RETHINKING ADDICTION

Drug addiction has become a pervasive and pernicious problem, not
simply because of the wide availability of drugs, but also because
nearly everyone inherits a vulnerability for addiction to
mind-altering chemicals, according to new research.

Just as certain genes make some people more prone to heart disease,
cancer or Alzheimer's disease, scientists now believe other genes may
make them more susceptible to becoming addicted to heroin, marijuana
or other compounds that affect the brain's natural reward system.

"It appears that the genetic vulnerability for substance and alcohol
abuse is fairly general in our society," said Dr. David Goldman, chief
of neurogenetics at the National Institute on Alcohol Abuse and Alcoholism.

"It's probably not wise for anyone to think that they're not
vulnerable to some substance of abuse," he said. "If you tested an
entire population and identified everybody who's vulnerable to drug
abuse, you could probably put everybody's name on the list."

In underscoring the roles that genes and environment play in causing
addiction, the new findings open the possibility of developing the
first effective prevention and treatment strategies for drug abuse.

The findings reveal the inherited biology that turns some people into
mean drunks, and they debunk long-held beliefs, such as the notion
that marijuana use puts an individual on the slippery slope to cocaine
or heroin use.

Western cultures tend to view addiction as a sin to be condemned, or
as a disease to be treated, Goldman said.

"The fact that we have failed too often with either approach suggests
that a better understanding of the origins of addiction could be
useful to help people make better decisions and to improve the basis
of intervention," he said.

A study of identical and fraternal twins found that, in general,
genetic influences account for one-third of addiction, family another
third, and peers, friends and co-workers the remaining third.

Between 60 million and 70 million Americans have tried an illegal drug
sometime in their lives, and 4.2 million have become addicted.
Sixty-five million Americans drink alcohol and slightly more than 8
million have become dependent. Thirteen percent of Americans age 12
and older are heavy cigarette smokers, more than a pack a day, and 57
percent of them say they find it difficult to quit.

But all types of addiction are not equal when it comes to the impact
of genes. The study, which appears in the Archives of General
Psychiatry, found that genes accounted for more than half of the risk
of heroin addiction, but only 26 percent of the addiction to
psychedelics. The biggest factor influencing addiction to psychedelics
is the non-family environment, including friends, schoolmates and
co-workers, which accounts for 53 percent.

For marijuana addiction, the non-family environment also has the
biggest influence, accounting for 38 percent and with genes at 33 percent.

"Some of these addictions--for example, alcohol and opioid abuse--are
more heritable than susceptibility to coronary artery disease or
obesity," Goldman said.

"While there's a clear environmental component, it nevertheless works
out that for somebody living in modern society, a prediction as to
whether they would have a problem with alcohol or another substance
would be substantially dependent on their genetic background," he said.

Although addiction-predisposing genes are not yet known, finding them
has become a major goal of the National Institute on Drug Abuse. Early
success by researchers in linking some genes to alcoholism has
persuaded the drug abuse institute to do the same thing for the genes
of addiction.

"With the emergence of new genetic technologies and ways to actually
look inside the human genome, we decided the time is right to mount a
major initiative to try to understand the role of genetic influences
on the vulnerability to addiction," said Dr. Alan Leshner, director of
the drug abuse institute.

The ability to diagnose genes that make a person more susceptible to
specific addictions could result in lifestyle changes to prevent
addiction, or the development of medicines that block the individual
action of each drug of abuse.

"Drug addictions join a series of other conditions--for example, lung
cancer, cardiovascular disease, acquired immunodeficiency syndrome and
alcoholism--that are recognized as common, complex, genetically
influenced diseases," Goldman said.

"Each of these disorders can be profoundly influenced both by
inherited genes and by such life choices as smoking, diet, exercise,
condom use and abstinence from alcohol."

