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Breakthroughs in Addiction Research

Hear from the NIH's Nora D. Volkow and George K. Koob about the neurobiology of addiction.

Published March 15, 2016

Breakthroughs in Addiction Research

Expanding addiction studies to include the brain has been challenging for researchers, despite promising results on the neurobiological aspects of addiction. Recently we spoke with two of the speakers from the upcoming event "The Addicted Brain and New Treatment Frontiers: Sixth Annual Aspen Brain Forum," Nora D. Volkow, MD, of the National Institute on Drug Abuse (NIDA), and George F. Koob, PhD, of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Here, they described how research in biomedical science illuminates the puzzle of addiction and also highlights of their careers as addiction scientists.

How would you expect that new knowledge gained from major initiatives from the NIAAA and the NIDA will help to move forward national efforts to improve prevention, treatment, and policies on addiction issues?

Nora D. Volkow: Addiction is a disease of the brain. So, just like any other disease--cancer, diabetes, or asthma--the more we know about the etiology and trajectory of the disorder, the smarter and more targeted the approaches we will be able to develop. This research helps us, among others, identify promising targets for the development of medications and other treatments. And this focus will also lead to a better understanding of the factors that influence the trajectory or course of the disease such as genetics and epigenetics, comorbid conditions, social support, treatment access and availability, and social stigma. We are constantly improving the quality of this information, which is helping us translate it into more effective and personalized prevention and treatment interventions.

George F. Koob: A significant milestone was the identification of a framework for the three stages of the addiction cycle (intoxication, withdrawal/negative affect, and craving), which represent neuroadaptations in three neurocircuits. This knowledge provides multiple viable targets for medications to return disrupted neurocircuitry to homeostasis and promote recovery. At the NIAAA, our hope is that our longitudinal research programs will converge to provide us with both genetic and environmental factors that will allow us to promote resilience and avoid vulnerability to alcohol-related problems. We know there is high genetic hereditability in alcohol use disorders but that one is not condemned to contracting a disorder. The current work will allow us to identify what environmental factors exacerbate or remove vulnerability.

What are some of the significant obstacles that you have encountered in your research over the course of your career? How have sought to overcome these hindrances?

GK: The biggest obstacle in my research work, was, and remains a misunderstanding of the addiction process. Addiction is a brain disease and more importantly it is a disease of the brain motivational systems. However, motivation comes from two sources: positive reinforcement and negative reinforcement. To a large extent convincing the scientific community of the negative reinforcement piece has been a challenge. I like to say that I spent the first half of my career trying to understand how we feel good and the second half of my career trying to understand how we feel bad. We now know that what I call "motivational withdrawal" (comprised of a reward deficit and a stress surfeit) is a critical part of the addiction cycle and a key part of the neurocircuitry driving compulsive drug seeking and drug taking.

NV: I began my research career at a time when brain imaging techniques were emerging and providing us, for the first time, the ability to study the human brain's function and neurochemistry noninvasively. I immediately saw that brain imaging offered a unique opportunity to investigate how drugs affect the human brain and how these changes influence behavior. However, it took us several years to convince the scientific community that the brain of cocaine abusers showed evidence of cerebrovascular toxicity, a finding that now has been corroborated by multiple clinical and preclinical studies. But, even more challenging was the stigma I had to face regarding my interest on addiction. I had to convince my colleagues of the value and importance of studying the neurobiology of addiction, which was viewed by many, including some scientists and physicians, as a moral failure, thus undeserving of my efforts to use modern medical methodologies to study it.

Are there specific moments from your career that you are particularly proud of, or that stand out to you?

NV: My proudest moments have always been when an addicted person, or their relatives, contact me to thank me for giving them a better understanding of what they or their loved ones are going through, and for giving them hope that their disease can be treated.

GK: I am particularly proud of having trained 80 postdoctoral fellows, most, if not all of whom worked in science for their careers. I am also proud of pushing "the dark side of addiction" and weaving the frameworks of opponent process, stress and self-medication back into the fabric of our understanding of the addiction process.

Nora D. Volkow, MD, and George F. Koob, PhD, will speak at the upcoming event "The Addicted Brain and New Treatment Frontiers: Sixth Annual Aspen Brain Forum." Click here for more information and to register for the event. The event will also be available as a webinar.