27. Caffeine | The Wakefulness That Stays

In this episode of Mohivate, Dr Mohi Sarawgee explores caffeine beyond the morning habit, bringing clarity to the world’s most widely consumed psychoactive substance.

Caffeine is not just a pick-me-up. It is a molecule with a thousand-year history, a fascinating pharmacology, and a surprisingly complex relationship with your body.
This episode traces caffeine from its origins in the Ethiopian highlands, through the coffeehouses of the Ottoman Empire and the penny universities of Oxford, to the biology of what happens the moment it enters your bloodstream.

The conversation covers how caffeine works in the brain, why your genetics determine how long it stays in your system, and what that means for your heart, your sleep, and your health.
It explores the science behind energy drinks, the truth about decaf, the clinical reality of caffeine dependence, and emerging research linking caffeine to neurodegeneration.

Alongside the science, the episode draws on history, culture, and a little Sufi poetry to place caffeine in its full human context, and asks what it means to consume something so powerful, so unconsciously.

A grounded, science-based, and warmly delivered look at the molecule the world runs on, and what it is actually doing to you.

References: 

1. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction. JAMA. 2006;295(10):1135-1141.
https://jamanetwork.com/journals/jama/fullarticle/202502

2.Silverman K, Evans SM, Strain EC, Griffiths RR. Withdrawal Syndrome after the Double-Blind Cessation of Caffeine Consumption. New England Journal of Medicine. 1992;327(16):1109-1114.
https://www.nejm.org/doi/full/10.1056/NEJM199210153271601

3.Gardiner C, Weakley J, Burke LM, et al. The Effect of Caffeine on Subsequent Sleep: A Systematic Review and Meta-Analysis. Sleep Medicine Reviews. 2023;69:101764.
https://pubmed.ncbi.nlm.nih.gov/36870101/

4.Zhao Y, Lai Y, Konijnenberg H, et al. Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease. Neurology. 2024;102:e209201.
https://www.neurology.org/doi/10.1212/WNL.0000000000209201

5.StatPearls. Caffeine Withdrawal. National Library of Medicine. Updated 2025.
https://www.ncbi.nlm.nih.gov/books/NBK430790/
Comprehensive clinical reference on caffeine withdrawal including DSM-5 criteria, symptoms, and timeline.

Just a gentle reminder: this episode is for information, education, and inspiration only. It’s not a substitute for your doctor’s advice. For any personal health concerns, always seek guidance from your doctor.

