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Chemical Boosts Marijuana-Like Substance in Brain

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May 04,00
By Amy Norton
Source: Reuters Health
Journal of Neuroscience
A chemical that boosts a marijuana-like substance in the brain may inspire new treatments for brain disorders such as schizophrenia, Parkinson's disease, and attention-deficit/hyperactivity disorder (ADHD).
Researchers at the University of California, Irvine, have developed a compound--dubbed AM404--that bolsters the natural function of anandamide, a brain chemical that acts on the same brain receptors as marijuana does.
Experiments in rats show that anandamide normally inactivates another brain chemical called dopamine, which has been implicated in a number of brain disorders. Daniele Piomelli, a professor of pharmacology, and colleagues report their findings in the May issue of the Journal of Neuroscience.
In the case of Parkinson's disease, patients have too little dopamine, while people with ADHD, schizophrenia or Tourette's syndrome may have too much.
The hope is that AM404 will lay the groundwork for a new class of drugs that either boost or block dopamine, without the side effects linked to current treatments, Piomelli told Reuters Health in an interview.
``Our results are interesting,'' he said, ``because they show that you can modulate dopamine without acting on the dopamine system.''
This is important, Piomelli noted, because Parkinson's, schizophrenia, Tourette's syndrome and other disorders are all currently treated with drugs that act directly on the dopamine system. These drugs, he added, carry side effects such as lethargy and impaired sexual activity.
Last year, Piomelli and his colleagues showed for the first time that in rats, anandamide naturally counters dopamine. Usually, though, anandamide is inactive in the brain. The California team's latest experiments in rats reveal that AM404 stops anandamide from being ``drained from the brain,'' which allows it to suppress dopamine.
Although dopamine's role in brain disorders is not completely understood, an elevated level is a ``common element'' in conditions such as ADHD, schizophrenia and Tourette's syndrome, Piomelli explained. These disorders are all marked by hyperactive ``intrusions'' into normal brain function, he said. For example, people with Tourette's experience physical ''tics,'' while schizophrenics suffer from delusions.
The potential for anandamide-boosting drugs to work against these disorders has some anecdotal backing. Anandamide's counterpart, marijuana, is used by many schizophrenics who report that it relieves their symptoms, Piomelli noted.
``But,'' he said, ``we are not implying that marijuana is useful for these conditions.''
Marijuana, according to Piomelli, is far less selective than anandamide in activating brain cells. Because pot smoking overstimulates the brain, he said, cells eventually become desensitized to any benefits the drug initially brings.

New York (Reuters Health)
Wednesday May 3 2:24 PM ET
SOURCE: Journal of Neuroscience May 2000.
Journal of Neuroscience
Copyright © 2000 Reuters Limited.