Chemists identify immune system mechanism for methamphetamine binges
Chemists at The Scripps Research Institute have found evidence in laboratory
studies that the immune system may be able to recognize methamphetamine (glass,ice, or crystal and crank or speed in less pure form)
and boost tolerance to the drug through an unusual vaccine-like mechanism.
Their finding, if confirmed in human studies, could help explain why chronic
users go on long binges with the illicit drug, also known as speed. While there is no definitive cure yet for drug addiction, a stint at a drug rehab centre is still the best treatment available today.
Recent studies by others have documented the drug's apparent ability to
suppress the immune system, making abusers more vulnerable to diseases such
as HIV. The new study is the first to suggest that the drug can engage the
body's defense system to attack methamphetamine in such a way that makes
users inclined to use more of the drug, the researchers say. Their study,
which paints a clearer picture of the drug's effect on the immune system and
its potential for abuse, was described today at the 229th national meeting
of the American Chemical Society, the world's largest scientific society.
"Test animals injected with methamphetamine actually developed antibodies to
the drug, which is highly unique for a molecule of its relatively small
size," says study co-leader Kim Janda, Ph.D., a chemist at Scripps in La
Jolla, Calif. Developing antibodies to the body's invaders, such as viruses
and bacteria, is normally a good thing and forms the basis of modern
vaccines, he explains. But ironically, people who abuse methamphetamine may
build up antibodies to the drug itself, so they require increasing amounts
to get high, resulting in binging behavior, he says.
"Without knowing it, they're essentially vaccinating themselves against the
drug, and that's not a good thing as it requires more of the drug to get
high," says Janda. His findings were first reported in a recent issue of the
Journal of the American Chemical Society, the Society's peer-reviewed
journal.
In a test tube study designed to simulate the chemical 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 believes that highly specific
methamphetamine antibodies can be made in a laboratory and then used as a
clinical treatment for addiction. In theory, antibodies to the drug could be
mass produced and administered at therapeutic levels that are high enough to
clear the drug from the body, he says.
"Methamphetamine has become the 'crack' of the 21st century," Janda says.
"We're just starting to unravel its mechanism of addiction." Further studies
of the drug are planned, he adds.
Methamphetamine is a powerful psychostimulant that goes by a number of
common names, including "speed," "ice" and "crank." It is often made in
make-shift laboratories using over-the-counter drug ingredients,
particularly cold and allergy medicines. Available as a powder or crystal,
the drug can be injected, snorted, swallowed and smoked to provide users
with a sense of euphoria. Drug effects can last for up to 12 hours. Frequent
use is associated with serious health problems, including memory loss,
aggression, psychotic behavior, and potential heart and brain damage.
The Skaggs Institute for Chemical Biology (at Scripps) and the National
Institute on Drug Abuse provided funding for this study. In addition to
Janda and Dickerson, other study co-authors include Noboru Yamamoto and
Diana Ruiz, also of Scripps.
The American Chemical Society is a nonprofit organization, chartered by the
U.S. Congress, with a multidisciplinary membership of more than 159,000
chemists and chemical engineers. It publishes numerous scientific journals
and databases, convenes major research conferences and provides educational,
science policy and career programs in chemistry. Its main offices are in
Washington, D.C., and Columbus, Ohio.