UPTON, NY -- Two studies by researchers at the U.S. Department of Energy's Brookhaven National Laboratory provide evidence for the first time that abuse of methamphetamine the drug commonly known as "speed" -- is associated with physiological changes in two systems of the human brain. The changes are evident even for abusers who have not taken the drug for a year or more. The studies also found that methamphetamine abusers have reduced cognitive and motor functions, even at one year after quitting the drug. The findings appear in the March issue of the American Journal of Psychiatry.
"These studies provide some of the first clear evidence that methamphetamine at dose levels taken by human abusers leads to dopamine transporter reduction," said Brookhaven psychiatrist Nora Volkow, lead investigator on the study. "For the first time we can also see that this transporter reduction is associated with motor and cognitive impairment." Previously, in animal studies and two small human studies, researchers documented reductions in dopamine transporters. Past studies did not test whether these reductions were associated with changes in cognitive and motor function. "We also have the first evidence that methamphetamine affects circuits of the brain other than those regulated by dopamine, and that the drug causes changes that are consistent with inflammation throughout the brain," Volkow continued. "This is objective evidence that methamphetamine is damaging to the brain. These changes are much greater than what wehave seen with heroin, alcohol, or cocaine. We need to further study whether these changes are long-lasting and result in long-term impairment of memory and motor functions, such as motor speed and motor coordination."
Reduced Dopamine Transporters, Cognitive and Motor Function
In the first study, Volkow and colleagues tested both dopamine transporter levels and motor and cognitive function in 15 detoxified methamphetamine abusers and 18 control subjects who had not previously used methamphetamine. Dopamine transporters help transport "used" dopamine, a neurotransmitter that contributes to feelings of satisfaction and pleasure, back into the nerve cells that produce it, thus terminating the pleasure signal.
Each study volunteer was given an injection called a radiotracer, a radioactive chemical "tag" designed to bind to dopamine transporters in the brain. The researchers then scanned the subjects' brains using a positron emission tomography (PET) camera. The PET camera picks up the radioactive signal of the tracer and shows where it is bound to dopamine transporters. The strength of the signal indicates the number of transporters.
Within two weeks of the PET scans, the researchers administered a battery of neuropsychological tests. These included tests of fine and gross motor function and tests of attention and memory.Methamphetamine abusers showed a significant reduction in dopamine transporters in the caudate (27.8%) and putamen (21.1.%) two areas of the striatum, a section of the brain that controls movement, attention, motivation, and other higher functions -- compared with non-abusers in the study. The reduction was evident even in abusers who had been detoxified for 11 months or more. Study subjects with reduced dopamine transporters also exhibited memory impairment and slowed motor function.Increased Brain Glucose Metabolism and Inflammation
In the second study, Volkow's team looked at brain glucose metabolism in order to see if there was any functional change in regions of the brains of methamphetamine abusers other than those in which dopamine cells are active. The same 15 detoxified methamphetamine abusers who participated in the first study, and 21 non-abusers, received PET scans following administration of a radioactive tracer. The scans showed a 14% higher whole brain metabolism in abusers than in non-abusers. Differences were most accentuated in the parietal cortex an area of the brain that regulates sensation and coordinates information on space and spatial relations where abusers showed a 20% higher rate of metabolism.
"This finding was a complete surprise," Volkow says. "Most drug studies have shown decreased metabolism. The increased metabolism we saw is consistent with an inflammatory response. This result, taken together with our other findings, indicates that this is a very toxic drug." The presence of inflammation signals that there is a physical insult to the brain.
"We cannot reach any definite conclusions about long-term effects, because only three of the subjects had been detoxified for an extended period. But our three primary findings -- dopamine transporter loss, whole brain inflammation, and loss of motor and cognitive abilities -- document the adverse effects of methamphetamine to the human brain. We believe more studies must be done to assess if there is long-term damage from this drug," says Volkow. "We can say unequivocally that methamphetamine abusers need to be watched by their physicians as they age to determine whether they begin seeing any effects of neurodegenerative diseases like Parkinson's." The reduction in brain dopamine that occurs as these subjects age, in addition to the loss they experience from use of methamphetamine, may result in symptoms similar to those seen in Parkinson's disease, a severe movement disorder that results from a loss of dopamine in the brain.
Methamphetamine is a highly addictive stimulant that dramatically affects the central nervous system. Long reported as a dominant drug problem in southern California, methamphetamine abuse has recently become a substantial problem in other areas of the West and Southwest as well. Usage has also recently increased in areas of the Midwest and South. According to a survey by the National Institute on Drug Abuse, an estimated 4.9 million Americans have tried methamphetamine at some point in their lives.
Brookhaven scientists have done extensive research on addiction. Studies by Dr. Volkow and colleagues have shown that dopamine plays an important role in addiction to cocaine, nicotine, alcohol, heroin, and other drugs. Previous research at Brookhaven has shown that addictive drugs increase the level of dopamine in the brain while the subject is intoxicated, and that addicts have fewer dopamine receptors than non-addicts.
This study was funded by the U.S. Department of Energy; the National Institute on Drug Abuse, part of the National Institutes of Health; the Office of National Drug Control Policy; and the General Clinical Research Center at University Hospital Stony Brook. It was done in collaboration with researchers from the State University of New York at Stony Brook and the University of California, Los Angeles.
The full text of these studies will appear on the American Journal of Psychiatry web site at: http://www.ajp.psychiatryonline.org.
The U.S. Department of EnergyΉs Brookhaven National Laboratory creates and operates major facilities available to university, industrial and governmental personnel for basic and applied research in the physical, biomedical and environmental sciences and in selected energy technologies. The Laboratory is operated by Brookhaven Science Associates, a not-for-profit research management company, under contract with the U.S. Department of Energy.
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