., Tao, R., Geng, F., Liu, T., Liu, Y., Liu, H., & Tang, Y. (2023) · Alcohol · doi:10.1016/j.alcohol.2023.08.006 · Cited by 3
Subjective stress and any drinking during alcohol treatment: Disentangling within and between person autoregressive effects
Witkiewitz, K. A., Garcia, C. C., & Muthén, B. (2023) · Neurobiology of Stress · doi:10.1016/j.ynstr.2023.100602 · Cited by 3
“Empirical human studies over the past six decades have provided compelling evidence that alcohol and stress are associated (Becker, 2017; Blaine and Sinha, 2017; Keyes et al., 2012) and that exposure to stress predicts subsequent craving for alcohol (Bach et al., 2023; Blaine et al., 2019; Fox et…”
Influential
Explaining factors contributing to alcohol consumption among elderly men: a qualitative study
Bazrafshan, M.-R., Mansouri, A., Salmani, A., Masmouei, B., Kavi, E., Elahi, M., & Barghi, O. (2024) · Journal of Substance Use · doi:10.1080/14659891.2024.2356582 · Cited by 3
“…pain, which has been proven in an integrated review study (Zale et al., 2015) and this finding has also been proven physiologically that stress In people, it causes alcohol consumption, and alcohol, with its effect on the brain, causes a decrease in the perception of stress (Blaine & Sinha, 2017).”
Changes in Alcohol Consumption During and After the Covid-19 Pandemic From 2020 to 2023 in a Prospective Cohort of Italian Adults
Cerrai, S., Carreras, G., Monti, F., Stival, C., Lugo, A., Bosetti, C., Biagioni, S., Fanucchi, T., Gorini, G., Amerio, A., et al. (2024) · Journal of Epidemiology · doi:10.2188/jea.je20230340 · Cited by 3
“42 – 44 Alcohol use and misuse are well-known to be linked to increased levels of stress, 45 and higher level of stress and anxiety probably contributed to the use of alcohol to cope with the pandemic situation.”
The Neuroimmune System in Psychiatric Disorders
Hassan, Y., ESTEVES, S. C., Leyrer‐Jackson, J. M., & Thomas, M. P. (2024) · Springer eBooks · doi:10.1007/978-3-031-68237-7_56 · Cited by 2
Excess after stress—A three‐study validation of the salzburg stress drinking scale as a new tool to measure the stress–drinking relationship
Reichenberger, J., van Alebeek, H., Messer, T., & Jens Blechert, A. (2023) · Stress and Health · doi:10.1002/smi.3293 · Cited by 2
Elevated GABAergic neurotransmission prevents chronic intermittent ethanol induced hyperexcitability of intrinsic and extrinsic inputs to the ventral subiculum of female rats
Bach, E. C., & Weiner, J. L. (2024) · Neurobiology of Stress · doi:10.1016/j.ynstr.2024.100696 · Cited by 2
“The basolateral amygdala (BLA) and the ventral hippocampus (vHC) are two such interconnected brain regions (Almonte et al., 2017; Blaine and Sinha, 2017; Chappell et al., 2013; Grace et al., 2021; Rau et al., 2015; Silberman et al., 2009).”
Recent Alcohol Use Influences Associations between Cortisol Levels and Negative Affect: The New Orleans Alcohol Use in HIV Study
Fitzpatrick‐Schmidt, T., Oral, E., Welsh, D. A., Molina, P. E., Ferguson, T. F., & Edwards, S. (2025) · AIDS and Behavior · doi:10.1007/s10461-025-04815-7 · Cited by 2
Contributions of testosterone to excessive alcohol drinking in males: Potential role for interactions with the HPA axis
Zegarelli, R. A., & Radke, A. K. (2025) · Alcohol · doi:10.1016/j.alcohol.2025.09.005 · Cited by 2
“Interactions between alcohol, stress, and the HPA axis have been thoroughly studied, revealing an important role for this system in initiation, maintenance, and relapse to drinking (Blaine & Sinha, 2017; Dunne & Ivers, 2023; Stephens & Wand, 2012).”
Alcohol exposure significantly influences gene expression in the hypothalamus, highlighting complex links with gonadotropin-releasing hormone signaling and thyroid hormone production in adolescent mice
Sun, G., Peng, Y., Hu, C., Zheng, Y., Cheng, Y., Qi, X., & Jin, Y. (2025) · BMC Medical Genomics · doi:10.1186/s12920-025-02235-z · Cited by 2
“Altered activity of the hypothalamic–pituitary–adrenal (HPA) axis is closely tied to dependence maintenance and relapse vulnerability [7].”
Sex/gender differences in orbitofrontal cortex reactivity underlying the associations between stress, social relationships, and problematic alcohol use
Maxwell, A. M., Rawls, E., & Zilverstand, A. (2025) · Psychological Medicine · doi:10.1017/s0033291725102250 · Cited by 2
“…that social support modulates threat and stress neural networks (Eisenberger, 2013; Hornstein et al., 2024; Hyde, Gorka, Manuck, & Hariri, 2011; Lin et al., 2023), both of which overlap with alcohol-related reward circuitry (Blaine et al., 2019; Blaine & Sinha, 2017), including the OFC/vmPFC.”
Alcohol and the endocrine system: A critical review of disruptions, potential mechanisms, and health implications
Molina, P. E., & Simon, L. (2026) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.70221 · Cited by 2
“These alterations in HPA function further reinforce anxiety, craving, and risk of relapsing, highlighting the complex and bidirectional relationship between AUD and stress-related neuroendocrine signaling (Blaine & Sinha, 2017 ).”
Mobile Health for Alcohol Use Assessment: Longitudinal Effects of Breathalyzer Self-Monitoring in Everyday Contexts
Lu, Y., Fairbairn, C. E., Han, J., & Bosch, N. (2026) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20241170 · Cited by 2

Authors: Blaine, S. K., & Sinha, R.
Affiliations: Yale University (US)
Corresponding author: Sinha, Rajita
ORCID: Blaine, Sara K.
Sinha, Rajita
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2017-08
Volume: 122
Pages: 136-147
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2017.01.037
PMC: PMC5479733
OpenAlex: W2583762848
Cited by: 257
References: 133
Citations by year: 2026: 21 · 2025: 20 · 2024: 25 · 2023: 35 · 2022: 38 · 2021: 30 · 2020: 39 · 2019: 13 · 2018: 29 · 2017: 7
FWCI: 3.19
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Alcoholism (R01-AA13892, R01-AA020504)
Alcohol Abuse at the National Institutes of Health (R21-AA025277)
Topics: Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: alcoholism, stress, glucocorticoids, hypothalamic-pituitary-adrenal axis, relapse, drinking motives, binge drinking, prefrontal cortex, alcohol withdrawal, alcohol cue reactivity, interoception, conditioning, biomarkers, personalized medicine, treatment goals
MeSH terms: Alcohol Drinking, Alcoholism, Animals, Brain, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Recurrence, Stress, Physiological, Stress, Psychological, Prefrontal Cortex

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Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders

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