← Coffee and Your Brain

Teacher guide

Middle school, high school and college

Coffee makes people feel awake, yet caffeine gives the body no energy. Students watch Raven’s video, then work out how caffeine blocks adenosine’s tired signal and what that means for sleep.

Hot coffee being poured into a mug, seen from above

At a glance

Middle school
Grades 6 to 8 · About 25 minutes
High school
Grades 9 to 12 · About 40 minutes · A calculator
College
College · About 35 minutes · A calculator
Materials
The worksheet for your level, a screen for the video, a calculator for the high school Going further and the college worksheet.
Grouping
Students work alone. For partners, pair students for Questions.
Phenomenon
Coffee makes people feel more awake, yet caffeine adds no fuel to the body. Caffeine blocks the receptors for adenosine, a leftover of the brain’s energy use that signals tiredness.
Topics
Coffee and caffeine, sleep, the brain, the heart and blood pressure, a heart drug used in hospitals.

Preview the video before sharing it with your class.

Video and transcripts

  1. 1

    Your coffee is not GIVING you “energy”!

    Introduces adenosine, the tired signal it sends, and how caffeine blocks its receptors.

    Watch on YouTube
    Transcript

    Transcribed from the posted video on YouTube.

    You thought your morning coffee was giving you energy? You’re wrong. What?

    The reality is that the caffeine in your coffee is blocking the molecule that tells your brain that it’s tired. Your word of the day is adenosine. Say it with me. Adenosine.

    Adenosine makes you sleepy because it builds up in your brain as a byproduct of daily energy use. More pressure. More energy. More energy. More footwork. [unclear] And it creates this biological sleep pressure.

    The thing is this, though. Caffeine is just sitting in the seat. The longer you stay awake, the more this chemical accumulates and binds to specific places in your brain that slows down your brain activity and turns off the wakefulness. It also triggers a stress response in your body, kind of like that fight or flight that gets your heart racing.

    Caffeine is shaped enough like adenosine that it can sit in that same place that adenosine is supposed to sit. It just blocks the seat. It’s just like, yeah, I’m just gonna sit here. You know, it’s not like you need to feel like you’re tired or anything.

    Adenosine is still building up in your system. You’re just not getting that tired message as strongly as you would because caffeine is sitting where the adenosine is supposed to sit.

    But the thing is that when that caffeine starts clearing out, all that adenosine finally gets bound to all of those places in your brain that the caffeine was sitting in, which is why people feel that caffeine crash. Because all of a sudden, boom, adenosine now has a place to sit, and it’s gonna do what it’s supposed to do. Make you feel tired. But instead of having a little bit, you got a whole lot built up, and now you’re crashing.

    How much coffee do you drink every day? Let me know in the comments. I’m Dr. Raven Baxter. Follow me for more science. Bye!

Your word of the day is

uh-DEN-uh-seen

aden-glandfrom Greek adḗn
-os-a kind of sugarfrom German Ribose
-inean ending for chemical namesfrom Latin -ina

Adenosine. A molecule found in all living cells. In the brain, adenosine builds up while you’re awake and helps signal that you’re tired.

Word partComes fromMeaning
aden-Greek adḗngland
-os-ribose, from German Ribosea sugar found in RNA
-ineFrench and Latin -inaan ending used in the names of chemical substances, as in caffeine
receptor (bonus word)Latin receptor, related to receivea protein on or in a cell that a molecule binds to, starting a change in the cell
antagonist (bonus word)Greek antagōnistḗs, from antagōnízesthaito contend against; an opponent

Same roots, other subjects

  • HistoryThe word coffee traveled from Arabic qahwah to Turkish kahve to Italian caffè and reached English around 1590 to 1600. Caffeine was named from the French café, “coffee,” plus the -ine ending.
  • ArtRibose got its name by rearranging and shortening arabinose. Arabinose was named for gum arabic, a gum from acacia trees used to make inks.
  • BiologyThe adenoids, a mass of lymph tissue at the top of the throat, and the adenoviruses carry the same aden- root.
  • ChemistryThe -ine ending marks many compounds that contain nitrogen, such as caffeine, nicotine and purine. Chlorine and bromine carry the same ending.
  • EnglishIn a story, the antagonist is the hero’s opponent. At a receptor, caffeine plays the antagonist to adenosine.
  • Physical educationAn antagonist muscle opposes another muscle, relaxing while the other contracts.
  • World languagesSpanish says adenosina and French says adénosine.

Word hunt. Ask students to find three more chemical names that end in -ine and say where each substance is found.

