TALKING WITH ALAN I. LESHNER, PHD, NATIONAL INSTITUTE ON DRUG ABUSE DIRECTOR

Bethesda, MD -- Since Alan I. Leshner, PhD, took the helm of the National
Institute on Drug Abuse (NIDA) in 1994, the agency's annual budget has
nearly doubled, to $781 million, supporting much of the world's research on
the biology of addiction, genetic and environmental risk factors, and
addiction prevention and treatment.

Of the two dozen institutes that comprise the National Institutes of Health
(NIH), NIDA is in a unique position. Addiction is, arguably, more
politicized than any other medical issue, putting Leshner and his views
under a spotlight. He is quoted almost weekly in major newspaper and
magazine articles as the authority on the subject. Such visibility comes
with a price, though, as Leshner has been attacked on all fronts -- for
being both too soft and too harsh on drug issues.

Before joining NIDA, Leshner enjoyed a highly regarded research career,
which largely focused on the biology of behavior. He has also served as
acting director of the National Institute of Mental Health (NIMH) and
earlier worked at the National Science Foundation, Bucknell University, the
Postgraduate Medical School in Budapest, Hungary, and the Wisconsin
Regional Primate Research Center in Madison. He has a PhD in physiological
psychology.

JAMA: I've heard you say that one of the things you'd like to do is "change
the national discourse" about illicit drug abuse and addiction. Does this
mean making addiction more of a medical problem and less of a criminal problem?

Dr Leshner: No, no. I am ferociously against polarizing the debate. I think
that's one of the terrible problems we've made with this issue. People say
that it's either a public health or a public safety issue. The truth is,
it's both. And it begins with a voluntary behavior: people choose to use
drugs. I don't call it morality, but I call it voluntary. And there's no
question it's a medical illness and once you have it, it mandates
treatment. It's a myth that millions of people get better by themselves.

But having said that, my own view is that this tendency to polarize the
issue has stalled the issue. Now whether you can stop [illegal drugs from]
coming across the border or not, I would not pull the plug and increase the
[disease] vector. But on the other hand, you've got to worry about the
victim, the patient, the collateral damage to society. I try to keep in
mind the complexity of the issue because we'll never have a simple
solution. And everybody wants to polarize the issue.

JAMA: How does that make your job harder?

Dr Leshner: I hate the fact that people say [illicit drug use] is either a
brain disease or an issue of behavior. That's ridiculous. You don't have a
separate mind and body; it can be a brain disease and an individual is
going to have to be involved in his or her own treatment. That means they
have to learn personal responsibility, and that's a behavior. So until we
understand this in its complexity, we aren't going to get a handle on it.

JAMA: How far are we from getting a full handle on the biology of addiction?

Dr Leshner: That depends on what you mean by "full handle." Is it the case
that the act of engaging in drug use and the contextual cues that surround
it become embedded in the addiction? Sure. Do we know that? Absolutely. Do
we know a lot of the brain circuits and mechanisms? Absolutely. Do we know
all the nitty-gritty about the brain changes? Absolutely not. But we are
starting to see how prolonged drug use changes the brain at the level of
gross circuit changes, responsivity of the brain, and a whole series of
molecular changes that go on with prolonged drug use. To understand that
switch mechanism that moves you from being a voluntary drug user to an
addict, a compulsive drug user, is to understand the molecular mechanisms.
We're getting there; we have a lot of research going on, and it's very
rapidly productive.

JAMA: It sounds as if there are specific targets for drug development.
There's been a lot of research directed at a dopamine receptor called D1.
Is this a promising target? What are some others?

Dr Leshner: I like the D1 agonist notion, but I don't think that's the only
target. The two big targets for [treat ing cocaine addiction] have been D1
agonists and substances that block the dopamine reuptake transport. But
there are a lot of other targets that may turn out to be very important
that go to the common essence of addiction, as well as ones that go to
specific mechanisms for specific drugs. We have 60 compounds [for cocaine
addiction] in clinical trials, targeting 10 different mechanisms.

JAMA: Which are most promising?

Dr Leshner: One of them that's very promising is disulfiram, Antabuse.
There have been a few positive clinical trials that look very impressive.
Disulfiram blocks cocaine craving in people. We also have a multisite trial
with selegiline [Eldepryl], an antidepressant and anti-Parkinson drug. For
a subset of patients, desipramine may be useful; it's also an antidepressant.

JAMA: The drug ecstasy (3,4-methylenedioxymethamphetamine, or MDMA) has
been getting a lot of press lately. What specifically should physicians be
doing about ecstasy?

