SCIENTISTS FIND HOW BRAIN CHEMICAL ACTS LIKE POT

WASHINGTON -- When scientists recommended the medicinal use of marijuana's
ingredients last week, they were relying on a little-known fact. Our brains
already are flooded with the plant's active agents -- chemicals called
cannabinoids that may play key roles in keeping us healthy, happy and free
of pain.

Scientists have known since 1992 that the brain contains compounds that
latch onto the same sites in the brain as the active ingredient in
marijuana. On Monday, scientists funded by the National Institute on Drug
Abuse announced they have discovered how one of these compounds causes a
behavior characteristic of marijuana use, the inhibiting of movement.

Since the discovery of the first identified human cannabinoid -- christened
``anandamide'' from the Sanskrit word meaning ``internal bliss'' -- these
compounds have become one of the looming mysteries of the nervous system
because they touch so many aspects of human life, including how we eat,
fight illness and form memories.

Scientists want to learn how these natural chemicals mimic the effects of
the active ingredient in marijuana known as delta-9-tetrahydrocannabinol
(THC).

This week's announcement describes how anandamide counteracts another brain
chemical, dopamine.

Animal studies showed that anandamide and dopamine act in opposite ways to
control movements in an area of the brain called the dorsal striatum,
according to the scientists, who will publish their findings in the April
issue of the journal Nature-Neuroscience. ``Dopamine stimulates movements
by acting in this area, and anandamide normally inhibits this action of
dopamine,'' said lead researcher Dr. Andrea Giuffrida of the University of
California-Irvine.

``Research on drug abuse can lead to possible treatments for seemingly
unrelated diseases,'' said Dr. Alan Leshner, National Institute on Drug
Abuse director. ``Abnormalities in the dopamine system are thought to play
a major role in several neurological and psychiatric disorders, as well as
in drug addiction, so new medications that can counteract these
abnormalities might prove useful in treating more than one disease.''

Developing medication

The THC-like natural compounds may prove useful in the development of
medications for treating diseases that seem to involve dopamine imbalances
in the brain, Giuffrida suggests. Some diseases such as schizophrenia and
Tourette's syndrome may be caused by too much dopamine in certain brain
regions, or perhaps hypersensitivity of brain sites targeted by dopamine.
Medications that mimic anandamide might reduce symptoms by dampening
dopamine overactivity.

While cannabinoids are common in animal nervous systems, marijuana is the
only plant known to contain them. In fact, it has dozens, including THC,
which is far more powerful than the cannabinoids found in humans and other
animals.

Last week's report from the Institute of Medicine notes that cannabinoids
produced by our bodies affect pain, appetite, motor control and memory. The
most recent studies show cannabinoids may regulate the immune system,
enhance reproduction and protect the brain.

Here are some of the most intriguing findings:

In December, two University of Buffalo researchers reported that
cannabinoids help control the exquisite timing of reproduction by slowing
the sperm that approach an egg before it's ready for fertilization.

Cannabinoids have been found to both suppress and enhance the body's
defenses against diseases and tumors, a duality that has researchers puzzled.

While anti-drug messages spotlight the drug's damaging effects on the
brain, research last summer from the National Institute of Mental Health
showed cannabinoids protected brain cells from stroke or trauma damage.

Last year, scientists at the Neurosciences Institute in San Diego showed
that cannabinoids block the formation of memories in animal brain tissue.
This might keep the brain from getting overwhelmed with unimportant memories.

The latest report is no news to the nation's medical establishment. The
National Institutes of Health and the American Medical Association have
been calling for aggressive research into marijuana, citing pioneering work
on cannabinoids.

Perhaps these compounds help in stressful situations, such as helping cope
with pain perception. Or perhaps anandamide disregulaton -- when the body
produces too much or too little of the chemical -- is linked to mood
disorders.

Scientists speculate that pot smokers manipulate a naturally occurring
system when they light up a joint, creating an effect that they might not
otherwise have at that moment.

Chemically, these compounds don't look quite like THC. But they are similar
enough to bind to a THC receptor in the brain, like a key in a lock. This
triggers the release of chemicals, called neurotransmitters, that send
impulses down the body's central nervous system pathways that control motor
skills, memory and other functions.

Until recently, the existence of these receptors was mystifying. Had they
evolved in anticipation of that day when someone would smoke a joint? Or
did they play some normal, natural role?

The discovery of anandamide and other cannabinoids helps solve that mystery.

Researchers also hope that cannabinoids can be used to ease pain,
especially chronic nerve pain that doesn't respond to other painkillers.
Studies show cannabinoids work as well as morphine by short-circuiting pain
signals before they reach the spinal cord or brain, and they are less
addictive than narcotic pain relievers.

Several years away

For that to be realized, researchers will have to develop cannabinoid-based
drugs or inhalers. Those are not expected to be widely available for
several years. In the meantime, the Institute of Medicine recommended that
patients whose pain and nausea do not respond to any other treatment be
given marijuana cigarettes, even though that violates federal law and
carries its own health risks from smoke.

That political battle probably will be waged through more state ballot
initiatives across the country. Meanwhile, researchers are staying far away
from the political fray. Instead, they plan to keep working on what they
call the ``Holy Grail'' of their field: separating marijuana's therapeutic
effects from side effects such as euphoria and disorientation.

Kenneth Hargreaves, a pharmacologist at the University of Texas Health
Science Center in San Antonio, has shown that injecting small
concentrations of cannabinoids directly at a site of injury relieved pain
and swelling without affecting the brain. He hopes to develop a cannabinoid
pill that wouldn't cross the body's blood/brain barrier and cause mental
side effects.

While some advocates of marijuana say its power lies in its complex mix of
chemicals, Hargreaves argues that harnessing cannabinoids and tailoring
them to medical needs is the best approach. ``For a fever, you're going to
take an aspirin,'' he said. ``You're not going to boil willow bark off a
tree.''