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Neurobiologic Advances from the Brain Disease Model of Addiction
Open accessAbstract
This article reviews scientific advances in the prevention and treatment of substance-use disorder and related developments in public policy. In the past two decades, research has increasingly supported the view that addiction is a disease of the brain. Although the brain disease model of addiction has yielded effective preventive measures, treatment interventions, and public health policies to address substance-use disorders, the underlying concept of substance abuse as a brain disease continues to be questioned, perhaps because the aberrant, impulsive, and compulsive behaviors that are characteristic of addiction have not been clearly tied to neurobiology. Here we review recent advances in the neurobiology of addiction to clarify the link between addiction and brain function and to broaden the understanding of addiction as a brain disease. We review findings on the desensitization of reward circuits, which dampens the ability to feel pleasure and the motivation to pursue everyday activities; the increasing strength of conditioned responses and stress reactivity, which results in increased cravings for alcohol and other drugs and negative emotions when these cravings are not sated; and the weakening of the brain regions involved in executive functions such as decision making, inhibitory control, and self-regulation that leads to repeated relapse. We also review the ways in which social environments, developmental stages, and genetics are intimately linked to and influence vulnerability and recovery. We conclude that neuroscience continues to support the brain disease model of addiction. Neuroscience research in this area not only offers new opportunities for the prevention and treatment of substance addictions and related behavioral addictions (e.g., to food, sex, and gambling) but may also improve our understanding of the fundamental biologic processes involved in voluntary behavioral control. In the United States, 8 to 10% of people 12 years of age or older, or 20 to 22 million people, are addicted to alcohol or other drugs. 1 The abuse of tobacco, alcohol, and illicit drugs in the United States exacts more than $700 billion annually in costs related to crime, lost work productivity, and health care. 2-4 After centuries of efforts to reduce addiction and its related costs by punishing addictive behaviors failed to produce adequate results, recent basic and clinical research has provided clear evidence that addiction might be better considered and treated as an acquired disease of the brain (see Box 1 for definitions of substance-use disorder and addiction). Research guided by the brain disease model of addiction has led to the development of more effective methods of prevention and treatment and to more informed public health policies. Notable examples include the Mental Health Parity and Addiction Equity Act of 2008, which requires medical insurance plans to provide the same coverage for substance-use disorders and other mental illnesses that is provided for other illnesses, 5 and the proposed bipartisan Senate legislation that From the National Institute on Drug Abuse (N.D.V.) and the National Institute of Alcohol Abuse and Alcoholism (G.F.K.) — both in Bethesda, MD; and the Treatment Research Institute, Philadelphia (A.T.M.). Address reprint requests to Dr. Volkow at the National Institute on Drug Abuse, 6001 Executive Bld., Rm. 5274, Bethesda, MD 20892, or at nvolkow@ nida . nih . gov.
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“There is a growing consensus that SUDs, once developed, tend to be chronic disorders 161 , reflecting long- lasting changes in brain function 50,51 , that are exacerbated by the cumulative mental health and social consequences that they trigger.”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [50]
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“The transition from controlled drug use into addiction mani fests itself in a repetitive cycle of intoxication, withdrawal and craving 49 , occurring along with a deterioration of mood that the addicted individual experiences as dysphoria/depression, anxi ety, irritability and anhedonia when not intoxicated 50 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [50]
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“Animal models have shown that both ethanol intake and anticipation prompt dopamine release in the NAc, impacting the mesocorticolimbic system associated with craving, reward, and behavioral control”
From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [111]
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“emerging evidence has pointed out that addiction is in fact associated with structural and functional brain alterations, including deficits in reward, attention, memory and motivation mechanisms (3)”
From Addiction Psychotherapy: Going Beyond Self-Medication (2022) · cites this paper as [4]
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“Further research demonstrated the reciprocal nature of these neurobiological deficits, suggesting that they serve both as a cause for addiction, in predisposing individuals toward the onset of addiction, and as the effect of addiction, in further altering some neurobiological mechanisms, and even genetics, following intensive and prolonged intoxication (4).”
From Addiction Psychotherapy: Going Beyond Self-Medication (2022) · cites this paper as [4]
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“Case–control neuroimaging studies of the brain with high-resolution provide early evidence for altered brain integrity in brain regions with a high density of CB1 receptors in heavy cannabis users [75].”