Transcript

SPEAKER_00 0:04

Hi everyone, welcome back to Mohivate. I'm Dr. Mohi Saraugi, a GP by profession, but here I'm swapping prescriptions for perspective. Wherever you're in the world right now, there's a statistically high chance you're either holding a warm drink, have just finished one, or are about to go and get one. A cup of coffee, a cup of tea, maybe your first, maybe your third, or you've quietly stopped counting. Either way, congratulations, you've already agreed to consume the world's most widely used psychoactive substance. Not nicotine, not alcohol, caffeine. And before you feel smug about your matcha latte, that's caffeine too. Your builders tea, your chai. We've built entire economies, religions of productivity, and a billion dollar artisanal beverage industry around one molecule. And if you're listening to this at midnight or just before bed, I see you. This one's for you too. The cup you had at 3 p.m., it might still be very much with you. Today on Mohivade, let's talk about caffeine. Scientifically, honestly, with a little warmth. And I promise you, by the end of this, you may not stop your morning cup, but you will understand it differently. So let's begin. If you've been listening to this podcast, you know that before we talk molecules and mechanisms, we like to know where things come from because context is everything, and the backstory of caffeine is far too good to skip. Legend has it that the caffeine story begins in the highlands of Ethiopia in a region called Kafa, which many historians believe is the very origin of the word coffee itself. Somewhere around the 9th century, a goat herder named Kaldi noticed his goats were acting unusually energetic, dancing, jumping, refusing to sleep. They'd been eating bright red berries from a particular tree. Curious, he tried them himself and couldn't sleep. Just like that, humanity met caffeine. The goats were essentially the world's first documenteca consumers. Completely wired, possibly annoying. Carlie poured the berries to a nearby monastery. One monk threw them into a fire, declaring them the devil's work. Moments later, an extraordinary aroma filled the room. The monks gathered the roasted beans from the embers, poured hot water over them, drank, and discovered it kept them awake through evening prayers and meditation. Word spread. You may wonder, is this story true? Almost certainly it is apocryphal. But Ethiopia is, with historical confidence, the birthplace of Coffia Arabica, the coffee plant. Those bright red berries are called coffee cherries. The flowers of coffee arabica are white and highly fragrant. Their scent remarkably close to jasmine. From Ethiopia, the story crosses the Red Sea to Yemen to the Sufi mystics of the 15th century. The Sufis discovered that this dark, bitter brew kept them awake through their night prayers, their poetry and meditations. In candlelit courtyards under Arabian skies, it became a companion to devotion. They called it keva. Medieval Arab lexicographers traced its roots to an Arabic verb meaning to have no appetite, to be sustained without food. You'll hear echoes of it everywhere. In the Kashmiri, keva, in the Turkish, kawe. In your own word, coffee. One word, centuries of travel. The Sufis called it the wine of Islam, not because it contained alcohol, it didn't. But because in Sufi tradition, wine was never really about alcohol. Wine in Sufi poetry, and if you know Rumi, you know this is a metaphor for divine ecstasy, for losing yourself in something greater than yourself, for being so present, so awake, so alive that the ordinary world falls away. And here was a drink that did exactly that. From Yemen, it spread through Mecca, Cairo, Damascus, until it reached the coffee houses of the Ottoman Empire in Constantinople. These became some of the most remarkable spaces in human history, places of poetry, music, philosophy, and debate, called the Schools of the Wise. Some historians argue this helped lay the groundwork for the Age of Enlightenment. Finally, it reached Venice, the first European coffee house in the 1600s. Then England. In 1650, the first English coffee house opened at the Angel Inn in Oxford. It charged a penny for entry. That penny bought you a cup of coffee, a newspaper, and the right to sit among scholars, merchants, thinkers, and argue about anything you liked. They called these places penny universities. And in a detail almost too good to be true, Isaac Newton once dissected a dolphin on the table of the Grecian coffee house in London. Science apparently waited for no one. If you are ever in Oxford, the Grand Cafe at 84 High Street stands on that exact site, still serving coffee. Rumi wrote, The breeze at dawn has secrets to tell you. Don't go back to sleep. Perhaps he knew something about caffeine after all. It's almost certainly a legend, but it's a beautiful one, and it reminds us that humanity's relationship with caffeine didn't begin in a laboratory. It began with curiosity, a sleepless night, and some very energetic oats. So, what exactly is this thing we've been consuming for centuries? Caffeine, chemically known as 137 trimethyl xanthine, is a naturally occurring alkaloid found in plants. And here is the first thing that should make you pause. Plants don't make caffeine out of generosity, they make it as a pesticide to poison insects, to protect themselves. So, yes, you're actually drinking bug repellent. Humans