So Much for Big Pharma's 'Anti-Pot' Pill

So Much for Big Pharma's 'Anti-Pot' Pill

By Paul Armentano, AlterNet
Posted on June 15, 2007, Printed on June 15, 2007
http://www.alternet.org/story/54191/

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.

Paul Armentano is the senior policy analyst for the NORML Foundation in
Washington, D.C.

© 2007 Independent Media Institute. All rights reserved.
View this story online at: http://www.alternet.org/story/54191/