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Meth-hooked mice may help humans

• OHSU research group looks at why addiction levels aren't dropping
by: sARAH TOOR, OHSU neuroscientist Gregory Mark holds one of his subjects in a study of how meth affects brain function.

Many people can tell you the how, what and when of methamphetamine's devastating spread across the country.

Gregory Mark, however, is one of relatively few people who can tell you why. He's on the frontlines of battling meth - but he's not a cop.

The longtime Oregon Health and Science University neuroscientist studies the mechanics and chemistry of how addicts' brains respond to drugs. And of all the drugs that are out there, he says meth has a singular ability to take hold of people and make them a slave to their habit.

'We've never seen a drug like this,' he said recently in his cramped but busy lab.

Mark is part of a research group called MARC, the Methamphetamine Abuse Research Center. A joint project of OHSU and the Portland VA Medical Center, the assemblage of scientists and doctors is one of five in the country whose meth research is funded by a federal grant from the National Institute on Drug Abuse.

Despite being hardly more than a year old, the center already is paying off with significant research in areas that are still largely a mystery, such as treating the underlying cravings of meth abuse, as well as mapping the damage it wreaks to the brain.

'We're playing around in the dark here,' Mark said. 'We have some encouraging results but they're not finalized yet.'

The efforts of Mark and his colleagues are significant because, although Oregon two years ago adopted some of the most aggressive anti-meth laws in the country, the number of addicts entering treatment has not dropped, and some local drug cops say there is more meth than ever.

'This is a sad commentary, but the price and availability of illicit drugs hasn't really changed that much since I was in high school,' said Aaron Janowsky, the administrator of the research center. 'What that tells you is the dealers are controlling the market. The supply is unregulated; the price is being regulated by the dealers.'

With supply remaining largely uncurbed, Janowsky, Mark and their colleagues at MARC are zeroing in on the human side of the equation, demand - specifically, the brain chemistry and influences that make people susceptible to methamphetamine addiction, as well as to relapse.

What they are finding is that more than with most substances, methamphetamine addicts are subject to impulsiveness. Given a choice between receiving $5 now or $100 in a year's time, a meth addict almost always will opt for the immediate payoff, said Bill Hoffman, a psychiatrist who works with MARC.

'That's unusual,' he said.

Quick treatments often fail

Hoffman uses the MARC's state-of-the-art magnetic resonance imaging equipment, or MRI, to map out decision-making by looking at which areas of the brain are active during different activities.

It's hoped that looking at such things will help people not decide to resume using meth.

That's important, because treatment for meth addicts is notoriously unsuccessful. Some insurer-funded drug rehab programs follow a standard 28-day program used for other addictions - which providers say is completely inadequate to prevent relapse.

Groups that offer longer-term treatment programs, like the Salvation Army's Adult Rehabilitation Center in Portland, meanwhile, say their problem is lack of space to accommodate those wanting to get in.

So Mark and others are looking at whether pharmacological assistance could help.

He and his grad students keep a stable of test mice who can be hooked up to a clear tube extending from the roof of the cage to what looks like a hat on their heads.

When the mouse presses a certain lever, it sends a signal to a computer, which in turn releases a dose of meth to the mouse.

The mice are just as good as humans at taking meth, Mark says. But they are more easily tracked, with the results providing important clues to how to rein in meth's effects.

Drugs go at brain chemistry

Like most addiction researchers, Mark's focus is on dopamine, the hormone that in the brain acts to regulate feelings of anticipation, motivation, reward and pleasure.

The addictive rush one gets from playing video poker or gaming with your Xbox is all about dopamine - and so is meth addiction.

There are drugs that interfere with dopamine production, and thereby reduce the cravings that make addicts relapse. The problem is that those drugs frequently also interfere with all pleasure-inducing behavior, including eating, socializing and sex.

The MARC group is going beyond dopamine to study some of the lesser-known chemicals that essentially trigger dopamine's release and effects.

As part of that approach, they are studying drugs that more selectively affect brain chemistry. One drug that has shown promise is mecamylamine, a drug that already is used for hypertension as well as alcohol and nicotine addiction.

Studies with mice have found a dose level that allows mice to retain their appetite for food - suggesting that regular dopamine reward systems are functioning normally - but while leading them to cut their use of the drug in half.

A drug that cuts cravings in half could be of help in helping people kick the habit - especially during the first month of going cold turkey, when cravings are strongest.

Though such a drug still would have to be coupled with a treatment program, 'it would be of tremendous benefit,' said Neil Leibowitz, a counselor with the Salvation Army.

Mark and Janowsky caution that although mecamylamine is approved by the Food and Drug Administration for other purposes, it still has not been shown to be safe for usage by meth users.

That means that any meth user taking it before such tests are completed is risking serious health effects and possibly death.

Other MARC researchers are making important strides in looking at genetic predisposition toward meth addiction, as well as to the long-term damage of 'meth babies,' people who were exposed in utero due to their mothers' usage.

Janowsky's big concern is that his lab's $5 million grant lasts for only three and a half more years, meaning that its work may be stifled just when it is poised to tackle genetic answers to meth addiction.

A gene-based, individualized treatment 'would be closer to being a cure for addiction,' Janowsky said, 'as opposed to just being a treatment.'

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