evolve to find this delightful. Your brain produces a compound called adenosine. Adenosine is simply your body's tiredness signal. The longer you're awake, the more adenosine builds up in your brain. The more it builds up, the sleepier you feel. Caffeine works by doing something brilliantly sneaky. The moment your body receives caffeine, it blocks the adenosine receptors. The talking points where adenosine would normally land and tell your brain it's tired. Caffeine goes and sits in those seats instead. Meanwhile, adenosine is still building up, but your brain can't see the signal anymore. So you're not actually less tired, you just feel less tired. Once those receptors are blocked, two things get activated. Dopamine signaling increases, driving motivation and pleasure, and norepinephrine makes you feel alert, sharp, focused, possibly invincible. You're not invincible. Remember, the adenosine is still accumulating, and when the caffeine wears off, all that tiredness comes back at once. The crash is not a myth, it is pharmacokinetics. And this brings us to the half-life of caffeine. Half-life simply means the time it takes for your body to eliminate half of a substance from your bloodstream. Every drug has a half-life, and it is precisely why medications are prescribed once, twice or three times daily. Caffeine's plasma half-life in a healthy adult is roughly 5 to 6 hours. Let's make that real. A standard 8-ounce cup of brewed coffee contains around 150 milligrams of caffeine on average. So if you have a coffee at 3 p.m., by 9 p.m. 75 milligrams is still circulating in your bloodstream. By 3 a.m. you still have around 37 mg on board. Remember that 3 p.m. coffee we mentioned at the very start of this episode? This is why sleep is not the problem. You're just still caffeinated. And yet, every office in the world has a coffee machine that activates at 2.30 p.m. like a loaded weapon. We have built entire architectural infrastructure around a decision that neurologically undermines a third of human existence. Sleep researchers are not okay. They are just caffeinated. Most sleep scientists would say no caffeine after 2 pm. For some people, 12 noon. And it depends on your genetics, which is exactly where we are going next. Now, this is where it gets personal. Not everyone metabolizes caffeine the same way, and the reason comes down to one gene, CYP1A2. This gene codes for a liver enzyme responsible for breaking down approximately 95% of the caffeine you consume. If that felt a bit technical, here's the takeaway. Some people clear caffeine quickly and some don't. And that changes everything. Fast metabolizers clear caffeine quickly. They can have an espresso at 10 pm and sleep soundly. Slow metabolizers, and this is more than half the population, clear it sluggishly. Their caffeine lingers. For slow metabolizers, research shows that higher caffeine intake is associated with an increased risk of myocardial infarction, heart attack. Same molecule, same cup, completely opposite outcomes based entirely on one inherited gene. This is also why a colleague who drinks four coffees a day and sleeps like a baby is not superhuman. They are simply a fast metabolizer. That argument about coffee at brunch, pharmacogenomics, just settled it. CYP1A2 is also affected by things you may already be taking. Smoking speeds it up. Smokers metabolize caffeine roughly 50% faster than non-smokers, which is why many smokers feel they need more caffeine to feel the same effect. Certain medications slow it down, the antibiotic ciprofloxicin and the combined oral contraceptive pill, specifically the one containing ethanol estradiol, not the progesterone only mini pill. If you are on any of these and you notice that caffeine affects you more strongly than it should, now you know why. You may be walking around in a prolonged caffeinated state without even realizing it. Same cup, different pharmacological reality. A small but fascinating clinical detail. Adenosine, a medicine used in hospitals to treat certain fast heart rhythms, can be less effective if someone has had caffeine beforehand because caffeine blocks the very receptors adenosine is trying to act on. And if you are curious which metabolizer you are, dedicated caffeine metabolism DNA tests exist through companies such as Easy DNA, Affinity DNA, and 23andMe. In the US, formal CYP1A2 genotyping through a healthcare provider is available. That information is there if you want it. So we've talked about your genes, your liver, your sleep. Now let's go deeper because caffeine has a conversation with your heart too. And like most conversations about the heart, it's complicated. Acutely, right after you consume it, caffeine raises blood pressure, typically 3 to 4 mm of mercury systolic by stimulating your sympathetic nervous system, increasing the release of adrenaline and noradrenaline. Regular caffeine drinkers largely develop tolerance to this over time. The encouraging news large-scale meta-analysis involving hundreds of thousands of people suggest that moderate coffee consumption is associated with reduced risk of cardiovascular disease and type 2 diabetes. This is consistent, replicated, significant. But if you are a slow CYP1A2 metabolizer, which, as we discussed, is more than half the population, the cardioprotective effect may simply not be your story. Now everyone's favorite question: how much caffeine would actually kill me? The