Anticocaine Vaccine Prevents Drug from Reach Brain

Scientists have effectively evaluated a novel anticocaine vaccine in primates, bringing them nearer to initiating clinical testing in humans.

The study findings published online May 10, 2013, in the journal Neuropsychopharmacology, used a radiologic imaging modality to demonstrate that the anticocaine vaccine prevented the drug from reaching the brain and producing a dopamine-induced high.

“The vaccine eats up the cocaine in the blood like a little Pac-Man [an arcade video game] before it can reach the brain,” says the study’s lead investigator, Dr. Ronald G. Crystal, chairman of the department of genetic medicine at Weill Cornell Medical College (New York, NY, USA). “Even if a person who receives the anticocaine vaccine falls off the wagon, cocaine will have no effect.”

Dr. Crystal reported that he expects to begin human testing of the anticocaine vaccine within one year. Cocaine works to generate feelings of pleasure because it blocks the recycling of dopamine—the so-called “pleasure” neurotransmitter—in two brain regions, the putamen in the forebrain and the caudate nucleus in the brain's center. When dopamine accumulates at the nerve endings, “you get this massive flooding of dopamine and that is the feel good part of the cocaine high,” said Dr. Crystal.

The innovative vaccine Dr. Crystal and his colleagues developed combines fragments of the common cold virus with a particle that mimics the structure of cocaine. When the vaccine is injected into a mouse, its body “sees” the cold virus and mounts an immune response against both the virus and the cocaine imitator that is hooked to it. “The immune system learns to see cocaine as an intruder,” said Dr. Crystal. “Once immune cells are educated to regard cocaine as the enemy, it produces antibodies, from that moment on, against cocaine the moment the drug enters the body.”

In their first study in animals, the researchers injected billions of their viral concoction into laboratory mice, and found a strong immune response was generated against the vaccine. Moreover, when the scientists extracted the antibodies generated by the mice and place in test tubes, it guzzled up cocaine. They also revealed that mice that received both the vaccine and cocaine were much less hyperactive than untreated mice given cocaine.

In the study, the researchers attached a short-lived isotope tracer to the dopamine transporter. The activity of the tracer could be seen using positron emission tomography (PET) imaging. The tool measured how much of the tracer attached to the dopamine receptor in the presence or absence of cocaine. The PET studies showed no difference in the binding of the tracer to the dopamine transporter in vaccinated compared to unvaccinated animals if these two groups were not given cocaine. But when cocaine was given to the primates, there was a significant decline in activity of the tracer in nonvaccinated animals.

Earlier studies had shown in humans that at least 47% of the dopamine transporter had to be occupied by cocaine to generate a drug high. The researchers discovered, in vaccinated primates, that cocaine occupancy of the dopamine receptor was reduced to levels of less than 20%. The researchers do not know, however, how frequently the vaccine needs to be administered in humans to maintain its anticocaine effect. One vaccine lasted 13 weeks in mice and 7 weeks in non-human primates.

“An anticocaine vaccination will require booster shots in humans, but we don’t know yet how often these booster shots will be needed,” noted Dr. Crystal. “I believe that for those people who desperately want to break their addiction, a series of vaccinations will help.”

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