MARIJUANA 'MUNCHIES' LEAD TO POSSIBLE DIET DRUG

Marijuana users call them "the munchies," those intense food
cravings sparked by inhaling the illicit weed's smoke. Normally blamed
for weight gain, these urges to wolf down everything in sight now have
led to the development of a drug that may help millions slim down.

Called Rimonabant, the experimental pill appears to stop the
flow of "feed me " signals to the brain.

"This drug makes people feel satiated so they eat less," says
Dr. Louis J. Aronne, an obesity specialist at the Weill Cornell
Medical Center in New York who has tested Rimonabant. "If it proves
effective, it may become a potent weapon in our fight against obesity,
which is difficult to treat."

Exercise and willpower go only so far in helping us to lose
weight and keep it off. Scientists now know that it's tough to shed
those extra pounds because, in essence, our bodies become addicted to
food.

"As we become overweight, a cascade of physiological changes
occur in the body that interferes with our normal weight-controlling
mechanisms, and overrides the messages to the brain that tell us we
are full," says Aronne, director of the center's Comprehensive Weight
Control Program.

A pill that makes people feel full may help them reduce the
amount of food they consume.

Scientists developed Rimonabant after the discovery of a
pleasure circuit in the brain activated by cannabinoids. The
compounds, which our bodies produce, are chemical cousins of THC
(tetrahydrocannabinol), the active ingredient in marijuana.

Like a key in a lock, these chemicals latch on to the
cannabinoid receptors that cover the brain, which sparks the
sensations associated with a marijuana high: the calm euphoria, fuzzy
memory and that voracious hunger.

Because these chemical messengers prompt people to eat more,
researchers wondered whether a drug that halted their action might
curb appetite. In a 2001 study at the National Institute of Alcohol
Abuse and Alcoholism in Bethesda, Md., genetically altered mice that
lacked these cannabinoid receptors ate less than their litter mates,
even after 18 hours of fasting. When the normal mice were given
Rimonabant, which blocks the cannabis receptors, they reduced their
food intake.

In 2002, Sanofi-Synthelabo, the French drug company that
makes Rimonabant, began human tests. Of 45 obese patients on a
calorie-restricted diet, those taking Rimonabant lost an average of
almost 10 pounds in four months; those taking a placebo lost about 2
pounds.

A two-year trial of 4,200 patients in the United States and
Europe was recently completed, and the results should be released this
year. Rimonabant also is being tested as a stop-smoking aid because
the drug seems to block the same brain circuitry governing nicotine
cravings for cigarettes.

Despite the encouraging early results, experts are cautious.
"While the loss of interest in food may be good, tinkering with this
newly discovered signaling system may have unwanted side effects,"
says Daniele Piomelli, a UC Irvine pharmacologist who has studied the
cannabinoid system. "We need to be very careful that this doesn't
cause other psychological disorders."

Cannabis Derivatives

Only one marijuana-derived drug has been approved by the Food
and Drug Administration. That drug, Marinol, is prescribed to combat
chemotherapy-related nausea and to stimulate the appetites of AIDS
patients.

Another drug, called Sativex, probably will be approved for
sale in Britain later this year. The liquid marijuana extract is used
to treat people suffering from multiple sclerosis and severe pain.

Several drug companies are experimenting with other chemicals
that either dampen or activate the cannabinoid system, which seems to
play a role in regulating appetite, pain, emotions and anxiety.

One compound, for example, called ajulemic acid, is being
tested on humans to reduce pain and relieve inflammation. European
researchers are testing a cannabis-derived stroke treatment that, if
used quickly enough, may limit brain damage. And still other
scientists have unearthed cannabis-like chemicals that ease anxiety in
lab animals. "There's any number of promising therapeutic
applications. Rimonabant is only the beginning," says pharmacologist
Daniele Piomelli of UC Irvine.