Subjects: R and D
Although cocaine use has declined steadily since its peak in the early 1980s, public health officials estimate that about 7 million Americans used the drug at least once last year. Many of these folks are addicted to the drug, and its intense, short-lived euphoric effects mean the addiction is terribly difficult to overcome.
Addiction specialists believe existing treatment paradigms for cocaine addiction can be enhanced by a vaccine that prevents the drug from crossing the blood-brain barrier, thus blunting its euphoric effects. Scientists have worked hard to develop such a vaccine, but have had limited success so far.
About a year ago for example, Thomas Kosten and colleagues at Baylor reported partial success in a human trial of a cocaine vaccine. In that trial, 38% of subjects who received all 5 shots in the vaccine series achieved sufficient antibody levels to blunt the effects of the drug. In that subset, 53% of the subjects stopped using cocaine, meaning that overall, the vaccine worked about 20% of the time.
Unfortunately, some subjects began snorting massive amounts of the drug in an effort to overcome the vaccine’s effects. Some people managed to amass 10 times more of the drug in their systems than was present before the trial began. Cocaine levels like that can kill people. In addition, the cocaine antibodies, when they developed at all, remained in the bloodstream of subjects for only 8-10 weeks; it takes longer than that to assure the behavioral aspects of the addiction are overcome.
Last week, Martin Hicks, Ronald Crystal and colleagues at Cornell reported that they had developed an alternative vaccine and that it was quite effective…in mice.
The Cornell team attached a chemical congener of cocaine onto a specially prepared version of an adenovirus, the virus responsible for many common colds. The latter vector was chosen to assure that the body’s immune system would recognize the newly created molecule as foreign and create antibodies against it. The trick of course, was to assure that the antibodies so created would recognize “pure” cocaine after it was ingested, and prevent it from crossing the blood brain barrier.
So the team vaccinated mice with their concoction and proved that it generated a strong immune response against it. They subsequently isolated the murine antibodies in a test tube, and added pure cocaine to it. Sure enough, the antibodies attacked the cocaine.
The team subsequently compared the behaviors of 2 groups of mice after they ingested cocaine. The first group, which had been vaccinated, displayed less hyperactive behaviors than the non-vaccinated group. The salutary effect was demonstrable even among mice that had ingested prodigious amounts of the drug, and it was demonstrable for 13 weeks after the vaccine was given.
“Our data shows that we can protect mice against the effects of cocaine, and we think this approach could be very promising in fighting addiction in humans,” Crystal said.
But Baylor’s Kosten was circumspect. “First of all, the immune response is less robust in people than in animals,” he told Health Day. “Secondly, for people to get close to the animal response, we have to give them a lot more vaccinations than we have to give the animals.”
“And people have more genetic diversity than mice,” he added. “That ends up producing important differences in response in people. About 25 to 30 percent of the people who you vaccinate don’t produce much antibody at all.”
“The data we have suggests that it takes people about two years of abstinence to change their lifestyle and get over all the behavioral aspects of addiction,” Kosten said. “And because the duration of the vaccine’s effectiveness is only two to three months, we will need to offer repeated vaccinations for two years.”
Oh well, the Cornell team’s write-up appears in Molecular Therapy.