Vaccine Blocks Cocaine High, Animal Study Shows

Fran Lowry

January 07, 2011

January 7, 2011 — A new vaccine consisting of a cocaine analog coupled to the capsid proteins of noninfectious, disrupted adenovirus (aka the common cold virus) has been shown to blunt cocaine highs in mice, according to new research published in the January 4 online edition of Molecular Therapy.

The vaccine works by producing antibodies that specifically engulf cocaine molecules in the blood, preventing them from entering the brain to activate the reward centers and thereby blocking cocaine's effects.

This approach could also stop addiction to other drugs, including heroin and nicotine, say the researchers, from Weill Cornell Medical College, The Scripps Research Institute, and Cornell University.

"Our very dramatic data show that we can protect mice against the effects of cocaine, and we think this approach could be very promising in fighting addiction in humans," said senior investigator Ronald G. Crystal, MD, chairman of the Department of Genetic Medicine at Weill Cornell Medical College in New York City.

"The vaccine suppresses the stimulant effects of cocaine," said coinvestigator Kim D. Janda, PhD, the Eli R. Callaway Jr Chair in Chemistry at The Scripps Research Institute, La Jolla, California.

"Unlike other types of treatment, a vaccine such as this one does not interfere with the neurological targets of the drug but instead blocks cocaine from ever reaching the brain in the first place," Dr. Janda added.

Immune to Cocaine's Effects

The current research builds on previous anticocaine vaccine work from Dr. Janda's laboratory and that of George F. Koob, PhD, chair of the Committee on The Neurobiology of Addictive Disorders at Scripps and another coauthor.

Earlier, Dr. Janda and his team had developed several alternative formulations of anticocaine vaccines, which also acted by stimulating an active immune response against cocaine in the bloodstream. A drawback of these vaccines, however, was a lack of ready transferability to clinical trials.

In the new study, the team took advantage of a cocaine-hapten-scaffold — a cocaine antigen that would elicit cocaine-producing antibodies, developed by Dr. Janda in the early 1990s. This was chemically modified so that it could be attached to components of the adenovirus and elicit high-titer antibodies against cocaine.

To test the efficacy of the vaccine, the researchers injected it into mice at 0, 3, and 6 weeks and found that a strong immune response was generated against the vaccine and that these antibodies, when put in test tubes, consumed cocaine.

They then tested the vaccine's effect on behavior and found that the mice that received the vaccine before being administered cocaine were much less hyperactive while receiving the drug than mice that were not vaccinated.

The same effect was seen in mice that received large, repetitive doses of cocaine. These doses reflected amounts that humans might use, the researchers explain.

"When you administer cocaine to mice, they start running around and stand up and exhibit a lot of unusual behavior," Dr. Crystal told Medscape Medical News. "But if we administer the vaccine beforehand, if we pretreat the mice so they have the vaccine and we give the cocaine, nothing happens. It's like giving them water. That's why this vaccine is so exciting."

Long-Term Effect

In their discussion, the researchers note that general disadvantages to addictive drug immunotherapy include the difficulty of activating an immune response that evokes antibody titer levels that are high enough to thwart a large dose of the targeted drug and the difficulty of maintaining a persistent active immune response in the long term.

This vaccine appears promising because its effects lasted for at least 13 weeks, say the researchers.

"While other attempts at producing immunity against cocaine have been tried, this is the first that will likely not require multiple, expensive infusions and that can move quickly into human trials," Dr. Crystal said. "This is important because currently there are no therapies for cocaine addiction, which is an intransigent problem worldwide."

The real issue is whether this will work in humans, he continued. "We have to do safety studies. We have a facility to manufacture these viruses; they actually come out of our gene therapy program, so we know a lot about them, and we know how to manufacture them in a way that would be approved by the [Food and Drug Administration]. But the real work is showing it works in larger animals. We're in the middle of doing that and it looks very good."

The next step will be to see whether high levels of antibodies against cocaine can be elicited in healthy volunteers. After that, it would be tested in people addicted to cocaine.

Dr. Crystal said that if the vaccine works in humans, it will work best in people who are already addicted to cocaine and who are motivated to quit. "The vaccine may help them kick the habit because if they use cocaine, an immune response will destroy the drug before it reaches the brain's pleasure center," he said.

Preventing Relapse

David Shurtleff, MD, director of the Division of Basic Neuroscience and Behavioural Research at the National Institute on Drug Abuse (NIDA) in Bethesda, Maryland, told Medscape Medical News that NIDA has been supporting this area of research and moving ahead with it for some time.

"We do have a nicotine vaccine under phase 4 clinical trials for treating tobacco dependence, and we look at it as a promising area, at least initially, for treating relapse to drugs."

These vaccines prevent the drug from getting into the brain, and this is crucial for preventing recidivism.

"We know that 1 trigger for relapse is just 1 slip. One lapse can lead to a full-blown relapse with compulsive drug taking, so if there is a way to protect a person who has been exposed to drugs and whose brain has been sensitized to the addictive properties of drugs, the vaccine can be very protective in that it prevents the drug from triggering relapse. That is a very significant thing."

There are behavioral cognitive therapy programs that are somewhat effective to get people abstinent that tend to work for a while, he said.

"But, as we saw with Lindsay Lohan, once they are out of treatment, they get in the same situation, they slip 1 time, and that leads to a cascade of events that result in substance use disorder all over again, compulsive drug taking, poor judgment, bad behavior, that can get them right back where they started. So if there's a way to protect them from the initial lapse, you may prevent a full-blown relapse."

This research was funded by the National Institute of Drug Abuse of the National Institutes of Health. Dr. Crystal, Dr. Janda, Dr. Koob, and Dr. Shurtleff have disclosed no relevant financial relationships.

Mol Ther. Published online January 4, 2011.


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