NIDA BOSS TOUTS ADDICTION STUDIES

Editor's Note: Scientists looking for a crash course in effective
communication of their research findings should catch Alan Leshner in
action. During recent months, the personable director of the Rockville,
Md.-based National Institute on Drug Abuse (NIDA) has been moderating a
series of "Town Meetings" in such metropolises as Philadelphia, Dallas,
Chicago, and Atlanta. In the keynote talk he gives on the myths and
realities of drug abuse and addiction, he juxtaposes graphs and cartoons
with anecdotes, jokes, and research findings (NIDA funds more than 85
percent of the world's research on health aspects of drug abuse and
addiction), keeping large audiences rapt.

Leshner supports his central message-that drug addiction is a chronic,
relapsing brain disease-with such ear-catching sound bites as, "We know
more about drugs in the brain that we know about anything else in the
brain." Listeners tend to nod in agreement when he declares, "Drugs hijack
the brain." He explains many research projects that have helped to
establish structural and functional differences between drug-addicted and
normal brains at the molecular and cellular levels. He advocates a
"whole-person treatment," encompassing biology, behavior, and social
context, an approach he says recognizes addiction as a bio-behavioral
disorder. And he lambastes what he calls "The Great Disconnect" between
ideology and science that he believes is impeding the formulation of more
effective national policies in prevention and treatment of drug abuse and
addiction. In the following edited transcript of an interview with Senior
Editor Steve Bunk, Leshner elaborates on some of these points.

Q Which group has been the hardest for you to convince that addiction is a
chronic, relapsing brain disease-the general public, the medical science
community, or politicians?

A I would say each of them carry very different baggage. Politicians seem
to be among the easiest. The public carries strong beliefs. The medical
profession seems to be tied to their ideologies about the efficacy of
treatment. They think treatment is not quite possible, and therefore it's
not real. But, of course, treatment is possible and it is real. The easiest
group to impact are criminal justice people. They get it immediately. They
deal with addicts in nontherapeutic situations, and they know there's
something wrong with them.

Q How much progress has been made in understanding the intracellular
processes after an addicting drug binds to receptors?

A A lot. I just saw the other day we spend about $45 million a year on
molecular and cellular neurobiology. We know what's happening in the
biochemical cascade after the receptor is activated, in excruciating
detail, for heroin, cocaine, alcohol, less for marijuana, less for
nicotine. And we know, in a good amount of detail, the difference between
the addictive brain and the nonaddictive brain at the cellular level. We've
made a lot of progress. That's where some of the targets are coming for
medication development. Some are gross, at the level of a receptor-you
know, pick the receptor, activate it or deactivate it. But we also are now
seeing some of the changes in transcription factors, and maybe we should be
intervening there.

Q Does NIDA have drugs in the pipeline that will have chemical activities
similar to some of these addictive drugs but will exert therapeutic effects?

A I'm trying to avoid substitute medication. I think the ideology around
substitute medications is so bad that no one will ever accept them. And so,
I keep saying we're not going to develop any substitute medications. We are
looking at molecules that are similar in some ways to, say, cocaine, but I
don't acknowledge that they're substitutes. I call them analogs.

Q You recently announced that NIDA would fund a study on medicinal use of
marijuana [no such study had been funded for 10 years, until a team led by
professor of medicine Donald I. Abrams at the University of California, San
Francisco, was awarded a grant in October]. Tell us about the new project.

A It's a study of smoked marijuana vs. Marinol [a tablet containing
marijuana's active ingredient, tetrahydrocannabinol] and the variety of
metabolic factors in HIV-infected patients taking indinavir [a protease
inhibitor]. It's an inpatient study with controlled dosing, beautifully
designed to answer the questions. They're going to give people three joints
a day, one before each meal. It's over two years. I love this study,
because it shows that you can do research on difficult topics, and I think
it also says that by sticking to our scientific standard, we get better
science. There was a lot of pressure to either do or not do earlier
iterations. I think what the data show is that you can design a good study
and [the National Institutes of Health] will deliver. It's about $900,000
total cost, provided by four [NIH] institutes.

Q In 1995, you said your goal was for science to replace ideology as the
foundation of the nation's anti-drug abuse strategies by the year 2000
(K.Y. Kreeger, The Scientist, Aug. 21, 1995, page 12). Is that still the goal?

