Want to lose weight but lack the willpower to just say no to fatty foods and sweets? Help may be on the way. The first clinical trials of an experimental weight-loss drug show that it helps curb appetite—and burn more fat—even at low doses.

[See update at the end of this story.]

Researchers report in the journal Cell Metabolism that taranabant, developed by drug giant Merck, is the second drug found to be successful in fighting flab by blocking cannabinoid receptors (responsible for the psychological effects of marijuana a.k.a. Cannabis sativa) in the brain's reward circuitry.

"The effects of marijuana on appetite have been known for millennia from its medicinal and recreational use," said study author Steven Heymsfield of Merck Research Laboratories. "The ingredient responsible stimulates cannabinoid receptors. When you block the cannabinoid system with an antagonist like taranabant, you suppress appetite."

The first indication that the cannabinoid-1 (CB1) receptor might be a prime weight-loss target came during studies of an earlier drug called rimonabant (manufactured by sanofi-aventis), which is now available as a diet aid in several European countries but has yet to receive the Food and Drug Administration's nod for use in the U.S.

Heymsfield and his team found that obese people given low doses of taranabant consumed fewer calories, expended more energy and shed pounds. The scientists initially tested the drug on animals, which lost weight on doses that inhibited just 30 percent of their cannabinoid receptors. Armed with this knowledge, the researchers used positron emission tomography (PET) imaging to determine the amount (four to six milligrams) of taranabant that would achieve a similar goal in humans.

They found that obese patients lost significant weight during the 12-week trial at surprisingly low doses ranging from 0.5 to six milligrams; those who took a 12-milligram dose consumed 27 percent fewer calories than subjects given a placebo. The researchers reported that plump participants on the drug also expended more energy while at rest and appeared to burn more fat.

But lest you think more is less—literally—take note: The medical team said higher doses had some potential negative side effects, most notably nausea, vomiting and moodiness. This was not entirely unexpected, Heymsfield said, given that it has the opposite effect of marijuana, which has been known to quell nausea associated with cancer treatments and, also, to calm rather than irritate people.

Next up: A larger phase III clinical trial to further explore the drug's potential benefits and risks. "All we have here is 12 weeks," Heymsfield said. "We don't yet know what will happen at six months or a year.

Update (posted 1/2/09): As the Wall Street Journal Health Blog reported in October, Merck has cancelled its studies of taranabant because subjects had " an increase in anxiety, irritability and depressed mood."