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StarTalk Radio

What Loneliness Does To Your Brain with Ben Rein

with Ben Rein

Published October 31, 2025
View Show Notes

About This Episode

Neil deGrasse Tyson, Gary O'Reilly, and Chuck interview neuroscientist Ben Rein about what loneliness and social isolation do to the brain and body. They distinguish between objective isolation and the subjective feeling of loneliness, explain the stress and inflammatory pathways involved, and discuss how personality, aging, technology, and drugs like alcohol, painkillers, and MDMA affect social behavior and health. Rein also shares research on empathy, dogs and oxytocin, and practical ideas for rebuilding social connection in an increasingly automated world.

Topics Covered

Loneliness Social isolation Social bonding Mental health Brain health Dopamine Serotonin Oxytocin Emotional empathy and cognitive empathy Psychedelics Aging

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Quick Takeaways

  • Loneliness (a felt lack of social connection) is distinct from isolation (physically being alone), and each has its own biological signature in the brain.
  • Social isolation activates the body's stress systems, elevating cortisol and chronic inflammation, which in turn increase risks for stroke, dementia, heart disease, diabetes, and early death.
  • Humans are wired to find social interaction rewarding via oxytocin, serotonin, and dopamine, while prolonged isolation gradually blunts these reward responses and can make reconnecting harder.
  • Extroverts tend to live more socially rich and often healthier lives, but introverts still benefit from social contact; they simply reach their "enough" point earlier and need smaller, better-tailored doses of interaction.
  • Virtual interactions (video, phone, text) strip away social cues, engage the social brain less, and are less mood-boosting than in-person contact, though still better than total isolation.
  • Empathy is strongest for people we see as part of our in‑group, and propaganda plus online dehumanization can weaken empathy for out‑groups, making hostility and even war more psychologically feasible.
  • Common drugs subtly reshape social behavior: over‑the‑counter painkillers can blunt empathy for others' pain, alcohol reduces social anxiety but also impairs reading of negative cues, and MDMA strongly enhances sociability and empathy but is too toxic for everyday use.
  • Dogs and close relationships can literally act like "medicine" by stimulating oxytocin and other protective systems, while marriage and social ties measurably improve survival in certain diseases and in old age.
  • Modern life's "automation of everything" has quietly removed countless daily micro‑interactions, contributing to today's loneliness epidemic.
  • We systematically underestimate how much others like us and overestimate the risk of rejection, which leads us to avoid social opportunities that would almost certainly make us feel better.

Podcast Notes

Episode setup and guest introduction

Framing the loneliness epidemic

Hosts describe reports of a loneliness epidemic affecting people across age, gender, and socioeconomic lines[2:42]
Core questions: what does loneliness do to the brain, are brains equipped for modern social isolation, and does loneliness affect physical health[2:59]
They flag drugs like MDMA as potential tools to modulate social experience, which leads into the neuroscience discussion[3:12]

Introducing neuroscientist Ben Rein

Ben is welcomed back to StarTalk, this time in person rather than virtually[3:48]
His roles: neuroscientist, Chief Science Officer of the Mind Science Foundation, clinical assistant professor at SUNY Buffalo, adjunct lecturer at Stanford University[4:03]
Neil notes that Ben recently authored a book titled "Why Brains Need Friends: The Neuroscience of Social Connection"[4:40]

Defining loneliness vs isolation and basic brain mechanisms

Distinguishing loneliness from isolation

Ben clarifies that isolation is the objective state of being by yourself[5:32]
Loneliness is the subjective feeling that your social needs are not being met[5:44]
You can be alone but not lonely (e.g., decompressing after an intense family vacation)[5:57]
You can be lonely in a crowd (e.g., at a concert with 20,000 people yet not interacting with anyone)[6:13]
• Seeing others enjoying themselves with friends or loved ones can intensify one's own sense of loneliness in the same setting

Apollo astronaut example: isolated vs lonely

Neil recounts the common claim that the command module pilot orbiting the Moon alone was "the loneliest person"[7:07]
He walks through the scenario of two astronauts on the lunar surface and one in orbit, with the orbiter at times one lunar diameter away from both Earth and crewmates[7:12]
Ben notes the better term is "most isolated" rather than "most lonely" because the person may not feel lonely[8:05]
They joke about how someone in that position might be relieved to finally have time alone after three days of close quarters[8:13]

Isolation as a form of stress

Ben states that being isolated or lonely is a form of stress for humans because we are social animals[8:36]
When separated from our group, the body's stress system (HPA axis) is activated and cortisol levels rise[8:54]
Cortisol is released via the pituitary component of the HPA axis and floods into the blood during stress[9:02]
Humans survive best in groups, so isolation triggers a brain "threat" signal implying risk of being picked off from the tribe[9:16]

