Methamphetamine, a highly addictive stimulant drug, whose abuse has reached epidemic proportions in many parts of the United States, causes long-term changes in the human brain that are associated with impaired memory and motor coordination, according to a study published in the March 2001 issue of the American Journal of Psychiatry. Researchers found that these effects are seen even in methamphetamine addicts who have been off the drug for 10 months or more. A second study by the same research group reveals additional long-lasting brain changes caused by the drug, including an unexpected increase in cellular activity in certain areas of the brain.
"These findings show a direct relationship between changes in brain chemistry in methamphetamine abusers and functional changes in behavior," says Dr. Alan I. Leshner, director of the National Institute on Drug Abuse (NIDA). "The results underscore the serious nature of methamphetamine abuse and emphasize the need to alert users and potential users to the long-lasting, profound effects of this drug."
NIDA funded the research with the NIH National Center for Research Resources, the US Department of Energy, and the White House Office of National Drug Control Policy.
Methamphetamine, also known as "speed," "meth" or "chalk" (and, in its smoked form, as "ice," "crystal" or "glass"), can be smoked, snorted, injected or taken orally. The drug, often made in clandestine laboratories from inexpensive over-the-counter ingredients, is widely abused by diverse groups, including young adults who attend "raves" or private clubs, motorcycle gang members, male and female commercial sex workers, and bisexual and homosexual men.
In one study, researchers led by Dr. Nora D. Volkow of Brookhaven National Laboratory in Upton, NY, and the State University of New York at Stony Brook used an imaging technique called positron emission tomography (PET) scanning to measure the levels of molecules called dopamine transporters in the brains of 15 former methamphetamine abusers and 18 healthy comparison subjects (controls). The number of dopamine transporters (DAT) marks the presence of nerve cells that are part of a brain circuit that transmits signals using the chemical dopamine, which plays a role in movement control and feelings of pleasure. The researchers administered a battery of tests to assess attention, memory, mood, general intelligence and motor function.
Results showed that, on average, DAT levels in the striatum of the brain were 24 percent lower in methamphetamine abusers than in control subjects. Like other addictive drugs, methamphetamine is known to trigger short-term release of high levels of dopamine, which stimulates brain cells in the dopamine circuit, thereby enhancing mood and body movement. But previous animal studies show that long-term exposure to methamphetamine damages dopamine-producing brain cells and leads to reduced dopamine levels. The current finding of reduced DAT levels in chronic methamphetamine abusers indicates that in humans, too, the drug causes dysfunction in dopamine circuits, Dr. Volkow says.
Particularly noteworthy, she says, is the finding that "the lower the levels [of DAT], the worse the performance in motor tasks and the worse the performance in tasks of verbal learning" used to assess memory. "That is telling us chronic methamphetamine use is affecting many functions of the brain in a negative way."
In a second study, Dr. Volkow and her colleagues used PET scanning to measure glucose metabolism in the brains of the same group of methamphetamine abusers and in control subjects. Glucose metabolism is a measure of brain cell activity, and reduced glucose metabolism can be a very sensitive indicator of brain damage and an early indicator of neurodegenerative disease.
To their surprise, the researchers saw a marked overall increase in glucose metabolism in the brains of methamphetamine abusers, suggesting an inflammatory reaction. This effect was most marked in the parietal cortex region, which is involved in sensation and in spatial perception. Animal studies show this area to be particularly sensitive to the damaging effects of methamphetamine.
However, after controlling for this overall increase in metabolism in the methamphetamine abusers, the investigators showed that metabolism was significantly reduced in two brain regions?the thalamus and striatum. These regions are involved in dopamine signaling, but the parietal cortex is not involved in the dopamine pathway. Thus, Dr. Volkow says, the results of this study add to the researchers' findings "by clearly documenting that the changes that are produced by methamphetamine are not limited to the dopamine system."
Questions remain about whether the effects of methamphetamine abuse on the human brain are permanent, and whether these effects can predispose some people to develop neurodegenerative diseases later in life.
Note to reporters: The full text of these articles appears in the March 2001 issue of the American Journal of Psychiatry (Am J Psychiatry, Volume 158, Number 3, pgs. 377-382; 383-389) will be available on the journal's Web site, http://ajp.psychiatryonline.org/.