Adenosine is a blend. The name comes from the German Adenosin (1905 to 1910), which joins adenine and ribose, the two parts of the molecule. Adenine took its name from the Greek word for gland. Caffeine is an adenosine receptor antagonist, the bonus word the high school and college worksheets use.

Lesson flow

Lesson flow level
  1. 3 minPredictStudents answer the question and write one sentence.
  2. About 2 minVideo
  3. 4 minWord of the dayBreak the word into its parts together.
  4. 8 minQuestionsStudents answer on their own, then share out. With partners, pairs discuss first.
  5. 5 minExit ticket
  1. 3 minPredictStudents answer the question and write one sentence.
  2. About 2 minVideo
  3. 4 minWord of the dayBreak the word into its parts together.
  4. 8 minQuestionsStudents answer on their own, then share out. With partners, pairs discuss first.
  5. About 15 minClaim, evidence, reasoning and Going furtherGoing further needs a calculator.
  6. 5 minExit ticket
  1. About 2 minVideo
  2. 4 minWord of the dayBreak the word into its parts together.
  3. 3 minPredict
  4. About 20 minRead the paperStudents read Tables 2 and 3 of the sleep study and answer the questions. The paper reading works as homework or a discussion section.
  5. 5 minExit ticket

Video simplifications

“It builds up in your brain as a byproduct of daily energy use”
Adenosine forms when brain cells use up ATP, and animal studies found adenosine outside brain cells rising during waking and falling during sleep. Faster measurements in mice show adenosine levels shifting within minutes. A 2022 review calls extracellular adenosine unlikely to drive normal day-to-day sleepiness, while it may add to sleep pressure when waking runs long. Most human evidence comes from caffeine studies.
“Binds to specific places in your brain that slows down your brain activity and turns off the wakefulness”
The “specific places” are adenosine receptors. A1 stimulation lowers glutamate release, and A2A activation in one brain pathway strongly induces sleep in animals. “Turns off the wakefulness” simplifies those effects.
“Caffeine is shaped enough like adenosine”
Caffeine is a purine alkaloid, and adenosine contains adenine, a purine base. Caffeine binds A1 and A2A receptors with roughly equal affinity, and mouse studies point to A2A for its wake-up effect.
The stress response
In the posted Short, the line “It also triggers a stress response in your body, kind of like that fight or flight that gets your heart racing” comes right after a sentence about adenosine, so students may hear adenosine as the cause. Caffeine causes the stress response, not adenosine. In a 1978 study of nine young adults who did not drink coffee, 250 mg of caffeine raised epinephrine 207% and blood pressure 14/10 mm Hg within an hour. Heart rate fell slightly, then rose. The authors left open whether daily coffee drinkers respond the same way. Adenosine acts the other way at the heart. Emergency doctors inject adenosine to stop a racing heart rhythm called paroxysmal supraventricular tachycardia, and in a 1990 trial it stopped the rhythm in about 30 seconds on average.
“Adenosine is still building up”
Whether caffeine leaves sleep pressure untouched is not settled. In rats and humans, caffeine dampened brain-wave markers of sleep pressure after sleep deprivation. In rats, daily caffeine raised adenosine levels.
The crash
“Which is why people feel that caffeine crash.” In the video, Raven gives returning adenosine as the reason for the crash. The lesson calls returning adenosine part of the reason, which fits the evidence better. In a mouse study with daily caffeine, the mice slept more once the caffeine cleared, and the review authors suggest extra adenosine or extra receptors explain the extra sleep. Human findings on daily caffeine are mixed.
Plants
The posted video doesn’t include the plants line from Raven’s recording script. If students ask, caffeine occurs in the leaves and seeds of many plants and tastes bitter enough to deter pests. A 1984 study found that caffeine and related methylxanthines stop insects from feeding and kill them at concentrations found in plants. In insects the main effect comes from blocking an enzyme, phosphodiesterase, rather than adenosine receptors.
Half-life
Adult half-lives run from 3 to 7 hours. The high school Going further and college question 3 use 5 hours to keep the math simple.
Pronunciation
Adenosine is uh-DEN-uh-seen.

Worksheet

Worksheet level
Print the middle school worksheet
Coffee and Your BrainMiddle school learnscience.org

Predict

Many adults drink coffee in the morning to wake up. Coffee has a chemical in it called caffeine. Does the caffeine in coffee give your body energy?

