May 20 - fMRI Probes Anxiety

A new study may provide clues about why some people respond to anti-anxiety medication while others don’t. A paper published in the March 5 issue of Journal of Neuroscience by K. Luan Phan, MD, and his former University of Chicago colleagues reported intriguing findings from a brain imaging study of occasional, nondependent, marijuana users. Phan plans to apply his findings to a study of the anti-anxiety drug sertraline, the generic form of Zoloft.

“These two studies are trying to get to the same goal: to find better treatments for anxiety disorders that affect millions of Americans and seriously interfere with their functioning,” says Phan, an assistant professor of psychiatry at the University of Michigan and the VA Ann Arbor Healthcare System. “The cannabis study highlights a new avenue that we need to explore further as we try to develop novel medications, while the sertraline study will try to find out if we can tell which patients might or might not respond well, and by what mechanism, to an already existing medication known to have some efficacy in treating anxiety disorders.”

Phan led the cannabis study at the University of Chicago, collaborating with Harriet deWit, PhD, the director of the Human Behavioral Pharmacology Laboratory in the Department of Psychiatry there. Their results are based on brain scans of 16 recreational marijuana users who agreed to undergo functional MRI (fMRI). They chose fMRI because it allows them to see in real time which areas of the brain are most active while a volunteer is performing a certain task.

The study used delta-9-tetrahydrocannabinol (THC), the active ingredient in marijuana, and a placebo caplet that looked exactly like the THC caplet. The volunteers were then exposed to photographs of emotional faces, which served as signals of social communication. The researchers found that when the marijuana users received THC, their brain’s response to threatening faces was less than it was when they received a placebo. The difference in response was seen in an area of the brain called the amygdala, which is a hub for the brain’s ability to process signs of danger or warning, and to decide how to respond. But there were no differences between THC and placebo in the areas of the brain that process nonemotional visual signals or govern body movement, suggesting that THC had a specific effect on a specific brain region and on a specific task of processing fear. For ethical reasons, the researchers did not give THC to nonmarijuana users, and the study was small.

The sertraline study will involve people with social anxiety disorder and a comparison group of people without anxiety. The anxiety patients will be scanned before and after they are prescribed the medication. The healthy volunteers in the study will also have fMRI scans, though they will not receive the drug. Phan and his colleagues will also look for variations among several genes in individual subjects. All study participants must between 18 and 55 years old, and those with anxiety disorders must not be taking any other medication that could be affecting the brain in order to enter the study. The idea is to see whether variations in the genes for certain brain receptors and transporters are linked with variations in how the brain reacts to pictures of emotional faces and how it responds to the anti-anxiety drug. This information could lead to an individualized or personalized approach to medical care.

Understanding how drugs such as marijuana affect the brain may also help reveal more about why people become addicted to illicit drugs or abuse certain prescription drugs, Phan notes. Some individuals may be using illicit drugs and misusing prescribed drugs to alleviate their anxiety. He hopes to investigate this issue further by studying people who have used prescription pain drugs recreationally (such as oxycodone), using new funding from the National Institutes of Health.

Source: Reported by Kara Gavin, University of Michigan Health System

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