Opioid users could benefit from meth-relapse prevention strategy, study finds

[Nergal]

 

New research raises the possibility that a wider group of people battling substance use disorders may benefit from a Scripps Research-developed relapse-prevention compound than previously thought.

The research, published recently in the journal Learning and Memory, shows that the compound appears to be effective even if multiple drugs of abuse are involved, such as methamphetamine in combination with either opioids or nicotine. Polysubstance use is common among people addicted to methamphetamine, in part because the rate of smoking is high among meth users. In addition, the meth available today is so potent that many users turn to opioids to dampen the high.

The potential medication, a modified form of the compound blebbistatin, works by breaking down methamphetamine-linked memories that can trigger craving and relapse. The opportunity to boost treatment success by modulating emotional memory is a novel concept, and a promising one, says Courtney Miller, PhD, associate professor on the Florida campus of Scripps Research and senior author of the study.

For people in recovery from substance use disorder, memories can drive uncontrollable urges to return to drug use. Handling money, tasting certain foods or returning to places linked to their drug use can all trigger those intense cravings.

"A lot of current users aren't even aware of what their triggers are until they encounter them. These triggers can maintain their ability to drive craving for a person's entire life, meaning a lifetime relapse risk. That's what makes this new finding exciting," Miller says. "This would be the first compound to directly target the motivational power of craving triggers."

Importantly, the compound doesn't appear to act on other forms of memory or motivations, and this selectivity is key to its powerful potential.

How the drug works to target cravings

The modified blebbistatin, tested in animal models for this study, works by interfering with storage of memories in the amygdala, the brain's emotional memory center, Miller says. The medication inhibits a protein called nonmuscle myosin II. That protein organizes another, called actin, which is involved in neural plasticity, the extension of brain cells' finger-like projections that form new connections.

Normally, actin and nonmuscle myosin II stabilize within minutes of learning, lending stability to long-term memory storage. However, the actin and myosin supporting meth memories behaves differently. They remain active and, therefore, uniquely vulnerable to a drug designed to inhibit nonmuscle myosin II. In animal models, treatment with the compound eliminated the animals' learned preference for a place where they had ingested addictive drugs.