Circle one. Yes / No

Watch

  1. Coffee doesn’t give you energyyoutube.com/shorts/qIIaPqW8qkk

Word of the day

Adenosine (uh-DEN-uh-seen). A molecule found in all living cells. In the brain, adenosine builds up while you’re awake and helps signal that you’re tired.

Word partComes fromMeaning
aden-Greek adḗngland
-os-ribosea kind of sugar
-ineFrench and Latinan ending for chemical names

Bonus word. Receptor (rih-SEP-tur). A protein on a cell with a spot, like a seat, that one kind of molecule fits into. The word comes from Latin and is related to the word receive.

Questions

  1. Your brain uses energy all day long. Adenosine is a leftover from the brain’s energy use, and it builds up while you are awake. As adenosine builds up, what message does it send your brain?

    Hint. Think about how you feel at the end of a long day.

  2. Adenosine sends its message by fitting into receptors on brain cells. In the video, Raven says caffeine is shaped enough like adenosine to sit in the same receptors. What happens to the tired message when caffeine takes adenosine’s seat?

    Circle one. The tired message gets stronger / The tired message gets blocked / The adenosine turns into energy

    Hint. Caffeine fits in the receptor, but caffeine doesn’t send the tired message.

  3. In the video, Raven says adenosine keeps building up while caffeine sits in the receptors. What happens when the caffeine finally leaves adenosine’s receptors?

    Hint. Think about all the adenosine that was waiting for a receptor.

  4. When you drink coffee, caffeine moves from your small intestine into your blood. Your blood carries caffeine to your brain and your heart. Name two body systems that caffeine travels through or changes.

    Hint. Follow the caffeine from your mouth to your brain. Which body systems move the caffeine along the way?

Exit ticket

In the video, Raven says coffee is not giving you energy. What does the caffeine in coffee do in your brain instead?

Hint. Think about adenosine and its receptors. What does caffeine do when it sits in a receptor?

Print the high school worksheet
Coffee and Your BrainHigh school learnscience.org

Predict

Many adults drink coffee in the morning to wake up. Coffee has a chemical in it called caffeine. Does the caffeine in coffee give your body energy?

Circle one. Yes / No

Watch

  1. Coffee doesn’t give you energyyoutube.com/shorts/qIIaPqW8qkk

Word of the day

Adenosine (uh-DEN-uh-seen). A molecule made of adenine joined to the sugar ribose. In the brain, adenosine builds up during waking and signals the need for sleep.

Word partComes fromMeaning
aden-Greek adḗngland
-os-ribosea sugar found in RNA
-ineFrench and Latin -inaan ending used in the names of chemical substances

Bonus words. Receptor (rih-SEP-tur) is a protein on or in a cell that a molecule binds to, starting a change in the cell. The word comes from Latin and is related to receive. Antagonist (an-TAG-uh-nist) is a molecule that binds a receptor and blocks the receptor’s signal. The word comes from the Greek antagōnízesthai, “to contend against.” In a story, the antagonist is the hero’s opponent.

Questions

  1. Caffeine is an adenosine receptor antagonist. An antagonist binds a receptor and blocks the receptor’s signal without turning the receptor on. Caffeine gives brain cells no energy. Why does blocking adenosine receptors still make a person feel more alert?

    Hint. Think about what adenosine’s signal does in the brain. What happens when less of adenosine’s signal gets through?

  2. Caffeine blocks two kinds of adenosine receptors, A1 and A2A, about equally. In one set of experiments, caffeine still kept mice awake when the mice had no working A1 receptors. Caffeine did not disrupt sleep in mice with no working A2A receptors. Which receptor do the mouse experiments point to for caffeine’s wake-up effect?

    Circle one. A1 / A2A / Both equally

    Hint. Find the mice that slept normally after caffeine. Which receptor were those mice missing?

  3. Caffeine is absorbed in the small intestine and carried by the blood. Caffeine binds adenosine receptors in the brain and in organs such as the heart and blood vessels. In a 1978 study, 250 mg of caffeine raised adrenaline in the blood by 207% and raised blood pressure within an hour. Caffeine goes in your mouth and ends up changing both your brain and your heart. How does caffeine get there? Name the body systems at each step.

    Hint. Trace caffeine from the small intestine to the brain and the heart. Which systems carry the caffeine, and which systems respond?

  4. In rats and mice, daily caffeine increased the number of adenosine receptors in the brain. How could extra adenosine receptors change what a daily coffee drinker feels when the caffeine wears off?

    Hint. Picture the receptors once caffeine leaves. Which molecule is waiting to bind, and how many places can that molecule bind now?

