T H E   N I H    C A T A L Y S T     S E P T E M B E R   –  O C T O B E R   2003

NIDA's New Image: Nora Volkow

text and photos
by Fran Pollner
Nora Volkow

In the 22 years since she got her M.D. degree from the National University of Mexico, in Mexico City, Nora Volkow has taken brain research by storm, almost single-handedly harnessing brain imaging to the service of addiction research.

She is uncovering the neural pathways to addiction—be it to stimulant drugs, alcohol, or food—and charting the potholes left in addiction’s wake.

She has contributed enormously to the scientific literature—in words and pictures—and, this spring, she became a "first" at NIH: She is the first woman to become NIDA director since the institute was founded in 1974.

Volkow officially took office on Thursday, May 1, and on Monday, May 5, she delivered a neuroscience seminar lecture at Lipsett Auditorium on "Mechanisms Underlying Use and Abuse of Stimulant Drugs," an exploration of why the strength of cocaine’s addictive grip exceeds methylphenidate’s despite the fact that inhibition of the dopamine transporter is the pivot on which both of their actions turn.

In accepting the NIDA position, Volkow exchanged several hats for one. She’d been based at the Brookhaven National Laboratory in Upton, N.Y., since 1987, serving as director of nuclear medicine, director of the NIDA-DOE Regional Neuroimaging Center, associate director for life sciences, and chair of the medical department. She had also served concurrently as professor of psychiatry and associate dean of the medical school at the State University of New York, Stony Brook.

The NIH Catalyst interviewed Volkow in mid-August, three and a half months into her NIH job.

Q: What factors informed your decision to accept the offer to become NIDA director?

VOLKOW: It was a very difficult decision. I loved my job (at Brookhaven).

But I recognized what a great opportunity it would be. I have been in the field of drug addiction since medical school and devoted all my professional career to understanding why drugs of abuse promote addiction and the changes in the brain of people who become addicted.

The possibility of going beyond the constraints of my own work and actually having an impact on so many people and on the research of the future was very challenging.

My predecessor, Alan Leshner, had set an example of how you can shape a field. He fought the stigmatization of addiction. He changed the perception that addiction is something an individual chooses out of weakened moral standards. Addiction is a disease, not a choice.

Q: How did this approach dovetail with your own research?

VOLKOW: My own research has concentrated on identifying the changes in the brains of addicted people that lead to loss of control, at how these drugs take away a fundamental aspect of human behavior—free will.

In addiction, the volitional component of human behavior is very much disturbed. You can exert some control in not putting yourself in certain situations, but once you are in those situations, it’s almost like a reflex that overtakes the ability to choose.

How have you got to that state? What has happened to the brain?

The other question is, why can some drugs do that? You know, very few compounds can. What are their characteristics?

I have been investigating multiple drugs of abuse in parallel—cocaine, alcohol, heroin, methamphetamine—to determine the common elements, to identify the main skeleton of what each addictive drug has done.

The great-granddaughter of assassinated Russian revolutionary Leon Trotsky ("Trotsky had two sons and two daughters; my father was the son of one of the daughters"), Nora Volkow grew up in the house-turned-museum in Mexico in which Trotsky was killed. She has three sisters—a writer, an economist, and an infectious diseases researcher—all of whom live in Mexico.

When she graduated from medical school in 1981, she earned not only a degree but a "National Award for the Outstanding Medical Student" as well. She came to the United States for her residency and to pursue her research career because "the possibilities for doing this kind of research in Mexico, the resources, were much more limited."

Though the resources in the United States were excellent, she did occasionally encounter discrimination. In one situation, her being Mexican was cited as a "disadvantage" when she was applying for a particular postgraduate program; in another, her being a woman was cited as a reason she should not be considered for a supervisory position. In the latter instance, more enlightened minds prevailed; in the former, she was not admitted to the program. "But I’m flexible—not having that particular program did not stop me," she recalls. "My task was to understand the brain. I simply did something else to get there."

Q: And your methodology?

Volkow: Imaging. Most of my work has concentrated on positron emission tomography [PET], which shows the neurochemical changes in the brain and the pharmacologic properties of drugs in the brain.

Q: What are some of your findings?

Volkow: I was the first to document that cocaine is toxic to the human brain. The belief at the beginning of the ’80s was that cocaine was a benign drug. I did studies that showed areas of small cerebral strokes in the brains of cocaine abusers. Nobody believed it, and it took me a long time to get published.

The first study where I documented these brain changes was in 1985; I presented my findings at the Society of Nuclear Medicine, and they didn’t believe it. And when I submitted the study, the reviewers said, "There is no evidence that cocaine is toxic to the human brain." I finally got it published in 1988. (Br J Psychiatry, 152:641–648, 1988).

I actually started working with imaging in 1981, when it was not very common. I was one of the first people to use PET technology, first for the investigation of brain tumors, then to study schizophrenia [during a psychiatry residency at New York University from 1981 to 1984, which involved research at Brookhaven] and then with cocaine and alcohol [at the University of Texas Medical School in Houston, as an assistant professor of psychiatry and behavioral science from 1984 to 1987].

I returned to Brookhaven in 1987 specifically to learn what happens in the brain of drug abusers and why drugs of abuse cause addiction.

