"What we found implies that these subjects may, later in life, have a higher likelihood of neuro-degenerative diseases, particularly of becoming Parkinsonian," Dr. Nora Volkow, lead researcher and associate laboratory director for life sciences at the U.S. Department of Energy's Brookhaven National Laboratory in Upton, N.Y., told United Press International.
Abuse of methamphetamine, also known as "speed" or "crank," "has become a significant public health problem," Volkow said. Her team has worked for years to uncover the neurological mechanisms of addiction.
Other imaging studies at Brookhaven and elsewhere indicate a common abnormality in alcoholics, cocaine abusers and heroin abusers -- a lower than normal level of so-called dopamine D2 receptors. Brookhaven scientists had previously found in cocaine abusers, dopamine D2 receptor levels are linked with lower metabolic activity in the orbitofrontal cortex of the brain.
"Disruption of the orbitofrontal cortex is associated with obsessive and compulsive behaviors," Volkow said. "So we hypothesized that disruption of this brain region, resulting from depletion of dopamine receptors, could lead to compulsive cocaine intake."
Studying this same mechanism in methamphetamine abusers, the researchers measured dopamine D2 receptor levels and orbitofrontal cortex activity in 15 subjects who were not using drugs during the study and 20 people who did not have a history of drug abuse.
Each subject was injected with a radiotracer, a chemical "tag" designed that binds to D2 receptors in the brain. Brain scans using a positron emission tomography picked up the radioactive signal of the tracer and indicated where it had bound to receptors.
The signal strength indicated the concentration of receptors. The researchers also used a PET scan to measure metabolic activity in the orbitofrontal cortex with a radiotracer designed to bind to glucose, the brain's metabolic "fuel." Higher levels of glucose on PET scans indicated higher metabolic activity.
The methamphetamine abusers showed significantly lower levels of D2 receptors than the control subjects. The fewer D2 receptors, the lower the metabolic activity in the orbitofrontal cortex which "reduces the ability of all other stimuli to trigger a reward response," Volkow said.
"Ordinary stimuli are not strong enough to activate the circuits," she said.
Methamphetamine releases an enormous amount of dopamine and all available dopamine receptors are activated, no matter how few. Drug abuse becomes the only stimulus capable of boosting activity in the orbitofrontal cortex, Volkow said, making it very difficult for the addict to resist the drug.
"Following up with five of the drug abuser subjects who claimed to have stayed clean, we found that, over time, the brain is able to heal receptor damage from methamphetamine abuse, as it does when cocaine abuse ends," Volkow added. "To what degree, we cannot say with certainty. But if users will get clean and stay clean, healing can happen. That's the good news here. Drug abusers who get clean can, we hope, avoid Parkinsonian symptoms adding more injury to their lives."
"I've done research on methamphetamine for almost 20 years and have been involved in the neurotoxicity story almost from the beginning," Dr. Glen Hanson, acting director of the National Institute of Drug Abuse in Bethesda, Md., told UPI. "Dr. Volkow is demonstrating in humans what we have seen in laboratory animals. We've said that the laboratory models using animals predict the human responses, and she has shown that it does predict it in terms of long-term consequences. They are there, and they are something we should be paying attention to."
The study appears in the December issue of the American Journal of Psychiatry.
(Reported by Bruce Sylvester from West Palm Beach, Fla.)
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