My father often jokes that hundreds of years from now, future anthropologists will speak of the cult of the Seattle goddess, her shrine adorning every airport, shopping mall, and train station in America.  The worshippers partake in a holy communion of coffee, tea, and espresso.  In fact, anthropologists today tell us that in some indigenous American cultures, drinking psychoactive peyote tea is an important part of religious ceremony.  And yet, the very phrase psychoactive tea is somewhat redundant.  All tea and coffee, unless decaffeinated, is psychoactive, albeit usually not to the same extent as peyote, a cactus native to the American Southwest that contains a hallucinogenic alkaloid called mescaline.

Like mescaline, caffeine is also a psychoactive alkaloid, a bitter tasting organic base containing nitrogen atoms.  Many plants produce alkaloids like caffeine and mescaline to poison insects and small animals that feast on them.  Unlike mescaline, caffeine won’t make you hallucinate — unless you consume it in obscenely large quantities.  We all know the usual effects of caffeine: increased alertness, reduced fatigue, trembling hands, mild anxiety, and, of course, a constant urge to pee.  Caffeine withdrawal, characterized by splitting headaches, fatigue, and difficulty focusing, is recognized as a mental disorder in the fifth edition of the Diagnostics and Statistics Manual, the bible of psychiatry.  In fact, caffeine is the most widely consumed psychoactive drug in the world. Whether that use constitutes abuse is up to you to decide.

Caffeine is a cunning impostor that fools and manipulates adenosine receptors in your brain.  You’re probably familiar with adenosine as one of the four nucleosides that make up the genetic code of DNA, or as the substrate for ATP (adenosine triphosphate), the energy currency of cells.  What you may not know is that this multipurpose molecule also serves as a neurotransmitterChemicals that cross some synapses and carry a signal to the... More and a regulator of vasodilation, or widening of arteries and veins.  During the course of a day, adenosine slowly accumulates postsynaptically, activating receptors that promote sleepiness.  Like a mischievous kid stuffing Play-Doh in a keyhole, caffeine binds to adenosine receptors without actually activating them, giving adenosine no means to promote normal sleepiness.  In short, caffeine is just similar enough to adenosine to bind to its receptors, but not similar to enough to actually stimulate them.  This results in the overwhelming feeling of alert, confident energy experienced by coffee aficionados.

Myth or Fact? The mechanism by which caffeine keeps humans awake is a mystery

Who amongst us hasn’t gratefully tasted the black gold of a much needed espresso, relishing the sweet bliss of an afternoon pick-me-up?  In our high energy culture of 24/7 stimulation, the allure of caffeine’s legal high is undeniable.  And yet, go deep enough down the rabbit hole, and you might wake up one morning with a throbbing headache.  Because adenosine regulates vasodilation, blocking its receptors will result in the constriction of blood vessels.  Once this effect wears off, the rush of blood into newly dilated vessels is often painful.  Furthermore, neurons add more adenosine receptors to the synapseConnections between neurons where a signal is passed from on... More to compensate for the caffeine blockade, leading to daytime sleepiness and needing more caffeine.  In fact, at least one study in mice suggests that frequent caffeine usage also changes the density of many other neurotransmitter receptors, including epinephrine, GABAGamma aminobutryic acid, the principal inhibitory neurotrans... More, acetylcholine, and serotoninA monoamine neurotransmitter with a variety of functions.!

Western culture often promotes the view that sleep is inconvenient at best, slothful at worst.  Whether you’re a professional overachiever or a weekend warrior living by the motto “I’ll sleep when I’m dead,” it’s easy to get caught in a vicious cycle of needing more and more caffeine to stave off the sandman.  Yet sleep is critically important in memory formation, and new evidence suggests it may even detox the brain.  In fact, a study by Xie and colleagues showed that the activity in the glymphatic system, akin to the brain’s “clearance pathway,” is boosted during sleep to promote movement of cerebrospinal fluid (CSF), which bathes the brain and spinal cord.  Through glymphatic system clearance, neurotoxins including beta-amyloid, a protein commonly implicated in Alzheimer’s diseaseA neurodegenerative disease characterized by neuronal loss i... More, can be emptied from the brain.  Xie and colleagues tested this idea in mice and found that sleeping mice cleared beta-amyloid faster than mice that were awake.

