CONTACT: Ron Hartung, College of Medicine
ronald.hartung@med.fsu.edu; 850-645-9205

October 2018

TALLAHASSEE, Fla. — People who get no depression relief from Prozac-type medicines have found a fast-acting substitute in a drug called ketamine. But is it safe? The National Institutes of Health has awarded a Florida State University researcher nearly $2 million to investigate ketamine, which some have called a wonder drug.

Over the next five years, College of Medicine researcher Mohamed Kabbaj and his lab will seek answers to these and other questions: Is ketamine addictive when administered in low doses? In what ways does it affect females and males differently? How does it interact with alcohol?

“Hopefully, by the end of these five years we’ll have more information for psychiatrists to decide whether ketamine can be safely prescribed for suicidal patients and for patients who do not respond to classic antidepressant treatment,” said Kabbaj, a professor in the Department of Biomedical Sciences.

Ketamine was developed in the 1960s as an anesthetic to replace PCP, which was giving patients hallucinations and other so-called “dissociative effects.” In the last decade, psychiatrists discovered that ketamine in low doses also worked remarkably fast to relieve the symptoms of depression and reverse thoughts of suicide.

“A lot of clinics have popped up around the country treating depression and bipolar disorder with repeated infusions of ketamine,” Kabbaj said. “But no studies have been done to look into the safety of these treatments related to ketamine’s potential addictive and cognitive effects.”

In large doses, ketamine (called “special K” and other names on the street) is abused by people seeking a quick high. With that dosage, side effects include addiction. Kabbaj’s goal is to find out whether low doses of ketamine also are addictive and determine the mechanisms of ketamine’s actions at both high and low doses in both sexes.

Kabbaj’s previous studies, also funded by the NIH, demonstrated sex differences in ketamine’s antidepressant effects. Women require much lower doses than men to get those benefits.

“We’re also going to determine which brain areas are implicated in ketamine’s addictive properties at low and high doses,” he said. “Our work will focus on the nucleus accumbens, an area that is associated with reward and behavioral reinforcement.”

The release of dopamine in this brain area, in response to ketamine administration, leads to activation of two populations of neurons that express either dopamine D1 receptors or dopamine D2 receptors. This project, Kabbaj said, will try to assess the role of those neuron populations in ketamine’s addictive effects.

Since a large population of depressed patients abuse alcohol, another aim of this study is to examine the interaction between ketamine, depression and alcohol in male and female subjects.

“If you have a patient who drinks alcohol and you give him ketamine, is it safe?” Kabbaj asked. “What is the interaction between ketamine and alcohol?

“Women metabolize alcohol much more slowly than men and are more prone to depression. Ketamine and alcohol share some similarities in their mode of action in the brain, so it is critical to examine the ketamine-alcohol interaction in both sexes.”

Some of ketamine’s effects on drinking alcohol might be therapeutic, he said.

“There are some studies now showing that ketamine can reduce alcohol drinking,” he said. “Our study will directly test these interactions and examine the potential mechanisms behind them.”

Kabbaj is one of many researchers trying to learn more about this promising drug.

“It’s a very hot topic right now,” he said. “Soon we’ll know what ketamine is doing, in terms of the molecular and cellular mechanisms mediating its fast-acting antidepressant properties. So maybe we can develop other drugs that act similarly but without causing dissociative effects and leading to addiction.”

CONTACT: Ron Hartung, College of Medicine.
ronald.hartung@med.fsu.edu; (850) 645-9205

Oct. 26, 2018

TALLAHASSEE, Fla. — A new Florida State University College of Medicine study involving data from 12,000 participants collected over 10 years confirms the heavy toll that loneliness can take on your health: It increases your risk of dementia by 40 percent.

The risk is across the board, regardless of gender, race, ethnicity or education — or whether you have regular social contact with friends and family.

The study was published in the Journal of Gerontology: Psychological Sciences.

“We are not the first people to show that loneliness is associated with increased risk of dementia,” said Angelina Sutin, the principal investigator on the study. “But this is by far the largest sample yet, with a long follow-up. And the population was more diverse.”

The Sutin team’s paper made use of the federally funded Health and Retirement Study, a longitudinal look at Americans 50 and older and their spouses. Participants reported on their loneliness and were also administered a cognitive battery every two years, up to 10 years after their reports of loneliness. During this time, 1,104 people developed dementia.

Participants who reported greater feelings of loneliness were more likely to develop dementia over the next 10 years. Individuals who feel lonely are likely to have several risk factors for dementia, including diabetes, hypertension and depression, and are less likely to be physically active and more likely to smoke. Even after adjusting for those shared risks, loneliness still predicted dementia.

“Lonely” can have many interpretations, said Sutin, an associate professor in the college’s Department of Behavioral Sciences and Social Medicine. Her team’s study referred to “the subjective experience of social isolation,” which is separate from actual social isolation.

“It’s a feeling that you do not fit in or do not belong with the people around you,” Sutin said. “You can have somebody who lives alone, who doesn’t have very much contact with people, but has enough — and that fills their internal need for socializing. So even though objectively you might think that person is socially isolated, they don’t feel lonely. The flip side is that you can be around a lot of people and be socially engaged and interactive and still feel like you don’t belong. From the outside it looks like you have great social engagement, but the subjective feeling is that you’re not part of the group.”

Sutin urges against blaming the victim for feelings of loneliness.

“People might say, ‘You’re lonely. Go make a friend,’” she said. “But it’s not that easy.”

There are significant long-term consequences to having these kinds of feelings. It’s not the individual’s fault or choice to be lonely.

“I think this study adds to the literature highlighting the importance of psychological factors and how individuals subjectively interpret their own situation," Sutin said. "That’s equally important and separate from what we objectively measure. It also lends credibility to the idea of asking people how they feel about things — in this case, how they feel about their social interactions.”

There are a number of ways that loneliness may put one at risk for dementia. One way may be physiological, such as through higher inflammation — the body’s natural response to infection that can be harmful when it lasts a long time. A second way may be through behavior. People may cope with loneliness through behaviors that can damage the brain, such as heavy drinking or being sedentary. A third way is through lack of meaningful social interaction. Keeping the mind engaged in a meaningful way can promote cognitive health that provides the motivation and structure to help maintain cognitive functioning.

In the end, Sutin said, loneliness is a signal that your social needs are not being met. And there are ways to counter that.

“Loneliness is a modifiable risk factor,” she said. “Most people might describe periods where they felt lonely and then periods where they didn’t feel lonely. So just because you feel lonely now, you don’t always have to feel this way.”

Sutin’s co-authors are Martina Luchetti, a research faculty member in Behavioral Sciences, and Antonio Terracciano, a professor in the medical school’s Department of Geriatrics. The other co-author, Yannick Stephan, is from the University of Montpellier in France.