The influence of stress and early life adversity on addiction: Psychobiological mechanisms of risk and resilience
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Preclinical, clinical, and population research demonstrates that stress and early life adversity (ELA) increase vulnerability to initiate, maintain, and relapse in addiction. Individuals with addiction problems have higher prevalence of trauma exposure than nondrug users; and this association extends to young populations (e.g., adolescents). Mechanisms for these associations likely involve multiple systems, including changes in the mesolimbic reward functions, HPA axis stress response, and other stress- and reward-related pathways. Other brain morphological and functional changes are also likely involved and directly contribute to the neurohormonal and behavioral alterations observed during adulthood in those exposed to ELA. Stress-related risk is influenced by sex, genetic factors, and resilience, among other factors. Our heuristic model proposes that long-term effects of stress and ELA on the brain contribute to dysregulation of the stress response, emotional reactivity, reward systems, cognitive dysregulation, and delay discounting that lead to impulsive and high-risk behaviors, such as drug use and relapse.
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Various forms of ELA are associated with illicit drug use later in life.
“In humans, various forms of ELA are associated with illicit drug use later in life [21,22,23].”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [23]
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Wiss, D. A., Avena, N., & Gold, M. (2020) · Nutrients · doi:10.3390/nu12113521 · Cited by 66 · see citing works
Enduring disruption of reward and stress circuit activities by early-life adversity in male rats
Levis, S. C., Birnie, M. T., Bolton, J. L., Perrone, C. R., Montesinos, J. S., Baram, T. Z., & Mahler, S. V. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01988-w · Cited by 42 · see citing works
Resilience to the effects of social stress on vulnerability to developing drug addiction
Calpe-López, C., Martínez-Caballero, M. Á., García-Pardo, M. P., & Aguilar, M. A. (2022) · World Journal of Psychiatry · doi:10.5498/wjp.v12.i1.24 · Cited by 38 · see citing works
Wiss, D. A., Brewerton, T. D., & Tomiyama, A. J. (2021) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-021-01293-3 · Cited by 26 · see citing works
Al’Absi, M., DeAngelis, B. N., Fiecas, M. J. A., Budney, A. J., & ALLEN, S. S. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06087-8 · Cited by 15 · see citing works
“These blunted stress responses among nicotine users may reflect long-term effects of nicotine use on stress response systems, leading to increased risk for maintaining use (to compensate for such dysregulation) and to increased vulnerability to stressrelated disorders, such as depression (al’Absi 2020; al’Absi et al.…”
BackgroundSelf-citationEitan, S., Madison, C. A., & Kuempel, J. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.04.019 · Cited by 8 · see citing works
Loreto, B. B. L., Sordi, A. O., de Castro, M. N., Ornell, F. R., Guarnieri, E. P., Roza, T. H., Schuch, J. B., Cima, M. D. S., Pechansky, F., Grevet, E. H., et al. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1298002 · Cited by 9 · see citing works
Calpe-López, C., Martínez-Caballero, M. Á., García-Pardo, M. P., & Aguilar, M. A. (2023) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2023.173574 · Cited by 6 · see citing works
Early life stress and body-mass-index modulate brain connectivity in alcohol use disorder
Agarwal, K., Joseph, P. V., Zhang, R., Schwandt, M., Ramchandani, V., Diazgranados, N., Goldman, D., & Momenan, R. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02756-8 · Cited by 3 · see citing works
Associations Between Childhood Trauma and Tobacco Use Outcomes in Adults after Overnight Abstinence
Palmisano, A. N., Schwartz, E. K. C., Gueorguieva, R. V., & Sofuoglu, M. (2023) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntad135 · Cited by 5 · see citing works
Opioid drug seeking after early-life adversity: a role for delta opioid receptors
Levis, S. C., Birnie, M. T., Xie, Y., Kamei, N., Kulkarni, P. V., Montesinos, J. S., Perrone, C. R., Cahill, C. M., Baram, T. Z., & Mahler, S. V. (2024) · Addiction Neuroscience · doi:10.1016/j.addicn.2024.100175 · Cited by 5 · see citing works
Keogh, T. M., Howard, S., Nakajima, M., & Al’Absi, M. (2024) · Psychophysiology · doi:10.1111/psyp.14719 · Cited by 4 · see citing works
“…proposed to increase the risk of poorer physical health, and the findings may reflect the enduring effects of smoking on multiple self-regulatory systems (e.g., autonomic, adrenocortical; al'Absi, 2006; al'Absi, 2020), with increased risk of subsequent disease (al'Absi et al., 2022; Burns, 2003).”
Self-citationWhy do people use drugs? A neglected question
McLoughlin, A. (2023) · Irish Journal of Medical Science (1971 -) · doi:10.1007/s11845-023-03416-4 · Cited by 4 · see citing works
Xiaodi, M., Li, B., Nie, H., Ding, W., He, R., He, W., & Liu, W. (2025) · Scientific Reports · doi:10.1038/s41598-025-24317-9 · Cited by 3 · see citing works
“…as a chronic psychological stressor, promotes addiction via an endocrine pathway: by activating the HPA axis to elevate cortisol levels, which thereby suppresses prefrontal inhibitory control and enhances reward sensitivity to online stimuli, thus establishing a vicious “stress-reward” cycle 48 .”
Early life adversity increases risk for chronic post-traumatic pain, data from humans and rodents
McKibben, L. A., Woolard, A., McLean, S. A., Zhao, Y., Verma, T., Mickelson, J., Lu, H., Lobo, J. J., House, S. L., Beaudoin, F. L., et al. (2025) · Pain · doi:10.1097/j.pain.0000000000003555 · Cited by 3 · see citing works
Pirri, F., Akbarabadi, A., Sadat‐Shirazi, M., Zadeh‐Tehrani, S. N., Mahboubi, S., Goudarzi, A. K., & Zarrindast, M. (2021) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10094 · Cited by 3 · see citing works
“It has been shown that stress and ELS have a prominent role in addiction [for review, see (al'Absi, 2020)].”
