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Marijuana-Like Chemicals May Treat Epilepsy

But researchers caution against overdoing it

THURSDAY, Oct. 2, 2003 (HealthDayNews) -- Researchers have found naturally occurring proteins in humans that are similar to the active ingredient in marijuana may protect the brain against epileptic seizures.

The research, which appears in the Oct. 3 issue of Science, found the substances produced by the body, called cannabinoids, may play a role in keeping excitable neurons in the brain from becoming fatally overstimulated.

Dr. Giovanni Marsicano, of the Max Planck Institute of Psychiatry in Munich, Germany, and his German, Italian and Spanish team, used kainic acid to induce seizures in mice and found a certain set of the brain's CB1 receptors, which bind with the "endocannabinoid" compounds produced in the brain, helped protect against the induced seizures.

They found this signaling system might be a useful target for treating epilepsy or some neurodegenerative diseases, in which this sort of neuron damage, or "excitotoxicity," plays a key role.

"Our research shows that the cannabinoids act as a brake on the brain," says Dr. Beat Lutz, a co-researcher from the Max Planck Institute. "It's incredible; in something like within 10 and 15 minutes the brain reacts. This is very important. It shows that when you need them, when you have problems, they react."

But if you flood your brain with external cannabinoids and activate receptors over a fairly broad period of time, you can exacerbate the problem and make it worse in some types of seizures, Lutz adds. "I think that it's an important line of research to look at manipulating our indigenous cannabinoids and not to simply flood the brain with them."

Epilepsy is one of the most common neurological conditions, characterized by spontaneously recurrent seizures. Approximately 1 percent of Americans have epilepsy, and 30 percent of those patients are resistant to conventional anticonvulsant drugs.

New findings by U.S. researchers seem to back the European discovery.

In that study, a team of researchers at Virginia Commonwealth University injected chronically epileptic rats with different combinations of drugs, including an extract of marijuana and two synthetic drugs that include THC, the key psychoactive ingredient in marijuana.

Additionally, the common anticonvulsant drugs phenobarbital and phenytoin were administered, as was a drug that blocks the absorption of cannabinoids by the brain.

The marijuana extract and synthetic marijuana drugs completely eliminated the rats' seizures, which had averaged three over a 10-hour period, while the phenobarbital and phenytoin failed to completely eliminate the seizures.

Injection of the CB1 antagonist significantly increased both the duration and frequency of seizures, in some cases to a level consistent with a severe, prolonged form of epilepsy known as status epilepticus.

"This study indicates that cannabinoids may offer unique advantages in treating seizures compared with currently prescribed anticonvulsants," Dr. Robert J. DeLorenzo, a professor of neurology in Virginia Commonwealth's School of Medicine, says in a statement. "It shows not only the anticonvulsant activity of exogenously applied cannabinoids, but also suggests that the brain's cannabinoid system works to limit seizure duration by activating the CB1 receptor. Understanding the factors that contribute to seizure initiation and termination has important implications for our ability to treat epilepsy and for the potential development of novel anticonvulsant agents."

"But the psychoactive side effects of marijuana make its use impractical in the treatment of epilepsy," adds DeLorenzo. "If we can understand how marijuana works to end seizures, we may be able to develop novel drugs that might do a better job of treating epileptic seizures."

DeLorenzo's team is currently assessing dosage requirements and evaluating the long-term effects of using cannabinoids for epilepsy in animals.

That study appears in the Oct. 1 issue of the Journal of Pharmacology and Experimental Therapeutics.

The European researchers point out that cannabinoids have been used as a natural remedy for seizures for thousands of years, and studies since at least 1974 have found the primary psychoactive compound in marijuana displays anticonvulsant properties.

An article accompanying the Planck piece added that the use of cannabis in epilepsy can be traced at least as far back to a 15th century treatise on hashish by an Arab writer named Ibn al-Badri.

Although the recreational use of cannabis is illegal in the United States, its use in medicine has been controversial. Several states have allowed it, but this has put them in potential conflict with the federal government, which has not completely recognized its use.

In Europe and Canada, however, recreational use of marijuana has been tolerated for years in several counties and its use in medicine has been legalized in many others, and in some cases, even produced by health authorities.

More information

Read more about the use of medicinal marijuana from the Institute of Medicine, while you can get a primer on seizures from the Epilepsy Foundation.

SOURCES: Beat Lutz, M.D., Max Planck Institute of Psychiatry, Munich, Germany; Virginia Commonwealth University news release; Oct. 1, 2003, Journal of Pharmacology and Experimental Therapeutics; Oct. 3, 2003, Science
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