A novel anti-cocaine vaccine has been successfully tested in primates, suggesting that human clinical trials are not far off, according to new research by Weill Cornell Medical College.
The finding, published in the journal Neuropsychopharmacology, used a radiological method to show that the anti-cocaine vaccine stopped the drug from reaching the brain as well as from causing a dopamine-induced high.
The study’s lead researcher, Dr. Ronald G. Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medical College, said:
“The vaccine eats up the cocaine in the blood like a little Pac-man before it can reach the brain. We believe this strategy is a win-win for those individuals, among the estimated 1.4 million cocaine users in the United States, who are committed to breaking their addiction to the drug,” he says. “Even if a person who receives the anti-cocaine vaccine falls off the wagon, cocaine will have no effect.”
Cocaine is a tiny molecule drug which functions by causing feelings of pleasure. It blocks the recycling of dopamine – the “pleasure” neurotransmitter – in two regions of the brain, the putamen in the forebrain and the caudate nucleus in the center of the brain. After dopamine builds up at the nerve endings, it results in a large flooding of dopamine and that is the “feel good” part of the cocaine high.
Dr. Crystal and his colleagues developed a novel vaccine that is a combination of the common cold virus with a particle that acts like the structure of cocaine. After the vaccine is given to an animal, its body “sees” the cold virus and produces an immune response to fight it off, as well as the cocaine impersonator that it is attached to.
This way, the immune system learns to see cocaine as a trespasser. As soon as the immune system cells learn that cocaine is an enemy, from that point on they make antibodies that fight against cocaine as soon as it enters the body.
In the current study, investigators set out to define how successful the anti-cocaine vaccine is in non-human primates – which are biologically closer to humans than mice.
Researchers configured a tool to examine how much cocaine attaches to the dopamine transporter – which collects dopamine in the synapse between neurons and takes it out to be recycled. If cocaine is in the brain, it binds on to the transporter, successfully blocking the transporter from transporting dopamine out of the synapse – allowing the neurotransmitter to be active, resulting in a drug high.
Investigators attached a short-lived isotope tracer to the dopamine transporter. The activity of the tracer could be measured using positron emission tomography (PET). The tool calculated how much of the tracer attached to the dopamine receptor in the presence or absence of cocaine.
The PET studies revealed no difference in the binding of the tracer to the dopamine transporter in vaccinated animals when compared with unvaccinated animals when cocaine was not present.
When cocaine was administered to the primates, there was a prominent decrease in activity of the tracer in the non-vaccinated animals. This finding suggests that without the vaccine, cocaine stopped the tracer from binding to the dopamine receptor.
Earlier studies have suggested that in humans, close to 47% of the dopamine transporter had to have cocaine present in order to make a drug high. In vaccinated primates – researchers found that the cocaine occupancy of the dopamine receptor was decreased to levels of under 20%.
Dr. Crystal said:
“This is a direct demonstration in a large animal, using nuclear medicine technology, that we can reduce the amount of cocaine that reaches the brain sufficiently so that it is below the threshold by which you get the high.”
When the time comes that the vaccine is examined in humans, the non-toxic dopamine transporter tracer can be used to aid in the analysis of its successfulness as well, he said.
The investigators do not yet know how frequently the vaccine needs to be given in humans to maintain its anti-cocaine effect. One vaccine lasted about 13 weeks in mice and seven weeks in non-human primates.
Dr. Crystal concluded, “An anti-cocaine vaccination will require booster shots in humans, but we don’t know yet how often these booster shots will be needed. I believe that for those people who desperately want to break their addiction, a series of vaccinations will help.”
Written by Kelly Fitzgerald