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Study shows high amounts of cocaine cause brain cell ‘suicide’

ByLouise Munro

Jan 28, 2016

Image: United States Drug Enforcement Agency 

A century ago, we thought that cocaine was some kind of ‘wonder drug’. Since then, many studies have demonstrated that the drug can cause a loss of grey matter in the brain, or an increased cardiovascular risk to the rest of the body. Nevertheless, cocaine has remained one of the most abused drugs in society.

Yet, perhaps more opinions will be swayed in the wake of a new study from Johns Hopkins University, where researchers have discovered that cocaine usage can increase autophagy, the process which controls cell death, to damaging levels in the brain.

Cells can die due to environmental factors but they can also commit ‘suicide’. The researchers added cocaine to nerve cell cultures from mice who died of an overdose, to determine which type of programmed cell death pathway was involved. These cultures were screened for protein changes characteristic of the specific pathways and their finding of cocaine-induced overactive autophagy correlates with that of other researchers.

Autophagy, when regulated by the body, acts as a cellular ‘housekeeper’, getting rid of debris within cells by enabling enzymes to digest it. However, uncontrolled autophagy is detrimental as the cell degrades essential metabolites and organelles, such as mitochondria, which crucially produce energy for the cell.

Next, the team experimented with live animals and gave single doses of cocaine to pregnant mice whose pups’ brains were then screened. Specific antibody and protein levels, as well as physical changes, indicated uncontrolled autophagy in both adults and mouse pups whose mothers had been given cocaine.

These results of the study also bring with them a possible antidote – an experimental compound dubbed CGP3466B. Previous research by the same team had highlighted that nitric oxide is involved in cocaine-induced cell death through interactions with a specific enzyme and that CGP3466B disrupts this interaction to prevent enzyme modification and therefore overactive autophagy.

Other compounds have been known to prevent other forms of cell ‘suicide’ but so far only CGP3466B has protected mouse nerve cells in the brain from the cytotoxic actions of cocaine.  Furthermore, upon treatment with CGP3466B, drug-seeking behaviour of cocaine-addicted mice was reduced, suggesting the possibility of a therapeutic tool to block cocaine’s effects on the brain.

Controversy arises over whether drug users should be protected when they have chosen to use cocaine. Yet, there is also potential use to help infants exposed in utero.

Treatments that selectively target cocaine-induced autophagy are likely to be beneficial and whilst CGP3466B is known to be safe for humans, due to previous successful clinical trials involving Parkinson’s disease and ALS, it will take subsequent studies on mice and humans to determine if it is an antidote to cocaine usage.

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