Whether you’re a college student ingesting more coffee than food to stay awake studying or a young professional with an imminent deadline, the temptation to use caffeine at inappropriate times and in dangerous amounts can be detrimental to your health.  Anecdotally, nearly all of us are likely familiar with the consequences of sleep deprivation — difficulty focusing, impaired memory and fatigue — but what happens when this sleep deprivation becomes habitual and not just a one-time ordeal?  Although we may become accustomed to the symptoms of sleep deprivation and dismiss them as a part of life, consistent sleep deprivation can wreak havoc on your health and nervous system.  Long-term sleep deprivation has been linked to developing depression and other mood disorders and an increased risk of obesity, among other health consequences.

So why exactly is your afternoon cup of coffee so dangerous when you won’t go to sleep until hours later?  Some estimates indicate that 80% of plasma caffeine levels are present in the brain, and the half-life of caffeine is 3-7 hours, meaning that caffeine levels in your blood only drop by fifty percent every several hours.  Given caffeine’s well-defined role in maintaining alertness and its propensity to linger in the brain, it is no surprise that a cup of coffee in the morning is so tempting.  In the right amount and at the right time, coffee can be a pleasant and productive part of your morning routine.  Just be careful when lured for an afternoon cup ‘o joe!

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Written by Joel Frohlich and Jenn Tribble

Images by Cari Ritzenthaler and Jooyeun Lee

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References:

Shi, Dan, et al. “Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain.” Cellular and molecular neurobiology 13.3 (1993): 247-261.

Alvarez, Gonzalo G, and Ayas, Najib T. “The Impact of Daily Sleep Duration on Health: A Review of the Literature.” Progress in Cardiovascular Nursing, 2004.

Owens, Judith. “Insufficient Sleep in Adolescents and Young Adults: An Update on Causes and Consequences.” Pediatrics, 2014.

Xie et al “Sleep initiated fluid flux drives metabolite clearance from the adult brain.” Science, October 18, 2013. DOI: 10.1126/science.1241224

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Joel Frohlich

Joel Frohlich graduated from the College of William and Mary in 2012 with a BS in neuroscience. He is currently working towards his PhD in the lab of Shafali Jeste at UCLA, examining EEGElectroencephalogram, a technique that places electrodes on ... More biomarkers of neurodevelopmental disorders. His recent research has focused specifically on autism and duplication 15q11.2-13.1 (Dup15q) syndrome. He is also a student intern at F. Hoffmann-La Roche in Basel, Switzerland and an expert blogger for Psychology Today. When he is not engaged in neuroscience, Joel's other hobbies include exploring national parks and reading about other fields of science such as astronomy and space exploration.
Profile photo of Joel Frohlich

Joel Frohlich

View posts by Joel Frohlich
Joel Frohlich graduated from the College of William and Mary in 2012 with a BS in neuroscience. He is currently working towards his PhD in the lab of Shafali Jeste at UCLA, examining EEG biomarkers of neurodevelopmental disorders. His recent research has focused specifically on autism and duplication 15q11.2-13.1 (Dup15q) syndrome. He is also a student intern at F. Hoffmann-La Roche in Basel, Switzerland and an expert blogger for Psychology Today. When he is not engaged in neuroscience, Joel's other hobbies include exploring national parks and reading about other fields of science such as astronomy and space exploration.

2 Comments

  1. Fascinating post, given the worldwide use of coffee. I’ve sustained for years that drinking it is an addiction (and that I live in a country of addicts in denial 🙂 ). I only have a cup when I have to give myself an extra boost for a specially demanding meeting. Precisely because I’m not a habitual “user” the boost I get is that of a very strong drug ….

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