The study, headed by Harvard University's Dr. Ming Tsuang, also
overturns the old belief that the use of less addictive drugs, such as
marijuana, sets people on the path to becoming hooked on cocaine or
heroin, the "marijuana gateway."

While some people abuse every drug they can, because these drugs
affect a major chemical path in their reward system, others have genes
that make them addicted to one type of drug that affects only a very
specific part of the reward mechanism.

"There are genetic effects that make some people predisposed to
substance abuse," said Dr. Jack Goldberg of the University of Illinois
at Chicago School of Public Health.

"It doesn't mean that addiction is predetermined by genes. It just
means that some of us are more susceptible than others to abusing
drugs if we try them," said Goldberg, who participated in the study.

The study involved 3,372 male twin pairs from the Vietnam Era Twin
Registry. The twins had a variety of experiences. In some cases one
twin served in Vietnam while the other stayed home. In other cases
both twins served in Vietnam, and in other cases neither did.

The registry, located at the Hines VA Medical Center in Maywood, was
originally established to study the effects of Agent Orange exposure
on soldiers in Vietnam. It has since been used to examine the roles
that genes and environment play in sleep disorders, post-traumatic
stress disorder, alcoholism and other problems.

Twins are used to evaluate the relative influences of genes and
environment because identical twins share 100 percent of their genes
and fraternal twins share 50 percent.

The health, life course, education, occupation and other
characteristics of twin brothers is fairly similar. By studying the
similarities and differences between such things as drug addiction and
alcoholism, researchers can determine the influences of genes and
environment in causing these behaviors.

Ten percent of the twins had or still have drug abuse problems. Those
twins who served in Vietnam were exposed to more stress and drugs than
the ones who remained in the U.S.

Yet when a Vietnam twin had become addicted to heroin, his brother
also was likely to be addicted, showing a strong genetic link.

Addiction to sedatives and psychedelics had the weakest genetic links,
only about 25 percent. These addictions were much more likely to be
influenced by friends and peers.

"If you're not genetically predisposed to drug abuse, but are in an
environment where everyone uses drugs, and you do too, you might
become addicted," Goldberg said.

Children are especially at risk when family members abuse drugs. An
estimated one out of 10 children, 7.5 million, from birth to age 17
live in a home where a parent is addicted to illicit drugs or alcohol.

Drugs of abuse tend to alter levels of natural chemicals called
neurotransmitters, such as serotonin and dopamine, which are involved
in impulse control and the ability of the brain's reward system to
dole out sensations ranging from pleasure to euphoria.

"Nobody gets addicted the first time they use a drug; that's a myth,"
said Leshner. "But people do become addicted at different rates. The
problem is that you as an individual have no idea how susceptible you
are to being addicted.

"At its core, addiction is about changed brains. We need to be looking
at genes to see whose brain is more or less susceptible to being changed."

Researchers recently found a gene that is linked to antisocial
alcoholism. It is a mutant form of a gene known as HTR1B, which lowers
levels of serotonin and increases the risk of impulsive aggression.

The mutant alcoholism gene was discovered through genetic analysis of
Finnish alcoholic criminal offenders and a Southwest American Indian
tribe with a high rate of alcoholism.

"These drugs talk directly to the brain in a way a therapist never
can," Goldman said. "Once somebody becomes addicted to a drug, it
appears that the brain is forever changed. They have a greater
vulnerability for relapse."

Discovering the genes that predispose to addiction will help
scientists track their chemical pathways in the brain, allowing them
to devise counter-measures to block a drug's ability to cause a "high."

"In order to prevent drug abuse, we need to find the genetic or
environmental risk factors," Tsuang said. "For marijuana, the
environment seems to be more important than genetics. For heroin,
genetics is more important than environment.

"We need to identify the genes that predispose to addiction, learn
what those genes do, and figure out what kind of medication we can
develop to correct those gene mutations," he said. "For marijuana we
need to concentrate on the family--is it dysfunctional?--and the
school--are other students using it?"