Comparison with solitary animals like tigers

Ben contrasts humans with solitary species such as tigers, which typically do not live in groups[9:29]
In humans, isolation raises cortisol and stress; in tigers, being around other tigers elevates cortisol[10:01]
• Tigers experience other tigers as competitors for food and resources, so proximity is the stressful condition for them
Humans and tigers are chemically wired according to their evolutionary survival strategies (group vs solitary)[10:23]

Social reward chemistry: why being with others feels good

Ben identifies oxytocin, serotonin, and dopamine as three key neurotransmitters involved in social reward[11:31]
Social reward is reinforcing; it makes social interaction feel pleasant so that we are motivated to seek it again[11:33]
• He compares social reward to eating a delicious, nutritious meal that stimulates dopamine release, signaling "do this again"
Being around others both reduces stress and activates reward pathways, whereas being alone is treated as a threat state[11:18]
Neil asks why the absence of this pleasurable chemistry is harmful rather than simply neutral[12:33]
Ben explains that the negative state of isolation (stress response) is distinct from merely missing out on positive reward; the brain encodes them separately[13:16]

Onset and detection of loneliness

Gary asks how long isolation must last before cortisol and stress responses become problematic[13:13]
Ben says it likely happens around the point when a person begins to feel that something is wrong and that the isolation is a problem[13:28]
He argues humans are generally bad at noticing when they are lonely but good at noticing when they are socially "satiated"[13:32]
• People tend to attribute feeling bad to work stress, poor sleep, etc., rather than recognizing lack of social contact as a cause
Over time, more isolation is associated with increased depression, anxiety, and various physical health problems[14:22]

Health impacts of chronic isolation and inflammation

Chronic stress, cortisol, and inflammation

Ben explains that in acute stress, cortisol has anti-inflammatory properties and helps reduce inflammation temporarily[18:35]
With chronic elevation of cortisol, tissues become desensitized to it and its anti-inflammatory effects diminish[18:57]
He notes that this desensitization is analogous in some ways to addiction, where the same dose yields less response over time[18:50]
Loss of cortisol's anti-inflammatory action promotes chronic inflammation throughout the body[19:27]

Mouse stroke study linking isolation and worse outcomes

Ben cites stroke research by Luis McCullough at the University of Houston using controlled artery occlusion in mice to induce strokes[20:19]
Despite identical, precisely timed reductions in blood flow, some mice showed much larger brain damage from the stroke[20:29]
Researchers discovered that the mice with worse strokes were singly housed (living alone) while others had cage mates[20:23]
Hypothesis: chronic isolation had increased inflammation and reduced neuronal resilience to ischemic insult[20:33]
When they pharmacologically blocked inflammatory markers in isolated mice, the stroke damage shrank to expected levels[20:57]
• This suggests that isolation-driven inflammation directly worsened brain injury outcomes after stroke

Personality, extroversion/introversion, and aging

Extroversion, health, and happiness

Neil brings up extrovert vs introvert labels and asks whether extroverts live longer and happier with less disease[22:07]
Ben notes studies showing extroverts tend to be happier in general[22:19]
He raises the chicken‑and‑egg question: are people extroverted because they are happy or happier because they behave more extrovertedly[22:22]
When people already high in extroversion are asked to act more extroverted, their mood improves further, suggesting behavior has causal effects[22:30]
However, prescribing heavy socializing to introverts could be counterproductive and stressful for them[23:05]

Super-agers and extroversion

Ben describes research on "super-agers" whose brains at age 80+ resemble typical 60‑year‑old brains in thickness and function[23:19]
The unifying trait across these super-agers was high extroversion and very social lifestyles[23:26]
Brain imaging showed lower inflammation and thicker key brain areas in super-agers, consistent with the idea that socializing is "exercise" for the brain[23:44]

Social battery and trait extroversion scale

Ben explains trait extroversion as a relatively stable personality dimension rather than something that flips hour to hour[23:26]
More extroverted individuals have larger "social batteries"-they gain more energy from interaction and tolerate more before feeling drained[25:12]
Introverts also benefit from social contact but their threshold for fatigue is lower; prolonged forced extroversion can leave them miserable[24:49]
Ben includes a 20‑item trait extroversion questionnaire in his book (derived from the Big Five personality test) to help people locate themselves on the scale[26:19]
• Sample items include making friends easily, warming up quickly to others, taking charge, being enthusiastic, and not holding back opinions

Context-specific extroversion ("on/off" behavior)