estimated lethal dose of caffeine in humans is approximately 150 to 200 mg per kilogram of body weight. For a 50 to 70 kilogram adult, that is roughly 7.5 to 14 grams of caffeine, somewhere between 50 and 90 cups of coffee in rapid succession. You would almost certainly encounter water intoxication, an extremely full bladder, or the quiet concern of a very attentive barista long before caffeine toxicity became a problem. However, and this is where it stops being lighthearted. Pure caffeine powder and highly concentrated liquid caffeine are a different story, a genuinely concerning one. The FDA has acted against these products because one teaspoon of pure caffeine powder equals roughly 28 cups of coffee. You may wonder who is taking pure caffeine powder. It is sold legally as a supplement, often marketed to athletes, gym goers, and students as a performance enhancer or energy booster. At high doses, caffeine can trigger serious cardiac arrhythmias, abnormal heart rhythms. This risk is significantly higher in individuals with underlying heart conditions they may not even know they have. This is why sudden cardiac events during intense exercise, while rare, do occur, and caffeine in high concentration can be a contributing factor in susceptible individuals. Dosing errors are easily made. There have been documenteds. Young, healthy individuals who believe they were taking a reasonable amount. This is the danger of taking a compound with a reasonable safety profile in its natural form, concentrating it to the point of lethality and marketing it as a performance enhancer. Regulation exists for a reason. The dose makes a poison. In your cup, perfectly reasonable. In a measuring spoon of pure powder or liquid, potentially lethal. Context matters. Speaking of performance enhancement, let's address energy drinks, specifically the ones marketed aggressively to university students during exam season. A standard 500 ml energy drink contains roughly 150 to 160 milligrams of caffeine comparable to a strong coffee. Fine. But they also contain taurine, B vitamins, and megadoses and sugars led under branding that implies consuming it will give you the cognitive abilities of a navy seal. The scientific evidence for taurine, meaningfully enhancing caffeine's effects in humans, is modest at best. What you're largely buying is caffeine, sugar, and the psychological effect of a logo that looks aerodynamic. The can is doing a lot of work. Libraries during finals week become de facto energy drink dispensaries. There is a specific subtype of academic, typically in their second year of a demanding program, who believes that consuming three energy drinks back to back will unlock some tier of cognition unavailable to the merely caffeinated. Excess caffeine causes anxiety, reduces fine motor control, and impairs the very working memory they are desperately trying to enhance. This is not studying. This is pharmacological self-sabotage with excellent marketing. Now let's compare sauces because caffeine content varies more than you might expect. A standard brewed coffee averages around 95 mg per 8 ounce cup, varying enormously by bean, roast, and brew method. Espresso around 63 mg per shot. Counterintuitively, lighter roasts have slightly more caffeine than dark because roasting degrades caffeine. Green tea 28 mg. Black tea 47 mg. Matcha around 70 milligrams. But with L-theanine, which softens caffeine's edges and is likely why tea drinkers describe a calmer, more focused alertness than coffee drinkers. Dark chocolate 12 mg per ounce. And that diet coke you're having because you're being good, 46 milligrams. Slightly more caffeine than regular coke, just with fewer calories and more optimism. Decaf coffee 2 to 15 milligrams, not zero. Decaffeinated means reduced, not absent. You're welcome. And your mocha, named after Mocha, a small port city on the Red Sea coast of Yemen, which for over 150 years was the only place in the world exporting coffee. The Ottomans even boiled the beans before export so nobody could grow their own. A very effective monopoly. When Europeans finally tasted that dark, slightly chocolatey Yemeni brew and couldn't recreate the flavor, they added chocolate to their own beans. That is where your mocha latte comes from. Not a flavor syrup, history. And now the good news. Long-term data on regular coffee consumption is associated with a reduced risk of Parkinson's disease. One of the most consistently replicated findings in this, as well as type 2 diabetes, liver cirrhosis, and certain liver cancers. The hepatoprotective effects are particularly well documented. It is worth noting that acutely, caffeine can temporarily reduce insulin sensitivity. So if you are managing blood sugar, timing your coffee aftermeans rather than before may be worth considering. Interestingly, some of these benefits appear in decaf drinkers too, suggesting it is not caffeine alone doing the work, but the polyphenols and chlorogenic acids present in coffee itself. The whole cup taken in moderation may be the medicine. Caffeine is also genuinely a medicine. Caffeine citrate is FDA approved for apnea of prematurity in newborn babies. It enhances the effect of paracetamol and NSHs by around 40%, which is why it appears in many headache tablets. The same molecule in your morning cup is a legitimate pharmaceutical. The line between drug and beverage in this case is mostly aesthetic. Caffeine and athletic