Claim, evidence, reasoning

In rats and cats, adenosine outside brain cells rose during waking, fell during sleep and rose higher after long stretches of waking. When adenosine binds A1 receptors, brain cells release less glutamate, a signal that excites other brain cells. In negative feedback, a change triggers a response that undoes the change. Does adenosine work as a negative feedback signal that keeps sleep and waking in balance? Make a claim, back it up with evidence, and explain your reasoning. Then name one measurement that would test your claim.

Hint. Follow the loop. What does waking do to adenosine, what does adenosine push the brain to do, and what does sleep do to adenosine?

Going further: caffeine and energy

  1. In a 2013 study, adults took 400 mg of caffeine 6 hours before bed. Use a 5-hour half-life. About how much of the 400 mg dose was still in the body at bedtime?

    Circle one. About 50 mg / About 100 mg / About 175 mg / About 400 mg

    Hint. After 5 hours, half of the 400 mg is left. The sixth hour removes a little more.

  2. ATP, short for adenosine triphosphate, carries energy inside cells. Cellular respiration breaks down food and oxygen and forms new compounds that carry energy, such as ATP. Brain cells make adenosine when brain cells use up ATP. Why can’t caffeine give cells energy the way food does?

    Hint. Follow where the energy in ATP comes from. Then think about what caffeine does at the receptor.

Exit ticket

In the video, Raven says coffee is not giving you energy. What does caffeine do in the brain instead? And why does the tired feeling come back later?

Hint. Think about what an antagonist does at a receptor. Then think about the adenosine that keeps forming while caffeine sits in the receptors.

Print the college worksheet
Coffee and Your BrainCollege learnscience.org

Watch

  1. Coffee doesn’t give you energyyoutube.com/shorts/qIIaPqW8qkk

Word of the day

Adenosine (uh-DEN-uh-seen). A nucleoside formed from the purine base adenine and the sugar ribose. In the brain, extracellular adenosine rises during waking and is proposed as a signal of sleep need.

Word partComes fromMeaning
aden-Greek adḗngland
-os-ribosea five-carbon sugar found in RNA
-ineFrench and Latin -inaan ending used in the names of chemical substances

Bonus word. Antagonist (from the Greek antagōnízesthai, “to contend against”) describes a substance that interferes with the action of another substance, especially by binding and blocking its receptor. Caffeine is an adenosine receptor antagonist.

Predict

  1. The study below gave adults 400 mg of caffeine 6 hours before bed and measured their sleep with a headband monitor. Make your guess before you read the paper, and give your reason in one sentence. How many minutes of sleep do you think 400 mg of caffeine, taken 6 hours before bed, cost compared with a placebo night?

    Hint. In adults, half of a caffeine dose leaves the body every 3 to 7 hours. How much of the dose would still be in the body at bedtime?

Read the paper

Drake, Roehrs, Shambroom and Roth, “Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed,” Journal of Clinical Sleep Medicine, 2013. The paper is free to read.

Twelve healthy adults, ages 19 to 48, who regularly use caffeine slept at home for four test nights. On each test day they swallowed three pills, at 6, 3 and 0 hours before their usual bedtime. On three of the nights, one pill held 400 mg of caffeine and the other two were placebos. On the fourth night, all three pills were placebos. Neither the participants nor the researchers knew which pill held caffeine. Each morning, participants recorded their sleep in a diary (Table 2 of the paper), and a headband monitor that records brain waves measured their sleep each night (Table 3). The table below gives the mean total sleep time from both tables.

ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
  1. Quantitative reasoning Fill in the last column of the table. Subtract each caffeine row from placebo, then multiply by 60. In Table 3, all three caffeine nights differed from placebo (p < 0.05). How many minutes of sleep did caffeine cost at each time? Did taking caffeine earlier in the evening shrink the loss?

    Hint. Compare your three answers with one another, then with 60 minutes.

  2. Process of science In the diaries, caffeine taken 6 hours before bed cut sleep by 41 minutes, a difference that was not statistically significant (p = 0.08). The monitor showed a larger loss on the same nights. Why might the diary and the monitor disagree at 6 hours? Which features of the study design make the monitor result more convincing?

    Hint. Think about what a sleeping person can notice. Then look at the pills, the placebo night and who knew which pill held caffeine.

  3. Structure and function Caffeine is a purine alkaloid, and adenosine contains adenine, a purine base. Caffeine binds A1 and A2A adenosine receptors with roughly equal affinity without activating the receptors. In adults, caffeine’s half-life runs from 3 to 7 hours. Use a 5-hour half-life. About how much of the 400 mg dose remained at bedtime in the 6-hour condition? How does caffeine’s structure explain why that amount still shortened sleep?

