GENETICS AND DRUG ABUSE

Addiction Is A Tough Nut To Crack. You Can't Call It An Inherited
Illness, But Genes Do Play A Role. That Discovery Fuels Hope For
Powerful New Treatments.

It wrecks neighbourhoods, families and lives, and might be the most
important public health problem faced by Western societies. Yet
since chemists first isolated cocaine, morphine and heroin in the
19th century, physicians and scientists have struggled to explain addiction.

There's still much to learn, but with advances in genetics,
technology and neuroscience, scientists say they're closer than ever
to understanding why some people who try drugs get addicted and some don't.

"I think we made more progress in the last 10 years than in the
previous history of mankind," said Frank Vocci, director of
treatment and research at the National Institute on Drug Abuse,
which spends $1 billion annually on drug research.

"We're a heck of a lot further along than we were 30 years ago,"
said Dr. Paul R. McHugh, a psychiatrist at the Johns Hopkins School
of Medicine. That progress, he added, "tells me that we don't have
to be quite as hopeless as we were before."

In the past decade, scientists have come to recognize that genetics
plays a major role in all addictions.

It was long suspected that alcoholism was at least partly inherited
because of its presence in some families and not others.

But studies of addicts in the United States, Japan and elsewhere
have shown that methamphetamine users, heroin addicts and other
habitual drug users share similar variants of dozens of brain receptor genes.

One day, scientists say, genetic testing could enable drug
counsellors to warn parents if their children carry an unusually
high risk of addiction, or tailor existing treatments to individual
drug users.

But the ultimate hope, of course, is that the genetics of addiction
will help find powerful new treatments.

So far, the development of new addiction treatments has lagged far
behind the basic science. "There have been modest, incremental
improvements," said Dr. Sol-omon H. Snyder, a Johns Hopkins
neuroscientist and psychiatrist who is one of the world's
authorities on the biochemistry of addiction.

In general, he said, advances have come slowly because major
pharmaceutical companies see little profit in tackling the problem.
But by defining what addiction is, researchers have helped the
industry identify what it calls "targets" for drug research --
genes, proteins, neurotransmitters that could be modified to block
the compulsive use of drugs.

One thing addiction is not, scientists say, is a simple inherited
illness. There is no single gene that inevitably leads to habitual
drug use. Instead, some people appear to carry an array of genes
that raises their risk of addiction.

"Nobody has to become addicted," said Dr. George R. Uhl, a clinical
neurologist and chief of the National Institute on Drug Abuse's
molecular neurobiology branch at Hopkins' Bayview, Md., campus.

"Genes have an influence on behaviour," McHugh said. "They're not a
determining influence on behaviour, in that if you've got them
there's nothing you can do about them. They are an influence."

Overall, researchers say, about half of an individual's
susceptibility to addiction is inherited, while the other half is
the product of a person's environment -- pressures of family, peers
and neighbourhood.

Discussions of addiction usually focus on people living in the most
desperate circumstances, in the poorest neighbourhoods. But the
problem, of course, extends far beyond the inner city.

Lee Krol was a skilled marine electrician, homeowner and father who
lived in suburbia. But he had a problem that anguished and mystified
his family for most of his life. As a teenager, he began to drink
and use drugs. While he would quit for awhile, it was never for
long. "There's nothing like this stuff," he once told his brother, Tom.

So his family was devastated, but not surprised, when they found the
50-year-old on the floor of the computer room of his home Dec. 7,
dead of a heroin overdose.

"I want him to be portrayed as a good person," said Tom Krol. "He
just had a terrible disease."

Since the early 1970s, scientists have identified all the brain cell
switches, called receptors, that respond to addictive drugs. Using
advanced imaging technology such as MRI machines and PET scanners,
they have watched drugs alter the way the biochemical
signals called thoughts and feelings are transmitted through the brain.

Addiction research has zeroed in on a group of brain cells in the
nucleus accumbens, nestled deep within the brain, the location of
what has been called the "pleasure reward" system.

