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Chronic Stress, Drug Use, and Vulnerability to Addiction
Open accessAbstract
Stress is a well‐known risk factor in the development of addiction and in addiction relapse vulnerability. A series of population‐based and epidemiological studies have identified specific stressors and individual‐level variables that are predictive of substance use and abuse. Preclinical research also shows that stress exposure enhances drug self‐administration and reinstates drug seeking in drug‐experienced animals. The deleterious effects of early life stress, child maltreatment, and accumulated adversity on alterations in the corticotropin releasing factor and hypothalamic‐pituitary‐adrenal axis (CRF/HPA), the extrahypothalamic CRF, the autonomic arousal, and the central noradrenergic systems are also presented. The effects of these alterations on the corticostriatal‐limbic motivational, learning, and adaptation systems that include mesolimbic dopamine, glutamate, and gamma‐amino‐butyric acid (GABA) pathways are discussed as the underlying pathophysiology associated with stress‐related risk of addiction. The effects of regular and chronic drug use on alterations in these stress and motivational systems are also reviewed, with specific attention to the impact of these adaptations on stress regulation, impulse control, and perpetuation of compulsive drug seeking and relapse susceptibility. Finally, research gaps in furthering our understanding of the association between stress and addiction are presented, with the hope that addressing these unanswered questions will significantly influence new prevention and treatment strategies to address vulnerability to addiction.
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“two emotions known to increase the risk of relapse in substance use (115, 116).”
From Mobile intervention for individuals with psychosis, dual disorders, and their common comorbidities: A literature review (2019) · cites this paper as [116]
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In the citing paper
“This is an important concept in the field of addiction (Burke and Miczek, 2014b; George et al., 2012; Sinha, 2008), that is hypothesized to mediate the relationship between ELS and increased risk of substance use disorders (Andersen and Teicher, 2009).”
From The effects of early life stress on reward processing (2018) · cites this paper as Sinha, 2008
In the citing paper
“Stress was considered to be a common risk factor of both chemical addictions [e.g., drug dependence; (42)] and behavioral addictions [e.g., excessive smartphone use; (43)].”
From COVID-19 stress and addictive social media use (SMU): mediating role of active use and social media flow (2021) · cites this paper as [42]
In the citing paper
“Given known linkages between stress and addiction [42, 43], MBIs might ameliorate addictive behavior by attenuating stress reactivity and augmenting stress recovery.”
From Mindfulness-based treatment of addiction: current state of the field and envisioning the next wave of research (2018) · cites this paper as [42]
In the citing paper
“Stress, negative affect, and pain provide additional interoceptive input to elicit drug use schemas and further dysregulate prefrontal control over automaticity,20–23 amplifying addictive behavior.24”
In the citing paper
“Considerable evidence from population-based and clinical studies indicates a significant and positive association of high uncontrollable stressful events and chronic stress states with both substance addiction (Sinha, 2008) and with adiposity, BMI and weight gain”
From Role of addiction and stress neurobiology on food intake and obesity (2018) · cites this paper as Sinha, 2008
In the citing paper
“Abundant research has demonstrated an association between substance dependence and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis (Clarke et al., 2008; Koob, 2008; Sinha, 2008).”
From Effects of adverse childhood experiences on the association between intranasal oxytocin and social stress reactivity among individuals with cocaine dependence (2015) · cites this paper as Sinha, 2008
In the citing paper
“Previous situations of reduced well-being and impaired social environment have been found to be associated with overeating and being overweight as well as increased substance and screen use [3-5].”
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Goldfarb, E. V., Shields, G. S., Daw, N. D., Slavich, G. M., & Phelps, E. A. (2017) · Learning & Memory · doi:10.1101/lm.045179.117 · Cited by 30
Jastreboff, A. M., Potenza, M. N., Lacadie, C., Hong, K. A., Sherwin, R. S., & Sinha, R. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.194 · Cited by 32
Self-citationMontagud-Romero, S., Reguilon, M. D., Roger-Sanchez, C., Pascual, M., Aguilar, M. A., Guerri, C., Miñarro, J., & Rodríguez-Arias, M. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.07.008 · Cited by 31
Stress-induced cross-sensitization to amphetamine is related to changes in the dopaminergic system
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Stress as a Risk Factor for Substance Use Disorders: A Mini-Review of Molecular Mediators
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Gupta, H., Gupta, S., & Rozatkar, A. R. (2022) · Indian Journal of Psychological Medicine · doi:10.1177/02537176211032366 · Cited by 14
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Insights into US life expectancy stagnation from birth cohort mortality dynamics
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Metadata
- Authors
- Sinha, R.
- Affiliations
- Yale University (US)
- Corresponding author
- Sinha, Rajita
- ORCID
- Sinha, Rajita
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2008-10
- Volume
- 1141
- Issue
- 1
- Pages
- 105-130
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- PMC
- PMC2732004
- OpenAlex
- W2043559838
- Cited by
- 1,904
- References
- 342
- Citations by year
- 2026: 129 · 2025: 122 · 2024: 120 · 2023: 136 · 2022: 156 · 2021: 143 · 2020: 176 · 2019: 114 · 2018: 150 · 2017: 109 · 2016: 103 · 2015: 97 · 2014: 83 · 2013: 73 · 2012: 66
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1ul1rr024925-01)
- National Institute on Alcohol Abuse and Alcoholism (R01AA013892, R01-AA-13892)
- National Institute on Drug Abuse (R01-DA18219, R01DA018219, P50-DA165556, PL1DA024859)
- National Center for Research Resources (U01-RR24925, UL1-RR024925)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- chronic stress, addiction vulnerability, early life stress, child abuse, corticotropin-releasing factor, hypothalamic-pituitary-adrenal axis, noradrenergic system, mesolimbic dopamine system, glutamate, GABA, self-administration, drug-seeking behavior, stress regulation, impulse control, compulsive drug seeking, substance use risk factors
- MeSH terms
- Arousal, Chronic Disease, Corticotropin-Releasing Hormone, Disease Susceptibility, Emotions, Female, Humans, Hypothalamo-Hypophyseal System, Limbic System, Male, Pituitary-Adrenal System, Reward, Self Medication, Illicit Drugs, Stress, Physiological, Stress, Psychological, Substance Withdrawal Syndrome, Sympathetic Nervous System, Neurotransmitter Agents, Substance-Related Disorders
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