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Chemists identify immune system mechanism for methamphetamine binges

l reactions that occur with the drug when it enters the bloodstream, the researchers showed that methamphetamine reacts with glucose and proteins to form a larger-size "glycated" product. This product is then recognized by immune system components, stimulating the production of antibodies to the drug. In follow-up studies using mice, those injected with the drug developed antibodies to it.

"Antibodies are usually produced only in response to large molecule invaders such as proteins, not to small drug molecules," Janda says. "Glycation acts like a linker that allows [the methamphetamine] to be displayed to the immune system, triggering a vaccine-like reaction."

Just as a vaccine is able to remove invading pathogens by using antibodies to the pathogen, antibodies to methamphetamine attack and begin to clear the drug, Janda says. If the antibodies prevent some of the drug from reaching its place of action in the brain's pleasure center, users might require more of the drug because some of it is bound up by antibodies and "soaked up like a sponge," according to the researcher.

"If the mechanism we proposed proves true in humans, then it will help explain why addicts go on prolonged binges, requiring more frequent intake and ever-increasing amounts of the drug in order to achieve a high," says Janda, who led the study with his former student, Tobin Dickerson, Ph.D., also a chemist at Scripps.

Other drugs of abuse, including nicotine and ecstasy (which is structurally similar to methamphetamine), might share a similar mechanism of action involving immune system recognition and a consequent rise in tolerance to the drug, Janda and his associates theorize. Tolerance refers to the capacity to have a decreased response to a drug after prolonged use. Increased drug tolerance raises the likelihood that a person will become addicted.

"Right now, there's nothing really effective in getting people off methamphetamine," says Janda, who believ
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Source:American Chemical Society


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