Contact: Ellen Bank
843.792.2626
June 20, 2003
“Addiction to drugs of abuse causes permanent changes in the brain that
can cause addicts to crave the drug for years after last using the drug,”
said Peter Kalivas, Ph.D., chair of the Department of Physiology & Neurosciences
at MUSC and an author of the study. Through funding from the National Institute
of Drug Abuse, Kalivas and his colleagues have been investigating the nature
of these changes with the hope that once the changes are characterized, they
will point to new treatments and even cures for addiction. The published paper describes a surprising change produced in the brains of
cocaine-addicted rats, and when this change is reversed, the animals no longer
demonstrated addicted behavior. They also found that the addicted behavior was
reversed by the amino acid derivative, N-acetylcysteine, which is used as a
food supplement, antioxidant and a treatment for acetaminophen (Tylenol) overdose.
Because of the highly promising results in the animal trials, a second group
of MUSC researchers, working in close consultation with the first team, designed
a clinical trial to test the safety and efficacy of the compound on humans.
They recruited cocaine-addicted individuals to participate. To date two individuals
have been tested. “We are very excited about this research,” said Robert Malcolm,
M.D., an MUSC psychiatrist, specializing in addiction and principal investigator
in the clinical trial. “Cocaine addiction is a major public health problem
and current treatments are not effective. This drug appears to be very promising,
and the trial will provide valuable information. Our ultimate goalis to provide relief to addicts who are desperately seeking help.” The participant in human research trial, who must be free of cocaine for three
days prior to the trial, is admitted to the university’s General Clinical
Research Center, a highly specialized patient unit designed for clinical research.
During the first week, the participant is given four doses of either the compound
or placebo, and the second week he is given the opposite, with neither the patient
nor investigators knowing in which week, which compound is administered. During the trial, the subject is carefully monitored for adverse reaction to
the compound. Additionally, following administration of either the compound
or placebo, the subject is tested for craving reaction in two ways. He/she is
placed in a high speed MRI, where researchers can observe changes in the brain
related to a craving response when the subject is shown pictures of people using
cocaine or drug paraphernalia. Additionally, physiological responses to drug
cues such as sweating, heart rate and facial muscles are also monitored. The researchers anticipate that the preliminary trial with 12 patients will
be completed early in 2004. In the animal trial the researchers discovered that there is a marked reduction
in the levels of a neurotransmitter called glutamate in the part of the brain
long known to be important in addiction called the nucleus accumbens. They found
that the lower glutamate levels occurred because a protein called the cystine-glutamate
exchanger was defective. Treatment with N-acetylcysteine increased the activity
of the exchanger and restored glutamate levels to normal. When N-acetylcysteine
had restored the levels of glutamate the rats no longer engaged in drug-seeking
behavior which is a model of craving and relapse in human addicts. Importantly,
N-acetylcysteine had no effect on seeking other rewards, such as food. MUSC researchers participating in the animal trial along with Kalivas are David
Baker, Ph.D., Krista McFarland, Ph.D., Russell W. Lake, Hui Shen, M.D., Xing-Chun
Tang, M.D. and Shigenobu Toda, M.D. The paper can be viewed online at http://www.nature.com/neuro/.
Nature Neuroscience is a multidisciplinary journal that publishes papers of
significance in all areas of neuroscience. Developed with the assistance of Kathleen Brady, M.D., Ph.D., the clinical trial
is being conducted by Malcolm, Steven LaRowe, Ph.D., and Hugh Myrick, M.D.
CHARLESTON, SC -- A derivative of a common amino acid has been found to be effective
in preventing relapse to cocaine use in experimental animals. The findings by
Medical University of South Carolina (MUSC) researchers will be published in
the July, 2003 issue of Nature Neuroscience. Another team of MUSC investigators
has begun testing the compound in humans.
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