December 2, 2002
University of California - Irvine
Man-made chemicals that are distant relatives of marijuana may eventually become new drugs to combat anxiety and depression, according to a UC Irvine College of Medicine study. The study is the first to show how anxiety is controlled by the body's anandamide system, a network of natural compounds known for their roles in governing pain, mood and other psychological functions.
While marijuana relieves anxiety by working on the same system, laboratory rats given the new drugs don't seem to suffer the side effects produced by THC, marijuana's active ingredient. The study appears on Nature Medicine's Web site and will be published in the January 2003 issue.
After designing and testing a number of different chemicals, pharmacology professor Daniele Piomelli and his team found two, called URB532 and URB597, which relieved anxiety and worked in ways far gentler than THC.
"THC reduces anxiety by binding directly to receptors in the brain and resulting in its familiar 'high' sensation," Piomelli said. "This reaction is too strong, creating marijuana's side effects."
URB532 and URB597, on the other hand, inhibit the activity of an enzyme that breaks apart natural anandamide, leaving more of the neurotransmitter to help reduce anxiety and depression. This is similar to the way Prozac works on serotonin, another natural anti-depressant neurotransmitter. With this gentler biochemical approach, URB532 and URB597 were able to keep brain anandamide levels high for many hours after a single dose without producing visible side effects.
"While the study's results are promising, the road from laboratory discovery to available medication is years long, often winding, and definitely expensive," Piomelli said. "In fact, most drugs never make it beyond the discovery stage, for a number of scientific and commercial reasons. But nearly all drugs on the market today saw their start at the laboratory discovery phase."