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Ongoing research

Tackling meth addiction—through the immune system

Posted August 27, 2013
(Fall 2013 VA Research Currents; online ahead of print)

Methamphetamine is one of the toughest addictions to break, say experts. Up to 6 in 10 people who go through treatment will use the drug again.

Part of the reason, says VA researcher Jennifer Loftis, PhD, may be the thinking and mood problems that linger long after someone stops using the drug.

"After they've managed to stop using the drug, they still don't feel good," says Loftis, with the Methamphetamine Abuse Research Center at the Portland VA Medical Center and Oregon Health and Science University. "Convincing them they should stay clean and sober, and they'll eventually feel better, is hard to do, because it could be two years later and they're still not feeling better. That makes it more challenging to keep people in treatment."

She and co-investigator Marilyn Huckans, PhD, have support from VA and the National Institutes of Health to develop a new approach to easing the mood, memory, and other thinking problems that wrack the brains of people who have been on meth.

While most drugs targeting addictions work on neurotransmitters—brain chemicals such as dopamine—Loftis' lab is focused on the immune system. They've learned from animal experiments that changes in the immune system contribute to the memory problems linked to addiction. "People who take meth have compromised immune systems," she says. "They get sick more easily. In the brain, there may be inflammation and other immune responses. We're trying to tone that down, but at the same time not hurt the body's ability to fight infection."

The field is known as psychoneuroimmunology—an intimidating term, even by medical-jargon standards. It focuses on how the immune system interacts with the central nervous system and affects the brain to cause psychiatric and neurological symptoms such as low mood and poor memory and attention.

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Dr. Jennifer Loftis studies methamphetamine addiction at the Portland VA Medical Center and Oregon Health and Science University. (Photo by Michael Moody)

Dr. Jennifer Loftis studies methamphetamine addiction at the Portland VA Medical Center and Oregon Health and Science University. (Photo by Michael Moody)

Loftis and Huckans are now hot on the trail of a new drug—a type of immunotherapy—they believe will make a big difference in meth-induced brain symptoms. It's called RTL551. It's part of a family of compounds that researchers at the Portland VA and elsewhere are exploring for a range of immune conditions, such as multiple sclerosis and rheumatoid arthritis. The drug works by blocking the flow of inflammatory cells to the brain. In experiments with mice, it lowered the inflammatory response, and—importantly—also improved the animals' thinking skills.

If RTL551 or a similar agent pans out in further animal studies, and eventually human clinical trials, Loftis says it could be a game changer for Veterans and others struggling with meth addiction.

"Our goal is to figure out a way to help these cognitive and mood symptoms get better during early withdrawal and recovery periods, so patients can stick with their treatment programs and regain a meaningful life."

Disclosure note: VA and OHSU own the RTL drug technology. One investigator involved in the research has stock options in Virogenomics/Artielle, a company that has licensed the technology. VA and OHSU, as well as Drs. Loftis, Huckans, and Vandenbark, have rights to royalties from the licensing agreement with Artielle. These potential conflicts of interest have been reviewed and managed by the Portland VA Medical Center and OHSU.

Facts about meth

  • Methamphetamine-or meth-is a white, bitter, odorless powder that is a highly addictive stimulant drug.
  • It can be eaten, snorted, smoked through a glass pipe, or mixed with liquid and injected. It is known in slang as crank, ice, crystal, glass, or chalk.
  • The drug releases a wave of adrenaline and dopamine in the brain, thus increasing confidence, alertness, mood, energy, sex drive, and talkativeness. The high can last up to 16 hours.
  • Negative mental effects from chronic use include confusion, memory loss, low mood, tiredness, paranoia, anger, and violent behavior. Physical effects include extreme weight loss, damaged immune function, severe tooth decay, and prematurely aged skin.
  • Cognitive and mood problems can persist long-term even after a person stops using the drug, making rehabilitation more difficult. Relapse rates are up to 60 percent.

Sources: Medline, National Institute on Drug Abuse

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How many Veterans are affected?

Methamphetamine is not as pervasive a problem as some other substances—such as alcohol—among Veterans, but there are still significant numbers of Veterans affected.

According to the federal Center for Behavioral Health Statistics and Quality, out of 17,641 Veterans, ages 21 to 39, who accessed substance abuse treatment at non-VA facilities in 2010, around 6 percent were primarily meth users. By comparison, 51 percent primarily used alcohol, 9 percent heroin, 12 percent marijuana, and 6 percent cocaine.

On a related note, in a 2008 survey of active duty troops by the Department of Defense, around 1 percent of respondents reported using meth in the past 12 months.

Sources: SAMHSA Center for Behavioral Health Statistics and Quality; Data Spotlight, Nov. 8, 2012; 2008 DoD Survey of Health Related Behaviors Among Active Duty Military Personnel

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What happens to mice on meth?

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Mice exposed to methamphetamine display impaired memory. (Photo: Getty Images)

Dr. Jennifer Loftis' research at the Methamphetamine Abuse Research Center involves animals and people. She describes MARC's "translational" approach: "We look at both animal models and humans who are actually using, to get at the underlying mechanisms in the brain, as well as learn how the things we discover in mice relate to people. By looking at both, we can figure out new drugs, or behavioral interventions."

Loftis, who has a doctorate in behavioral neuroscience, describes what her team has observed in lab experiments in which mice are exposed to the drug:

"Meth impairs their ability to remember. We put them in boxes where they are introduced to different objects, and they investigate them like all animals will. The next day we give them a new object to explore. A healthy animal will go right over to the new object in their environment to check it out. A mouse that's been exposed to meth won't do that. They can't remember what they've seen before and what they haven't."

She says her group is "looking at what's going on in the brains of these mice to cause them to have these memory problems."

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