Potential medication can reduce effects of marijuana smoked in humans

April 12, 2001

Scientists at the National Institute on Drug Abuse's (NIDA) Intramural Research Program in Baltimore, MD, have confirmed for the first time in humans that chemically blocking the body's cannabinoid receptors can significantly reduce the effects of smoked marijuana. The study appears in the April 14th issue of the Archives of General Psychiatry.

Cannabinoid receptors - proteins on the surface of brain cells -- are most dense in brain regions involved in thinking and memory, attention and control of movement. Their exact role in humans is not well understood, but animal studies have shown that cannabinoid receptor agonists - compounds that activate the receptor sites - impair learning and memory and increase appetite and food intake. Previous studies in animals have shown that the major effects of tetrahydrocannabinol (THC), the primary psychoactive compound in marijuana, are due to its binding to specific cannabinoid receptors located on the surface of brain cells. These effects appear to be lessened when cannabinoid receptors are blocked by an antagonist.

"This research helps point the way toward possible treatment for those addicted to marijuana and perhaps may be useful in finding effective treatments for other disorders related to the cannabinoid system, " says NIDA director Dr. Alan I. Leshner.

In the study, Dr. Marilyn Huestis and her NIDA colleagues used a cannabinoid receptor antagonist - a compound that binds to the receptor and blocks agonist compounds from activating it. The antagonist, SR141716, was discovered by Sanofi-Synthelabo of Paris, France, and was used in this study with NIDA under a Cooperative Research and Development Agreement (CRADA).

Participants in the study were given either SR141716 or a placebo and two hours later smoked one marijuana cigarette. Those who received SR141716 showed significantly reduced marijuana effects, while those who received the placebo showed typical marijuana intoxication. The results of the study are an important step in understanding the complex role of the cannabinoid receptor system in the human brain. "Our findings of a significant blockade of marijuana's effects after treatment with SR141716, which is highly selective for the CB1-cannabinoid receptor sites, demonstrates for the first time in humans that these receptors play a major role in mediating the effects of marijuana," Dr. Huestis says.

In their investigation of the role of the cannabinoid system in humans, Dr. Huestis and her colleagues gave increasing doses of SR141716 or placebo to 63 adult men with histories of marijuana use. When individuals received SR141716 before smoking marijuana, there was a dose-dependent reduction in psychological and physical effects of marijuana. At the highest dose of SR141716 (90 mg), volunteers reported a 43% reduction in how "high" they felt, a 38% reduction in how "stoned" they were, and a 43% reduction in "drug effect" as compared to those who received active marijuana and no antagonist. In addition, they had a 59% less increase in heart rate, one of the primary physical effects of marijuana.
Contact: Beverly Jackson, Blair Gately, 301-443-6245

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and other topics can be ordered free of charge in English and Spanish by calling NIDA Infofax at 1-888-NIH-NIDA (644-6432) or 1-888-TTY-NIDA (889-6432) for the deaf. These fact sheets and further information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov.

NIH/National Institute on Drug Abuse

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