BackgroundHeidrich, N., Nin, M. S., Almeida, F. B., Constant, H. M. R. M., Freese, L., & Barros, H. M. T. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1514365 · Cited by 2 · see citing works
Adverse Childhood Experiences and Neurodevelopment
Brewer‐Smyth, K. (2022) · Springer eBooks · doi:10.1007/978-3-031-08801-8_2 · Cited by 1 · see citing works
Rayan, H., Gross, Z., & Efrati, Y. (2025) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2025.107588 · Cited by 1 · see citing works
Brewer‐Smyth, K. (2022) · Springer eBooks · doi:10.1007/978-3-031-08801-8_5 · Cited by 1 · see citing works
Trask, C. L., Roth, R. M., Henricks, A. M., Hickey, S. M., & Brunette, M. F. (2024) · Psychiatry Research Communications · doi:10.1016/j.psycom.2024.100179 · Cited by 1 · see citing works
Ramakrishnan, N., Tiba, S., Goldstein, A. L., & Erb, S. M. (2024) · Brain Sciences · doi:10.3390/brainsci14111081 · Cited by 1 · see citing works
“Extending on Lovallo’s (2013) model, al’Absi (2020) [23,24] proposed a modified conceptual model that addresses the temporal relationship between factors influencing the relationship between childhood maltreatment and problem substance use [22].”
InfluentialToole‐Anstey, C., Carr, L., Deans, E., & Sidis, A. (2025) · Advances in Dual Diagnosis · doi:10.1108/add-08-2024-0019 · Cited by 1 · see citing works
Introduction, Epidemiology, Measurement, and the Cycle of Trauma
Brewer‐Smyth, K. (2022) · Springer eBooks · doi:10.1007/978-3-031-08801-8_1
Potential Lifelong Neurobiological, Bio-behavioral, and Other Outcomes of Trauma
Brewer‐Smyth, K. (2022) · Springer eBooks · doi:10.1007/978-3-031-08801-8_3
Early life adversity increases risk for chronic posttraumatic pain, data from humans and rodentsPreprint
McKibben, L. A., Woolard, A., McLean, S. A., Zhao, Y., Verma, T., Mickelson, J., Lu, H., Lobo, J. J., House, S. L., Beaudoin, F. L., et al. (2024) · medRxiv · doi:10.1101/2024.11.01.24316303
Stress across systems and lifespan: emerging biomarkers and mechanisms of resilience
Al’Absi, M. (2025) · Journal of Neural Transmission · doi:10.1007/s00702-025-03030-x
“…insights extend existing literature (Kudielka and Wüst 2010; Mifsud et al. 2011 ; Lemieux and al’Absi 2016 ; O’Donnell 2024 ; al’Absi et al. 2021; al’Absi 2020) and are particularly timely, as public health systems world-wide grapple with the downstream effects of chronic stress at both…”
Self-citationMental health, climate anxiety, and progression of Parkinson’s disease
Lau, Y. H., Popławska-Domaszewicz, K., Haridas, S., Chopra, S., Koh, K. L., & Chaudhuri, К. R. (2026) · International review of movement disorders · doi:10.1016/bs.irmvd.2026.03.003
Yang, H. U. I., Liu, Z. H., Miao, Z., Peng, W., Cheng, M., Zheng, K., Liu, S., Chen, Q., & Yi, J. (2026) · BMC Psychology · doi:10.1186/s40359-026-04816-8
Chemsex et usages de substances en contexte sexuel : les problématiques sexuelles spécifiques
Papazian, P., & Miele, C. (2026) · Annales Médico-psychologiques revue psychiatrique · doi:10.1016/j.amp.2026.04.005
He, W., Hu, A., Zhao, T., Deng, L., Wu, H., & Xiang, X. (2026) · Addiction Biology · doi:10.1111/adb.70173
Adverse Childhood Experiences (ACEs) and Age of First “Gateway” Substance Use
Maxwell, C. D., & Maxwell, S. R. (2026) · Emerald Group Publishing Limited eBooks · doi:10.1108/s1530-353520260000037008
Neuroscience and neurocircuitry of substance use disorders
Thomas, D. C., Somaiya, T. S., Prabhakar, S., Thomas, D., Ravi, A., & Pandian, A. P. G. (2026) · The Journal of the American Dental Association · doi:10.1016/j.adaj.2026.05.016
- Authors
- Al’Absi, M.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Mustafa Al’Absi
- ORCID
- Mustafa Al’Absi
- Venue
- International review of neurobiology
- Publisher
- Elsevier
- Published
- 2020
- Volume
- 152
- Pages
- 71-100
- ISSN
- 0074-7742 (ISSN-L)
- PMC
- PMC9188362
- OpenAlex
- W3021998954
- Cited by
- 34
- References
- 249
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 3 · 2020: 1
- FWCI
- 24.93
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International review of neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01DA027232, R01DA016351)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- childhood adversity, stress, addiction, resilience, trauma exposure, hypothalamic-pituitary-adrenal axis, mesolimbic reward system, stress response dysregulation, emotional reactivity, delay discounting, impulsivity, drug relapse, sex differences, genetic factors, brain structural changes, cognitive dysregulation, adolescents
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Neural Pathways, Stress, Psychological, Behavior, Addictive, Adult Survivors of Child Abuse, Resilience, Psychological
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