Shortly after relocating to Texas from California three years ago, Cheryl Webster started hosting a game night at her home as a way of meeting new people. They stopped meeting due to Covid-19, and Webster has only heard from one person in the group in the months since they were able to play.

Eventually, she decided to pick up the phone herself – but nobody called back.

“I think that’s the hardest part about loneliness,” she said. “Is it my fault? Am I not a very nice person? Or is there something wrong with me?”

Webster, 65, is a proactive doer who volunteers regularly and has even helped finance the education of several friends’ children. She sits on the board of the Austin housing authority and the chamber of commerce, and is sure the Christian business leaders’ group she meets with monthly would say flattering things about her. Though divorced and childless, Webster is not a Havisham spinster – putting herself “out there” comes naturally. And so she supposes many people in her life would be surprised to learn that she’s lonely. Despite following the advice of experts to ward off the feeling, her heart still aches.

Webster is not alone. A growing number of people share her affliction – so much so that some governments are incorporating loneliness into their health public policy. To help people like her, a number of scientists are researching medical solutions, such as pills and nasal sprays. But will treating loneliness like a disease, rather than an existential question, work to ease their pain?

There is no standard definition for what, exactly, it means to be lonely. In his book Loneliness, the neuroscientist John Cacioppo described it as a perceived social lack, a “subjective experience”, making the point that one need not be physically isolated to feel painfully lonely (ever been alone in a crowded room?).

Everyone experiences loneliness to varying degrees throughout life, and common circumstances contribute to situational loneliness: the death of a loved one, moving to a new city, being the new kid at school, divorce, loss of mobility or illness.

Chronic loneliness has a different flavor to it. In her book A Biography of Loneliness, the cultural historian Fay Bound Alberti wrote that it has little to do with being alone: “It is a conscious, cognitive feeling of estrangement or social separation from meaningful others; an emotional lack that concerns a person’s place in the world.” It is harder to define, and harder still to treat, especially the longer the feeling lasts.

In 2014, Cacioppo and his wife and research partner, Stephanie Cacioppo, reported in a journal article that feeling socially isolated can raise levels of the stress hormone cortisol, disrupt sleep, and also lead to long term health consequences, such as earlier morbidity. Julianne Holt-Lunstad’s 2015 study found that loneliness was “more dangerous than obesity”.

For individuals like Webster, who says she’s felt “like the odd one out” her entire life, the potential physical health effects of an already emotionally painful experience are a double whammy.

A few years later, in 2017, the former US surgeon general Vivek H Murthy sounded the alarm, deeming loneliness an “epidemic”. His concerns were supported a few months later by Cigna’s 2018 Loneliness Survey, based on the UCLA Loneliness Scale, a questionnaire which asks respondents to indicate whether each of 20 statements describes how they often, sometimes, rarely or never feel. For instance: “I am unhappy doing so many things alone;”; “there is no one I can turn to”; “my interests and ideas are not shared by others”.

The results found that nearly 50% of Americans said they sometimes or always felt alone, and one in four rarely or never felt that others understood them (in the 2020 survey, 61% of Americans report being lonely, an 11% increase in just two years).

Those catchy statistics kicked off a spate of alarmist news articles about loneliness. Soon after, the UK appointed Tracey Crouch as its first minister of loneliness. According to a government press release, by 2023, general practitioners in England “will be able to refer patients experiencing loneliness to community activities and voluntary services” – prescribing social solutions in much the same way they prescribe medications.

Over the past few years, social interventions such as therapy groups, get-togethers and special benches that invite lonely people to sit down and meet others have proliferated throughout North America and Europe to address the problem.

The solution, however, might not lie in meeting casual acquaintances more often. Science says that it is meaningful relationships that ease loneliness, not a full social calendar. This led some researchers to turn their interest towards medicine: could a pharmaceutical treatment help lonely people form the meaningful relationships they crave?

Inside the Brain Dynamics Laboratory at the University of Chicago, Stephanie Cacioppo hooks up subjects to electrodes to measure brain activity. Since May 2017, she’s been conducting clinical trials, seeking the answer to loneliness in pill form.