Many of the brain cells, or neurons, in this network communicate
with each other with two of the brain's chemical messengers,
serotonin and dopamine.

The system produces feelings of well-being, the reward for engaging
in actions such as eating and sex, vital to survival and
reproduction. Illicit drugs, it turns out, switch on this system --
specifically, by raising the level of dopamine available to neurons.

Dopamine receptors, scientists say, seem to be important in all
three of the main features of addiction -- tolerance, withdrawal and
compulsive drug seeking. While much of the way this system works
remains a mystery, recent research offers some clues.

Using advanced imaging technology, scientists have discovered that
people whose brains have a higher concentration of the so-called D2
dopamine receptor reacted with indifference to a mild stimulant --
in this case, Ritalin -- while those with fewer D2 receptors tended
to enjoy the experience.

Dr. Nora Volkow, one of the U.S.'s leading addiction researchers and
director of NIDA, led studies showing that cocaine users have lower
concentrations of D2 receptors than non-users.

It's not clear whether people are born with higher D2 receptor
densities, develop higher densities as a result of experience, or
both. In a paper in the journal Nature Neuroscience in 2002,
scientists at Wake Forest University showed that macaque monkeys
that achieve high status in small groups tend to develop a higher
concentration of D2 receptors. The D2 density of subordinate
macaques did not change.

This work suggests there is a link between low status, D2 density
and vulnerability to addiction.

But this picture might not be as simple as it seems, said Snyder,
who helped launch modern addiction research in 1973, when he and his
student, Candace Pert, discovered the opiate receptor.

When researchers in his lab exposed rodents to mind-altering drugs,
Snyder said, they typically would find that hundreds of genes in the
rodents became more active -- raising, say, the number of receptors
- -- and hundreds became less active.

"From our experience with rodents, D2 receptors went up, but
probably another 299 things went up, too," he said. Tracking a
single change in a single receptor does not establish a
cause-and-effect relationship.

Some scientists say that advances in genetics research could have
benefits. Uhl, the NIDA neurologist at Bayview, notes that
Naltrexone, used to block the effects of alcohol, works better for
people with one form of a gene than another.

Drugs developed to treat other diseases are helping addicts. Smokers
often are given anti-depressants to help them overcome their
dependence on nicotine -- which ranks with cocaine as the most
powerfully addictive of the widely used drugs. (Without treatment,
only one out of 20 smokers quits successfully, researchers say.)

One of the most successful treatments for habitual drug users are
Alcoholic Anonymous-style "12-step" programs. Addicts guaranteed
anonymity encourage one another to overcome their dependence.

Many drug users will need more intensive, residential treatment. Tom
Krol said his brother, Lee, needed residential treatment, but could
not afford to take the time off from work.

The public, frustrated by the seeming intractability of addiction,
is reluctant to pay for expensive treatment programs, researchers
say. As a result, there is a chronic shortage of spaces or "slots"
in such programs in the U.S..

Los Angeles Times-Washington Post News Service

RESOURCES to overcome addiction:

*Drug and Alcohol Registry (DART) dart.on.ca or 1-800-565-8603

FIGURES Addiction rates in Canada

*About 13.6 per cent of all Canadians are considered high-risk
drinkers, in a 2004 survey of past-year drinkers.

*About 1 in 20 Canadians report a cannabis-related concern.

*The illicit drug most commonly used during one's lifetime is
hallucinogens, followed by cocaine, speed and ecstasy.

*Self-reported rates of illicit drug use are increasing in Canada.

*The rate of self-reported use of cocaine (in a lifetime) rose from
3.5 per cent in 1989, to 3.8 per cent in 1994, to 10.6 per cent in 2004.

*The rate of self-reported use of LSD/speed/heroin (in a lifetime)
rose from 4.1 per cent in 1989 to 5.9 per cent in 1994 to 13.2 per
cent in 2004.

*Data indicates the number of Canadians who report having used an
injectable drug at some point in their life increased from 1.7
million in 1994 to a little over 4.1 million in 2004.

(Source: 2004 Canadian Addictions Survey)