performance briefly. Caffeine is one of the most evidence-backed ergogenic aids in sports science. It improves endurance, reduces perceived exertion, enhances neuromuscular function, and improves reaction time. The World Anti-Doping Agency removed caffeine from its prohibited list in 2004, though it remains on the watch list. Elite athletes use it strategically, timing intake to peak plasma levels at competition, sometimes abstaining beforehand to enhance the acute effect. Caffeine and anxiety and underappreciated connection. Caffeine exacerbates anxiety disorders. It activates the sympathetic nervous system, raises cortisol, adrenaline, and increases heart rate, which in individuals prone to panic disorder can trigger a panic attack. Caffeine's pharmacological signature is remarkably similar to the somatic experiences of anxiety itself. Fast heart rate, heightened alertness, slight tremor. In a calm person, this reads as awake. In someone with underlying anxiety, particularly undiagnosed, it reads as something is wrong. Clinicians evaluating anxiety, arrhythmias, and insomnia always take a thorough caffeine history. You would be surprised how often the answer is not a diagnosis. It is for Americanos before noon. Pregnancy and caffeine. The guidance is clear. Current consensus from major obstetric bodies recommends limiting caffeine to under 200 mg per day during pregnancy. Caffeine crosses the placenta freely. The fetal liver lacks mature CYP1A2 expression, meaning the fetus cannot metabolize caffeine effectively. Accumulated caffeine may affect fetal heart rate and development. The precautionary principle applies strongly here. This is one of those areas where probably fine is simply not good enough. Caffeine and sleep. Beyond delaying sleep onset, caffeine suppresses slow wave sleep. The deep restorative stage, critical for memory consolidation, metabolic regulation, and immune function. You may fall asleep after a late coffee, but the quality of that sleep is measurably degraded. Reduced slow wave sleep impairs next day's cognitive performance, which may compensate for with more caffeine, which further degrades the following night's sleep. This is the caffeine sleep spiral. Millions live inside it without realizing the loop is self-generated. Caffeine also stimulates gastric acid secretion, which is why coffee on an empty stomach causes discomfort in many people. It also stimulates colonic motility, which is why roughly a third of people experience a strong urge for a bowel movement within minutes of their morning coffee. Decaf produces the same effect in many people, implicating other compounds in coffee entirely. The morning coffee ritual for a meaningful portion of humanity is also a bowel preparation protocol. Medicine is humbling in the most specific ways. One last clinical truth: caffeine produces physical dependence, recognized in the DSM 5. Caffeine withdrawal is a documented clinical entity. Headache, fatigue, irritability, difficulty concentrating, and low mood. Onset occurs within 12 to 24 hours of stopping, peaking around 20 to 51 hours and lasting up to 9 days. The headache occurs because adenosine receptors previously blocked are suddenly flooded and caffeine-induced vasoconstriction reverses, causing blood vessels in the brain to dilate. That is a real physiological pounding headache. This is why I'll quit caffeine this weekend is an optimistic fiction. If you want to reduce your intake, do it gradually. Emerging research worth watching, caffeine and neurodegeneration. Beyond Parkinson's, there's growing interest in caffeine's potential role in Alzheimer's prevention. Proposed mechanisms include adenosine receptor antagonism, reducing neuroinflammation, and a possible role in reducing accumulation of amyloid beta protein. The world's most consumed psychoactive substance may also have neuroprotective properties. Science continues to be stranger and kinder than expected. And yet for something we experience so simply, we've built an entire ritual around caffeine. Exposed bricks, ambient playlists, oat milk steam to precisely 65 degrees Celsius. And that ritual matters. Research shows the anticipation of caffeine, the smell, the warmth, the cup in hand produces measurable physiological changes before the caffeine is even absorbed. The barista who knows your order is in a very real sense practicing a form of medicine. They are absolutely not paid enough. So here we are, one molecule, a naturally occurring pesticide that humanity decided to build civilizations around. It blocks adenosine, moves through your liver at a speed your genes determine, raises your blood pressure transiently, fuels athletes, scholars, night shift workers, new parents, students, and quite possibly the age of enlightenment. And every morning it finds its way into your cup. Caffeine has been humanity's companion for over a thousand years. Treat it like one with warmth, with awareness, and with the occasional day off. And if you're listening to this at midnight with something warm in your hands, just maybe make the next one chamomile. I hope something today stirred a thought, gave you a smile, or simply made you pause. Thank you for listening. I am Dr. Mohi. Until next time, remember this like all good things, caffeine is best savored, not surrendered to that awareness of what moves through you, what serves you, what doesn't. That in itself is coming home to yourself.