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DURHAM, N. C. -- Dr. Jonathan Davidson can't help but
chuckle. The national study he is going to lead, on a humble
little roadside weed, has brought out all the big guns in his
field. "The level of interest extends to the innermost reaches
of orthodox psychiatry," he said dryly. "The phone hasn't
stopped ringing. People want to be a part of it."

What clinicians are calling about is the $4.3 million
awarded to Duke Oct. 1 from the National Institutes of Health
(NIH) to study St. John's wort, an herbal "remedy" for mild
depression. It will be the first extensive clinical trial the
federal government has financed to compare a health- food store
dietary supplement with a prescribed drug, and a number of
academic medical centers were vying for it.

To Duke, winning the contract offers medical center
researchers a chance to demonstrate the expertise of their
Department of Psychiatry and Behavioral Sciences, as well as to
show off the muscle of its Clinical Research Institute, which
has organized huge clinical trials around the world.

For Davidson, a native of Great Britain who took a side
interest in homeopathy while training in medicine, the grant
validates his belief that progress is made when "people are
willing to take a fresh perspective."

It's much ado focusing on a weed, Hypericum perforatum,
commonly called St. John's wort, that grows prolifically on
disturbed land, like the side of the road. Wort is an Old
English word for plant, and this one was said to be named for
St. John the Baptist, because it opens its yellow blooms on his
birthday in late June.

But what makes the leaves and flowers of this lowly weed an
object of considerable medical interest is its unique mixture
of chemicals which reputedly have therapeutic effects on
depression. St. John's wort, known and used for centuries among
practitioners of phytotherapy, or plant-based medicine, is an
accepted remedy for depression in Europe, particularly Germany,
where 66 million doses of the herb were prescribed in 1994.

In the United States, interest in St. John's wort has zoomed
in the past several years as word spread that the herb may be
at least as good as some prescription antidepressants, and, to
boot, may be cheaper, readily available, and have fewer side
effects.

It isn't just the public that is gravitating to wort
therapy. Scientists in Europe have conducted a number of small
investigations, culminating in an overview of 23 clinical
studies published last year in the British Medical Journal that
found that the herb may be as useful as prescription
antidepressants in cases of mild to moderate depression.

The American medical community too has come to see St.
John's wort as a possible therapy. The fact that there have
been no studies of its long-term use prompted the NIH to launch
its first large-scale test of a health-food store product.

The three-year study is sponsored by the NIH's Office of
Alternative Medicine, the National Institute of Mental Health,
and the Office of Dietary Supplements. "This study will give us
definitive answers about whether St. John's wort works for
clinical depression," the mental health institute's director
Steven Hyman said in a prepared statement. "The study will be
the first rigorous clinical trial of the herb that will be
large enough and long enough to fully assess whether it
produces a therapeutic effect."

The NIH says that up to 17 million Americans suffer from
depression, costing the nation up to $44 million in treatment,
disability, and lost productivity – a figure comparable to
heart disease.

"Pressure is being put on the establishment to come up with
responses because people are using it," Davidson says of the
unusual NIH contract, adding that "there's a need to do a good
study to see whether it is safe and effective. It is in the
public's interest."

He is coordinating with physicians at Duke and up to 12
other centers around the country to enroll 336 psychiatric
outpatients with moderate depression. The patients will be
divided into three groups – those receiving either the herb, a
placebo, or a commonly prescribed drug for depression – and
results after six months of therapy will be compared.

What the study may not be able to answer, however, is
exactly how hypericum works in the brain. Davidson says the
plant's alkaloid extracts likely affect the action of at least
two neurotransmitters – dopamine and GABA – both of which are
linked to depression or anxiety, but to what extent is not
known. And while there are remarkably few side effects reported
to date, Davidson points out that "herbal treatments are raw
medicine," varying in potency and purity from one manufacturer
to another. Indeed, St. John's wort is available in health food
stores in capsules, tablets, teas, and liquid extracts, often
in different strengths.

The most popular antidepressants, by contrast, work
primarily on a different neurotransmitter, serotonin, which is
said to affect mood. These drugs, which include Prozac, Zoloft,
Paxil and Elavil, are serotonin reuptake inhibitors --- they
work because they keep serotonin available for longer than
usual in the brain, providing an emotional boost.

Davidson says that while he believes a lot of depression is
undiagnosed and untreated, he notes that a lot of people seem
to be self-medicating with St. John's wort. What isn't clear is
whether people are taking the herb because they are, indeed,
depressed, or because they have a transient case of the blues,
or because they feel just fine – but would like a little boost,
nevertheless. And that raises the issue of how safe the
preparation, which is unregulated by the FDA, really is for
everyone who wants to use it.

Still, he says he is "willing to consider that it might be
effective, subject to the proper clinical demonstration," and
that it is the researchers' job to figure out where St. John's
wort belongs in the continuum of treatment.

The study is a departure of sorts from his own current focus
of interest, the study and treatment of post traumatic stress
and of social phobias. He has found, for example, a link
between victims of rape who suffer from post traumatic stress
and a family history of depression, and that a combination of
drug and behavioral therapy can effectively treat social
phobias.