Vaccine against cocaine makes headway

Antibodies generated by a new vaccine can capture molecules of cocaine in the precious few seconds that lapse before the drug reaches the brain, a study in mice shows. Although the antibody brigade doesn’t snag all the cocaine, it seems to collar enough to greatly subdue the agitation that mice exhibit when given the drug.

Based on these findings, the researchers are moving on to studies in rats and monkeys in hopes of testing the vaccine in people. The new report will appear in the March Molecular Therapy.

“When someone takes cocaine — whether snorted, smoked or injected — you don’t have much time,” says study coauthor Ronald Crystal, a pulmonary physician at Weill Cornell Medical College in New York City.  “It takes about six second to pass from the lungs to the blood to the brain.”

A vaccine would need to elicit a standing army poised to intercede.  “You need avid antibodies, at high levels,” Crystal says.

In the new study, Crystal and his colleagues gave mice three injections over six weeks. Some of the animals received a placebo while the others got the experimental vaccine, which combines a cocainelike substance with noninfectious portions of an adenovirus that stimulate an immune response but don’t cause disease. Four weeks later, all the mice were exposed to cocaine by injection.

Antibodies elicited by the vaccine kept about two-fifths of the cocaine from reaching the brain in vaccinated animals, according to examinations of the mice, which were given the maximum dose of cocaine. This effect translated into behavioral changes:  Cocaine makes mice hyperactive, Crystal says, and in this study the unvaccinated mice were running around much of the time. In contrast, vaccinated mice ran one-third as much and performed repetitive motions half as much, behavior similar to that of mice not given cocaine at all.

Crystal says the vaccine might be ready to test in people in a year or two. “The most obvious strategy is to use it in people who are addicted but who want to stop and have enrolled in a program. This would help them,” he says.

Cocaine dependence accounts for more than one-third of illicit-drug-related emergency room visits, according to the U.S. Drug Abuse Warning Network.

About 40 percent of cocaine users are in denial about their addiction, and another 40 percent are not yet willing to take on the challenge of quitting, says Stephen Ross, an addiction psychiatrist at New York University. “The other 20 percent are ready to make a change,” he says. Such people need behavioral therapy and all available support. “The more tools we have, the better,” Ross says. “A vaccine could be part of that arsenal.” Vaccination might also prevent cocaine addiction in young adults and adolescents who are at high risk, he says.

Any prospective anticocaine vaccine needs a lot of testing, in part because it isn’t clear whether just taking more of the drug might overwhelm a vaccine’s effect, says Frank Orson, a physician and immunologist at the Baylor College of Medicine in Houston. Also, the researchers in the new study used an additive called complete Freund’s adjuvant to boost the immune reponse in the mice. The adjuvant cannot be used in people because of side effects, he says.

Other researchers have sought to build vaccines using adenoviruses, which normally cause the common cold and other ailments, Orson says. These efforts include work on vaccines for HIV, influenza, malaria and other ailments. Adenovirus particles are good at triggering an immune response, he says, which is important for vaccines against addictive drugs because the drugs otherwise go largely unnoticed by immune forces, which are geared up to catch infectious microbes, he says.

Nevertheless, Orson says, “I think there is a good chance we will have vaccines against some of these agents — cocaine being pretty high on the list because of its properties of being fairly short-lived.” Since cocaine is naturally degraded in the blood stream more rapidly than some other illicit drugs, such as methamphetamine, cocaine might make a better target, he says. Orson and his colleagues are currently working on vaccines against cocaine, heroin and methamphetamines.