The brain on cocaine: Study shows drug's role in cell death, points to possible treatment

A new Johns Hopkins University study supports the idea that high doses of cocaine can cause brain cells to cannibalize themselves—but researchers have also identified an experimental compound that could be a possible antidote, able to prevent the damage.

The research team hopes that this compound, called CGP3466B, eventually could lead to treatments that protect adults and infants from the devastating effects of cocaine on the brain. A summary of their recent findings will be published online this week in the Proceedings of the National Academy of Sciences.

Working with mice, the Hopkins researchers discovered that cocaine-induced brain cell death occurs through a process called autophagy, during which cells literally digest their own insides. They also found signs of autophagy in the brain cells of mice whose mothers received cocaine while pregnant.

The process of autophagy is a normal and much-needed cellular "cleanup" that rids cells of accumulated debris. Only when this process accelerates and spins out of control does it cause cell death.

"A cell is like a household that is constantly generating trash," says Prasun Guha, a postdoctoral fellow at Johns Hopkins and lead author of the paper. "Autophagy is the housekeeper that takes out the trash—it's usually a good thing. But cocaine makes the housekeeper throw away really important things, like mitochondria, which produce energy for the cell."

From their past studies the researchers already knew that nitric oxide, a gas which brain cells use to communicate, and GADPH, an enzyme, were involved in this process. They also knew that the experimental compound CGP3466B was proven to disrupt nitric oxide/GAPDH interactions. So they tested the compound to see if it could halt the cocaine-induced autophagy.

Their results indeed confirmed that CGP3466B worked to protect the mice's nerve cells from death by cocaine.

The researchers are hopeful that their continued work with CGP3466B could lead to treatments for brain damage associated with cocaine use. But they caution that many more years of studies, in both mice and humans, are necessary to show definitively whether the compound is effective for this purpose.

CGP3466B is already known to be safe for humans, since it's been tested in past (though unsuccessful) clinical trials to treat Parkinson's disease and ALS.

The Johns Hopkins research team had previously found that CGP3466B was able to protect the brain cells of live mice from the fatal effects of cocaine, but only in this new study did they connect that phenomenon to autophagy.