From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [75]
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“The primary subcortical brain target is the nucleus accumbens (NAc) which is considered the center of the reward circuitry and heavily implicated in substance use and craving [18–22].”
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“CRH affects hormones involved in the stress response, including cortisol, and has been associated with the stress response and relapse to drug taking in animals39,40.”
From Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use (2019) · cites this paper as [40]
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Citations
Cites
Durlak, J. A., Weissberg, R. P., Dymnicki, A. B., Taylor, R. D., & Schellinger, K. B. (2011) · Child Development · doi:10.1111/j.1467-8624.2010.01564.x · Cited by 10,854
Brain development during childhood and adolescence: a longitudinal MRI study
Giedd, J. N., Blumenthal, J., Jeffries, N. O., Castellanos, F. X., Liu, H., Zijdenbos, A., Paus, T., Evans, A. C., & Rapoport, J. L. (1999) · Nature Neuroscience · doi:10.1038/13158 · Cited by 5,552
Koob, G. F., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.110 · Cited by 5,340
Self-citationBardo, M. T., & Hammer, R. P. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90226-e · Cited by 3,229
Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications
Goldstein, R. Z., & Volkow, N. D. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3119 · Cited by 2,749
Self-citationGetting formal with dopamine and reward
Schultz, W. (2002) · Neuron · doi:10.1016/s0896-6273(02)00967-4 · Cited by 2,574
Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety
Davis, M., Walker, D. L., Miles, L., & Grillon, C. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.109 · Cited by 1,513
Synaptic plasticity and addiction
Kauer, J. A., & Malenka, R. C. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2234 · Cited by 1,397
The brain on drugs: from reward to addiction
Volkow, N. D., & Morales, M. (2015) · Cell · doi:10.1016/j.cell.2015.07.046 · Cited by 1,306
Self-citationCocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction
Volkow, N. D., Wang, G.-J., Telang, F., Fowler, J. S., Logan, J., Childress, A.-R., Jayne, M., Ma, Y., & Wong, C. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1544-06.2006 · Cited by 1,164
Self-citation
Research works printed but not linked: 2
- Busch SH, 2014, Am J Manag Care, 20, 76
- 10.15288/jsads.2014.75.108 · DOI
Cited by
Sorted by citations
Brand, M., Wegmann, E., Stark, R., Müller, A., Wölfling, K., Robbins, T. W., & Potenza, M. N. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.06.032 · Cited by 2,126
23andMe Research Team, Liu, M., Psychiatry, H. A.-I., Jiang, Y., Wedow, R., Li, Y., Brazel, D. M., Chen, F., Datta, G., Davila-Velderrain, J., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0307-5 · Cited by 1,896
Liking, wanting, and the incentive-sensitization theory of addiction
Berridge, K. C., & Robinson, T. E. (2016) · American Psychologist · doi:10.1037/amp0000059 · Cited by 1,440
Handbook of Religion and Health
Koenig, H. G., VanderWeele, T. J., & Peteet, J. R. (2023) · doi:10.1093/oso/9780190088859.001.0001 · Cited by 1,160
The dopamine motive system: implications for drug and food addiction
Volkow, N. D., Wise, R. A., & Baler, R. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.130 · Cited by 939
Self-citationThe Neuroscience of Drug Reward and Addiction
Volkow, N. D., Michaelides, M., & Baler, R. (2019) · Physiological Reviews · doi:10.1152/physrev.00014.2018 · Cited by 863
Self-citationCarvalho, A. F., Heilig, M. A., Perez, A., Probst, C., & Rehm, J. T. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31775-1 · Cited by 714
Johnson, M. W., Hendricks, P. S., Barrett, F. S., & Griffiths, R. R. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.11.010 · Cited by 506
Volkow, N. D., & Blanco, C. (2023) · World psychiatry · doi:10.1002/wps.21073 · Cited by 503
Self-citationGenetic diversity fuels gene discovery for tobacco and alcohol use
Saunders, G., Wang, X., Chen, F., Jang, S.-K., Liu, M., Wang, C., Gao, S., Jiang, Y., Khunsriraksakul, C., Otto, J. M., et al. (2022) · Nature · doi:10.1038/s41586-022-05477-4 · Cited by 481
“…and projection GABA neurons from medium spiny neurons of the striatum (telencephalon inhibitory projecting neurons), along with neurons in various subcortical structures such as the hypothalamus and midbrain, consistent with aspects of the mesolimbic theory of addiction 7,8 (Extended Data Fig.”