Dr Leshner: First of all, they need to understand that it's not a benign
substance at all. It's not harmless. It's an incredibly potent stimulant;
that's why people love it. It's both a stimulant and a hallucinogen. It
causes tremendous increases in blood pressure, heart rate, et cetera. It
has a dramatic hyperthermic effect; it increases body temperature
tremendously. So it's dangerous in raves [extravagantly energetic dance
parties] and situations like that. And it's been shown from a decade of
animal research, which is now being confirmed in humans, that ecstasy is
toxic to serotonin-containing neurons.

What physicians need to know is that it's dangerous, and that when people
come in [with questions about using it], it has to be taken seriously. More
and more people are losing control over their ecstasy use. Whether it's
truly addicting or not, we don't know. But the fact that they are coming to
treatment programs saying, "I can't get control over this" means it has to
be taken seriously.

One of the things I'm most interested in is distinguishing between when a
compound is a medicine and when a compound is an abusable substance. It can
be both, and that is very important for physicians to understand. Morphine
is my favorite example, but it's also true of cocaine historically, and
it's true of Ritalin [methylphenidate hydrochloride] and a lot of other
medications. When used properly under controlled conditions, they're
incredibly effective medicines. When misused, they're incredibly addicting.

Now, drugs like ecstasy have been purported to have clinical use, but
there's never been a clinical trial demonstrating the efficacy of ecstasy
for anything. And the fact that four psychiatrists claim it was useful for
them is not evidence (J Nerv Ment Dis. 1992;180:345-52). The plural of
anecdote is not evidence.

JAMA: Would NIDA support a clinical trial of ecstasy for depression or
anything else?

Dr Leshner: We've never received a proposal. If [such a trial] were for a
psychiatric therapeutic indication, it would have to go to the NIMH for
support. The NIH supports studies on marijuana as a medicine; we support
studies on all kinds of things as medicines. There's an awful lot of hype
that ecstasy is a medicine, but there's no evidence. And the assertions are
not dissimilar to [those made about] LSD [lysergic acid diethylamide] in
the '60s and cocaine in the '70s.

JAMA: What you're saying is that the substance itself is not bad, not evil
. . . .

Dr Leshner: That's right. It's the way the substance is used. That doesn't
mean drug abuse is not bad. The war is not on drugs, the war is not on drug
addicts. The war is on drug abuse and addiction, right? That's very
important. The reason you want to keep the supply down and the reason you
want to control the demand is because you're concerned about the health
aspects of it, not because there's something intrinsic in the substance
itself. And that nuance, I think, has been hard for people to understand.

If ecstasy turns out to be a wonderful psychotherapeutic drug, let science
show that. The assertion that "it saved my life because it gave me great
insight" doesn't mean it's true. And the insight could be wrong. The
assertion that the insight was terrific is an assertion; it's empirically
untestable.

JAMA: Overall drug use has been relatively stable during the past 10 years.
What does that say about the nation's entire drug control policy?

Dr Leshner: If you look at national drug policy over the past 5 years, it's
certainly moved toward a blending of public health and public safety
approaches. We have advocates for treatment in prison, which we've never
had before. We have national figures in the new administration advocating
for more emphasis on [reducing] demand, but without giving up the emphasis
on controlling the border flow and controlling the sales. That's vitally
important. We know that availability is a tremendous stimulus to use. So
why would we, as public health officials, advocate anything that would
increase availability or increase use? But the discourse is moving more and
more in the direction [of focus on reducing demand].

JAMA: I recently read that 80% of people arrested for drug crimes are
arrested for possession. Is prison the right place for them?

Dr Leshner: I'm the wrong person to ask. Do I think drugs should be
legalized? Absolutely not. That's my personal view; it's not a scientific
question. It really isn't. The last time we legalized a substance, or
manipulated its legality, it did decrease use.

JAMA: You mean alcohol?

Dr Leshner: Absolutely. [Prohibition] had collateral damage, but it did
decrease use. And it's very different. If we knew 5000 years ago that
alcohol would cause all the havoc it's caused, would we have made it legal?
Would we have made nicotine legal if we knew [what we know now] 400 years
ago? I don't have an answer.

JAMA: You've talked about making drug treatment part of the medical
mainstream. What does that mean?

