Memory research offers promise for a meth addiction treatment

Promising developments continue to mount in research on a compound that someday could prevent relapse in patients with methamphetamine addiction. Results of the latest study involving this drug, called blebbistatin, suggest it also could be of value in helping drug users who combine use of methamphetamine with other substances of abuse.

This observation carries great significance, a researcher suggests, because the high potency of the methamphetamine now arriving into the United States from Mexico raises the likelihood of users' enaging in polydrug use to combat meth's effects.

“The methamphetamine from Mexico is cheap and very pure, and if users experience getting too high, they may use opioids to come down,” says Courtney A. Miller, PhD, an associate professor in the Department of Neuroscience at the Florida campus of The Scripps Research Institute. Identifying a drug that could inhibit drug-seeking for more than one substance would therefore be a major development.

The latest study in this area, published in the journal Learning & Memory, found that when nicotine or morphine was administered to mice concurrently with meth administration, memories associated with use of these substances were susceptible to the same disruption from blebbistatin that was seen with memories associated with meth use. This suggests that polydrug users might benefit greatly from this compound, for which Phase I clinical trials could begin by 2020.

Research history

A history of the research surrounding blebbistatin, and what has been learned about the factors that contribute to relapse to methamphetamine addiction, is instructive.

Miller tells Addiction Professional that among the many potential triggers to relapse to drug use, memories associated with use are particularly potent. “The brain is really good at maintaining salient memories,” she says. Efforts of her research team, therefore, have sought to identify ways to disrupt those memories while leaving other brain processes intact, thus not interfering with other memories.

Five years ago, Miller and her colleagues discovered a unique aspect of memory storage as it applies to methamphetamine and amphetamine. The protein actin, which strengthens the connections between neurons that contribute to memory storage, is known to stabilize in most areas of the brain after memories are stored. But the research team found that actin remained active in areas of the brain's amygdala region where meth memories are stored. This finding led the researchers to speculate that a therapy could target actin and disrupt memory associated with methamphetamine use.

However, because actin is highly prevalent throughout the body, a compound acting on it could also produce numerous unwanted effects. Miller's team discovered that another protein, myosin, showed the same results as actin when targeted. They found that the drug acting on both actin and myosin, blebbistatin, could be administered to rodents in the lab just once and make the memory associated with methamphetamine go away.

“We were excited about the single administration, because the chances for [treatment] success are higher,” Miller says.

The most recent study sought to determine whether meth memories would remain susceptible to the compound when more than one drug was being administered in the lab. The study found that when mice were conditioned to both meth and nicotine or to both meth and morphine, a single administration of blebbistatin resulted in drug seeking going away entirely, Miller explains.

Looking ahead

Once this research moves into human clinical trials, Miller believes the trials' time frame could be shorter than what is typical in these studies, because of the immediate changes in the brain that could be seen with a single administration of blebbistatin. She says researchers are envisioning an intravenous administration of the drug, which is classified as a non-muscle myosin small molecule inhibitor.

“We would see this as part of a [medication-assisted treatment] approach,” she says, in which a treatment program might administer the drug in the first week of treatment while also offering therapeutic services and support.

“We don't think we have a pill that cures it all,” she says.

Miller adds that if this drug ultimately proves effective in human trials, it might be advisable over a patient's lifetime to offer it several times, since individuals with a methamphetamine addiction history could experience a relapse for a variety of reasons.