Trying to comprehend how meth damages brain


This is one in a series of articles written by research students in The University of Toledo College of Medicine’s Biomedical graduate program exploring basic issues of human health.

In 2012, the National Survey on Drug Use and Health reported that more than 12 million people in the United States have tried methamphetamine at least once.

Even that single exposure to the drug can be incredibly addictive because of the intense feelings of well-being it produces short-term; however, the drug has other consequences including impaired decision making, decreased need for sleep, hallucinations, and increased anxiety, aggression and violent behavior.

Not only does methamphetamine alter brain and behavior, but it also can significantly increase heart rate, blood pressure and body temperature. These systemic effects of the drug contribute to the significant increase in emergency room visits resulting from drug exposure. In fact, the number of emergency room visits as a result of methamphetamine exposure has increased to more than 100,000 per year, as reported by the Substance Abuse and Mental Health Services Administration.

In addition to the dangerous short-term effects, methamphetamine is especially harmful because it causes long-term damage to the brain and, in particular, to the cells in the brain that produce dopamine and serotonin. These neurotransmitters are important for feelings of reward, pleasure, control of mood and emotions, as well as memory. Damage to regions of the brain where these neurotransmitters are localized has been seen to last for up to two years in those addicted to the drug and can have a significant impact on their lives.

Working in the laboratory of Dr. Bryan Yamamoto in the Department of Neurosciences at The University of Toledo Medical Center, I worked to understand how methamphetamine causes this long-term brain damage with the goal of preventing it and helping the recovery of those exposed and addicted to the drug. The research team also looked beyond what the drug is doing in the brain to examine its effects on other organs of the body to better understand why it is so damaging.

One of the organs affected by methamphetamine is the liver, which is one of the most important organs in the body because it performs many diverse tasks including removing hazardous substances from the blood, helping the body store energy and nutrients from the food we eat, and making many of the proteins that our bodies need to function normally. Laboratory rodents exposed to methamphetamine showed damage to the liver, which prompted additional research to see if that liver damage also could contribute to the damage the drug was causing in the brain.

Liver damage from other causes, such as hepatitis or alcohol exposure, is well known to contribute to brain dysfunction. One way that liver dysfunction can contribute to brain damage is through the actions of ammonia, which is a byproduct of protein metabolism and is normally processed by a healthy liver and removed from the body. When ammonia is not excreted, its levels increase in the body and can damage the brain. Results of our research demonstrate that methamphetamine does indeed increase the levels of ammonia in the blood and brain.

Having confirmed that methamphetamine exposure causes liver damage and increases ammonia in the blood and brain, research continued to examine whether these increases in ammonia were actually contributing to the long-term brain damage produced by the drug. To do this, methamphetamine-induced increases in ammonia were prevented with the drug lactulose. When the increases in ammonia were blocked, the brain damage produced by methamphetamine was prevented.

These research results showed that the liver damage and increases in ammonia produced by methamphetamine play a significant role in the long-term brain damage produced by the drug. These findings are significant because they demonstrate that brain damage produced by methamphetamine might not only be due to its direct action on the brain, but also could cause damage by first acting on other organs. Methamphetamine-induced or pre-existing liver damage and increases in ammonia could represent new targets for the treatment of the long-term brain injury produced by the drug.

Laura Halpin is a medical student in her fourth year at the University of Toledo College of Medicine and Life Sciences and recently earned her PhD in the college's Biomedical Science Program. For more information, email or go to​med/​grad/​biomedical.