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French marijuana study sparks experimental diet drug

Hollister H. Hovey

The Nando Times

Thursday 15 Aug 2002

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NEW YORK (August 14, 2002 5:03 p.m. EDT) - French pharmaceutical company
Sanofi-Synthelabo hopes scientific knowledge gained from marijuana will
help the masses curb the "munchies."

The company reasons that if smoking pot makes people hungry, a compound
that blocks the hunger-inducing effects of marijuana - like its
experimental drug Rimonabant - could make a great diet drug.

Such a drug could contract waistlines while fattening Sanofi's sales. The
National Institutes of Health estimates that a quarter of the country is
officially obese and more than half is overweight. Prescription diet drugs
brought in $417 million in the United States last year, a relatively small
amount that underscores the lack of a serious blockbuster in the marketplace.

Sanofi based Rimonabant's chemistry on the discoveries scientists have made
about the links between marijuana and hunger.

With a weed-induced high comes a voracious urge to eat, which smokers refer
to as "the munchies." Doctors initially thought marijuana affected the
brain in a fairly random manner, like alcohol, and that hunger was one of
those random effects.

But in the late 1980s, researchers discovered that the hypothalamus, the
part of the brain which controls our most basic functions like movement,
memory, perception and hunger, is covered in receptors which serve as
docking stations for cannabis molecules. When marijuana chemicals settle
into the receptors, the brain gets the message that the body needs food.

But these receptors aren't sitting there waiting for a person to light up a
joint. The human body makes its own marijuana-like substances called
cannabinoids which doctors now know play a large part in giving us an
appetite.

Based on this premise, Sanofi's researchers found a synthetic compound
called a cannabinoid receptor antagonist that caps off the receptors,
preventing cannabinoids from locking on and sending the "feed-me" message.

George Kunos, a neurobiologist with the NIH's National Institute on Alcohol
Abuse and Alcoholism, led a 2001 animal study on cannabinoids and eating
habits.

After seeing the successful results in animals, Sanofi started to test the
treatment on humans.

In a short, 16-week Phase IIb trial, Sanofi studied obese patients on
various oral doses of Rimonabant compared with patients receiving a
placebo. The heavier the dose, the more weight was lost, with a decrease of
around 4 kg, or 8.8 pounds, at the end of the trial in the highest dose group.

Rimonabant caused some gastrointestinal side effects at the highest dose,
but was generally well-tolerated, a Sanofi spokesman said.

However, other potential weight-loss remedies have worked in the first six
months of clinical trials, but then started losing effectiveness as the
body built up resistance to the treatments.

Of course, long-term safety is also a huge concern. The U.S. Food and Drug
Administration generally likes to see two years of safety data before
making final approvals for obesity drugs, doctors said.

Last August, the company initiated phase III trials of Rimonabant for
obesity, studying 6,180 patients. The first study is a two-year North
American trial of 2,800 patients comparing 5 milligram and 20 milligram
doses of Rimonabant to placebo for weight reduction and prevention of
weight regain.

The company is also conducting a two-year, 1,400-patient trial in Europe
with the same standards.

Alongside the trials, Sanofi is running two other 990-person studies
looking at the effects of the drug in patients with diabetes and lipid
problems.

Weight loss from the Phase II trials was "in the same ballpark as medicines
we've seen before, but you can't predict what's going to happen long-term,"
said Dr. Lewis Aronne, director of the Comprehensive Weight Control Program
at the Weill Cornell Medical Center in New York, which is participating in
the latest human trials.

But if the drug proves to have staying power, it would be entering a
potentially huge market for prescription diet drugs that remains fairly
untapped.

Meanwhile, insurers often balk at reimbursing patients for diet drugs,
which they commonly group with other "lifestyle medicines" such as erectile
dysfunction or baldness treatments. Without insurance coverage, the $90 to
$100 a month price tag can be a bit heavy for some consumers to pay out of
pocket.

However, Americans desperately need to lose weight. The NIH estimates the
prevalence of obesity in the U.S may have increased by more than 75 percent
in the last two decades.

Obesity and the diseases with which it's associated cost the, estimates
that the prescription diet drug market will climb to $1.4 billion by 2010.

 

 

 

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