It is well known that methamphetamine abuse damages the nerve endings of human brain cells containing dopamine, a chemical messenger that plays a role in memory, mood, and motor coordination. The damage affects dopamine nerve endings located in that part of the brain known as the striatum.
Two recently published studies about methamphetamine offer additional insights about the actions of this drug.
Methamphetamine's Effect on Dopamine System Similar to that of Cocaine and Alcohol
In the December issue of the American Journal of Psychiatry, Drs. Nora Volkow and Linda Chang and their colleagues at the Brookhaven National Laboratory report that methamphetamine acts on some of the same brain mechanisms as cocaine and alcohol.
The investigators used positron emission tomography (PET) scans and other technologies to measure the level of dopamine D2 receptors and to assess the rate of glucose metabolism, a sensitive measure of brain cell activity, in the brains of 15 methamphetamine abusers and 20 non-drug users. They found lower levels of dopamine receptors and a lower rate of glucose metabolism in the orbitofrontal cortex in the methamphetamine users than in the non-drug users. The orbitofrontal cortex is the part of the brain associated with compulsive behaviors. Disruption of the metabolism of the orbitofrontal cortex may contribute to compulsive drug intake in addicted individuals. This association between dopamine receptors and the metabolism of the orbitofrontal cortex has been observed previously in cocaine addicts and alcoholics, but this is the first time it has been documented in methamphetamine users.
Damaged Brain Cells May Recover After Prolonged Abstinence from Methamphetamine
In the December 1, 2001 issue of the Journal of Neuroscience, the same team of researchers reports that methamphetamine-damaged brain cells may recover after prolonged abstinence from the drug. However, the extent of recovery may not be sufficient to restore full cognitive function.
The researchers used PET scans to measure the levels of molecules called dopamine transporters in methamphetamine abusers enrolled in a California drug-court monitoring rehabilitation program. Dopamine transporter levels were assessed in five methamphetamine abusers who were able to stay drug free during the study. The first assessment was made within six months of last using methamphetamine; the second evaluation was conducted at least nine months later.
The second assessment revealed that dopamine transporter levels in specific brain regions had increased significantly, between 16 and 19 percent, since the first testing. The investigators also found that the longer the period between the first and second evaluation, the greater the amount of recovery of dopamine transporter levels.
Those who had used methamphetamine for less time and in smaller quantities recovered more dopamine transporter molecules than did long-time, heavy users of the drug. "This indicates," says Dr. Volkow, "that length and severity of use may ultimately limit the amount and speed of recovery of dopamine transporter levels."
In addition to measuring dopamine transporter levels, the investigators in this study gave the subjects a battery of tests to evaluate skills known to be associated with dopamine transporters. The tests were performed within two weeks of the PET studies, and included evaluations for gross motor function (walking as fast as possible in a straight line); fine motor coordination (inserting pegs into small holes as quickly as possible); and for memory function.
Slight improvement was noted in some motor and memory skills in the testing conducted in conjunction with the second PET scan, but the investigators did not find these improvements to be significant.
The researchers are not sure why the lack of improvement in cognitive function does not parallel recovery of dopamine transporter levels. Dr. Volkow says, "One explanation could be that neuropsychological function requires other brain systems that may have been affected by methamphetamine use for which recovery may be slower or not present."
Both studies were funded by the National Institute on Drug Abuse, one of the National Institutes of Health.