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March 01, 1999
NIDA Director Dr. Alan I. Leshner
NIDA Director, Alan I. Leshner

Only some people experiment with drugs, and among those who experiment, only some become addicted. Among those who become addicted, some eventually are able to stop taking drugs while others are not, despite the damage to their health and their personal lives.

What causes these differences? Certainly environmental factors - such as drug availability and peer groups - play a major role, but increasingly, scientists are finding that genetic factors are also very important.

Studies of the drug abuse patterns of twins, adoptees, and families are providing valuable information on the extent of genetic influences on drug abuse and addiction.

To shed light on the genetic and environmental factors that influence people's behavior toward drugs and how these factors interact, NIDA is launching a Vulnerability to Addiction Initiative. (See "New NIDA Initiative Focuses on Vulnerability to Drug Addiction"). Ultimately, the information we derive from this Initiative will give us a clearer understanding of the origins of drug abuse and addiction, and we will be able to apply that understanding to the development of more effective drug abuse treatment and prevention strategies.

The Initiative will support research to locate genes associated with drug abuse and addiction, elucidate their structure and function, and determine how environmental factors can interact with them to make an individual more or less vulnerable to addiction. Because evidence of a role for genetics in drug abuse and addiction comes from both human and animal studies, the Initiative will support both types of research. As part of the Initiative, an additional $7 million has been allocated during fiscal years 1999 and 2000 for a Request for Applications for studies to identify human genetic factors that increase vulnerability to addiction. Funds also will be available for other types of human genetic studies, such as twin studies, as well as studies with animals. Studies funded under the Initiative will build on a solid foundation of knowledge on vulnerability to addiction that NIDA-sponsored research has already produced.

In one line of studies in humans, NIDA-funded researchers have been investigating the drug abuse patterns of twins, adoptees, and families. Such studies are providing valuable information on the extent of genetic influences on drug abuse and addiction. For example, identical twins have exactly the same genes, while fraternal twins have, on average, only half of their genes in common. Thus, if the drug abuse patterns of identical twins are shown to be more similar than those of fraternal twins, this demonstrates that genes are playing a role in this behavior.

Researchers have determined that the relatives of drug abusers are eight times more likely to abuse drugs than the relatives of people who are not drug abusers.

In one recent twin study, researchers at NIDA's Intramural Research Program in Baltimore, the Henry Ford Health Science Center in Detroit, and the Medical College of Virginia in Richmond compared the extent of drug use, abuse, and dependence in twins. The researchers found that genetic influences played a greater role in clinically diagnosed drug abuse and dependence, while environmental factors played a greater role in occasional drug use.

In a study with male adoptees, NIDA-funded researchers at the University of Iowa in Iowa City found that adoptees whose biological parents were substance abusers were more likely to abuse drugs than adoptees whose biological parents were not substance abusers. Since no significant drug abuse problems existed in the adoptive homes of these children, genetic factors are assumed to play a significant role in the development of drug abuse in these individuals.

In a NIDA-funded family study, researchers at Yale University in New Haven, Connecticut, and the University of Lausanne and the University of Geneva in Switzerland determined that relatives of drug abusers are eight times more likely to abuse drugs than the relatives of people who are not drug abusers. These findings indicate that a family history of drug abuse is a potent risk factor for drug abuse.

With advances in molecular genetic technology, scientists are beginning to identify some of the genes that might affect a person's vulnerability to drugs. For example, preliminary findings from one NIDA-funded study indicate that a variation of the gene for the enzyme that breaks down nicotine in the can affect a person's vulnerability to smoking and nicotine addiction. People with a defective version of this gene are less likely to smoke than people with the fully functioning gene. If they do smoke, they smoke less. (See "Study Shows How Genes Can Help Protect From Addiction").

NIDA's animal genetics studies also provide a broad knowledge base for research under the Initiative. For example, NIDA-funded researchers have examined strains of mice and rats that vary greatly in their preferences for drugs of abuse and have found chemical differences in the brains of these rodent strains that may partly account for those drug preferences. Now they are attempting to identify the genes that are responsible for both the disparities in drug preferences and the chemical differences. In other animal research, NIDA scientists are manipulating the genes of animals to determine which genes influence drug preferences and sensitivity and how those genes work to cause these effects.

NIDA scientists have uncovered many intriguing clues to how genetics and environment influence people's behavior toward drugs and how these factors interact. Through the Vulnerability to Addiction Initiative, we will learn more about this critical area of research. As we increase our understanding of why some people are vulnerable to drug abuse and addiction while others are not, we can speed progress in treating and preventing these critical problems.

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