Chuck and Gary describe people who are quiet in general but become extremely outgoing in specific, safe contexts (e.g., with close friends or on the field)[27:44]
Ben suggests this shows how comfort and identity in particular settings shape how much of one's extroverted potential is expressed[28:18]
He recommends reflecting on which social situations feel energizing vs depleting to better "curate" one's social diet[30:38]
• He calls this practice "social journaling": jotting notes after interactions about context, feelings, and outcomes to identify patterns

Quality of interactions: in-person vs virtual and social media

Why in-person interaction is uniquely rich

Ben emphasizes that humans evolved for in-person social cues: facial expressions, vocal tone, body language, and even smell[31:38]
Neil reports that video calls during COVID felt less and less like real interaction to him; he missed smells, full body language, and subtle mood reading[32:52]
Ben notes that each technological medium strips away cues: video preserves some, phone preserves only voice, text preserves only words[34:00]
The less lifelike the medium, the less information the brain has to tag the interaction as truly social[33:35]

Mood benefits of virtual vs in-person contact

Existing data show people feel less good after online interactions than after in-person ones[34:52]
However, even less lifelike online interaction is still better for mood than no interaction at all[35:06]

Virtual Disengagement Hypothesis and online hostility

Ben describes a paper he co-authored proposing the "Virtual Disengagement Hypothesis"[42:19]
Hypothesis: when online, absent rich social cues, empathy-related brain regions may not fully activate, allowing more hostile behavior[42:38]
He connects this to widespread experience of harassment and unfiltered aggression on social media that would likely not occur face-to-face[43:08]
He notes the older research field of "computer-mediated communication" found that people behave more unfiltered and hostile when interacting via computers[43:05]

Likability, empathy, and in-group vs out-group

Psychology of being likable

Ben summarizes a study where participants interacted with an actress instructed to be either very likable or very unlikable[33:14]
• In the likable condition she made eye contact, listened attentively, was polite, and supportive
• In the unlikable condition she avoided eye contact, picked controversial topics and argued opposite views, faked phone interruptions, and ignored the participant
The study illustrates concrete behaviors that strongly influence perceived likability[35:30]

Brain regions for empathy and social evaluation

Ben notes that regions in the prefrontal cortex are heavily involved in determining how much we like someone and processing others' emotions[35:19]
He clarifies that the prefrontal cortex is the front-most part of the frontal cortex, a region especially expanded in humans[35:22]

Goldilocks zone of empathy

Ben compares empathy to a Goldilocks zone: too much would make others' pain unbearable to witness, too little makes us indifferent[39:05]
If someone fully felt another person's broken finger sensation, they would be overwhelmed and less able to help effectively[39:29]
With zero empathy, one would see a broken finger and feel no concern or motivation to help, which is characteristic of psychopathy at the extreme[39:29]

In-groups, out-groups, and war

Ben introduces the idea of self-other overlap using a Venn diagram: more overlap means more empathy[39:55]
Brain studies show empathy-related regions activate more for people we perceive as in-group members (same race, religion, politics, etc.)[40:45]
For out-group members, those empathy activations are weaker, making their suffering easier to tolerate or ignore[40:53]
Neil and Ben discuss how propaganda widens the separation in the Venn diagram, dehumanizing the enemy and making war psychologically easier[41:08]
Ben points out that similar dehumanizing dynamics may occur in online interactions where social cues are missing[42:38]

Drugs and the social brain: painkillers, alcohol, and MDMA

Over-the-counter painkillers and social pain

Ben says research shows common painkillers like acetaminophen not only reduce physical pain but also reduce empathy for others' pain[44:29]
Under the influence of acetaminophen, people feel less distress when seeing someone socially excluded or hurt[45:06]
These drugs also blunt social pain; insults or exclusion hurt less emotionally when acetaminophen is in the system[45:02]

Alcohol's effects on anxiety and inhibition

Ben argues alcohol is not a positive social drug overall, despite its short-term pleasant effects[49:48]
He cites a study where each standard drink reduced social anxiety by about 4%[49:57]
Alcohol enhances the brain's ability to turn neuronal activity down, including activity in the amygdala (involved in fear and emotion)[50:08]
Reduced prefrontal cortex activity impairs behavioral inhibition, making people more likely to act on impulses (kissing, fighting, saying inappropriate things)[50:46]
Alcohol also dampens sensitivity to others' negative social cues (e.g., rejection faces), making misreading of situations more likely[51:19]