Dr Leshner: One of the things that's come up five times in the last 2 weeks
is how few primary care physicians understand addiction as a health issue
and how infrequently they discuss it with their patients. We're not asking
physicians to become treatment experts, but we want them to see this as a
health issue. We want them to talk with their patients, assess their
patients, and refer them for specialty treatment just like they would for
any other illness. That's what "making it part of the mainstream" means. It
means medical schools and residencies giving people enough training that
they're comfortable discussing it. The fault does not lie with individual
physicians, but with the training that has not included this issue that has
tremendous health consequences. So, we want people to understand that [drug
abuse] is an illness, to view it as one of the illnesses to screen for in
the primary care setting, and to know [where to refer patients].

JAMA: What happens if a physician finds a candidate for treatment but there
aren't any treatment slots available?

Dr Leshner: It's conceivable that would happen, but it's not an excuse.
Many people who are addicted are privately insured. So they could go to a
private treatment program. They could be referred to a treatment provider.
It's a myth that all of the addicts are poor Medicaid patients. There are
poor Medicaid patients, but there are an awful lot of addicted individuals
who can afford treatment.

JAMA: What are the characteristics of good addiction treatment?

Dr Leshner: We've published a paper in JAMA on this [JAMA.
1999;282:1314-1316]. We know what makes bad treatment, what makes good. One
of the issues is that focusing on drug use per se is too limited a view.
This is a whole-person illness and it requires whole treatment. There is no
magic bullet. On the other hand, it doesn't mean we don't know how to treat
it, either. There's no magic bullet for strokes, for asthma. And these are
chronic, relapsing conditions that require management over time; they
require compliance by the patient. They require an array of rehabilitative
techniques.

JAMA: Does the fact that it often takes more than one pass through
treatment before people give up drug use make it harder to argue "We need
more treatment"?

Dr Leshner: One of the problems is that people misunderstand treatment.
They misunderstand the target of treatment and they think it's just drug
use, but it has to be the total functioning of the individual. The goal of
drug treatment is to restore functioning, not just to manage somebody's
drug use. Being an addict is a way of life and it affects every aspect of
life. The problem with the capacity issue is that people don't have great
confidence in drug treatment because they think that a single momentary
relapse is a failure of treatment, whereas we don't think that if
somebody's blood pressure or diabetes relapses. But good drug treatments,
that is, successive drug treatments, should increase the interval between
episodes until [the user] gets to full abstinence, and then it may have to
be maintained over time. That's the treatment approach we advocate.

JAMA: How do you see NIDA informing the overall national drug policy?

Dr Leshner: We're the science guys. Our role is to generate information,
and 99.8% of our energy goes toward science, just like any other NIH
institute. But what we can do is also educate the public and professionals
about the nature of drug abuse and addiction and what to do about it based
on that science. We believe that taking a scientific approach to this
problem will inform policy. It won't set policy; policy is made on value
plus facts. We're just the fact guys. But we are called upon frequently to
provide factual information, and we never violate the scientific data.

JAMA: Do you get political pressure to produce certain kinds of facts?

Dr Leshner: Yes, sure. But the thing with us is, don't ask a question you
don't want an answer to. Because, from us, as from any other NIH institute,
if you ask a question you get a factual answer. So if you're looking for a
specific answer, don't come here.

JAMA: Any examples you care to share?

Dr Leshner: No. We have tried very hard -- because there are data that show
that hyperbole and exaggeration are the enemy of getting a handle on this
problem -- we have tried to stick to the facts, and I have been accused of
being excessively honest. That is, we really draw the line on what we know
and what we don't know. And we try not to be hyperbolic. But we are
accused, by advocates of a substance, of being exaggerators. And we are
accused, by people who hate the substance, of understating the dangers. And
so I must be about in the right balance if both sides think we're doing the
wrong thing.

JAMA: How does a culture that stigmatizes drug abuse make your job harder?

Dr Leshner: It really is a big issue. Stigma overlays not only addiction
itself, but people who work with addicts and people who study people who
work with addicts. When I came to NIDA 7 years ago I declared as a goal to
have science replace ideology as a foundation for how we approach this
topic. And I actually think we're beginning to take a nick at it, partly
because people are so frustrated with purely moralistic views on the issue
that they're beginning to look to science as a way to help solve the problem.

JAMA: What are some top areas on your research agenda for the next few years?

Dr Leshner: Some of the big stuff has been our treatment initiative. We
declared as our millennial goal improving the quality of drug abuse
treatment nationwide using science as a vehicle. So that will continue to
be a big push. We decided we're going to crank up our emphasis on
prevention research, what actually works in preventing drug use. We've had
a big portfolio that we're going to increase in intensity and try to hone
it down. And we'll keep working at developing new medications. And we'll
continue to use the science to inform the public discussion about the
issue, in the hope that we can move it forward.