September 5, 2013

Discovery Lecture explores brain’s addiction mechanisms

Nora Volkow, M.D., director of the National Institute on Drug Abuse, delivers last week’s Discovery Lecture.

Since she was a medical student in her native Mexico, Nora Volkow, M.D., has been fascinated by drug addiction.

“It really did not make any sense … that someone would be risking actually their freedom, their families, just for the sole pleasure of taking a drug,” Volkow, director of the National Institute on Drug Abuse, said last week during the season’s first Flexner Discovery Lecture.
What she has discovered, of course, is that “sole pleasure” has little to do with it. “If you ask addicts why do you take that drug,” she said, “one of the most consistent answers is, ‘I don’t know. The drug is no longer even pleasurable. I just cannot stop it.’”

Understanding why addicts continue behavior that costs them their own freedom and self-determination has been a self-described “obsession” for Volkow since she began her career in the mid-1980s.

With colleagues at Brookhaven National Laboratory in Upton, N.Y., she used a new imaging technique, positron emission tomography (PET), to show that the brains of cocaine addicts had lower levels of the dopamine D2 receptor compared to normal controls.

Now, the dopamine signaling pathway is just one of many involved in one aspect or another of addiction. But, said Volkow, “all drugs abused by humans raise brain dopamine levels in the nucleus accumbens (a part of the brain) crucial for rewarding.”

Conditioning is important. Environmental cues associated with the use of or craving for cocaine can cause the release of dopamine, even in the absence of the drug. “This is a fundamental process to relapse,” she said.

Speed is also important. The faster that cocaine, for example, gets into the brain, the more rapid the increase in dopamine, and the greater the reinforcing effect of the drug.

Addiction also may involve a damaged frontal cortex, “the key component of the system that allows us to have self-control.” Volkow said. If the balance between executive function and reward is skewed, in part because of inadequate levels of the D2 receptor, reward can overcome control.

This is not a simple model. “Our recognition that these changes are multiple is fundamental for intervention,” she said. But thanks to imaging and, now, genetic studies, scientists like Volkow have begun to make sense of addiction and what might interrupt its tragic trajectory.

For a complete schedule of the Discovery Lecture series and archived video of previous lectures, go to