NERVES NEED MARIJUANA-LIKE SUBSTANCE TO STAY IN TOUCH, STUDIES FIND

Brain's Self-Made 'Cannabis' Essential To Normal Thought

Even if you have never smoked a joint in your life, a cannabis-like
substance occupies a special niche in your brain, fine-tuning the nerve
connections that control memory and most other thought processes.

New research into how these so-called "endogenous cannabinoids" work may
help scientists understand what goes on inside the heads of those who smoke
pot -- which floods the nervous system with far more of the active
ingredient than the brain can supply on its own.

Last week's U.S. Supreme Court ruling against the medicinal use of
marijuana came as brain scientists were celebrating profound new
discoveries about how cannabis works in our heads.

The landmark studies, published recently in the journals Nature and Neuron
by scientists at the University of California at San Francisco, Harvard
Medical School and Kanazawa Medical University in Japan, suggest the brain
cooks up its own marijuana-like ingredients in order to tweak the
all-important connections that link nerve cells.

Two of these marijuana-like substances have been discovered so far, docking
in the very same nerve-cell receptors used by THC, the active ingredient in
pot.

It's as if the brain has its own secret stash. But despite years of
research, scientists had no clear idea until now what its purpose might be.

"Were we built to smoke marijuana?" wondered Jeff Isaacson, an assistant
professor at the University of California at San Diego, who contributed to
the latest findings by UC San Francisco graduate student Rachel Wilson and
neuroscientist Roger Nicoll.

They set out to discover how nerve cells "talk back" to one another in a
brain region called the hippocampus, which is crucial in memory and learning --
but not, coincidentally, one of the principal areas affected by smoking pot.

The back talk involved is actually a feedback loop that allows a nerve cell,
or neuron, receiving an impulse from another neuron to fire back its own
signal, thus modifying critical neurochemical activity at the source.

This so-called "retrograde signaling" is one key way neurons can dial into
one another, allowing effective communication to take place at the cellular
level.

There are essentially two kinds of brain cells, according to Stanford
University neuroscientist Dan Madison. There are the principal cells that
make up what he likened to a superhighway system of long-range information
movement, and there are "interneurons," which are like traffic signals along that
highway.

"Cannabinoids are a way for the principal cells to regulate the traffic
lights," Madison said.

After two years of laboratory study and frustrating dead ends, Wilson and
Nicoll found that the role of the brain's cannabis is to make the feedback
system work. Harvard researchers, working independently, found an
essentially identical role for endogenous cannabinoids in another part of
the brain, called the cerebellum, which helps to control motor function.

"It's a way for a nerve cell to adjust the gain or intensity of the
information coming into it," Nicoll said. "It turns up the amplifier, in a way,
and allows more input to get through."

These adjustments seem to have an important role in the brain's uncanny
ability to synchronize the firing of nerve cells scattered throughout the
brain, linking behavior with mood and memory with vision or hearing.
Thousands of signals thus become molded into vast oscillations, helping the
brain bind together different aspects of perception into something we can
experience as a coherent state of mind -- a feeling of being in love,
perhaps, when we look at someone.

If that's the case, the implications for marijuana smokers seem rather
profound.

Marijuana receptors are just about everywhere inside our skulls, but the
brain's natural cannabis is present in minute amounts, and its effects are
subtle: a fleeting and localized shift in brain chemistry in particular
areas of the nervous system.

When you smoke a joint, researchers said, you essentially swamp that whole
system for however long the buzz lasts by flooding the brain with THC. This
may help to explain why marijuana users report the drug has such diverse
and often idiosyncratic effects on mood, memory, appetite, vision, pain and
motor control.

Some users report an odd stretching of their sense of time. Others make
connections -- humorous, sometimes -- between things that normally don't
seem related. And memory is clearly impaired, as is motor function.

Such effects start to make sense, researcher Wilson said, in light of the
new insights into how natural cannabinoids function.

"We suspect that marijuana is sort of hijacking the system, doing what the
brain normally does but in overdrive," she said.

Marijuana researchers have found no reliable evidence of permanent damage
arising from this hijacking, and the latest experiments are said to be
essentially neutral as to the merits of allowing medicinal use of pot.

The new brain findings may help drug researchers find ways to mimic pot's
effects, perhaps leading to development of drugs that similarly modify
synaptic connections but in a more controlled way.

The research also gives scientists a topic with which they can liven up
their social lives when they venture outside the lab.

Nicoll, for one, likes to look audiences right in the eye, wag his finger
and insist that during the entire two-year research project he "never once
inhaled."

"Marijuana and the brain is a fun field to be in," Isaacson, Nicoll's
former graduate student, said. "You talk about this with people at parties,
and they're actually interested."