Pregnenolone, a hormone produced primarily by the adrenal gland, has shown positive signs of reducing levels of anxiety that perpetuate, as the medical world puts it, perceived social isolation. June marked the study’s estimated completion date.

For years, her husband had been writing about how loneliness can alter the way an individual’s brain works. In his 2008 book he wrote that “loneliness itself is not a disease”, and that situational loneliness would never require “a remedy in the form of a pill”, but that medications might benefit “individuals caught in the feedback loop of loneliness and negative affect” in order “to first bring their depression or anxiety under control”. But neither he nor his wife had broached the possibility of fighting perceived social isolation with medicine until a few years later.

In a March 2015 review, they helped introduce the still-controversial notion that short-term pharmacological treatments such as oxytocin, in conjunction with psychotherapy, could help patients.

By December that year, the Cacioppos were focused on treating anxiety and depressive or aggressive behaviors with a version of a naturally-occurring neurosteroid (a steroid formed in the brain) called allopregnanolone. Studies, including some by the Cacioppos, had shown allopregnanolone to reduce anxiety and to promote the regeneration of brain cells, and was being considered as a possible therapy for PTSD, traumatic brain injuries and Alzheimer’s.

It went on the market last year as Zulresso, as a prescribed treatment for postpartum depression at about $34,000 a prescription (because of the secondary effects associated with taking it, the medication is only available through a restricted program.) The Cacioppos found that perceived social isolation, too, was probably associated with an impaired ability to synthesize allopregnanolone – which is how the current clinical trial started.

Meanwhile in Germany, Rene Hurlemann, a professor of psychiatry at the University of Oldenburg, began testing oxytocin about a decade ago. It is known as the “love” or “cuddle” hormone because of its release while giving birth, breastfeeding and physical affection. Oxytocin could have salutary effects, Hurlemann hypothesized, on a number of conditions. He studied its presence in flirting couples, and then turned to its potential in treating social anxiety disorder and PTSD. Based on animal research, Hurlemann said, we know oxytocin is crucial to social bonds – could the hormone also be used to treat loneliness?

Hurlemann and Simone Shamay-Tsoory, a colleague from Haifa University, then began work on several studies of people whose loneliness is not caused by mental illness. (The literature is clear that while loneliness and mental illness can go hand-in-hand, and can mimic or commingle with depressive symptoms especially, it is distinct from depression.)

Their subjects undergo group psychotherapy, with a focus on discussing loneliness and participating in social activities. In addition, half of the participants undergo treatment with oxytocin, and the other half receive a placebo. Hurlemann and Shamay-Tsoory are hoping to discern whether oxytocin in the form of a nasal spray might accelerate the therapy’s treatment effects. Hurlemann says you would never prescribe oxytocin in the absence of psychotherapy – rather, the idea is that the spray could help speed along the bond between therapist and client, allowing therapists to treat more patients.

While he doesn’t yet have conclusive results, Hurlemann said that the baseline oxytocin levels in the lonely people do not differ from the controllers, who aren’t lonely. But introduce a social trigger, and things change.

The team developed an experiment wherein subjects had to complete an interview regarding topics such as the happiest moment in their life, and other positive memories. “Not only do individuals tend to release oxytocin in that situation,” he said, “they have higher oxytocin levels afterwards and we could measure that. Whereas in the lonely people, this was not the case.” The lonely people had low oxytocin levels even after being confronted with positive memories – meaning lonely people experience a lower level of warm feelings than people who are not lonely, even when thinking about happy moments.

Hurlemann and his team found that there is a difference between lonely and non-lonely people in terms of activity in two brain areas, the amygdala – the brain’s fear center – and the nucleus accumbens – the brain’s reward center. Asked if this difference is permanent or if a lonely person could perhaps “fix” the affected parts of their brain, Hurlemann said it’s too soon to know.

The study was on track for completion by the end of 2020, but due to Covid-19, it will take an additional 18 months.

Many psychologists, social scientists and therapists I spoke with expressed hesitance and caution about clinical solutions, favoring a psychotherapy approach to treating chronic loneliness.

