In June 2006 pharmaceutical giant Sanofi-Aventis began selling a new weight-loss drug called rimonabant in Europe. Rimonabant worked in part by reducing appetite, and the company claimed it could also treat addiction, harmful cholesterol, and diabetes. Lab tests even suggested the drug produced healthier sperm. But within six months, the company had received more than 900 reports of nausea, depression, and other side effects.
By the following summer, the U.S. Food and Drug Administration had rejected rimonabant, noting that relative to a placebo, patients taking it were twice as likely to contemplate, plan, or attempt suicide. The European Medicines Agency soon asked Sanofi-Aventis to address the safety concerns, and on December 5, 2008, the company pulled the drug off the European market.
Rimonabant was a spectacular flop, and yet its lure today is stronger than ever. Researchers worldwide are pursuing novel drugs aimed at the exact same target: the endocannabinoid system, an elaborate network of receptors and proteins that operate within the brain, heart, gut, liver, and throughout the central nervous system. For drug designers, the system’s powerful role in regulating cravings, mood, pain, and memory makes it a tantalizing target. The challenge now is finding sharper, more refined ways to manipulate it without causing the sort of debilitating side effects that derailed rimonabant. “The system is very, very widespread and very effective at a variety of levels,” says neuroscientist Keith Sharkey, who studies the role of endocannabinoids in the gut at the Hotchkiss Brain Institute at the University of Calgary. “It seems to be very important in the body, which is a concern when you develop drugs for it because you will get a range of effects.”