Can a Pill Fight Loneliness?

A University of Chicago scientist thinks the hormone pregnenolone might reduce lonely people’s fear of connecting—and their risk of serious health problems

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We appear to be experiencing a loneliness epidemic. Ray Hendley/Getty

To truly understand the insidious nature of loneliness, it helps to think about snakes and sticks.

So suggests Stephanie Cacioppo, a University of Chicago scientist and a leading researcher on the subject. “Have you ever taken a walk in the woods and you jumped back because you saw a stick on the ground and thought it was a snake,” she says. “The lonely mind sees snakes all the time.”

Cacioppo is getting at one of the great paradoxes of being chronically lonely: While a person’s brain senses there’s something wrong and that they should connect with people, it also can, at the same time, make them defensive and hypervigilant in their judgment of others, causing them to zero in on the negative signals they think they’re getting. Which keeps them from connecting.

Put simply, their “social brain network”—the parts of the brain associated with such behaviors as empathy and social interaction—has changed, or in Cacioppo’s words, become “deactivated.” Instead, the fear of rejection takes over.

But what if a medication could help assuage that fear? Could a pill make social encounters feel less threatening?

Ratcheting down fear

That’s the focus of an ongoing clinical trial Cacioppo is overseeing. For the past year and a half—the study is scheduled to end this June—96 lonely, but otherwise healthy subjects, have been receiving 400-milligram oral doses of pregnenolone, a hormone primarily produced by the adrenal gland. It has been associated with memory enhancement, but also stress reduction.

The goal of the research, according to Cacioppo, is to measure the effect of “normalizing” pregnenolone levels in the subjects. The theory is that it could help rachet down the fear that causes lonely people to keep withdrawing.

The psychologist makes clear that the intent is not to extinguish the sensation of feeling lonely. That’s like thirst, Cacioppo notes, a way of your body alerting you to a need. But ideally, a medication could enable a lonely person to become more clear-eyed about their interactions with others.

“A lonely mind lies to you all the time,” she says. “It’s like when you’re driving in the winter and the visibility is really bad. The idea is that a pill could defrost the windshield for you, and finally you see things as they are, rather than being afraid of everyone. You become more open to listening to others.”

Bad for your health

If the research ultimately leads to a pharmacological treatment for loneliness, it would be a timely breakthrough. Whether the cause is demographical, cultural or technological change—or more likely a combination of the three—we appear to be experiencing a loneliness epidemic. Nearly half of the 20,000 American adults who participated in a Cigna study last year reported feeling alone or left out.

The potential impact on public health is sobering. Loneliness has been found to be a risk factor for cardiovascular disease and stroke. It can lower your immunity. It increases the chance of developing type 2 diabetes. It can worsen sleep habits, not to mention it can make you almost 30 percent more likely to die sooner than someone who isn’t lonely.

“Loneliness is a significant risk factor for premature mortality,” says Juliane Holt-Lunstad, a psychology professor at Brigham Young University who has studied the connection between loneliness and health problems. “Given all the health complications, many people are grappling with what we can do about loneliness, and they don’t think we have a good answer at this point.”

While Holt-Lunstad sees value in developing a pill that addresses disrupted brain signals that can exacerbate loneliness, she’s also concerned that it could be overused. “If we don’t give physicians and other health care professionals the tools to deal with loneliness,” she says, “and all they have in their toolbox is a prescription, that’s all people will get.”

It’s important, she adds, that being socially connected needs to be seen as much a part of a healthy lifestyle as eating right and exercising.

“Those connections can be very important as we go through life transitions, whether it’s adolescence or transitions to parenthood or transitions to retirement,” Holt-Lunstad says. “That’s when people might be at the highest risk of becoming disconnected. How do we better equip people to start thinking about this as part of their healthier lifestyle?”

Shutting down a lonely mind

Cacioppo agrees that, by itself, a pill is not the answer to treating loneliness. “We think about this medication as an adjunct therapy to go along with exercises that you can practice every day when you interact with others," she says. “Because the fight with loneliness is a daily fight.”

Cacioppo understands this in a deeply personal way. Last year, her husband John, a noted loneliness researcher with whom she worked every day, died. She was devastated.

“He was the love of my life. We were always together, like twins. I did not think I could survive without him, but I am. I had to go on very long runs to shut down my lonely mind,” she says. “Fortunately, biology helped me. Because when we run, we have endorphins kick in. That really helped me."

Cacioppo acknowledges that not everyone can run a 10K every day after a tragedy. That's why she and her late husband thought about developing a pharmacological treatment that could help people make a new start in life and in social relationships.

“I’m living proof of my science," she says. "If I can recover from loneliness, anyone can.”

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