Rachael Benjamin, a psychotherapist at Tribeca Therapy in New York, who leads a therapy group specifically for dealing with loneliness, thinks medicalizing it “makes us feel more isolated”. She is not anti-medication and acknowledges that it can in fact be life saving – but it doesn’t get to our most inner workings. “Pills can’t build intimacy,” she says.

At his practice in Seattle, the psychotherapist Caleb Dodson treats loneliness with a method called existential analysis, based on the idea that by deeply understanding others, while remaining separate from them, lonely patients can learn, over time, to not be wounded by perceived social rejection. “There are people that just won’t meet you where you are,” he says. “And that there is a lot of grief, but at the same time, in that grief, there is an intimacy that you can begin to cultivate with yourself, and the relationship with yourself [means] that you will never be lonely.”

In other words, being radically curious about the motivations and feelings of others can transform a lonely person’s experience of social pain.

Like Benjamin, Dodson is pro-medication in certain cases, and acknowledges that especially when treating clients with severe depression, sometimes medication is needed before their feelings and core issues can be accessed. But if the pendulum swings the other way and it gets to the point where medication keeps the client from “experiencing their experience”, that’s a problem.

He says: “In a way, it makes total sense that they would be developing a pill for this, because it’s such a common experience, and because we don’t know what to do with it, and it’s easier to give someone a pill than it is for them to go through therapy for – in my honest opinion, and the type of therapy that I do – years.”

Dodson says that while a loneliness pill could be helpful, “the physicians would need to be educated and the patients monitored in relationship with the therapist”. Obscuring or dulling the pain of loneliness could squelch the impetus to examine and learn from the feeling.

The sense of an “epidemic” now drives popular discussion of loneliness – and that can itself skew possible solutions, according to Fay Bound Alberti, the cultural historian. She went so far as to call Murthy’s framing a moral panic, warning that “epidemic terminology is politically and socially powerful. It leads to knee-jerk political soundbites rather than thoughtful, historically informed discussion about what loneliness might mean.”

Bound Alberti also challenged John Cacioppo’s description of loneliness as an evolutionary, transhistorical phenomenon rather than a product of economic and social conditions. She argued that it is a modern phenomenon, born of an ever-increasing individualistic society. Thinking of it as an unavoidable, universal experience takes the pressure off of institutions and society at large, to do anything about it.

John Cacioppo’s research pace slowed for the first time in three decades when he was diagnosed with cancer in 2015, and took time off to treat it. Nevertheless, the work continued until his death in 2018. To cope with her grief, Stephanie Cacioppo went on long runs to produce endorphins in an attempt to ward off a grief-stricken depression, but she’s hardly taken a break from loneliness research.

Until recently, she was recruiting for a study on how minorities experience loneliness. In November 2019, she co-authored a journal article proposing the possibilities of a genetic predisposition to loneliness and she told the Guardian last fall that she was cautiously optimistic that those in her study who received pregnenolone would report feeling less lonely than those who received the placebo. (Despite repeated requests and a preliminary conversation, she declined to be interviewed for this story.)

While some healthcare economists hesitate to put a hypothetical number on the potential market for loneliness drugs, Melissa Garrido, a health services researcher at Boston University, said pharmaceutical companies would be the greatest beneficiaries of pathologized loneliness. It’s unclear whether any of them are currently backing any loneliness research, but people can already purchase some forms of oxytocin and pregnenolone for self-medication online, for around $.50 to $2.00 a dose from retailers such as Vitamin Shoppe, Walmart and Amazon.

She believes God has a plan for her, but admits it’s not a very satisfying one. “I know my joy is supposed to be in the Lord, but Lord, there are other things that I want to be happy about.”

These days, she doesn’t talk much about how it hurts to not have children, to have not dated in 21 years, to be the one no one thinks to check on. She breezes past such topics and keeps a smile on her face, and before the pandemic, she made a habit of seeking out loners at parties and making them feel welcomed. Webster laughs and makes friends easily; people consider her popular. But none of these things bridges the gap between herself and others.