SO MUCH FOR BIG PHARMA'S 'ANTI-POT' PILL

An independent U.S. Food and Drug Administration advisory committee
determined yesterday that the controversial "anti-pot" pill Rimonabant
is unsafe for human consumption in the United States. Sanofi-Aventis'
would-be diet aid -- which has been linked to suicidal thoughts,
depression and even multiple sclerosis -- counteracts the effects of
marijuana and similar naturally occurring chemicals in the body
(so-called endocannabinoids), causing users to lose their appetites
and, according to the warnings of experts, a host of other unwanted
and dangerous side effects.

Rimonabant does not possess a "favorable risk-benefit profile" to
warrant U.S. market approval, members of the FDA's Endocrinologic and
Metabolic Drug advisory panel determined in a 14-0 vote. Panelists
reported that patients prescribed Rimonabant experienced increased
incidences of depression, nausea, vomiting, and suicidal tendencies.
Adverse neurological symptoms in some patients were also reported.

The expert panel's rejection sent shares of Sanofi stock plummeting
and may have worldwide implications. Last summer European regulators
gave preliminary approval to the pill, which has now been prescribed
to some 100,000 patients under the trade name Acomplia. However,
following Wednesday's unanimous decision, representatives of the
European Medicines Agency immediately announced that they will begin
hearings to consider recalling the drug.

For Sanofi stockholders and analysts, who had predicted that
pharmaceutical giant's "anti-pot" pill could one day rake in some $3
billion in annual profits, the news is a disappointing financial
setback. But to health experts familiar with the workings of
Rimonabant and similar drugs, the FDA panel's decision comes as little
surprise and is long overdue.

The Dark Side of Acomplia

As a weight loss drug, Rimonabant is far from a miracle cure. In
controlled studies, patients who ceased taking Rimonabant typically
gained their weight back -- implying that the drug may have to be
prescribed indefinitely. It's that likelihood, coupled with the drug's
reported and potential side effects, that have raised eyebrows among
the scientific community.

Because the endocannabinoid system is involved in the regulation of a
broad range of primary biological functions -- including appetite,
mood regulation, blood pressure, bone density, reproduction, learning
capacity, and motor coordination -- some experts are concerned that
the long-term use of Rimonabant and/or similar drugs to counteract it
could contribute to a host of significant adverse health effects.
Animal data appears to substantiate this concern. Newborn mice
injected with Rimonabant refuse feeding and often die days after
birth. Mice genetically bred to lack certain cannabinoid receptors
also suffer from numerous health defects such as cognitive decline,
hypoalgesia, decreased locomotor activity and increased mortality
compared to healthy controls. Could similar risks await long-term
users of Rimonabant?

Dr. Franjo Grotenhermen, director of the Association for Cannabis as
Medicine (ACM) in Germany, states, "One of the major functions of the
endocannabinoid system is the protection of nerve cells from damage by
overactivation of neurotransmitters," Grotenhermen says. "The
long-term use of [endocannabinoid] receptor antagonists may impair
this neuroprotective effect with an accelerated loss of nerve cells
and negative consequences on brain functions such as memory."

Investigators at Amsterdam's Vrije University (the Netherlands)
express a similar viewpoint. Writing recently in the journal Multiple
Sclerosis, they report of a 46-year-old woman who was diagnosed with
the disease after taking Rimonabant daily for seven months. They note
that the woman had no prior history of neurological symptoms before
taking the drug and that the patient recovered to "near normal"
several weeks after discontinuing the medication. "It does not seem
implausible that [endocannabinoid] antagonism may cause [central
nervous system damage] in susceptible subjects," they concluded.

Among patients administered Rimonabant in clinical trials, many
report experiencing adverse effects such as nausea, anxiety and
depression. According to published data, more than 15 percent of
subjects who try the drug discontinue its use because of intolerable
side effects. In addition, at least one study of the drug reported a
2.7-fold increased risk of psychiatric disorders in Acomplia users.
Dr. Mitch Earleywine, author of Understanding Marijuana: A New Look
at the Scientific Evidence (Oxford University Press, 2002), isn't
surprised. "Given what we are now learning about the endocannabinoid
system, one would think that any blocking of its receptors,
especially long-term, would be an invitation for a host of negative
health consequences involving pain, brain function, and mood --
particularly depression," he says.

At yesterday's hearing, FDA experts voiced similar concerns and
recommended the agency shelve the drug when it makes its official
determination next month. If so, it will be the second time the FDA
has refused to grant market approval to Rimonabant, which Sanofi
initially tried to sell in the United States as a prescription
smoking-cessation agent. Ultimately, in the eyes of the FDA, a healthy
body needs all the "pot" it can get.