Sunday, January 06, 2008

The Anti-Drug Drugs

Newsweek has a great overview of how immunotherapy for addiction might work.
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.


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."


Some limitations include the fact they do not appear to have the same effect on every one and that the immune response could be overwhelmed by high doses of drugs.

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