MDMA ("ecstasy") as an empathogen

Ben spells out MDMA's chemical name: 3,4‑methylenedioxymethamphetamine, noting its similarity to methamphetamine[52:11]
Unlike alcohol, MDMA robustly increases sociability and empathy; it is classified as an "empathogen"[52:43]
His research at Stanford in mice linked the empathogenic effect specifically to serotonin release in the nucleus accumbens[53:09]
• In mouse experiments, MDMA-treated mice spent much more time near another mouse than near an object, and even more time when both mice had MDMA
MDMA drives release of serotonin, dopamine, and norepinephrine, the same systems involved in natural social reward[53:17]
Repeated MDMA use can disrupt serotonin-producing neurons; it is too toxic for daily prescription use[54:21]
He recounts a famous study that mistakenly reported MDMA put holes in primate brains; it was later revealed the drug administered had actually been mislabeled methamphetamine[54:36]
Ben imagines a future, more targeted drug that would selectively boost serotonin release in the nucleus accumbens to increase empathy without MDMA's broad side effects[55:27]
He notes a philosophical question: should society rely on pharmacology to repair loneliness, or focus on behavioral and social solutions[54:57]

Oxytocin, pets, aging, and mortality risk

Oxytocin as "nature's medicine"

Ben describes oxytocin not only as a social bonding hormone but also as having anti-inflammatory and neuroprotective properties[56:59]
Researchers have called oxytocin "nature's medicine" because it supports immune function, bone growth, and general health[56:49]
He explains that during child-rearing and romantic bonding, high oxytocin ensures the caregiver or partner remains healthy enough to protect and reproduce[57:14]

Dogs as social support

Ben notes that looking into a dog's eyes triggers oxytocin release in both human and dog, unlike with wolves[57:14]
Dogs have co-evolved with humans over tens of thousands of years and taken on many social signaling roles[58:03]
For lonely people, dogs can partly substitute for lost social contact by engaging the same oxytocin pathways[58:11]

Marriage, illness survival, and aging

Ben cites studies where socially isolated people have a roughly 50% higher risk of death from any cause over about a decade[59:06]
Other studies report around 30% higher mortality risk from isolation, reinforcing the effect size across different samples[58:58]
Among people over 65, social isolation is linked to a 78% higher risk of death in men and 57% higher in women[1:01:08]
Isolated seniors show memory decline about twice as fast and are more prone to dementia[1:00:44]
Ben notes that in some cancers (including colorectal), being married substantially improves survival; in colorectal cancer, married patients are 28% more likely to survive[1:00:54]
• In some cancers, marriage can be a stronger predictor of survival than chemotherapy, partly because spouses encourage adherence to treatment
They discuss how even unhappy marriages still mean you are not lonely, though the emotional experience may be quite negative[1:01:56]

Old-young social contact in mice

Ben describes a mouse study where old mice interacted with adult younger mice for 15 minutes a day[1:02:37]
Those old mice lived about 33% longer than old mice without that brief daily social interaction[1:03:09]
He suggests that a similar dynamic might apply when older humans regularly spend time with younger, more energetic people[1:03:31]

Modern causes of loneliness and strategies to reconnect

Automation of everyday life and loss of micro-interactions

Ben blames much of modern loneliness on the "automation of everything"-the ability to do nearly all tasks without human contact[1:01:30]
• Examples include withdrawing cash at ATMs instead of bank tellers, grocery delivery instead of in-store shopping, Zillow tours instead of in-person visits, and telemedicine instead of office visits
He argues these conveniences quietly removed countless daily micro-interactions from our lives without us fully noticing[1:01:50]
COVID amplified this shift, normalizing virtual replacements for many in-person contacts[1:02:07]

Loneliness as a self-perpetuating brain state

Ben explains that chronic loneliness changes how the brain processes social information[48:36]
Lonely individuals show reduced social reward from interactions (lower oxytocin responses) and often have more difficulty with trust[50:01]
As a result, early attempts to re-engage socially may feel bad or unrewarding, reinforcing withdrawal and continuing the cycle[49:51]

Finding community and tailoring social life

Chuck suggests that the first practical step is to find a small community built around something you like and show up consistently[1:01:36]
Ben agrees and stresses the value of commonality (hobbies, interests, beliefs) because the brain favors those perceived as similar[1:02:19]
Shared identity helps mute other potential divisions (like politics or background) that might otherwise block connection[1:00:35]

