HUMAN BODY FOUND TO PRODUCE ITS OWN VERSION OF MARIJUANA

Scientists hope to isolate the pain-killing powers of the natural compounds

Amid the various 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 may also 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.

Already, 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, absentmindedness and "female
disorders." African tribes used it to treat snakebite and the pain of
childbirth, while Indian physicians prescribed it for headaches.

Sifting through the plant's chemical stew in the early '60s, 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:

Herbert Schuel and Lani J. Burkman of the University of Buffalo have
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 W. 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.

In 1997, 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.

Researchers' largest hopes are focused on using a synthetic form of
cannabinoids to block pain, including chronic nerve pain that
existing drugs block inadequately.

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.

"These kind of manipulations may not have the unwanted side effects
of marijuana and aren't going to carry the same kind of political
baggage."