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OHSU, PVAMC Launch First Comprehensive Meth Center

MARC will study genetics of addiction as basis for targeted drug therapies, prevention

Oregon is now home to the nation's first federally funded center for studying methamphetamine abuse from its genetic underpinnings to its prevention through public education programs.

Oregon Health & Science University and the Portland Veterans Affairs Medical Center have jointly launched the Methamphetamine Abuse Research Center, or MARC, which is funded by a five-year, $5 million grant from the National Institute on Drug Abuse, National Institutes of Health. OHSU and PVAMC also are providing a total of $50,000 per year toward the center.

Employing 20 world-class researchers and physicians, the center will typify "bi-directional" translational research, the so-called bench-to-bedside approach of quickly translating laboratory discoveries into clinical treatments, and using the findings by the clinicians to guide the basic scientists toward the questions that can best be answered with animal models or bench chemistry.

Their goals: better understand the genetic predisposition behind meth addiction and withdrawal symptoms; use rational drug design to develop new therapies; create educational programs for school-age children that improve science education and reduce initiation of meth use; and educate rural clinicians about new information and therapies for their patients affected by meth.

"Very little is understood about meth. There are few, if any, effective pharmacological treatments for addiction. The rate of recidivism is pretty high," said the MARC's director, Aaron Janowsky, Ph.D., professor of psychiatry and behavioral neuroscience, OHSU School of Medicine, and research career scientist, PVAMC. "There's a significant amount of evidence showing that when you take just one dose, it has long-lasting effects. We're interested in preventing that one dose, but if it happens, reversing its effects."

Meth addiction is the world's most persistent drug abuse problem. Globally, more people use meth than use cocaine and heroin combined. In the United States, the primary meth-related hospital admissions rate increased from 10 to 52 per 100,000 people aged 12 and older between 1992 and 2002. In 2002, 19 states had rates in excess of the national rate, and 12 had primary meth admission rates of more than twice the national rate, or 104 or more admissions per 100,000 people.

Locally, the meth problem is worse. There were more admissions directly related to meth in Oregon than in any other state tracking the data. And while alcohol is responsible for the most admissions at the Portland VAMC, patients admitted with meth addiction are often more psychiatrically ill than patients addicted to other drugs.

A key difference between cocaine and meth that might account for meth's more addictive characteristics is that while cocaine and meth both block the recycling of dopamine at the nerve terminal, meth also prevents the second step of recycling inside the terminal where dopamine is repackaged and ready for release again.

"You get a dump of dopamine into the synapse, the space between the nerve cells," Janowsky said. "Meth is taken up by the transporter, causing release of more of the neurotransmitter, but cocaine only blocks the re-uptake of the neurotransmitter."

The center contains four research themes to study the effects of meth use. One will focus on the areas and systems of the brain involved in drug craving and drug effects. Another will examine the changes in gene, nerve cell and brain function that accompany meth exposure and withdrawal. A third theme will look at the effects of stress on drug craving and the potential for relapse. The fourth will study impulsivity and the decision-making process associated with meth use.

Several pilot projects already are in progress at the MARC. One involves using functional magnetic resonance imaging, or fMRI, to examine the brains of former meth users while they take a test that measures their impulsivity. For example, study subjects are asked whether they'll take $10 now or $100 in a week.

"It turns out that people addicted to drugs of all sorts, and particularly people addicted to meth, tend to discount the delayed rewards," said project head and MARC investigator William Hoffman, Ph.D., M.D.,assistant professor of psychiatry, OHSU School of Medicine, and staff psychiatrist in the Mental Health and Clinical Neurosciences Division, PVAMC. "Non-addicted people tend to wait for the delayed reward. Meth users are 'Go, go, go.' The question is: What is a person's brain doing when they make these kinds of decisions?"

MARC scientists also are developing new measures of impulsivity that can be used in both animal and human research.

Another pilot project is studying the prenatal and neonatal effects of meth abuse. Jacob Raber, Ph.D., associate professor of behavioral neuroscience and neurology in the OHSU School of Medicine, showed in a recent study that in mice, exposure to meth early in life causes sex-dependent impairments in the ability to recognize objects and navigate based on memory. These effects were much more pronounced in female than in male mice. He also found that a naturally released compound, histamine, mediates these long-term impairments, and that the histamine system may be an important link to developing an effective target for drug therapies.

One of the most important components of the MARC is its education program. Headed by William Cameron, Ph.D., OHSU associate professor of behavioral neuroscience, the education core will translate the center's findings into useful information for clinicians and students, and it will be instrumental in community outreach programs designed to reduce meth use. All members of the center will participate in these educational activities.

"What we need is a national mobilization of neuroscientists and clinicians to talk about the dangers of meth use and addiction," Cameron said.

Janowsky agreed. "It'd be great to get kids to not even be interested in meth," he said.

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