National Institute on Drug Abuse (NIDA) Director Nora Volkow, M.D., added another award to her ever-growing collection last month with the presentation of the Founders' Award from the American Academy of Addiction Psychiatry (AAAP). In bestowing the award, AAAP President Kathleen Brady, M.D., Ph.D., said Volkow "exemplifies the reality of addiction as a chronic, relapsing medical disorder that should be treated by physicians."

Due to scheduling conflicts, Volkow was unable to accept the award in person; however, she sent Timothy Condon, Ph.D., her deputy director at NIDA, to the group's annual meeting in Scottsdale, Ariz.

The work of Volkow and many of those in attendance, Condon told the group, has led to "phenomenal advances in science which have helped all of us to learn that addiction is truly a disease—not a behavioral problem, not a lack of moral fiber."

But fundamental questions continue to elude complete answers.

"What do we know today about vulnerability?" Condon asked." Why do some become addicted, while others do not?" Clearly, he said, it takes both a genetic predisposition to addiction as well as an environment in which substances of abuse are either available or promoted.

"Genes do not act on their own; however, it is a complex interaction between genes and environment, most notably during adolescence, that leads to addiction."

The discovery over the last several years that neuronal circuits continue to develop throughout adolescence and into adulthood provoked a "marked change in thinking" in the neurosciences, Condon said. And that discovery is very important to the science of addiction and potentially its treatment.

"How do drugs of abuse impact a plastic, evolving adolescent brain?" Condon asked. While a large amount of data exists in adult populations linking exposure to drugs of abuse to changes in dopamine receptors in specific brain regions, "we have very few human data in adolescents." Some adolescent animal data are available, said Condon, and those data suggest changes in dopamine receptors in response to adolescent exposure to such substances as nicotine and cannabinoids. But, he added, much is still to be learned.

Addiction researchers have known for some time that substance abuse is tied in some way to changes in the brain's circuits that utilize dopamine, Condon noted.

"Dopamine is the neurotransmitter involved in all reward/reinforcing circuits in the brain, not only for drugs," he added, "but also for things like sex and food." Yet new research is now showing that dopamine is not alone.

"We also know that glutamate, GABA, and possibly cannabinoid receptors may be involved [in modulating substance abuse behaviors]. And we've learned a lot about the circuits in the limbic system and how prolonged exposure to drugs of abuse changes these circuits," Condon added." We've been able to see dramatic reductions in striatal dopamine receptors in individuals addicted to heroin, cocaine, ethanol, and methamphetamine."

Addiction researchers have also discovered a great deal about craving, Condon continued, and how someone who is addicted to a substance of abuse shows abnormally elevated activation of brain circuits in the cingulate cortex and inferior cingulate gyrus.

Yet how these structural and functional changes in the brain caused by drug abuse lead to addiction is not clear-cut; however, addiction neuroscientists have learned two points: First, "comorbidity is absolutely the rule, not the exception," Condon said, "and we have to get others to understand this," not only from a clinical viewpoint but also from an administrative viewpoint, including reimbursement issues.

Second, "Is there recovery?" Condon asked. "Of course there is. But do these physical changes in the brain go back to baseline [when an addicted individual is no longer exposed to the substance of abuse]?" Some data, including Volkow's own work at the Brookhaven National Laboratories prior to joining NIDA, indicate the brain does repair some of the damage.

"Above all, we know that comorbidity is the rule, not the exception," Condon said. "And we must treat addiction as a chronic, relapsing disorder." The addiction psychiatry field must become better at spreading that message, he added.

"So where are we going with all this?" asked Condon." Research training and mentor grants continue to be ramped up, and the institute is "going to put [its] money where [its] mouth is in training the next generation of addiction psychiatrists."

Future NIDA initiatives include focusing on prescription drug abuse—particularly opiates, Condon said, as well as looking at the" social neuroscience" issues of clique or group interactions that support or reinforce addictive behaviors. Genetic influences in substance abuse weigh heavily.

Finally, Condon concluded, "we are advancing the science [of addiction], but we must still erase the stigma."

More information on the National Institute on Drug Abuse and its research and clinical programs is posted at<www.drugabuse.gov>.▪