Natural, Marijuana-like Chemical May 
Provide Treatment for Obesity
Study in Nature Shows Reduced Feeding, Weight Gain

Irvine, Calif., Nov. 7, 2001 -- A chemical related to marijuana that exists in the body may provide an effective treatment for obesity and perhaps other eating disorders, a UC Irvine College of Medicine study has found.

The chemical reduced rats' desire for food and significantly decreased their weight gain, indicating that the chemical eventually could be developed into a drug to treat weight problems.  The study appears in the Nov. 8 issue of Nature.

Daniele Piomelli, professor of pharmacology, led a team that found that giving a chemical called OEA (short for oleylethanolamide) to rats resulted in a sharp reduction in food intake and a decrease in weight gain.  In addition, they found that food-deprived rats had reduced natural levels of OEA, suggesting that the chemical plays a key role in mediating eating behavior and appetite.

The chemical did not affect various functions of the rats' nervous systems as do other weight loss drugs, indicating that OEA may not have many of the side effects associated with existing diet treatments.

OEA belongs to a group of chemicals called fatty acid ethanolamides, fats that are produced in response to nervous system activity and certain metabolic stimuli.  When food is ingested, OEA is manufactured in the small intestine and perhaps other areas of the abdomen.  During starvation, however, OEA production is curbed and its appetite-suppressing effects are removed.  OEA is related to a family of neurotransmitters known as anandamides, which are similar to marijuana's active ingredient and control a number of nervous system functions.  OEA's function had been unknown until now, though anandamides are thought to stimulate feeding.

"We first saw OEA levels change in rats that had been deprived of food," Piomelli said.  "But we didn't know what the role of OEA was.  We found then that administering OEA reduced both food intake and body weight gain.  This suggested to us that OEA is an important regulator of eating behavior and could be used as a tool to design new anti-obesity medicines."

Nearly 30 percent of Americans are obese, according to the Centers for Disease Control, which has declared obesity an epidemic disease.  The occurrence of obesity has risen by almost 60 percent since 1991.  Obesity greatly increases the risk of premature death and diseases such as diabetes, heart disease, stroke and some cancers.

The researchers found that after seven days, 11 rats given OEA had a weight gain of 4.1 grams on average.  In comparison, 10 rats that did not receive the chemical gained 15.6 grams in weight.  They also found that rats with OEA in their diet ate less--143.2 grams of food in rats without OEA compared to 115.9 grams in rats that had been given OEA.

Further, the researchers found that the first step in OEA-induced reduction in feeding is the stimulation of nerves outside the brain.  These nerves pass the message to stop eating to two brain areas that control feeding: the nucleus of the solitary tract and the paraventricular nucleus of the hypothalamus.

The change in OEA levels, which are low when deprived of food and high with normal food supplies, coupled with the actions in the brain, suggests that OEA is responding to feeding levels in the body and could have the effect of reducing weight as an appetite suppressant.

The researchers now are focusing on finding out how changes in OEA levels trigger appetite suppression.  Piomelli and his colleagues were the first to discover the function of the marijuana-like anandamide system in the brain and have been working for years to ferret out the ranges of effects the anandamide system has on the body.

Piomelli's colleagues in the study include Fernando Rodríguez de Fonseca, Miguel Navarro, Raquel Gómez and Leticia Escuredo of Complutense University, Madrid, and Jin Fu, Eric Murillo-Rodríguez, Andrea Giuffrida, Jesse LoVerme, Silvana Gaetani, Satish Kathuria and Christine Gall of UCI.  The study was funded by the National Institute of Drug Abuse.

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Contact:
Andrew Porterfield
(949) 824-3969
amporter@uci.edu