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Cocaine overdose 'antidote' in the future?

Flu Vaccines Reuters

 (Reuters)

The potential effects of a cocaine overdose can be devastating – including stroke, seizure, kidney failure and even death.

But now, a cocaine “antidote” could soon be available for emergency scenarios.

Scientists at The Scripps Research Institute in La Jolla, Cali., have come up with an injectable solution that has been shown to reverse the effects of cocaine overdose in mice.  After success with their experiments thus far, the researchers are eager to move on to human clinical trials – and potentially develop a viable treatment.

“Cocaine is a stimulant – so a huge amount affects the cardiovascular system,” said Kim Janda, a professor in the Department of Chemistry and Immunology at Scripps and senior author of the study.  “We’re trying to remove the cocaine from these major centers like the bloodstream and the brain, so that they won’t have any effect.”

Janda and his team have been working on developing vaccines for various other drugs such as heroin, nicotine and Rohypnol, the “date rape” drug.  However, most of the vaccines they’ve come up with have been “active” vaccines – drugs that provoke a long-term antibody response.  While these can be helpful in treating addiction and relapse, they can take weeks to take effect.

The antidote Janda’s laboratory has developed is a “passive” cocaine vaccine – a solution of drug-specific human antibodies that can quickly bind to the cocaine in the body and render them ineffective.

“It’s like a sponge, you spill something and you go soak it up,” Janda said.  “[When cocaine] is in the body, the antibodies bind to it and remove it either through the kidney or the liver - or it’s just degraded.  The antidote either sequesters [cocaine] in the blood or pull them out of the brain.  The antibodies can’t go into the brain themselves, but they act as a vacuum cleaner to remove it from the brain.”

Not only did the human antibodies trigger an immediate response, they also lingered in the body for some weeks after administration, continually reducing the effect of cocaine in the body – a trait could potentially keep cocaine addicts from relapsing after overdose.

In order to create their antidote, Janda and his research associate Jennifer Treweek used a genetically engineered mouse that produced human antibodies to target the cocaine.  The antibodies they found to be most effective were GNCgzk and F(ab’)2-gzk, a stripped-down version of GNCgzk.

In an attempt to mimic a real life scenario, mice were given a lethal cocaine overdose and were then administered the antibodies three minutes later.  About half of the untreated mice died while the GNCgzk antibodies reduced the mortality rate to 20 percent.  The stripped-down GNCgzk was even more successful – reducing the mortality rate to zero.

Not only were the researchers successful in preventing death from cocaine overdose, they were equally effective in reducing pre-morbid behaviors in the mice such as seizures, twitching and erratic movements – mannerisms that could indicate brain damage.

“That was just as important as reducing lethality,” said Treweek.  “You don’t want to bring someone back from death just to have them be a vegetable.”

According to the Centers for Disease Control and Prevention, over 400,000 emergency room visits each year are cocaine-related in the United States, while over 5,100 people die from overdose.  With a such a promising life-saving antidote on the horizon, the researchers are now trying to determine a way to produce a large amount of their vaccine inexpensively and efficiently – so they can make the case to move on to human trials.

Janda said that their vaccine could either come in the form of a solution or a powder – an option that could make it stored much more easily.  Also, in order for the antidote to be effective, only a small amount would need to be administered.

“When we tried to develop this in the past, if you give a lethal dose of cocaine to a human, you’d need a huge amount of antibodies to combat it – tens of grams,” Janda said.  “It would not be feasible to give them that much.  With this antidote, we can use a 100-fold less – it’s in a realm that you can give to a person.”

From helping to reduce the immediate effects of overdose to preventing relapse in addicts, Janda and his team feel their antidote could be a practical life-saver for the future.

“Is there a need for it? Yes,” said Janda.  “It could be something simple that a paramedic could have onboard [an ambulance] and just inject it. It’s easy.”