New Anti-Addiction Vaccines

A vaccine that would teach the immune system to attack and destroy cocaine before the drug reached the brain is poised to enter its first large-scale clinical trial in humans. The shot is years away from FDA approval, but the concept that it might someday be possible to inoculate those at risk of addiction has obvious appeal.

Researchers are developing a range of vaccines—which are normally used to combat infectious diseases—against such highly addictive substances as cocaine, nicotine, heroin and methamphetamine. If these new drugs come to market, experts hope they can overcome one big hurdle that previous anti-addiction medications have failed to clear. "The idea of vaccines is not anywhere near as stigmatized as giving medication to the addicted," says Thomas Kosten, the Baylor Medical School psychiatrist who is leading research on the cocaine vaccine. "Vaccine sounds more wholesome than drug." Addiction is often seen as a personal weakness, not a medical condition to be treated or cured. Some experts say that stigmatization has stymied research into potential treatments for the estimated 20 million Americans who struggle with drug addiction. According to Kosten, pharmaceutical companies may have shied away from addiction research because of that stigma. "It's easy to interest the scientists but not so easy to interest the marketing people," he says.

Each of the addiction vaccines now in development employs a similar medical strategy. Because the addictive drug molecules are small enough to evade the body's immune system, they can slip undetected from the respiratory and circulatory tracts that absorb them and make their way into the central nervous system, where they work their dark magic. But when attached to a larger molecule—like an inactivated protein from a cholera-causing bacterium—the addictive substances can't hide. The immune system develops antibodies that can latch on to the drugs when they are next ingested by themselves. Once attached to an antibody, a given drug cannot access its targets in the brain and is instead broken down by certain enzymes.

The medications now used to treat addiction do not prevent addictive drugs from entering the brain, as the vaccines would. Instead these treatments, known as small-molecule therapies, block the drugs' neural targets, so that when the drug reaches the brain it has no place to go. These treatments have met with limited success. For example, methadone, a drug used to treat heroin addiction, is itself a narcotic that has been associated with addiction. Naltrexone and Chantix, which treat alcohol and nicotine addiction, respectively, have been effective in only a small subset of patients. "In all three cases, the brain's receptors are still being manipulated, albeit with a replacement drug," explains Nora Volkow, director of the National Institute on Drug Abuse. In theory, says Volkow, anti-addiction vaccines would circumvent some of these problems by neutralizing the addictive substance before it reached the nervous system. And that means the drugs might someday be used to prevent substance abuse as well as treat it. "It would be great if we could give kids a vaccine that would make them impervious to the effects of alcohol and hard drugs," says Volkow. "In reality, we are still many years away from that."

For these vaccines to succeed, researchers will have to overcome several technical hurdles. In early studies, for example, not all of the subjects developed antibodies against the cocaine-cholera molecule, and some developed much stronger responses than others. "This is not like an antibiotic, which is directed against the invading microbe and has roughly the same effect on everyone," explains Volkow. "Here, we are stimulating the immune system, which can react differently depending on the individual."

Another concern is that a serious drug user could overwhelm the immune response by simply ingesting more cocaine than the immune system could handle. He could also switch to another drug, which the vaccine would be powerless to protect against. In the end, tapping the immune system to fight addiction may prove to be as tricky a proposition as targeting the brain itself.

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