Andrew Kent, 51, has been battling his addiction to cocaine for more than two decades. Though he has tried different recovery programs over the years, this Houston, Texas, native has relapsed time and time again.
Kent (a pseudonym to protect his family) says even a single hit can return him to the throes of addiction. “The drug just has you. You come off that high and it’s not enough. It makes you want some more and more. And you’ll do anything, even take from the ones you love, to get it.”
But what if there were a vaccine to ease or even remove the rush associated with cocaine? What if booster shots could help addicts like Kent avoid relapses by taking away the physiological high that kept them coming back for more? Researchers at Yale University School of Medicine and the Baylor College of Medicine have completed a trial testing just such a vaccine. The study results were published in October issue of the Archives of General Psychiatry.
Changes to the brain from addiction
In the past decade, neuroscientists have learned that there’s a lot more to kicking a drug habit than just saying no. In fact, continued use of drugs like cocaine can make lasting changes to the brain.
“Over time, cocaine appears to damage the brain’s natural reward mechanisms,” says Eric Nestler, director of the Brain Institute at Mount Sinai School of Medicine and a member of the Dana Alliance for Brain Initiatives. “You continually blast the reward circuit and it becomes less sensitive. So the person has this blunted reward circuit, doesn’t feel good at all, and soon the fastest way just to feel normal is to take the drug.”
The drug also alters the brain through subtle damage to the frontal cortex. “Cocaine diminishes the frontal cortex’s ability to oversee executive control over impulses,” Nestler says. “Everybody has impulses to do things they shouldn’t, but they don’t because it’s not right or illegal. Drugs of abuse corrupt that ability to stop, and keep bringing addicts back to the drug.”
Why a vaccine?
Despite all that neuroscientists have learned about addiction-related changes to the brain, they are still years away from developing drugs or other therapies based on those findings. And current drugs, such as methadone for heroin use and disulfaram (Antabuse) for alcoholism, show inconsistent results—mainly because they only work as long as the addict is willing to take the drug.
“This is a population that is perfect for a therapeutic intervention that does not involve daily medication,” says Bridget Martell, an associate director with Pfizer Global Research and Development Inc. and adjunct faculty at Yale University School of Medicine. “If you look at the cited statistics of people with hypertension, only 50 percent of those patients will take medication. And when you are talking about a dependence on substances—the loss of the ability to function, hold down a job, have a relationship with family—you can only imagine what compliance might be.”
Martell, lead author of the research paper, argues that a vaccine that blocks cocaine’s access to the brain and other organs by using the body’s natural immune response could be a great asset to addicts in recovery. “A vaccine can help these individuals develop antibodies and motivate them to stop using without needing to take a daily medication,” she says. “And it does so without any negative side effects.”
So simple it’s sexy
Martell says the idea behind a vaccine is basic. “It’s very simple biology—in fact, it’s sexy because it’s so simple,” she says. “You have a small molecule that the body can’t make antibodies to [cocaine] and stick it on to something else that will. In this case, we added it to the cholera toxin, which the immune system does respond to, and, in the process, makes anti-cocaine antibodies along with the anti-cholera ones.”
Those anti-cocaine antibodies take up the drug molecules and then use the body’s immune system to dispose of them before they cross blood-brain barrier. Since they don’t reach the brain, they can’t trigger the release of dopamine, the source of the drug’s physiological high. Without the promise of the high, a person is much less motivated to take the drug again.
Thomas Kosten, Martell’s colleague and a researcher at the Baylor College of Medicine, recruited addicts who were interested in recovery to test the vaccine. Of the 55 people who were given all five boosters, 38 percent developed enough of an antibody response to block entrance of cocaine to the brain and other organs. These individuals showed lower use of the drug over the course of the trial.
“It’s the kind of result you hope for in a first-generation vaccine,” Kosten says. “It’s not as good as we hope to be—we know that we need to see higher levels of antibodies in more people—but we have newer vaccines in development that can get 5-6 times as much antibody response in animals now.”
Challenges to getting the right response
Berma Kinsey, a researcher developing different drug vaccines at Baylor, says the biggest challenge is finding a way to get that adequate antibody response. In this case, that may mean going back to the drawing board to develop methods that would make the vaccine stronger.
“Maybe something besides the cholera protein would give a better response,” she says. “Or perhaps the adjuvant, the substance given with the vaccine that tickles the immune response and makes it strong, needs to be adjusted. Or maybe we need a better system to deliver the vaccine. Any of these things could change the antibody response.”
But beyond getting the contents of the vaccine right, there is also the question of maintenance. With a viral vaccine, the body will recognize the virus if a person is re-infected and produce the proper antibody response. Not so with drug molecules.
“Your body hasn’t made antibodies to just the cocaine – it’s made them to some combination of the drug and the cholera toxin,” Kosten says. “Just using the drug won’t boost the immune response. You need to give several boosters to get the antibody levels to where you need them.”
But perhaps the biggest challenge is addiction itself – which is not just a physiological disorder but also a psychological one. Both Martell and Kosten say the vaccine is not a panacea but a tool that can be used with existing psychosocial therapies.
“In general, it takes an addict about two years to turn their life around,” Kosten says. “Addicts might get the vaccine booster every two months or so for those two years. But addiction is a chronic disease and, if a person relapsed, we could give them a single injection to push those antibodies back up again. It would be like having a little insurance policy available to help people get back on the straight and narrow.”
Martell, Kosten and their colleagues are planning new trials of improved vaccines in hopes to attaining necessary, lasting antibody levels—and do so across wider populations of addicts. But even though the results are preliminary, Kent, for one, hopes that the vaccine will be made available soon.
“If there was a vaccine that would help me get this monkey off my back, I’d be number one on the list to try it,” Kent says. “This is a disease that is destroying America. This is a disease that is still trying to destroy me. So if this vaccine does come out, I want to be first.”