STANFORD STUDY FINDS CELLS CREATE POT-LIKE CHEMICALS

How Brain Produces A 'High'

Mother Nature created a way to ``tune in, turn on'' long before
pot-smokers rolled their first joint, Stanford scientists have found.

Eavesdropping on the conversations between brain cells, the research
team found that neurons make their own marijuana-like chemicals called
cannabinoids, which indirectly alter the way information is received
and filtered.

When the chemicals are released, ``neurons have a harder time deciding
which are the relevant things to pay attention to,'' said investigator
John R. Huguenard, associate professor of neurology and neurological
sciences at Stanford University School of Medicine.

For a long time, scientists thought that marijuana altered the mind in
a messy and random way that didn't involve any particular part of
brain chemistry.

Now they've identified an elegant modus operandi. It adds to a growing
body of research that explains the mechanism behind getting ``high.''
Marijuana mimics the cannabinoids made naturally by our brain --
chemicals that influence a smorgasbord of body functions including
movement, thought and perception.

The research sheds light on a powerful neurochemical system.
Researchers hope that when they understand the job the chemical does
in the day-to-day running of our bodies, they can design new
therapeutic drugs.

In their Stanford lab, Huguenard and colleagues David Prince and
Alberto Bacci injected electric current into rat brain cells, then
watched the chatter between the brain's two major types of cells.

When overly excited, one type of neuron releases cannabinoids, which
create a calming effect, they found. In effect, the brain cell drugs
itself.

But this mellowed-out cell falls down on its job, which is to filter
the flow of information rushing into a second type of cell.

Without a good filter, the researchers think, this second neuron is
flooded with sensory information that affects memory, perception, mood
and movement.

Marijuana similar

Something very similar happens with marijuana use, the scientists
believe.

In an accident of nature and chemistry, the compounds in pot are
shaped similarly and trigger similar effects.

``Marijuana use . . . affects the way we think,'' said Huguenard. The
new research shows that ``part of that is because of changes in the
way our brain cells receive incoming information, like sensory
information or memories or emotion.''

Because so much information is always flowing into the brain, ``each
neuron has to make a decision based on the signals it gets,'' he said.
``They have to make sense of it . . . and decide what's relevant.''

``Marijuana loosens a natural filter that exists in neurons, so they
tend to be flooded with information,'' Huguenard said.

`Long overdue'

The research is published in today's issue of the journal Nature.

``This type of research is so long overdue,'' said Gerald Uelmen, a
Santa Clara University School of Law professor who represents the
Santa Cruz-based Wo/Men's Alliance for Medical Marijuana. ``When
Congress classified marijuana as a controlled substance, the idea was
that, `We don't know enough about it.' There are many new studies that
are very exciting, showing the myriad of possibilities, and that
medical marijuana has great potential.''

What prompts a brain cell to release a cannabinoid? Pain, perhaps? Or
some other sensation? The Stanford team doesn't know yet, but one
possibility is that it seeks to calm the high level of nervous system
activity that occurs during epileptic seizures.

There remains much to be learned about the mechanisms that control
brain circuitry, Huguenard said. Further research will illuminate the
role that cannabinoids play in the normal brain -- and how they can be
exploited to control pain, seizures or appetite.

It may prove possible to tailor therapies by blocking or activating
production of particular cannabinoids or cell receptors, eliminating
the ``high'' while harnessing the most useful aspects of the chemical.