FDA Postpones Decision On Safety Of Controversial Cannabinoid Blocking Agent

US regulatory authorities announced that an independent Food and Drug Administration (FDA) advisory committee will hear testimony in June regarding whether the controversial cannabinoid receptor antagonist SR 141716A/Rimonabant is safe for human consumption. The agency had previously announced that it would decide by April 26, 2007, whether to grant US market approval for Rimonabant as a weight-loss drug.

Neither the FDA nor the drug's manufacturer, Sanofi-Aventis Pharmaceuticals, gave a reason for the postponement.

Under the FDA's revised timeline, the agency's Endocrinologic and Metabolic Drugs Advisory Committee will hear testimony regarding the drug's safety and efficacy on June 13, 2007. The FDA has previously denied Sanofi-Aventis Pharmaceuticals permission to market the drug in the US.

Rimonabant, marketed under the trade name Acomplia, recently received regulatory approval for sale in Europe as a prescription dietary aid. It is the first cannabinoid antagonist ever to be approved for human consumption.

Rimonabant blocks the natural binding of endogenous cannabinoids (as well as exogenous cannabinoids such as delta-9-THC, the psychoactive component of marijuana) to the neuronal CB1 receptors, causing users to lose their appetites. However, because the endocannabinoid receptor system is intricately involved in the regulation of a broad range of primary biological functions *-- including appetite, body temperature, mood regulation, blood pressure, bone density, reproduction, learning capacity, and motor coordination --* some experts are concerned that the long-term use of Rimonabant or similar drugs may eventually contribute to a host of significant adverse health effects.

In preclinical trials, newborn mice injected with Rimonabant refuse feeding and often die days after birth. Mice genetically bred to lack the CB1 receptor also suffer from numerous health defects such as cognitive decline, hypoalgesia, decreased locomotor activity, and increased mortality compared to healthy controls.

At least one published case study reports that daily use of the drug may have triggered neurological symptoms of multiple sclerosis in a volunteer with no known history of the disease. Mental health side effects, such as depression, are also commonly reported among volunteers administered Rimonabant.

In human trials, daily administration of Rimonabant is associated with lower blood sugar levels and weight loss compared to placebo. Sanofi is seeking to market the drug in the US under the trade name Zimulti.