A That's still the goal. And I think we're making what I would call very
good progress. There has been a lot more coverage in the last couple of
years, more and more, as there are people feeding back to me things about
drug abuse and addiction, and I think the climate is changing itself.

Q If science ultimately is to underpin policy-setting for drug abuse
prevention and treatment, does it follow that science should underpin all
social policy?

A Sure. But policy has two pieces to it. There's a fact part of policy, and
that should always be based on science, and then there's a value part of
policy, and that's separate. So when people ask me what my view is on this
or that policy, I only have a view on the fact end of it. I don't really
think it's my place to have an opinion about the value part.

Q But how can you expect science to replace ideology, when ideology is
based on values that sometimes run contrary to perceived facts?

A I want science to be the foundation for the decisions, but it's not
reasonable to expect it will be the only factor.

Q Would you agree that religion is the primary underpinning of Western
society's concepts of justice and values, which have to do with sin and
retribution?

A Sure, that's the foundation of how we do it now. It's not working.

Q What I'm suggesting is, it's such a sea change for people to think
differently. You're not worried about that? I am worried about it, but it
does not stop me from [keeping] my conviction that it is this disconnection
between the moral view and a pragmatic view that's giving us all the
trouble. So, my job is to generate the knowledge, and then make sure it
gets to the right people, and then pray like hell that they use it.

A What do you say to people who suggest that there's a difference between
addiction and other sorts of brain disorders, like Alzheimer's disease or
schizophrenia, because the latter conditions don't arise from a voluntary
act of will? But lung cancer does occur from a voluntary act of will, and
we still pay to treat people for it. The question is whether you want to
fix it or not. Whether you think the person is evil and you hate them is
not relevant. It's only relevant whether you want them to not do it
anymore, and stop robbing your mother [for drug money]. And if you want
them to not rob your mother, you need to treat them. You need to deal with
it as a health issue, even if you hate them while you're doing it.

Q If addicts are told that relapse is a statistical norm of their disease,
does this create a kind of self-fulfilling prophecy for them to relapse?

A Yes and no. But we don't lie to people in health settings, or we won't be
effective. And even if relapse is the norm, that doesn't mean we like it
when it happens, and it doesn't mean we don't have to do something about
it. We're not saying that controlled use is okay, which I object to, by the
way. And we're not saying that a relapse is okay. Just like it's not okay
to have a diabetic coma. All we're saying is a relapse is going to happen.
When it happens, we need to do an intervention.

Q You mentioned that you're against controlled use of drugs. How do you
define drugs in that context? For example, would they include sugar or
caffeine?

A It depends on how bad they are for you and how bad they are for me if you
use them. I have a very pragmatic view of it. I don't want people using
marijuana and driving. If they want to smoke it in their bedroom, that's
foolish, but I certainly don't want them smoking marijuana and driving the
car, flying an airplane, or in any of a number of settings where it could
endanger other people.

Q You reported during the town meeting that there now is some evidence of
withdrawal symptoms from marijuana. But earlier, you said that whether or
not an illicit drug causes physical withdrawal is irrelevant to its
dangerousness.

A There's an interesting paradox in our business. People seem to think that
the only drugs that are dangerous are drugs that cause physical withdrawal,
because they don't know about cocaine and amphetamines not causing it. And
everybody thinks cocaine and amphetamines are dangerous. My predecessors
and people in the health community have been saying for years that
marijuana is bad for you, marijuana is addicting. People kept saying, no it
isn't, because it doesn't cause great physical withdrawal symptoms. Well,
we now have rat studies that show that if you precipitate withdrawal with
an antagonist, you do get physical withdrawal symptoms, and everybody's all
excited. To me, it doesn't matter. I thought it was addicting before and I
think it's addicting now. It's just that other people now agree it's
addicting, because it causes this physical withdrawal. But the truth is,
it's addicting because it causes compulsive use. The thing that matters and
causes problems in families, society, for individuals, for anybody, is the
fact that compulsive use means that you do terrible things to get the drug.

Q Your message seems a simple one, although obviously the research behind
it is complex.

A My message is, "Add the health perspective." It's not, "Substitute a
health perspective." I believe drugs should be illegal, and I believe that
we should seize them at the border. But I also believe we need to treat
drug abuse or addiction as a health issue, as well. And the problem is,
we've missed that part in most of our strategies. Now we have to increase
its role.

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