Emotions and brain function are altered up to one month after a single high dose of psilocybin.
Barrett, F. S., Doss, M. K., Sepeda, N. D., Pekar, J. J., & Griffiths, R. R. (2020) · Scientific Reports · doi:10.1038/s41598-020-59282-y · Cited by 375
Alcohol use disorder relapse factors: A systematic review.
Sliedrecht, W., de Waart, R., Witkiewitz, K., & Roozen, H. G. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.05.038 · Cited by 358
Brain default-mode network dysfunction in addiction
Zhang, R., & Volkow, N. D. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.06.036 · Cited by 386
Self-citationAshok, A. H., Mizuno, Y., Volkow, N. D., & Howes, O. D. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.0135 · Cited by 330
Self-citationNeuroscience of Addiction: Relevance to Prevention and Treatment
Volkow, N. D., & Boyle, M. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.17101174 · Cited by 389
Self-citationThe role of neuroimmune signaling in alcoholism
Crews, F. T., Lawrimore, C. J., Walter, T. J., & Coleman, L. G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.031 · Cited by 321
Amaro, H. D. L. A., Sánchez, M., Bautista, T. G., & Cox, R. J. A. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108518 · Cited by 368
“Neurobiological studies have provided evidence of genetic vulnerability and sensitivity to stress leading to adaptations in the HPA axis responsiveness related to the development and maintenance of addiction (Koob and Volkow, 2016; Sinha, 2001).”
Ekhtiari, H., Tavakoli, H., Addolorato, G., Baeken, C., Bonci, A., Campanella, S., Castelo-Branco, L. E. C., Challet‐Bouju, G., Clark, V. P., Claus, E. D., et al. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.06.007 · Cited by 321
Ethics of the Attention Economy: The Problem of Social Media Addiction
Bhargava, V. R., & Velasquez, M. (2021) · Business Ethics Quarterly · doi:10.1017/beq.2020.32 · Cited by 292
Crescenzo, F. D., Ciabattini, M., D’Alò, G. L., Giorgi, R. D., Giovane, C. D., Cassar, C., Janiri, L., Clark, N. C., Ostacher, M. J., & Cipriani, A. (2018) · PLoS Medicine · doi:10.1371/journal.pmed.1002715 · Cited by 290
Use and misuse of opioids in chronic pain
Volkow, N., Benveniste, H., & McLellan, A. T. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-011817-044739 · Cited by 279
Self-citationZhang, M. X., & Wu, A. M. S. (2020) · Addictive Behaviors · doi:10.1016/j.addbeh.2020.106552 · Cited by 265
Benzodiazepines I: Upping the Care on Downers: The Evidence of Risks, Benefits and Alternatives
Guina, J., & Merrill, B. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm7020017 · Cited by 253
Online Porn Addiction: What We Know and What We Don’t—A Systematic Review
de Alarcón, R., de la Iglesia, J., Casado‐Espada, N. M., & Montejo, A. L. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8010091 · Cited by 306
Internet gaming disorder: Trends in prevalence 1998–2016
Feng, W., Ramo, D. E., Chan, S. R., & Bourgeois, J. A. (2017) · Addictive Behaviors · doi:10.1016/j.addbeh.2017.06.010 · Cited by 256
The self in context: brain systems linking mental and physical health
Koban, L., Gianaros, P. J., Hedy Kober, A., & Wager, T. D. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00446-8 · Cited by 258
The Impact of Stigma on People with Opioid Use Disorder, Opioid Treatment, and Policy
Cheetham, A., Picco, L., Barnett, A., Lubman, D. I., & Nielsen, S. (2022) · Substance Abuse and Rehabilitation · doi:10.2147/sar.s304566 · Cited by 232
“training, and brain stimulation), and foster more effective public health policies for prevention and treatment.(53,57)”
BackgroundPergolizzi, J. V., Raffa, R. B., & Rosenblatt, M. (2020) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.13114 · Cited by 234
Reward deficiency and anti-reward in pain chronification
Borsook, D., Linnman, C., Faria, V., Strassman, A. M., Becerra, L. R., & Elman, I. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.033 · Cited by 238
Stigma and substance use disorders: A clinical, research, and advocacy agenda.
