Taranabant New Diet Pill: Pot of Gold for the Obese?

America is getting fat. Really, really fat. According to the Centers for Disease Control, two-thirds of the U.S. population is either overweight or obese. The formula for calculating body mass index (BMI) is a bit complicated; it involves weight measured in kilograms divided by height measured in meters squared. Physicians classify anyone with a BMI of 25 to 29.9 as overweight, and anyone with a BMI of 30 or more as obese. The CDC estimates that about 30% of overweight Americans are obese. Suffice it to say that 200 million U.S. residents are losing the battle of the bulge.

That obesity is a problem is, of course, not news. Constantly we're assailed by claims of new "cures" to the problem and a big dose of skepticism is clearly in order when confronting these claims. But there is a recent development which, even if it must be treated with caution, certainly seems like good news for those carrying too many pounds. A 12-week clinical trial conducted by Merck Research Laboratories (a unit of pharmaceutical giant Merck & Co. Inc.) indicates that an experimental diet drug called taranabant can suppress appetite while simultaneously revving up calorie-burning metabolism, even at relatively low doses. The results of the trial were reported in the January 8, 2008 issue of Cell Metabolism.

Taranabant is an intriguing drug not only for its apparent effectiveness, but also for how it works. It blocks the very same neurochemical receptors in the brain that-when stimulated by smoking marijuana-drive ravenous potheads to their refrigerators.

The active ingredient in marijuana is THC or tetrahydrocannabinol. THC interacts with the brain's cannabinoid receptors to induce a mildly euphoric high accompanied by sudden food cravings like cookies (which users call "the munchies").

The active ingredient in marijuana (Cannabis sativa) is THC or tetrahydrocannabinol. THC interacts with the brain's cannabinoid receptors-which help regulate the body's energy balance-to induce the psychological and physiological effects associated with marijuana: a mildly euphoric high accompanied by a feeling of well-being and sudden food cravings (which users call "the munchies"). Because of those effects, California and a few other states have legalized the use of marijuana for medicinal purposes, such as easing the debilitating nausea suffered by patients undergoing chemotherapy for cancer. November 5, 1996]. However, possession of marijuana is still illegal under federal and most state laws.

Taranabant is a selective, acyclic cannabinoid 1 receptor (CB1R) inverse agonist, or drug that binds (temporarily blocks) cannabinoid receptors. "The effects of marijuana on appetite have been known for millennia from its medicinal and recreational use," explained Steven Heymsfield, Merck's director of obesity research, in a press release that coincided with the Cell Metabolism article. "The ingredient responsible [THC] stimulates cannabinoid receptors. When you block the cannabinoid system with an antagonist like taranabant, you suppress appetite."

Prior to the clinical trial, Merck discovered that laboratory animals lost weight with doses of taranabant that blocked just 30% of the animals' cannabinoid receptors. Using positron emission tomography (PET) imaging, the researchers determined that doses of taranabant as low as four milligrams to 6 milligrams could bind 30% of the same receptors in humans.

The clinical trial involved 533 overweight and moderately obese human subjects in a double-blind, placebo-controlled study. Half of the subjects received daily doses of a placebo, while the other half received daily doses of taranabant.

The clinical trial involved 533 overweight and moderately obese human subjects in a double-blind, placebo-controlled study. Half of the subjects received daily doses of a placebo, while the other half received daily doses of taranabant in amounts ranging from 0.5 milligrams to six milligrams. All of the participants followed a regimen of moderate-calorie meals and no exercise. After 12 weeks, the placebo recipients had lost an average of 2.6 pounds per person. The six-milligram taranabant recipients had lost an average of 11 pounds per person. But even at the lowest doses, the taranabant recipients lost more weight on average than the placebo group.

"That was surprising," Heymsfield revealed in the press release. "We didn't expect weight loss at all doses."

The Merck researchers also conducted a related study of food intake and energy expenditure during the trial. This study involved 36 overweight and moderately obese subjects who were monitored over a 24-hour period. The participants were divided into three groups. The members of one group received single four- or 12-milligram doses of taranabant. Those in another group each got a 30-milligram dose of a diet drug called Meridia (generically known as sibutramine). The third group received a placebo. Those who received the higher doses of taranabant ingested 27% fewer calories than the placebo group, and 15% fewer calories than the Meridia group. Also, all of the taranabant recipients burned more calories at rest than the members of the other groups.

Sources

Boyles, Salynn. "New Weight Loss Drug Shows Promise." WebMD, (January 8, 2008) www.webmd.com/ diet/ news/ 20080100/ new- weight- loss- drug- shows- promise.

Doheny, Kathleen. "New Weight-Loss Drug Shows Promise in Early Study." HealthDay News, (January 8, 2008) www.businessweek.com/ print/ lifestyle/ content/ healthday/ 611483.html.

"Experimental Weight-Loss Drug Cuts Appetite, Burns More Energy." Physorg.com, (January 8, 2008) www.physorg.com/news119022694.html.

"First Results of Merck's Taranabant Promising for Weight Loss." Medopedia, (January 9, 2008) www.medopedia.com/ merck- taranabant- weight- loss- study.