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Meth-relapse prevention compound may be effective for opioid users

By Allen Cone

Sept. 17 (UPI) -- A compound developed by researchers to fight methamphetamine relapse has shown wider benefits for people battling substance abuse than previously thought, a study found.

Scripps Research scientists found the compound appears to be effective, even if patients are using multiple drugs, such as methamphetamine in combination with opioids or nicotine. The findings were published in the September issue of the journal Learning and Memory.

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In a separate study published last month, Scripps researchers also developed a model of social stress in addiction that should provide researchers with better ways of evaluating therapies intended to improve treatment success.

Relapse rates for methamphetamine and heroin addiction often range between 40 percent and 60 percent, and can go as high as 90 percent, the researchers said.

People who abuse methamphetamine and heroin are almost three times more likely to overdose, the researchers noted. Many who are addicted to methamphetamine smoke cigarettes, and many turn to opioids to dampen the high.

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Modulating emotional memory is a novel and promising concept, and doesn't appear to act on other forms of memory or motivations, the researchers said.

The new compound is the first to directly target the motivational power of craving triggers.

"A lot of current users aren't even aware of what their triggers are until they encounter them," senior author Dr. Courtney Miller, an associate professor on the Florida campus of Scripps Research, said in a press release. "These triggers can maintain their ability to drive craving for a person's entire life, meaning a lifetime relapse risk."

The compound, which is a modified form of the compound blebbistatin, breaks down methamphetamine-linked memories that can trigger craving and relapse.

Cravings driven by memories of use can drive uncontrollable urges to do so again, and handling money, tasting certain foods and returning to places linked to their drug use are among things that can trigger cravings for former users.

The modified blebbistatin was tested in animal studies.

The drug interferes with storage of memories in the amygdala, the brain's emotional memory center, Miller said. The medication inhibits a protein called nonmuscle myosin II, which organizes another, called actin, which is involved in neural plasticity. These are an extension of brain cells' finger-like projections that form new connections.

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"What they are losing is that drive to go and drug seek when they see the familiar place," Miller said.

No medications exist to reduce the the lure of lifelong drug-linked memories.

"The height of drug cravings peaks around 30 days and goes out to about 180 days after cessation of use," Miller said. "That's when they are out of rehab and back in their environment, surrounded by the things that trigger their cravings, so it's a really problematic situation."

She noted many U.S. insurance plans now cover 30 days of inpatient drug treatment.

Encountering intense stress during that sensitive recovery period also can boost relapse risk.

In the earlier study, Miller and other Scripps researchers developed a unique animal model of social stress-potentiated meth seeking.

"There is data in humans that social stress -- combined with using a small amount of meth -- can drive a much stronger craving for the drug," Miller said. "We found we can recapitulate that in an animal model."

They placed a rat in the home cage of an aggressive rat. Some "intruders" handle the aggressive resident actively by defending themselves. But others are more aggressive and rapidly acquiesce to the resident by lying down.

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The passive rats were consistently more likely to self-administer methamphetamine after this event compared with rats that actively defended themselves. Passive coping strategies have been linked to behavioral and mental disorders, including an increased likelihood of developing addiction, she added.

"Having a reliable model of social stress in the context of drug use will be important to developing medication strategies to improve treatment response," Miller said.

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