Researchers trying medication-assisted treatment for meth addiction

Jan 02 2018

Researchers trying medication-assisted treatment for meth addiction

Certain FDA-approved medications already on the market could be used to help methamphetamine users to break free from one of the most addictive of all illicit drugs, according to University of Florida neuroscientists.

Currently, there are no market-approved medications being used to treat meth addiction. But the scientists say they have discovered a new way to use medications to reduce the reward effects of methamphetamine on the brain. The intensely pleasurable feeling caused by the drug is because meth causes the body to release 10 times its normal level of dopamine, the body’s pleasure chemical.

As reported in the journal Nature Communications, researchers demonstrated in laboratory rodents how the medications can be used to prevent that feeling of euphoria.

The team, led by Habibeh Khoshbouei, an associate professor of neuroscience and psychiatry at UF’s College of Medicine, found that, in mice, a low dose of a sigma-1 receptor agonist medication blocks the increase in firing activity of dopamine neurons in the brain caused by smoking, injecting or snorting meth.

Meth also interacts with a signaling modulator in the brain called the sigma-1 receptor, which the researchers identified as a potential molecular target to treat meth addiction. Sigma-1 receptor agonists include some commonly prescribed antidepressants, such as fluvoxamine, and antihistamines, such as dextromethorphan, that can activate the sigma-1 receptor.

Using electrophysiology – measurements of electrical activity generated by neurons – the team also found that sigma-1 receptor agonists, in the absence of methamphetamine, do not provoke the reverse transport of dopamine through its carrier.

The next step for the researchers will be conducting clinical trials in humans.

Khoshbouei compares the effect to the opiate-blocking effect of naloxone. One difference is that the sigma-1 receptor agonist for meth treatment would need to be taken before using meth, rather than afterward to reverse the illicit drug’s effects. Therefore, the therapy would be most effective to help people who want to recover from addiction.

“Methamphetamine is such a menace because the amount of dopamine released following meth abuse is so huge that after long-term abuse these people experience psychosis,” Khoshbouei said. If that effect were blocked, she said, “It could really help people to beat their addiction.”

In earlier studies, the researchers found that the increase is dopamine caused by meth is much longer than the rush caused by using cocaine. “Cocaine-induced increase in dopamine is about 30 minutes to a maximum of 45 minutes. Methamphetamine is 10 hours,” said Min Lin, an assistant professor in the UF department of neuroscience.

“With methamphetamine, the amount of dopamine released is extremely high, so high that people cannot have a semi-normal life,” said Khoshbouei, an associate professor of neuroscience and psychiatry at UF’s College of Medicine, part of UF Health, and a member of the Evelyn F. and William L. McKnight Brain Institute of the University of Florida. “The drug-seeking behavior is so intense that having a normal and productive life becomes all but impossible.”

“We were stunned by the finding,” Khoshbouei said. “When you pre-treat the dopaminergic neuron with a sigma-1 receptor agonist, you decrease the methamphetamine-induced increase in intracellular calcium and dopamine release. What this means is that if an animal or human is exposed to this compound, methamphetamine is less effective.”

In a 2015 article, Alcoholism and Drug Abuse Weekly reported that other researchers have also used prescription stimulants to to treat methamphetamine and cocaine addiction, but that funding for further research has been difficult to obtain. The National Institute on Drug Abuse has not been “enthusiastic” about pursuing such research, the article reported.

John Grabowski, a University of Minnesota professor of psychiatry who has pioneered research on using prescription stimulants to treat cocaine addiction, told ADAW that “The notion of harm reduction is not well loved by NIDA itself, and they have been resistant to the whole concept of stimulant replacement therapy.”

More studies are needed, David A. Gorelick, M.D., Ph.D., professor of psychiatry at the University of Maryland, told ADAW. Some studies using the treatment have been limited in their effectiveness, possibly because doses that were too low caused subjects to experience cravings.

Grabowski’s findings have also indicated that long-acting stimulants are better than short-acting types for the treatment of cocaine dependence, he added. “The limited evidence we have would say it’s more important to use the long-acting stimulants, and at the higher end of the dose range,” said Gorelick. “We need many more studies to flesh out the optimum dose.”