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Medical News & Perspectives
November 26, 2003

Nora Volkow, MD

JAMA. 2003;290(20):2647-2652. doi:10.1001/jama.290.20.2647

A funny thing happened to Nora Volkow, MD, the new director of the National Institute on Drug Abuse (NIDA), when she first applied for a grant from the agency: she was rejected.

Nora Volkow, MD, shown here in her office at the National Institute on Drug Abuse, divides her time between leading the agency and her own research aimed at understanding drug addiction. (Photo credit: Rhoda Baer)

In 1984, she was finishing her residency in psychiatry at New York University, where she had pioneered brain imaging studies of drug users. "I started to find out cocaine abusers had vascular pathology, sort of small vascular accidents," said Volkow, now 47. "NIDA came back to me and said, ‘there's no evidence that cocaine is toxic.'"

Discouraged, the young Volkow [pronounced VOHL-kov] abandoned further vascular pathology research. Although cocaine was gaining traction as a recreational drug, it had been licensed as an anesthetic for decades. The idea that it triggered tiny strokes in the brain was radical, and it took three years for a journal to accept Volkow's original paper for publication.

But she was right, as other researchers went on to show.

On meeting Volkow, her devotion to understanding addiction is immediately evident. During a recent sit-down interview, words spill out so quickly that a journalist abandons his notepad and keeps a close eye on his recorder. Sporting brown leather boots and a light leather jacket instead of one of the suits so common for those running Washington's billion-dollar agencies, the Mexico City native with a famous Russian heritage flutters her hands and leans forward when making a point.

Six months into Volkow's tenure, that office is a study in harried minimalism. Walls barren of art or photos, a few chairs and a sofa flank a desk that holds the conduit to Volkow's intellectual marrow: two huge flat-panel monitors. As the clock leaning against the foot of the sofa sweeps through the minutes, Volkow is reminded again of her struggle to find time to study the latest brain scans and data tables from Brookhaven National Laboratory, Upton, New York, where she previously headed the life sciences division and published dozens of pioneering brain imaging studies.

Volkow carries a computer nearly everywhere, popping it open in airports, cabs, and, this morning, at the Department of Motor Vehicles. She was supposed to fly to New York for her once-a-month visit to Brookhaven, but she was held back by her director's duties and a more quotidian chore—beating a 6-month deadline to get her Maryland driver's license.

While snaking through the notoriously long queues, Volkow absorbed Brookhaven data that show a brain region important for motivation "clearly activates in a person that is addicted but not in a non-addicted person." The data help cement a finding that has prompted addiction researchers to focus on not just the brain's pleasure centers, but its motivation zones too.

"When you are not addicted, a drug can feel good," said Volkow. "But what you don't feel is the drive, the need for more. And now we have the data to document that [this drive] is clearly associated" with the orbital frontal cortex.

Volkow said that discoveries like these make her "high." So much so that she made it known that giving up her Brookhaven laboratory would be a deal breaker when approached by NIH Director Elias Zerhouni, MD. Zerhouni acceded, confident that Volkow would sort out her schedule.

But still, Volkow feels constrained. More than anything, she wants to think. She runs 6 miles every morning, indoor on a treadmill if need be, to give her a "protected" hour to do so.

Some of her best ideas come during runs. She also uses the time to mentally prepare for speeches, something she's been doing a lot. Since joining NIDA in May, Volkow has been in high demand. She's given, by her estimation, 65 "major speeches" and countless minor ones. The week after meeting with JAMA, she was scheduled to deliver seven talks, including a headliner at the Institute of Medicine's annual meeting. A month earlier, she had jetted between Russia, Washington, and Los Angeles in the span of 6 days.

Volkow's rapid-fire and playful speeches typically draw rave reviews. At an October meeting in San Francisco, she brought 300 addiction specialists to their feet, a standing ovation that played in sharp contrast to the tepid applause given to a representative of the White House's Office of National Drug Control Policy at the same meeting.

As Volkow laid out her vision for NIDA, she was forced to pause after saying, "Look, I will be candid." When the applause quieted, she continued: "Because there's no point not to be. The fact is, there is not much interest from drug companies in addiction medicine . . . . We have to incentivize them to try [new medications] for addiction."

At that California Society for Addiction Medicine meeting and at the larger June gathering of the College on the Problems of Drug Dependency, attendees expressed surprise that such a straight shooter could win the top job at NIDA, a position fraught with political pressure. For example, some addiction specialists took issue with use in an antidrug campaign a couple of years ago of an image of a "plain brain" and a "brain on ecstasy" that showed what looked like a hole in the head of the drug user (JAMA. 2001;86:777-778). The methods behind the study that spawned that image (Lancet. 1998; 352:1433-1437) was repeatedly questioned and a larger, better controlled study reported conflicting findings (Arch Gen Psychiatry. 2001;58:901-906). So NIDA abandoned the $42 million "club drugs" campaign featuring the misleading brain image and replaced it with subtler materials, including, most recently, a Web site featuring straight-talking teens (http://www.teens.drugabuse.gov). Among the stories of pain and suffering, the site acknowledges that drugs can feel good.

