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    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.

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