Pubdate: Wed, 14 Aug 2002
Source: Wall Street Journal (US)
Copyright: 2002 Dow Jones & Company, Inc.
Author: Hollister H. Hovey
Bookmark: (Cannabis)


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 could make a great diet drug
. Hence, the development of Sanofi's experimental obesity treatment

Such a drug , should it move beyond its current clinical trials and win
approval, could contract waistlines while fattening Sanofi's sales. The
National Institutes of Health estimates that one-quarter of the country is
officially obese and more than half is overweight. Prescription diet drugs
brought in $417 million in the U.S. last year, a relatively small amount
that underscores the lack of a serious blockbuster in the marketplace. IMS
Health, a market-research firm for the pharmaceutical industry, estimates
that the market for prescription diet drugs will climb to $1.4 billion by

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

With a weed-induced high comes a voracious urge to eat, which tokers 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 that controls functions like movement,
memory, perception and hunger, is covered in receptors that 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

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.

Curbing the Urge

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

"Using genetically engineered mice which lacked the CB1 cannabinoid receptor
sites, we found as expected that the normal animals, when briefly food
restrained, ate more than the animals that lacked the cannabinoid receptor,"
Dr. Kunos said. "This was very strong evidence that the increase in food
intake is mediated in part by this system." Dr. Kunos's study then showed
that blocking off the receptors with Sanofi's compound produced the same
results as the mice who lacked the receptors -- less of an urge to feed.

After seeing the successful results in animals, Sanofi started to test the
treatment on people who qualified as clinically obese. In a 16-week Phase
IIB trial, Sanofi studied 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 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.

Long-Term Issues

It has yet to be seen if Sanofi's drug can help patients shed pounds over
the long term and prevent them from gaining the weight back. 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

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 five-milligram and 20-milligram
doses of Rimonabant to a placebo.

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 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.

Light Competition

Currently there are only two obesity medicines approved for long-term use by
the FDA -- Abbott Laboratories' Meridia and Roche Holding AG's Xenical. And
they "aren't suitable for all patients" and don't produce staggering
results, according to Kishore Gadde, director of Duke University Medical
Center's Obesity Clinical Trials Program.

Meridia shouldn't be taken by people with high blood pressure, and many
patients stop taking Xenical -- which blocks fat absorption in the gut --
after dealing with the side effects, like diarrhea.

The FDA approved Meridia, a drug that slows the body's dissipation of the
brain chemical serotonin, as a treatment for obesity in 1997. The drug can
increase the risk for heart attacks and stroke. It was removed from some
European markets earlier this year after reports associating it with heart
attacks, but European authorities recently concluded the drug remains

Sales of both Xenical and Meridia have failed to meet early expectations.

It is likely that more than physical concerns are holding back revenue from
these drugs . 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% in the
past two decades.
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MAP posted-by: Josh