Pubdate: Mon, 10 Apr 2006
Source: Hamilton Spectator (CN ON)
Copyright: 2006 The Hamilton Spectator
Author: Douglas Birch


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) 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)
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MAP posted-by: Beth Wehrman