    Hint. Remaining caffeine = 400 × (1/2)^(6 ÷ 5). Then think about what the adenosine that accumulated during the day can do at a blocked receptor.

  4. Pathways and transformations of energy and matter Adenosine forms when brain cells break down ATP, the molecule that carries energy in cells. The liver breaks caffeine down mainly with the enzyme CYP1A2. Caffeine’s main breakdown product, paraxanthine, also binds A1 and A2A receptors in animal studies. Why does caffeine change how tired a person feels without adding energy to cells? How could paraxanthine change how long caffeine’s effect lasts?

    Hint. Follow the matter. Where does adenosine come from, and what does the liver turn caffeine into?

Exit ticket

Table 3 of the Drake paper reports the sleep the headband monitor measured on each night. What does Table 3 show about caffeine taken 6 hours before bed? What’s one question Table 3 can’t answer?

Hint. Think about what the team did not measure in the participants’ blood, and who took part in the study.

Standards

The lesson builds toward five Next Generation Science Standards (NGSS), the most widely used US science standards. Some states, like Texas and Virginia, write their own. NGSS covers kindergarten through grade 12. The college worksheet uses the AAAS Vision and Change framework for undergraduate biology.

LevelStandardLesson partPracticeCrosscutting concept
Middle schoolMS-LS1-3. Argue from evidence that the body is a system of interacting subsystems (core idea LS1.A)Middle school worksheet, Questions 4Engaging in Argument from EvidenceSystems and System Models
Middle schoolMS-LS1-7. Model how food is broken down and rearranged to release energy (core idea LS1.C)Middle school worksheet, Questions 1 and exit ticketDeveloping and Using ModelsEnergy and Matter
High schoolHS-LS1-2. Model how interacting body systems are organized in levels (core idea LS1.A)High school worksheet, Questions 3Developing and Using ModelsSystems and System Models
High schoolHS-LS1-3. Investigate how feedback mechanisms maintain homeostasis (core idea LS1.A)High school worksheet, claim, evidence, reasoningPlanning and Carrying Out InvestigationsStability and Change
High schoolHS-LS1-7. Model cellular respiration as a chemical process with a net transfer of energy (core idea LS1.C)High school worksheet, Going further question 2Developing and Using ModelsEnergy and Matter
CollegePathways and transformations of energy and matter; structure and function. AAAS Vision and Change core conceptsCollege worksheet. Question 1 covers quantitative reasoning, question 2 process of science, question 3 structure and function and question 4 pathways and transformations of energy and matter.Core competencies: quantitative reasoning; process of scienceCore concept: structure and function

Sources

This video draws on several research teams. The lesson credits each team.

TopicWho found itWhere it was published
Caffeine taken 0, 3 or 6 hours before bed cuts sleep by more than an hourChristopher Drake, Timothy Roehrs, John Shambroom and Thomas Roth, Henry Ford Hospital Sleep Disorders & Research Center in DetroitJournal of Clinical Sleep Medicine, 2013
Adenosine as a sleep signal, caffeine’s receptors, the mouse studies and daily caffeineReview by Carolin Reichert (University Psychiatric Clinics Basel), Tom Deboer (Leiden University Medical Center) and Hans-Peter Landolt (University of Zürich)Journal of Sleep Research, 2022
Caffeine absorption and clearance, half-life, caffeine in a cup of coffeeReview by Jennifer Temple (University at Buffalo) with colleagues at Aix Marseille University and Wayne State UniversityFrontiers in Psychiatry, 2017
Caffeine raises adrenaline and blood pressureD. Robertson, J. A. Oates and colleaguesNew England Journal of Medicine, 1978
Injected adenosine stops a racing heart rhythmJ. P. DiMarco and the Adenosine for PSVT Study Group, led from the University of VirginiaAnnals of Internal Medicine, 1990
Caffeine as a natural insecticideJ. A. NathansonScience, 1984
The chemical makeup of caffeine and adenosineChEBI records in PubChemCaffeine and adenosine

The Drake paper and the Reichert and Temple reviews are free to read. The 1978, 1984 and 1990 papers sit behind paywalls, and their PubMed abstracts are free. Zeo Inc, the company that made the headband sleep monitor, funded the Drake study, and one co-author had worked for Zeo. The paper states this in its disclosure, which gives college students a chance to talk about funding and trust.

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