Cocaine
A woman smokes as she smiles during a demonstration in support of the legalization of marijuana outside the Supreme Court building in Mexico City, Mexico, in this November 4, 2015 file photo. The legalization of marijuana is "irreversible" in drug-scarred Mexico following a key court ruling, former President Vicente Fox says, forecasting all drugs including cocaine and crystal meth will be freely available within a decade. Earlier this month, the Supreme Court gave the green light to growing marijuana for recreational use, a landmark decision that blasts open the door for an eventual legalization in Mexico, where warring gangs sparked a decade of drug violence. Reuters/Edgard Garrido

A research at Johns Hopkins University, supported by the National Institute on Drug Abuse, has revealed that excessive cocaine abuse may make brain cells cannibalise themselves. The process is known as autophagy, in which cells digest their own insides. Thus, high doses of cocaine can literally cause the brain to eat itself.

Researchers at the Johns Hopkins University worked with mice and noticed overactive autophagy with high doses of cocaine. However, their research has also led to a possible antidote in the experimental compound CGP3466B.

The study will be published in the journal Proceedings of the National Academy of Sciences. Researchers found signs of autophagy in brain cells of mice. Cocaine was injected into mice that were pregnant.

“We performed 'autopsies' to find out how cells die from high doses of cocaine. That information gave us immediate insight into how we might use a known compound to interfere with that process and prevent the damage,” said Solomon Snyder, MD and neuroscience professor at Johns Hopkins University School of Medicine.

The researchers have spent decades studying the impact of nitric oxide on brain cells, and in 2013, they found out that nitric oxide is responsible or at least involved in cocaine-induced cell death. It interacts with enzyme GAPDH. Next, researchers examined nerve cells from mouse brains. According to Snyder, cells commit suicide in three ways and one of them is autophagy, an important cellular cleanup process.

When taken in high doses, cocaine causes neuronal cell death through out-of-control autophagy, reports EurekAlert.

“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,” said Dr. Prasun Guha, lead author of the paper and postdoctoral fellow at Johns Hopkins.

The team of researchers also tested the ability of the compound CGP3466B to disrupt nitric oxide/GAPDH interactions and halt cocaine-induced autophagy. It successfully protected mouse nerve cells in the brain from death by cocaine. This has given scientists the hope of developing targeted therapeutics to suppress cocaine’s toxicity. It may eventually lead to treatments that will protect infants and adults from the devastating cocaine effects on human brain.

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