Pubdate: 23 Mar 1999 Source: San Jose Mercury News (CA) Copyright: 1999 Mercury Center Contact: Website: Author: Usha Lee McFarling and Lisa M. Krieger


WASHINGTON -- When scientists recommended the medicinal use of marijuana's ingredients last week, they were relying on a little-known fact. Our brains already are flooded with the plant's active agents -- chemicals called cannabinoids that may play key roles in keeping us healthy, happy and free of pain.

Scientists have known since 1992 that the brain contains compounds that latch onto the same sites in the brain as the active ingredient in marijuana. On Monday, scientists funded by the National Institute on Drug Abuse announced they have discovered how one of these compounds causes a behavior characteristic of marijuana use, the inhibiting of movement.

Since the discovery of the first identified human cannabinoid -- christened ``anandamide'' from the Sanskrit word meaning ``internal bliss'' -- these compounds have become one of the looming mysteries of the nervous system because they touch so many aspects of human life, including how we eat, fight illness and form memories.

Scientists want to learn how these natural chemicals mimic the effects of the active ingredient in marijuana known as delta-9-tetrahydrocannabinol (THC).

This week's announcement describes how anandamide counteracts another brain chemical, dopamine.

Animal studies showed that anandamide and dopamine act in opposite ways to control movements in an area of the brain called the dorsal striatum, according to the scientists, who will publish their findings in the April issue of the journal Nature-Neuroscience. ``Dopamine stimulates movements by acting in this area, and anandamide normally inhibits this action of dopamine,'' said lead researcher Dr. Andrea Giuffrida of the University of California-Irvine.

``Research on drug abuse can lead to possible treatments for seemingly unrelated diseases,'' said Dr. Alan Leshner, National Institute on Drug Abuse director. ``Abnormalities in the dopamine system are thought to play a major role in several neurological and psychiatric disorders, as well as in drug addiction, so new medications that can counteract these abnormalities might prove useful in treating more than one disease.''

Developing medication

The THC-like natural compounds may prove useful in the development of medications for treating diseases that seem to involve dopamine imbalances in the brain, Giuffrida suggests. Some diseases such as schizophrenia and Tourette's syndrome may be caused by too much dopamine in certain brain regions, or perhaps hypersensitivity of brain sites targeted by dopamine. Medications that mimic anandamide might reduce symptoms by dampening dopamine overactivity.

While cannabinoids are common in animal nervous systems, marijuana is the only plant known to contain them. In fact, it has dozens, including THC, which is far more powerful than the cannabinoids found in humans and other animals.

Last week's report from the Institute of Medicine notes that cannabinoids produced by our bodies affect pain, appetite, motor control and memory. The most recent studies show cannabinoids may regulate the immune system, enhance reproduction and protect the brain.

Here are some of the most intriguing findings:

In December, two University of Buffalo researchers reported that cannabinoids help control the exquisite timing of reproduction by slowing the sperm that approach an egg before it's ready for fertilization.

Cannabinoids have been found to both suppress and enhance the body's defenses against diseases and tumors, a duality that has researchers puzzled.

While anti-drug messages spotlight the drug's damaging effects on the brain, research last summer from the National Institute of Mental Health showed cannabinoids protected brain cells from stroke or trauma damage.

Last year, scientists at the Neurosciences Institute in San Diego showed that cannabinoids block the formation of memories in animal brain tissue. This might keep the brain from getting overwhelmed with unimportant memories.

The latest report is no news to the nation's medical establishment. The National Institutes of Health and the American Medical Association have been calling for aggressive research into marijuana, citing pioneering work on cannabinoids.

Perhaps these compounds help in stressful situations, such as helping cope with pain perception. Or perhaps anandamide disregulaton -- when the body produces too much or too little of the chemical -- is linked to mood disorders.

Scientists speculate that pot smokers manipulate a naturally occurring system when they light up a joint, creating an effect that they might not otherwise have at that moment.

Chemically, these compounds don't look quite like THC. But they are similar enough to bind to a THC receptor in the brain, like a key in a lock. This triggers the release of chemicals, called neurotransmitters, that send impulses down the body's central nervous system pathways that control motor skills, memory and other functions.

Until recently, the existence of these receptors was mystifying. Had they evolved in anticipation of that day when someone would smoke a joint? Or did they play some normal, natural role?

The discovery of anandamide and other cannabinoids helps solve that mystery.

Researchers also hope that cannabinoids can be used to ease pain, especially chronic nerve pain that doesn't respond to other painkillers. Studies show cannabinoids work as well as morphine by short-circuiting pain signals before they reach the spinal cord or brain, and they are less addictive than narcotic pain relievers.

Several years away

For that to be realized, researchers will have to develop cannabinoid-based drugs or inhalers. Those are not expected to be widely available for several years. In the meantime, the Institute of Medicine recommended that patients whose pain and nausea do not respond to any other treatment be given marijuana cigarettes, even though that violates federal law and carries its own health risks from smoke.

That political battle probably will be waged through more state ballot initiatives across the country. Meanwhile, researchers are staying far away from the political fray. Instead, they plan to keep working on what they call the ``Holy Grail'' of their field: separating marijuana's therapeutic effects from side effects such as euphoria and disorientation.

Kenneth Hargreaves, a pharmacologist at the University of Texas Health Science Center in San Antonio, has shown that injecting small concentrations of cannabinoids directly at a site of injury relieved pain and swelling without affecting the brain. He hopes to develop a cannabinoid pill that wouldn't cross the body's blood/brain barrier and cause mental side effects.

While some advocates of marijuana say its power lies in its complex mix of chemicals, Hargreaves argues that harnessing cannabinoids and tailoring them to medical needs is the best approach. ``For a fever, you're going to take an aspirin,'' he said. ``You're not going to boil willow bark off a tree.''