Marijuana 'munchies' lead to possible diet drug
February 01, 2004
Linda Marsa, Los Angeles Times
'This drug makes people feel satiated so they eat less,' says Dr. Louis J. Aronne, an obesity specialist at the Weill Cornell Medical Center in New York who has tested Rimonabant. 'If it proves effective, it may become a potent weapon in our fight against obesity, which is difficult to treat.'
Exercise and willpower go only so far in helping us to lose weight and keep it off. Scientists now know that it's tough to shed those extra pounds because, in essence, our bodies become addicted to food.
'As we become overweight, a cascade of physiological changes occur in the body that interferes with our normal weight-controlling mechanisms, and overrides the messages to the brain that tell us we are full,' says Aronne, director of the center's Comprehensive Weight Control Program.
A pill that makes people feel full may help them reduce the amount of food they consume.
Scientists developed Rimonabant after the discovery of a pleasure circuit in the brain activated by cannabinoids. The compounds, which our bodies produce, are chemical cousins of THC (tetrahydrocannabinol), the active ingredient in marijuana.
Like a key in a lock, these chemicals latch on to the cannabinoid receptors that cover the brain, which sparks the sensations associated with a marijuana high: the calm euphoria, fuzzy memory and that voracious hunger.
Because these chemical messengers prompt people to eat more, researchers wondered whether a drug that halted their action might curb appetite. In a 2001 study at the National Institute of Alcohol Abuse and Alcoholism in Bethesda, Md., genetically altered mice that lacked these cannabinoid receptors ate less than their litter mates, even after 18 hours of fasting. When the normal mice were given Rimonabant, which blocks the cannabis receptors, they reduced their food intake.
In 2002, Sanofi-Synthelabo, the French drug company that makes Rimonabant, began human tests. Of 45 obese patients on a calorie-restricted diet, those taking Rimonabant lost an average of almost 10 pounds in four months; those taking a placebo lost about 2 pounds.
A two-year trial of 4,200 patients in the United States and Europe was recently completed, and the results should be released this year. Rimonabant also is being tested as a stop-smoking aid because the drug seems to block the same brain circuitry governing nicotine cravings for cigarettes.
Despite the encouraging early results, experts are cautious. 'While the loss of interest in food may be good, tinkering with this newly discovered signaling system may have unwanted side effects,' says Daniele Piomelli, a UC Irvine pharmacologist who has studied the cannabinoid system. 'We need to be very careful that this doesn't cause other psychological disorders.'
Only one marijuana-derived drug has been approved by the Food and Drug Administration. That drug, Marinol, is prescribed to combat chemotherapy-related nausea and to stimulate the appetites of AIDS patients.
Another drug, called Sativex, probably will be approved for sale in Britain later this year. The liquid marijuana extract is used to treat people suffering from multiple sclerosis and severe pain.
Several drug companies are experimenting with other chemicals that either dampen or activate the cannabinoid system, which seems to play a role in regulating appetite, pain, emotions and anxiety.
One compound, for example, called ajulemic acid, is being tested on humans to reduce pain and relieve inflammation. European researchers are testing a cannabis-derived stroke treatment that, if used quickly enough, may limit brain damage. And still other scientists have unearthed cannabis-like chemicals that ease anxiety in lab animals. 'There's any number of promising therapeutic applications. Rimonabant is only the beginning,' says pharmacologist Daniele Piomelli of UC Irvine.