"If you present [addiction] in a way that people can comprehend and see it not as just a black-and-white situation but in all its complexity, they're very receptive," said Volkow. "We assume people want very simple [information], that NIDA should say it's just black-and-white. But . . . it's not." As an example, Volkow said that while exposure to drugs obviously plays in a role in whether an adolescent becomes addicted, so do the less-publicized influences of family, community, and culture.

Early influences

Early influences

Those factors profoundly steered the intellectual career of Volkow, who came of age in Mexico City as one of four precocious great-granddaughters of Russian revolutionary Leon Trotsky. In 1940, her young father had seen Trotsky die at the end of an ice ax wielded by a Soviet agent. But the family stayed, maintaining the house in Mexico City as a museum of sorts.

Early influences

Famous people visited often, and it was the job of Volkow and her sisters to lead impromptu tours. "We got to see people from all over the world, presidents, actors," said Volkow, a star student who became interested in science at age 5.

Early influences

"I was so excited, I was always learning," she said. "Here you have four girls playing together in this extraordinary house with all sorts of books and things that are fascinating and very old." A high point came during one of her "novelist obsessions." She routinely devours oeuvre after oeuvre and was in the middle of her Gabriel García Márquez obsession when he visited.

Early influences

The surfeit of intellectual stimulation rendered drugs of abuse a nonissue for the young Volkow. "I was extremely lucky," she said, her Spanish-Russian accent lengthening the "u".

Early influences

Volkow swigs her drug of choice—Coke, the kind in a can—and muses about why coffee, with twice the caffeine, is unpleasant to her.

Early influences

"It's an individual sensitivity," she says.

Early influences

So it goes with all drugs that affect the brain—each person responds differently. It's one of the principles that ignited Volkow's curiosity in addiction science when she reached medical school at age 18.

Loss of control

Loss of control

But it was a second principle, loss of control, that provided Volkow with an emotional stake in addiction. As she grew up, she watched a favorite relative succumb to alcoholism. "I loved him dearly," said Volkow. "He was very devoted to his family and yet he knew that he was destroying them [with] this behavior. And that's a classical process of addiction. It's not that they don't care but something has changed their ability to control."

Loss of control

Volkow is now in a position to focus NIDA's billion-dollar budget on why that is so, and how to prevent and treat it. In particular, she wants to learn how drugs of abuse affect children and adolescents.

Loss of control

"Addiction is a developmental disease," Volkow says, and ample statistics bear her out. "I don't think we've officially stated it in any way like that. We do know that [addiction] begins in childhood and adolescence. And yet we know so little about the adolescent brain." It's "shocking," for instance, that no one knows whether adults or adolescents will self-administer drugs at a more rapid rate.

Loss of control

However, researchers do know that the anterior cingulate gyrus, a region responsible for inhibition, continues growing in humans through about age 21. "That's why when you mature, your ability to say ‘no' is increased." She wants to use imaging to test strategies for enlarging and strengthening this region of the brain.

Loss of control

The concept may sound radical, Volkow readily admits, but she quickly points to an imaging study of London taxicab drivers. The cabbies' spatial memory centers in the hippocampus are significantly larger than those of noncabbies.

Loss of control

"It's because they are constantly exposed to spatial information . . . and that has led to synaptogenesis and enlargement," she explains. "Look, we can strengthen the reading abilities of kids who can't read [well]. So why don't we think of inhibitory control as a function like reading?"

Loss of control

It's a strategy as sophisticated as "just say no" was facile. And in fact, Volkow would love to turn her scanners on that campaign.

Loss of control

"In the first series of meetings we had [at NIDA], I said, ‘How do we optimize sending a message to adolescents about the deleterious effects of drugs?'"

Loss of control

One answer, she said, is using imaging to study the adolescent brain's response to effective and ineffective educational messages. "If we know from epidemiology that there is a particular ad that is protective in adolescents, we can look at how it activates the brain differently from an ad that we know has been a failure," she explains. "If you get a signal, say, for example, in the amygdala [a center for emotional memory], it's more likely to have an impact than an ad that stimulates the hippocampus [a center for spatial memory]."

Loss of control

The rest of Volkow's agenda is equally ambitious. She is determined to offer more support to young researchers. She also wants hard data on the deleterious effects of smoking during pregnancy, a deeper understanding of the brain's development, and a flowchart of how environmental stress affects different neurotransmitter systems, especially those that are crucial to mood and addiction.

Loss of control

But most of all, Volkow wants to think. "This is one of the things I say to people: ‘you have to protect me and allow me to think.' I say, ‘You don't want a director who doesn't think.'"

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