Q: And you went to Brookhaven because there was a program?

Volkow: No. I went to Brookhaven on condition that I could develop a program on drug addiction. People had not yet recognized how powerful imaging could be for the study of addiction. Brookhaven had the equipment but not yet the program. Now, 90–95 percent of the imaging research at Brookhaven is in drug abuse and addiction.

Q: Do you maintain a connection with Brookhaven?

Volkow: Yes. I keep my laboratory (as part of the NIAAA intramural program), although I handed over many of my ongoing projects to my colleagues there when I became NIDA director. I go there once a month for three or four days—it’s hard, but it’s very important to me to continue doing research.

We are investigating the long-term effects of drugs and alcohol on the reward circuits of the brain, the neurobiological mechanisms underlying vulnerability to addiction, and the effects of expectation and context of the effects of drugs of abuse. If you can understand this, you can manipulate the outcome.

Another area that fascinates me, and for which there is an ongoing project, is the study of the therapeutic effects of stimulant drugs that can also be abused, such as methylphenidate and amphetamine. Why are they addictive in some contexts and therapeutic in others?

More recently, about seven years ago, I started to work on obesity as a model of an addictive disorder.

Q: Will you be doing any work with NIDDK in the area of compulsive eating and obesity?

Volkow: Yes. I would like very much to work on that initiative and I’ve met with [NIDDK director] Allen Spiegel.

I am struck by the similarities of loss of control and compulsive behavior in people with compulsive patterns of eating and in people addicted to drugs. The difference, of course, is that you need food to survive, and so the interventions would be different.

But reward mechanisms, conditioned responses, environmental influences (such as stress and drug availability)—these variables that are so important in the prevention and treatment of drug addiction—can be brought to the prevention and treatment of obesity.

Q: Are you contemplating any other collaborations?

Volkow: Yes. We are very much interested in collaborating with other institutes, including those that study the brain, and we are working on a document that will allow us to integrate areas of common research in neuroscience.

I am also very interested in collaborating with NICHD regarding the special vulnerabilty of children and adolescents to addiction.

I want to collaborate with NIAID because drugs of abuse are extremely important in AIDS transmission, both through drug injection and through inducing mental states that lead to risky behavior.

Collaboration with NCI is also very important because overcoming nicotine addiction is the number-one public health intervention that will have an enormous impact on cancer.

Q: Dr. Zerhouni recently appointed a 10-member steering committee of NIH institute directors. You are among them and the member most newly arrived to NIH. Do you think your voice will be as strong as those who have been here longer?

Volkow: It’s actually very good to bring on someone who is new, who brings a fresh perspective. We have a very good combination on this committee of new people and people with knowledge of the system.

Q: What do you think of the suggestion in the recently released Institute of Medicine report that NIDA and NIAAA be integrated into one institute?

Volkow: What’s important is not whether there are one or two institutes but that we recognize that these addictive disorders are co-morbid, that they should be studied jointly. For example, there are very few alcoholics who don’t smoke, yet the animal models are mostly for alcoholism. They pertain, therefore, only to the 10–15 percent of alcoholics who do not also smoke. That gap has happened not because there are two institutes—NIAAA and NCI—instead of one but because people have not worked together.

T. K. Li [NIAAA director] and I have had several working meetings and are planning some brainstorming sessions to integrate our studies on genetics and drug and alcohol addiction—nicotine, too. And we will prepare an agenda for clinical trials in these areas.

Q: How long do you think you’ll be here, and where do you want to take NIDA?

Volkow: I don’t think anybody in their right brain would take the position of NIDA director if they are not committed to staying at least five years. I’d like to see NIDA use the tremendous developments in science and technology to fight drug abuse and addiction.

I’m very committed to blending basic and clinical research, to deriving concepts from basic research and applying them clinically, and to taking clinical findings back to the bench.

This is a common goal for all the institutes, and at NIH we can do it. I want to create an environment where scientists of different backgrounds and cultures blend together—physicists, mathematicians, biologists, geneticists, clinicians, chemists.

Q: Is there a dearth of certain disciplines within NIDA? Would you want to hire people?

Volkow: There are areas of expertise that may not be well represented, but we can either hire new people or create collaborations to take advantage of the expertise from other institutes. You don’t want to replicate resources. It’s not necessary for every single intramural program to have everything.

Q: Are there any research areas calling out for more NIDA support, any where there are huge gaps in knowledge?

Volkow: There are huge gaps in knowledge in the prevention sciences. Why is it that the brain of adolescents is more sensitive to drugs? What are those developmental changes that make it more sensitive? How do we introduce prevention at this stage? It is not so straightforward, not so simple.

Another area of missing information is the whole area of marijuana addiction. It has been, in a way, the forgotten drug, especially in light of the fact that it is the number-one illegal drug of abuse. What is the extent to which early exposure to marijuana increases vulnerability? What are the effects of early exposure on learning?

Q: Did your family background have any effect on your thinking when you were growing up?

Volkow: If your family has been persecuted and exterminated for a cause—my father was the only one in his family to survive Stalin, and my mother’s family experienced the same thing under Franco—you cannot take your life for granted. It is a privilege to be alive, a privilege to have capabilities and education. I have had all along a sense of responsibility—to give something back, to help. That may have come from my family.



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