Earnshaw, V. A. (2020) · American Psychologist · doi:10.1037/amp0000744 · Cited by 249
“As noted above, intentionally leveraging stigma to prevent substance use is a flawed tactic insofar as it overemphasizes the role of personal control in substance use (Volkow et al., 2016).”
BackgroundBrain lesions disrupting addiction map to a common human brain circuit
Joutsa, J., Moussawi, K., Siddiqi, S., Abdolahi, A., Drew, W., Cohen, A. L., Ross, T. J., Deshpande, H. U., Wang, H. Z., Bruss, J., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01834-y · Cited by 221
Self-citationRehabilitating the addicted brain with transcranial magnetic stimulation
Diana, M., Raij, T., Melis, M., Nummenmaa, A. R., Leggio, L., & Bonci, A. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.113 · Cited by 228
Sex Differences in the Neurobiology of Alcohol Use Disorder
Flores‐Bonilla, A. (2020) · Alcohol research · doi:10.35946/arcr.v40.2.04 · Cited by 218
“2 Alcohol Research: Current Reviews Vol 40 No 2 | 2020 include symptoms of (1) compulsive excessive drinking; (2) persistent desire to consume alcohol and unsuccessful efforts to quit; (3) increased time spent in activities necessary to obtain, consume, and recover from alcohol; (4) craving or strong desire to consume…”
BackgroundStochastic synaptic plasticity underlying compulsion in a model of addiction
Pascoli, V., Hiver, A., Van Zessen, R., Loureiro, M., Achargui, R., Harada, M., Flakowski, J., & Lüscher, C. (2018) · Nature · doi:10.1038/s41586-018-0789-4 · Cited by 185
Current interpretations of the I-PACE model of behavioral addictions
Brand, M., Müller, A., Wegmann, E., Antons, S., Brandtner, A., Müller, S. M., Stark, R. M., Steins‐Loeber, S., & Potenza, M. N. (2025) · Journal of Behavioral Addictions · doi:10.1556/2006.2025.00020 · Cited by 224
Addiction and the Brain: Development, Not Disease
Lewis, M. D. (2017) · Neuroethics · doi:10.1007/s12152-016-9293-4 · Cited by 202
The role of reward circuitry and food addiction in the obesity epidemic: An update
Leigh, S.-J., & Morris, M. J. (2018) · Biological Psychology · doi:10.1016/j.biopsycho.2016.12.013 · Cited by 191
Reeves, B. B., Ram, N., Robinson, T. N., Cummings, J. J., Giles, C. L., Pan, J., Chiatti, A., Cho, M., Roehrick, K., Yang, X., et al. (2019) · Human-Computer Interaction · doi:10.1080/07370024.2019.1578652 · Cited by 211
Domínguez‐Salas, S., Díaz, C., Lozano, O. M., & Verdejo‐García, A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.09.030 · Cited by 204
Opioid use and stigma: The role of gender, language and precipitating events
Goodyear, K., Haass‐Koffler, C. L., & Chavanne, D. (2018) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2017.12.037 · Cited by 218
Structural and functional correlates of smartphone addiction
Horvath, J., Mundinger, C., Schmitgen, M. M., Wolf, N. D., Sambataro, F., Hirjak, D., Kubera, K. M., Koenig, J., & Christian Wolf, R. (2020) · Addictive Behaviors · doi:10.1016/j.addbeh.2020.106334 · Cited by 190
Pediatric Irritability: A Systems Neuroscience Approach
Leibenluft, E. (2017) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2017.02.002 · Cited by 179
Dresp, B., & Hutt, A. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19116910 · Cited by 230
“This involves (1) automatisms in which the initially motivated behavior subsequently becomes a habit and (2) a gradual increase in the motivation to consume due to increasing tolerance and withdrawal symptoms when the drug is no longer taken [85].”
