A Shot to End Addiction

There aren't many tools to combat addiction. There are medications, like methadone, which block the drugs in the brain, plus behavioral therapy and cold turkey. But some scientists are now viewing drugs of abuse as toxic interlopers—and focusing on fighting them immunologically, like influenza.

Drugs of abuse zoom past the blood-brain barrier and stimulate the reinforcing reward centers in the brain. But hooking up an addictive substance with a foreign protein that acts as an immune stimulus, and then turning it into a vaccine, may be a promising way to outsmart the system. The resulting antibody response clears the drug from the system before much of it reaches the brain.

Further, a vaccine for addiction could stimulate immune memory. The next time the drug enters the system, the body recognizes it even in the absence of a carrier protein, and antibodies wrangle and destroy most of it. The resulting high is weaker, and researchers find that, rather than taking more drugs to compensate, users decrease their drug use—and many quit completely.

Daryl Shorter, a psychiatrist at Baylor College of Medicine who is currently developing a cocaine vaccine, suspects we'll see vaccines commercially available in 15 or 20 years. They might be used to kick-start rehab or to prevent relapse in those who've overcome addiction. One day, drug vaccines might even be used preventively in children. At right is an overview of progress in the field. —Tarah Knaresboro

• Cocaine Shorter's lab has a cocaine vaccine already in clinical trials. The shot produced a strong immune response—but only in about a third of coke users, who also went on to yield a high percentage of cocaine-free urine samples. More research is underway to discover why results are limited to so few. (Shorter suspects genetics may play a role.) Separately, a team of Cornell researchers has yoked a cocaine-like chemical onto the immunity-sparking components of a cold virus to produce a vaccine that yields lasting immunity in mice; clinical trials are a few years off.

• Nicotine Currently, three vaccines are in clinical testing, each with a different carrier protein. A first may be ready in three years, say Kim Janda, an immunologist at The Scripps Research Institute. It may not work for everyone—"It will need to be improved to get the efficacy we'd all like to see," he says—but he thinks it will be a good model for immunization against other drugs of abuse.

• PCP A phencyclidine vaccine is still in its infancy but the need is fully fledged: Usage has climbed in recent years, and chronic use induces schizophrenia-like symptoms. Because PCP toxicity can be acutely dangerous, researchers may first focus on finding an overdose treatment, rather than a vaccine.

• Meth A methamphetamine vaccine is still in its beginnings, and scientists haven't even agreed on the best candidate for a carrier protein. In the interim, researchers are exploring an alternative form of immune combat called passive immunization, currently used to give short-term immunity boosts against diseases such as lymphoma. In this case, drug-plus-carrier would be injected into an animal, the animal antibodies extracted, and the pre-formed antibodies injected into humans, where they'd go to work. The method could mitigate the effects of an overdose but not spark long-term immunity; so far, it's been approved for combating diseases such as cancer but not drugs of abuse.

• Heroin Researchers began developing a heroin vaccine in the '70s, but progress slowed to a near-halt with the wide use of methadone and buprenorphine. Both compounds quickly nullify overdose and prevent withdrawal symptoms by mimicking the drug in the brain and occupying receptors in the reward system. Methadone clinics have enabled many heroin addicts to lead normal lives, but Shorter believes a vaccine would be better than tying addicts to frequent visits to a clinic for a shot of decoy drug. A vaccine could stave off drug use for several months or more, enabling addicts to live more freely and to perhaps end their dependence permanently.