Pubdate: Thu, 12 Apr 2001 Source: Reuters Copyright: 2001 Reuters Limited Details: Author: Will Dunham

WASHINGTON -- Chemically blocking receptors in the brain that respond to a key compound in marijuana squelches the ''high'' caused by the drug, scientists said on Thursday in a finding that could lead to treatment for marijuana abuse and perhaps even for obesity.

Researchers with the U.S. National Institute on Drug Abuse ( NIDA ) have confirmed for the first time in people that chemically blocking the brain's cannabinoid receptors -- proteins on the surface of brain cells -- cuts the intoxicating effects of smoked marijuana. The study involved 63 adult men with histories of marijuana use.

Animal tests have found that the major effects of the active ingredient in marijuana, tetrahydrocannabinol ( THC ), result from its binding to specific cannabinoid receptors.

In the study, the researchers used a compound called SR141716, which was discovered by French drug maker Sanofi-Synthelabo. The compound binds to the cannabinoid receptor and blocks compounds such as THC from activating it. The findings appear in the journal Archives of General Psychiatry.

Cannabinoid receptors are most dense in brain regions involved in thinking and memory, attention and control of movement, the researchers said. Their precise function in people is not well understood, although animal studies have shown compounds that activate the receptor sites impair learning and memory and increase appetite and food intake.

Lead researcher Dr. Marilyn Huestis of NIDA, part of the National Institutes of Health ( news - web sites ), said the findings help point the way toward possible treatment for people addicted to marijuana.

"It's certainly an issue that is still a little controversial," she said of whether marijuana can cause addiction. "But there's been some beautiful work showing that marijuana is addictive, and that a number of people who utilize the drug on a chronic basis have developed dependence and have a very difficult time stopping taking the drug."

Obesity Treatment Possible

Huestis also said the compound, by blocking the brain's cannabinoid receptors, may prove useful in treating obesity and psychotic diseases such as schizophrenia and improving memory.

"One of the most promising aspects is the issue of obesity and the fact that marijuana produces hunger," Huestis said in an interview.

Sanofi-Synthelabo has completed one set of clinical trials involving treating obesity with SR141716 and is now in talks with the U.S. Food and Drug Administration about a next set of trials, said Dr. Joseph Palumbo, a research official with the firm. "We're still learning about some of the effects that we may have."

Subjects in the study were given either SR141716 or a placebo ( dummy pill ) and two hours later smoked one marijuana cigarette. Those who received the compound showed significantly reduced marijuana effects, while the placebo group showed typical marijuana intoxication, the researchers said.

Subjects given the highest dose of SR141716 ( 90 mg ) reported a 43 percent reduction in how "high" they felt compared to the control group, the study found. They also had a 59 percent smaller increase in heart rate, one of the primary physical effects of marijuana.