BackgroundThe genetic epidemiology of substance use disorder: A review
Prom‐Wormley, E. C., Ebejer, J. L., Dick, D. M., & Bowers, M. S. (2017) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2017.06.040 · Cited by 185
Substance use and addictive disorders in DSM-5 and ICD 10 and the draft ICD 11
Saunders, J. B. (2017) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000332 · Cited by 190
Adolescent cannabis use, cognition, brain health and educational outcomes: A review of the evidence
Lorenzetti, V., Hoch, E., & Hall, W. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.03.012 · Cited by 166
The brain’s reward system in health and disease
Lewis, R. G., Florio, E., Punzo, D., & Borrelli, E. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-81147-1_4 · Cited by 170
Treatment of Alcohol Use Disorder in Patients with Alcoholic Liver Disease
Leggio, L., & Lee, M. R. (2016) · The American Journal of Medicine · doi:10.1016/j.amjmed.2016.10.004 · Cited by 168
Neurobiology of cue-reactivity, craving, and inhibitory control in non-substance addictive behaviors
Antons, S., Brand, M., & Potenza, M. N. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.116952 · Cited by 187
Park, J. N., Rouhani, S., Beletsky, L. A., VINCENT, L., Saloner, B. K., & Sherman, S. G. (2020) · Milbank Quarterly · doi:10.1111/1468-0009.12470 · Cited by 165
Making the hard work of recovery more attractive for those with substance use disorders
McKay, J. R. (2017) · Addiction · doi:10.1111/add.13502 · Cited by 164
Enhanced Recovery After Surgery (ERAS)
Echeverria-Villalobos, M., Stoicea, N., Todeschini, A. B., Fiorda‐Diaz, J., Uribe, A. A., Weaver, T. E., & Bergese, S. D. (2019) · Clinical Journal of Pain · doi:10.1097/ajp.0000000000000792 · Cited by 169
Toll-like receptor signaling and stages of addiction
Crews, F. T., Walter, T. J., Coleman, L. G., & Vetreno, R. P. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4560-6 · Cited by 163
Lasco, G., & Curato, N. (2018) · Social Science & Medicine · doi:10.1016/j.socscimed.2018.12.006 · Cited by 156
Davis, C. A. (2016) · Appetite · doi:10.1016/j.appet.2016.11.001 · Cited by 155
Buying-shopping disorder—is there enough evidence to support its inclusion in ICD-11?
Müller, A., Brand, M., Claes, L., Demetrovics, Z., de Zwaan, M., Fernández-Aranda, F., Frost, R. O., Jimenez-Murcia, S., Lejoyeux, M., Steins-Loeber, S., et al. (2019) · CNS Spectrums · doi:10.1017/s1092852918001323 · Cited by 155
Dopamine and addiction: what have we learned from 40 years of research
Solinas, M., Belujon, P., Fernagut, P., Jaber, M., & Thiriet, N. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1957-2 · Cited by 163
Nunes-Neto, P. R., Köhler, C. A., Schuch, F. B., Solmi, M., Quevedo, J., Maes, M., Murru, A., Vieta, E., McIntyre, R. S., McElroy, S. L., et al. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.10.003 · Cited by 150
Neurobiology of comorbid post‐traumatic stress disorder and alcohol‐use disorder
Gilpin, N. W., & Weiner, J. L. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12349 · Cited by 154
Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice
Kakko, J., Alho, H., Baldacchino, A., Molina, R., Nava, F. A., & Shaya, G. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00592 · Cited by 140
Kohan, L. R., Potru, S., Barreveld, A. M., Sprintz, M., Lane, O. P., Aryal, A., Emerick, T. D., Dopp, A., Chhay, S., & Viscusi, E. R. (2021) · Regional Anesthesia & Pain Medicine · doi:10.1136/rapm-2021-103007 · Cited by 147
“70 Exposure to prescription opioids and undertreated pain can also lead to cravings and OUD recurrence.”
BackgroundAlcohol Use Disorders in ICD‐11: Past, Present, and Future
Saunders, J. B., Degenhardt, L., Reed, G. M., & Poznyak, V. (2019) · Alcoholism: Clinical and Experimental Research · doi:10.1111/acer.14128 · Cited by 135
Smith, K. E., & Lawson, T. (2017) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2017.08.034 · Cited by 135
21st century neurobehavioral theories of decision making in addiction: Review and evaluation
Bickel, W. K., Mellis, A. M., Snider, S. E., Athamneh, L. N., Stein, J. S., & Pope, D. A. (2018) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2017.09.009 · Cited by 134
Neuroscience-informed psychoeducation for addiction medicine: A neurocognitive perspective
Ekhtiari, H., Rezapour, T., Aupperle, R. L., & Paulus, M. P. (2017) · Progress in brain research · doi:10.1016/bs.pbr.2017.08.013 · Cited by 134
Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits
Hoch, E., Volkow, N. D., Friemel, C. M., Lorenzetti, V., Freeman, T. P., & Hall, W. (2025) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-024-01880-2 · Cited by 139
“Case–control neuroimaging studies of the brain with high-resolution provide early evidence for altered brain integrity in brain regions with a high density of CB1 receptors in heavy cannabis users [75].”
