NATURAL FORM OF MARIJUANA IN HUMANS A MEDICAL MYSTERY

WASHINGTON -- Amid this year's clamorous battles to legalize medical
marijuana stands this little-known fact: Our brains and bodies are flooded
with a natural form of the drug.

Called cannabinoids, after the euphoria-inducing plant Cannabis sativa,
this family of compounds blocks pain, erases memories and triggers hunger.
Newer studies show they also may regulate the immune system, enhance
reproduction and even protect the brain from stroke and trauma damage.

Discovered in humans just a few years ago and, until recently, virtually
unstudied, the compounds have become one of the looming mysteries of the
nervous system, and a field of exploding scientific interest.

Scientists are testing cannabinoids with hopes of harnessing the medical
power of marijuana to treat pain without its high, smoke or political
baggage. A key challenge is separating the curing power of the compounds
from their mind-altering side effects.

"That's the holy grail of this field," said Steven Childers, a
pharmacologist at the Wake Forest University School of Medicine in
Winston-Salem, N.C.

Because cannabinoids are so numerous in the brain, they also could help
explain the workings of some of our body's most complex, and least
understood, systems.

"It's obviously important because there's so much of it. And we never knew
it existed before," said J. Michael Walker, a Brown University psychologist
who has conducted some of the first studies of how cannabinoids block pain.

"It could help us understand movement, it could help us understand memory,
it could help us understand pain. We don't really know how any of these
things work."

There has always been evidence, from the intoxicating effects cannabis
evokes in smokers, that it contains powerful compounds.

The sticky, flowering buds of the plant have been harvested as medicine for
centuries. Five thousand years ago, Chinese physicians used the plant to
treat malaria, absent-mindedness and "female disorders."

African tribes used it to treat snakebite and the pain of childbirth.
Indian physicians prescribed it for headaches.

Sifting through the plant's chemical stew in the early 1960s, Israeli
pharmacologist Raphael Mechoulam discovered more than 60 cannabinoids in
marijuana, including the famous and psychoactive compound THC.

In 1992, a team led by Mechoulam and William Devane trumped that discovery
by showing that humans produced their own cannabinoids. They called the
substance anandamide (Sanskrit for "eternal bliss").

Our brains contain receptors that interact with the anandamide we produce.
In an accident of nature and chemistry, compounds in pot are shaped
similarly and therefore trigger similar but more potent effects. The same
is true of the plant drugs nicotine and cocaine.

Now, scientists are beginning to understand just what natural cannabinoids
might be doing in the human body.

"We're opening doors now we couldn't even have predicted existed," said
Childers, president of the International Cannabinoid Research Society.

For example:

- - This week Herbert Schuel and Lani J. Burkman of the University of Buffalo
reported that cannabinoids help control the exquisite synchrony of timing
during reproduction by slowing anxious sperm if they try to approach an egg
before it's ready for fertilization. This may also explain why heavy pot
users, both men and women, are sometimes infertile.

- - Cannabinoids have been found to both suppress and enhance the body's
defenses against diseases and tumors, a duality that has researchers
puzzled. "It's a science clearly in flux," said Thomas Klein, an
immunologist at the University of South Florida. "The more we learn, the
more confused we are."

- - While pot warnings--"This is your brain on drugs"--have long spotlighted
the drug's damaging effects on the brain, research last summer from the
National Institute of Mental Health shows cannabinoids protect brain cells
from stroke or trauma damage.

- - Last year, scientists at the Neurosciences Institute in San Diego showed
that cannabinoids block the formation of new memories in slices of animal
brain tissues. This power to forget might keep the brain from filling up or
getting overwhelmed with unimportant memories.

Cannabinoid research in animals already has scientists considering drugs
that might be quite powerful in exploiting an untapped chemical system
within the brain to solve an array of medical problems.

"While no one wants a drug that disrupts memory, maybe you could boost
memory by blocking cannabinoids," said Billy Martin, a professor of
pharmacology at the Medical College of Virginia and one of a handful of
people who have studied cannabinoids since the 1970s.

Researchers' largest hopes are focused on using a synthetic form of
cannabinoids to block pain, including chronic nerve pain that can't be
adequately blocked with existing drugs.

Animal studies show cannabinoids can block other kinds of pain almost
before they begin, stopping the pain signals before they reach the spinal
cord or brain, working as well as morphine. That power suggests they could
be substituted for morphine, which is addictive and must be used in
increasing doses over time.

Cannabinoids enhance morphine's power; combining the drugs could vastly
reduce the dosages needed to kill pain, offsetting problems of addiction
and drug tolerance. Cannabinoids also counteract nausea, another plus for
patients with cancer and AIDS.

"It might be possible to manipulate levels of the body's own cannabinoids.
You could create drugs like Prozac that block the body's reuptake of
cannabinoids or inhibit their breakdown so they stay active longer," said
Andrea Hohmann, who previously worked with Walker and now researches pain
at the National Institute of Dental and Craniofacial Research.

Checked-by: Richard Lake