Drugs that Influence Cannabinoid Receptors

Taranabant and rimonabant are drugs developed to effect cannabinoid receptors. Taranabant is a selective, acyclic cannabinoid 1 receptor (CB1R) inverse agonist, or drug that binds (temporarily blocks) cannabinoid receptors. Sanofi-Aventis Group, a Paris-based pharmaceutical conglomerate, developed rimonabant (sold internationally under the names Acomplia and Zimulti). Rimonabant is available in 20 countries, but not in the U.S. In 2007, an advisory panel of the U.S. Food and Drug Administration-the agency that regulates the safety and efficacy of prescription drugs-voted against approving rimonabant for the U.S. market. The decision in part was a response to alarming reports that some rimonabant users had experienced serious depression, including thoughts of suicide.

If taranabant and rimonabant suppress appetite instead of stimulating the munchies, then it is no surprise that the drugs might have other effects that contrast with those experienced by marijuana users. Sure enough, the Merck researchers reported that 53% of the subjects who received daily six-milligram doses of taranabant encountered gastrointestinal problems, including nausea, vomiting and diarrhea. And 27% of the six-milligram group endured negative psychological effects during the clinical trial. These included mood swings, anxiety, depression and insomnia.

Heymsfield informed HealthDay that "no suicidal thoughts were reported" by any of the participants in the trial. But he conceded that the Merck team had not paid special attention to the drug's psychological side effects.

Merck plans a longer-term, more-detailed clinical trial in 2008, with the aim of seeking FDA approval by the end of the year.

Steven R. Smith, an official with the Obesity Society as well as a researcher at the Pennington Biomedical Research Center in Baton Rouge, La., warned in a HealthDay interview: "This is not going to be a class of drugs that people take because they want to look good on vacation....I think this class of drugs, should it make it to market, is going to need to be reserved for people who have complications related to obesity, such as type 2 diabetes, high blood pressure, or severe osteoarthritis."

David Katz, an obesity specialist at Yale University, told Wired, "If [Merck] can deliver the benefit without the downsides, it has a good chance at [FDA] approval." However, Katz argued that Americans did not need a miracle weight-loss pill; they need to change their eating habits. "If people drown underwater, the solution is not to give people drugs that allow them to keep from drowning underwater....We're just drowning in calories."

Sources

"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.

Madrigal. Alex. "Obesity Treatment Gives You the Opposite of the Munchies." Wired, (January 8, 2008) www.wired.com/ medtech/ drugs/ news/ 2008/ 01/ reverse_cannabis.

Stein, Lisa. "New Diet Drug in Battle of the Bulge." Scientific American, (January 9, 2008) .