September 16, 2004 in Nation/World

Study: Brain creates own potlike chemicals

Lisa M. Krieger San Jose Mercury News

SAN JOSE, Calif. – Mother Nature created a way to “tune in, turn on” long before pot-smokers rolled their first joint, Stanford scientists have found.

Eavesdropping on the conversations between brain cells, the research team found that neurons make their own marijuana-like chemicals called cannabinoids, which indirectly alter the way that information is received and filtered.

When the chemicals are released, “neurons have a harder time deciding which are the relevant things to pay attention to,” said investigator John R. Huguenard, associate professor of neurology and neurologic sciences at Stanford University School of Medicine.

For a long time, scientists thought that marijuana altered the mind in a messy and random way that didn’t involve any particular part of brain chemistry.

Now they’ve identified an elegant modus operandi. It adds to a growing body of research that explains the mechanism behind getting “high.” Marijuana mimics the cannabinoids made naturally by our brain – chemicals that influence a smorgasbord of body functions including movement, thought and perception.

The research sheds light on a powerful neurochemical system. Researchers hope that when they understand the job the chemical does in the day-to-day running of our bodies, they can design new therapeutic drugs.

In their Stanford lab, Huguenard and colleagues David Prince and Alberto Bacci injected electric current into rat brain cells, then watched the chatter between the brain’s two major types of cells.

When overly excited, one type of neuron releases cannabinoids, which create a calming effect, they found. In effect, the brain cell drugs itself.

But this mellowed-out cell falls down on its job, which is to filter the flow of information rushing into a second type of cell.

Without a good filter, the researchers think this second neuron is flooded with sensory information that affects memory, perception, mood and movement.

Something very similar happens with marijuana use, the scientists believe.

In an accident of nature and chemistry, the compounds in pot are shaped similarly and trigger similar effects.

“Marijuana use … affects the way we think,” said Huguenard. The new research shows that “part of that is due to changes in the way our brain cells receive incoming information, like sensory information or memories or emotion.”

Because so much information is always flowing into the brain, “each neuron has to make a decision based on the signals it gets,” he said. “They have to make sense of it … and decide what’s relevant.”

“Marijuana loosens a natural filter that exists in neurons, so they tend to be flooded with information,” Huguenard said.

The research is published in today’s issue of the journal Nature.

“This type of research is so long overdue,” said Gerald Uelmen, a professor at Santa Clara University School of Law, who represents the Santa Cruz-based Wo/Men’s Alliance for Medical Marijuana. “When Congress classified marijuana as a controlled substance, the idea was that ‘We don’t know enough about it.’ There are many new studies that are very exciting, showing the myriad of possibilities, and that medical marijuana has great potential.”

What prompts a brain cell to release a cannabinoid? Pain, perhaps? Or some other sensation? The Stanford team doesn’t know yet, but one possibility is that it seeks to calm the high level of nervous system activity that occurs during epileptic seizures.

There remains much to be learned about the mechanisms that control brain circuitry, said Huguenard. Further research will illuminate the role that cannabinoids play in the normal brain – and how they can be exploited to control pain, seizures or appetite.

It may prove possible to tailor therapies by blocking or activating production of particular cannabinoids or cell receptors, eliminating the “high” while harnessing the most useful aspects of the chemical. Already, the Paris-based drug company Sanofi-Synthelab is using that approach to create appetite-control drugs.

Thoughts and opinions on this story? Click here to comment >>

Get stories like this in a free daily email