Self-citationOpioid Use Disorders: Perioperative Management of a Special Population
Ward, E. N., Quaye, A., & Wilens, T. E. (2018) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000003477 · Cited by 136
Drug-induced stress responses and addiction risk and relapse
Wemm, S. E., & Sinha, R. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100148 · Cited by 144
Luján, M. Á., Castro‐Zavala, A., Alegre-Zurano, L., & Valverde, O. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.09.043 · Cited by 135
Heavy cannabis use, dependence and the brain: a clinical perspective
Kroon, E., Kuhns, L., Hoch, E., & Cousijn, J. (2019) · Addiction · doi:10.1111/add.14776 · Cited by 133
Challenging the brain disease model of addiction: European launch of the addiction theory network
Heather, N., Best, D. W., Kawałek, A. G., Field, M., Lewis, M. D., Rotgers, F., Wiers, R. W. H. J., & Heim, D. (2017) · Addiction Research & Theory · doi:10.1080/16066359.2017.1399659 · Cited by 129
Costa, K. M., & Schoenbaum, G. M. (2022) · Current Biology · doi:10.1016/j.cub.2022.06.060 · Cited by 136
Berridge, K. C. (2016) · Neuroethics · doi:10.1007/s12152-016-9286-3 · Cited by 128
Review: Sex‐Based Differences in Treatment Outcomes for Persons With Opioid Use Disorder
Huhn, A. S., Berry, M. S., & Dunn, K. E. (2019) · American Journal on Addictions · doi:10.1111/ajad.12921 · Cited by 126
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“…a result, persons with addiction no longer experience the same degree of euphoria from a drug as they did when they first started using it,” and “the down-regulation of dopamine signaling…dulls the reward circuits’ sensitivity to pleasure” (Volkow et al. 2016, p. 366; but see Compton et al. 2022).”
InfluentialMahoney, J. J., Hanlon, C. A., Marshalek, P. J., Rezai, A. R., & Krinke, L. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.117149 · Cited by 121
Brain Change in Addiction as Learning, Not Disease
Lewis, M. D. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1602872 · Cited by 141
Optogenetic self-stimulation in the nucleus accumbens: D1 reward versus D2 ambivalence
Cole, S. L., Robinson, M. J. F., & Berridge, K. C. (2018) · PLoS ONE · doi:10.1371/journal.pone.0207694 · Cited by 108
Recent advances in biomimetic nanodelivery systems: New brain-targeting strategies
Liao, J., Fan, L., Li, Y., Xu, Q.-Q., Xiong, L., Zhang, S., Liu, J.-H., Xiao, Z.-C., Zhang, C., Yang, J., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.05.009 · Cited by 119
Is biological aging accelerated in drug addiction?
Bachi, K., Sierra, S., Volkow, N. D., Goldstein, R. Z., & Alia‐Klein, N. (2016) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2016.09.007 · Cited by 123
Self-citationRole of the endocannabinoid system in drug addiction
Manzanares, J., Cabañero, D., Puente, N., García‐Gutiérrez, M. S., Grandes, P., & Maldonado, R. J. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.09.013 · Cited by 118
Hatoum, A. S., Johnson, E. C., Colbert, S. M. C., Polimanti, R. A., Zhou, H., Walters, R. K., Gelernter, J. E., Edenberg, H. J., Bogdan, R., & Arpana Agrawal, A. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01209-w · Cited by 122
“Recent work argues that this vulnerability is captured by executive functioning [33].”
