Neurobiologic Advances from the Brain Disease Model of Addiction

Nora D. Volkow, M.D., George F. Koob, Ph.D., and A. Thomas McLellan, Ph.D.

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 would reduce prison sentences for some nonviolent drug offenders,6 which is a substantial shift in policy fueled in part by the growing realization among law-enforcement leaders that “reducing incarceration will improve public safety because people who need treatment for drug and alcohol problems or mental health issues will be more likely to improve and reintegrate into society if they receive consistent care.”7

Nonetheless, despite the scientific evidence and the resulting advances in treatment and changes in policy, the concept of addiction as a disease of the brain is still being questioned. The concept of addiction as a disease of the brain challenges deeply ingrained values about self-determination and personal responsibility that frame drug use as a voluntary, hedonistic act. In this view, addiction results from the repetition of voluntary behaviors. How, then, can it be the result of a disease process? The concept of addiction as a brain disease has even more disconcerting implications for public attitudes and policies toward the addict. This concept of addiction appears to some to excuse personal irresponsibility and criminal acts instead of punishing harmful and often illegal behaviors. Additional criticisms of the concept of addiction as a brain disease include the failure of this model to identify genetic aberrations or brain abnormalities that consistently apply to persons with addiction and the failure to explain the many instances in which recovery occurs without treatment. (Arguments against the disease model of addiction and counterarguments in favor of it8 are presented in Box S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org.)

Advances in neurobiology have begun to clarify the mechanisms underlying the profound disruptions in decision-making ability and emotional balance displayed by persons with drug addiction. These advances also provide insight into the ways in which fundamental biologic processes, when disrupted, can alter voluntary behavioral control, not just in drug addiction but also in other, related disorders of self-regulation, such as obesity and pathologic gambling and video-gaming — the so-called behavioral addictions. Although these disorders also manifest as compulsive behaviors, with impaired self-regulation, the concept of behavioral addiction is still controversial, particularly as it relates to obesity. (Behavioral addictions are described in Box S2 in the Supplementary Appendix.9) This research has also begun to show how and why early, voluntary drug use can interact with environmental and genetic factors to result in addiction in some persons but not in others.

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