Widespread social miscalibrations and fear of rejection

Ben notes robust evidence that people systematically misjudge social situations in pessimistic ways[1:02:14]
• We overestimate how likely others are to reject an attempt at conversation, even though actual rejection is rare
• We expect compliments to feel awkward, but recipients generally appreciate them
• We expect conversations to get worse the longer they go, but that usually does not happen
• After interactions, we underestimate how much others liked us; we are typically better liked than we think
He characterizes the human brain as "kind of sucks at socializing" in its predictive models, which stops people from engaging when they would benefit[1:02:22]
He frames social anxiety and fear of rejection as natural, evolutionarily grounded, but often overactive in modern contexts[1:02:47]
His prescriptive takeaway: don't put too much faith in those anxious forecasts; go to the event anyway, because you'll almost always feel better afterward than you predicted[1:02:23]

Closing notes: book, family, and final encouragement

Communicating science accessibly

Ben says his book opens with a "no big words" clause, promising to avoid unnecessary jargon so anyone can understand the neuroscience[1:03:17]
Neil praises avoiding over-technical language, contrasting it with long anatomical terms common in neuroscience[1:03:56]

Ben's personal milestones

Ben mentions that his first child and his first book are arriving about two weeks apart[1:02:56]
The hosts joke that the book may help pay rent while the child will consume resources, highlighting the different "cost profiles" of his two new "babies"[1:03:51]

Final message

Neil and the co-hosts thank Ben and underscore the importance of social connection for health and well-being[1:03:09]
Neil ends with his customary sign-off, encouraging listeners to "keep looking up"[1:04:04]

Lessons Learned

Actionable insights and wisdom you can apply to your business, career, and personal life.

1

Loneliness (a felt lack of connection) and isolation (physically being alone) are distinct states that trigger different brain responses, and both need to be recognized if you want to manage your social and emotional health effectively.

Reflection Questions:

  • • When do I feel most alone even if I'm technically around other people, and what does that reveal about my unmet social needs?
  • • How could I track my week to notice the difference between times I'm simply alone and times I genuinely feel lonely?
  • • What is one small change I could make in my routine to reduce either my objective isolation or my subjective sense of loneliness this month?
2

Chronic isolation is a biological stressor: it keeps cortisol and inflammation elevated, quietly damaging brain and body over time, so investing in social connection is as much a health behavior as sleep or diet.

Reflection Questions:

  • • How much priority do I currently give social connection compared to sleep, nutrition, or exercise in my health habits?
  • • In what ways might long periods of isolation or high stress have already been affecting my mood, focus, or physical health?
  • • What is one recurring opportunity each week (a class, club, walk with a friend) I could schedule as deliberately as a workout to protect my long-term health?
3

Your level of trait extroversion determines how much and what kind of social contact will energize you, so you need to design a "social diet" that fits your temperament rather than copying someone else's.

Reflection Questions:

  • • Do I generally feel more charged up or drained after group events, and how might that reflect my place on the introvert-extrovert spectrum?
  • • How could I experiment with different types and lengths of social activities (small groups, one-on-one, shorter events) to discover what feels best for me?
  • • What is one concrete boundary or habit I could set this week (for example, limiting large events or scheduling recovery time) to better match my social life to my natural "battery"?
4

Because online interactions strip away key social cues, they tend to weaken empathy and increase misinterpretation and hostility, so important or emotionally charged communication is usually better handled in richer, more human channels.

Reflection Questions:

  • • Which kinds of conversations in my life routinely happen by text or social media that might actually deserve a phone call or in-person meeting?
  • • How has my own tone or empathy shifted when I communicate online versus face-to-face, and what problems has that created?
  • • What specific conversation that matters to me right now could I deliberately move from a low-cue medium (text, comments) to a higher-cue one (video, call, in-person) this week?
5

Common substances like painkillers and alcohol subtly change how you perceive and respond to others' emotions, so being aware of their social and empathic effects is crucial when you're making decisions about relationships, conflict, or care for others.

Reflection Questions:

  • • When I think back on my most regretted social interactions, were any of them influenced by alcohol or other substances blunting my judgment or empathy?
  • • How might knowing that painkillers and alcohol can reduce sensitivity to others' pain change the way I approach social situations when I'm using them?
  • • What boundaries or rules of thumb could I set (for example, no serious talks when drinking, or extra reflection when medicated) to protect my relationships?
6

Your brain is systematically pessimistic about social situations-it overestimates rejection and underestimates how much others like you-so you often need to override your internal forecast and say yes to connection anyway.

Reflection Questions:

  • • In what kinds of situations do I routinely talk myself out of reaching out, joining, or speaking up because I assume others won't respond well?
  • • How might my life look different in a year if I acted based on actual outcomes of past social efforts rather than on my fearful expectations?
  • • What is one upcoming invitation, message, or introduction I can intentionally accept or initiate, even if my first instinct is to avoid it?

Episode Summary - Notes by Kai

What Loneliness Does To Your Brain with Ben Rein
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