BackgroundThe role of stress in drug addiction. An integrative review
Ruisoto, P., & Contador, I. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.01.022 · Cited by 132
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“In persons with SUD, stress and low mood due to loss of income or social isolation can elicit an increase in motivation to consume substances evident by strong cravings and substance preoccupation, culminating in substance relapse.(24) Previous studies suggest that stress predicts relapse to substance use among those…”
BackgroundDrug use disorders: impact of a public health rather than a criminal justice approach
Volkow, N. D., Poznyak, V. B., Saxena, S., Gerra, G., & UNODC‐WHO Informal International Scientific Network (2017) · World Psychiatry · doi:10.1002/wps.20428 · Cited by 111
Self-citationGrogans, S. E., Bliss‐Moreau, E., Buss, K. A., Clark, L. A., Fox, A. S., Keltner, D. J., Cowen, A., Kim, J. J., Kragel, P. A., MacLeod, C., et al. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105237 · Cited by 135
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Kowalewska, E., Grubbs, J. B., Potenza, M. N., Gola, M., Draps, M., & Kraus, S. W. (2018) · Current Sexual Health Reports · doi:10.1007/s11930-018-0176-z · Cited by 111
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Laube, G., & Bernstein, H. (2017) · Biochemical Journal · doi:10.1042/bcj20170007 · Cited by 110
Pickard, H. (2020) · Noûs · doi:10.1111/nous.12328 · Cited by 110
“Although labelling addiction a disease is often claimed to fight stigma and remove barriers to funding for research and treatment (Volkow et al., 2016), empirical studies suggest the effects of disease models of mental disorder are mixed.”
BackgroundBerríos‐Cárcamo, P., Quezada, M., Quintanilla, M. E., Morales, P., Ezquer, M., Herrera‐Marschitz, M., Israel, Y., & Ezquer, F. E. (2020) · Antioxidants · doi:10.3390/antiox9090830 · Cited by 115
“In addition to low compliance, unsuccessful treatments are the result of self-perpetuating brain alterations caused by the abused substance, which control behavior and hinder the ability of patients to reduce their consumption and avoid relapse [20].”
BackgroundGenetics of substance use disorders in the era of big data
Gelernter, J. E., & Polimanti, R. A. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00377-1 · Cited by 107
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Acuff, S. F., MacKillop, J. M., & Murphy, J. G. (2023) · Nature Reviews Psychology · doi:10.1038/s44159-023-00167-y · Cited by 119
Priddy, S. E., Howard, M. O., Hanley, A. W., Riquino, M. R., Friberg-Felsted, K., & Garland, E. L. (2018) · Substance Abuse and Rehabilitation · doi:10.2147/sar.s145201 · Cited by 101
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Frank, L. E., & Nagel, S. K. (2017) · Neuroethics · doi:10.1007/s12152-017-9307-x · Cited by 105
Volkow, N. D., Wiers, C. E., Kojori, E. S., Tomasi, D. G., Wang, G., & Baler, R. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.012 · Cited by 109
Self-citationCerebral gray matter volume in patients with chronic migraine: correlations with clinical features
Coppola, G., Petolicchio, B., Renzo, A. D., Tinelli, E., Lorenzo, C. D., Parisi, V., Serrao, M., Calistri, V., Tardioli, S., Cartocci, G., et al. (2017) · The Journal of Headache and Pain · doi:10.1186/s10194-017-0825-z · Cited by 103
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Metadata
- Authors
- Volkow, N. D., Koob, G. F., & McLellan, A. T.
- Affiliations
- National Institute on Drug Abuse (US)
- National Institute on Alcohol Abuse and Alcoholism (US)
- Treatment Research Institute (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-01-28
- Volume
- 374
- Issue
- 4
- Pages
- 363-371
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC6135257
- OpenAlex
- W2283026346
- Cited by
- 2,008
- References
- 52
- Citations by year
- 2026: 264 · 2025: 198 · 2024: 172 · 2023: 193 · 2022: 179 · 2021: 208 · 2020: 245 · 2019: 160 · 2018: 154 · 2017: 178 · 2016: 54
- FWCI
- 19.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99‐AA999999)
- National Institute on Drug Abuse
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
- Keywords
- brain disease model of addiction, neurobiology of addiction, substance use disorders, conditioned response, stress reactivity, drug craving, executive function, relapse, behavioral addiction, addiction genetics, social environment, addiction prevention, addiction treatment, public health policy, Mental Health Parity and Addiction Equity Act
- MeSH terms
- Brain Diseases, Humans, Models, Neurological, Substance Withdrawal Syndrome, Substance-Related Disorders
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