paul merritt: allright, well, we're going to continue withlecture number 6 or 6a-- this will probably be. caffeine and nicotineis the next topic up. today we're going to talkspecifically about caffeine.
dark roast coffee caffeine content, and then, next up, we'lltalk about nicotine. caffeine of course, is the mostwidely consumed psychoactive drug on the planet. so we'll first do anintroduction to caffeine,
talk about thepharmacokinetics of caffeine, talk about the mechanism ofaction, and then, finally, finish up with toleranceand dependence. caffeine is, as i said, themost widely used psychoactive substance in the world. it's used daily byapproximately 80% of the adult populationin the united states. caffeine was first isolatedfrom coffee in 1820 by a german chemist, whocalled it kaffeebase.
the word caffeine was firstused in the medical dictionary in 1823. so when it comes topsychoactive substances, this one's a relativelynew player in the field, certainly, if wecompare it to alcohol, which had been widely usedby western civilization for thousands of years. so we've just startto understand caffeine in the 19th century.
of course, it had beenused prior to that. but we finally start toget an understanding of it although, it had certainlybeen used long before that. to give you an ideaof the caffeine content in some beverages,black tea and brewed coffee have the highestlevels of caffeine. green tea has relativelylow levels of caffeine. instant and decaf coffee havemuch lower levels of caffeine, compared to brewed coffee.
not all brewedcoffee is the same. some types of coffee have higherlevels of caffeine than others. sodas have relativelylow levels of caffeine-- just jolt and surgeand mountain dew, which contain higherlevels of caffeine. compared to coffee, they'rerelatively low levels of caffeine. all chocolate has some modestcaffeine levels in them. so, certainly, hotchocolate and hot cocoa
have some caffeine in them. tablets-- caffeinetablets-- such as vibrant, contain about 200 milligramsof caffeine, so a little more than a cup of coffee,say, a cup and a half. and then, your average espressodrink has about 70 milligrams so relatively low levelscompared to brewed coffee. so a low dose of caffeinewould be somewhere around 50 to 300 milligrams of caffeine. this will increase alertness,energy, and ability
to concentrate. caffeine will relaxyour bronchials, increase gastric secretionsand urinary output. it's one of the reasons whycaffeine can be dehydrating. so if you consumea lot of caffeine, you're going to want to consumesome water along with that to prevent dehydration. moderate consumption wouldbe, rarely, any sort of health risk.
so when we start gettinginto higher doses, more than, say, 1,000milligrams a day, or no more than 500milligrams a day even-- depending onyour own tolerance-- this can produce anxiety,restlessness, insomnia, tachycardia, in somesensitive people. so, really, you want to stay inthe low to moderate dose range. everyone's tolerance isa little bit different. we're going to talk aboutcaffeine overdoses here
in a little bit when we talkabout caffeine powder, which is kind of an emergingproblem in the era of internet marketplaces,when you order things like caffeine powder. in terms of the epidemiologyof caffeine consumption, coffee varies across countries. it's high in the scandinaviancountries-- in the united states-- not surprising. varies across differenttypes of preparation,
anywhere from 20 to175 milligrams per cup, depending on the beansand the roast, et cetera. so if you look at thekinds of coffee beans-- arabica beans have abouthalf as much caffeine as robusta types of beans. most flavored coffeesand milder coffees are brewed from arabica beans. and more darker roastcome from robusta coffee. other consumption comesfrom tea, cocoa, candy bars,
soft drinks. and the average intake of a useris about 170 to 300 milligrams a day. so that's about an average user. pharmacokinetics ofcaffeine, of course, we're talking about gi absorption. it's about 99% in 45 minutes. so that's pretty fastand very complete. you reach peak plasmalevels about 120 minutes
after ingestion. so it takes about two hoursfor that caffeine to kick in. the metabolic half-lifeof caffeine in adults is pretty variable. it's around three and 1/2 tofive hours in adult humans. it's 60 to 100 hours ininfants-- so much slower in infants. and it's also a little bitslower in older adults, as well.
and so you tend to get longerlasting effects of caffeine. and so older adults tend toneed to discontinue caffeine earlier in the day. caffeine metabolism is reducedby about 30% to 50% in smokers. so it's much, much slower. and it is actually doubled inwomen on oral contraceptives. and it's also prolongedduring the last trimester of pregnancy. in fact, women areusually encouraged
from reducing oreliminating caffeine altogether during pregnancy. caffeine is metabolized intothree different endproducts-- theophyline, paraxanthineand theobromine. caffeine is metabolized by,of course, cytochrome p450. it's a cytochrome p1a2subgroup of hepatic enzymes. the two major metabolites aretheophyline and paraxanthine. they behave similarlyto caffeine. and the third metabolite,theobromine, does not.
some ssri-type antidepressantsinhibit the enzyme, while other types do not. that is somethingto keep in mind. how does caffeine work? well, caffeineexerts its influence by antagonizing adenosine. adenosine is generally ainhibitory neurotransmitter. so caffeine antagonizes twotypes of adenosine receptors-- a1 and a2a.
in mice that do nothave a2a receptors, caffeine only hasa depressant, not a stimulant effect on activity. so these two receptorstogether are how caffeine exerts its influence. the positive effectsof caffeine-- so the alertness,increases in attention-- appears to be dueto the antagonism of adenosine receptorsthat normally act on gaba
neurons to inhibitdopamine release. so removal of thatgabaergic inhibition increases dopamine release,increases that feeling of awareness, alertness,attention, that sort of thing. caffeine has a numberof beneficial effects. if you look at coffeeconsumption associations, you get reduced concentrationsof inflammatory markers, reduced stroke risk, improvedglucose metabolism and insulin secretion, andsignificantly reduced risk
for type 2 diabetes, reducedcancer risk, improved headache relief, decreased riskfor some diseases, increased subjective arousal,improved physical endurance and concentration. and we're going to talk here ina little bit about how caffeine is a major componentof most pre-workouts. you get reduced fatigue,increased secretion of gastric acids. one of the reasons whysometimes coffee or caffeine can
have some negative gastriceffects-- it can be positive. but, certainly,if you're someone who's prone to havingstomach difficulties, that can be problematic. but, certainly, it getsthings moving down there. and you get increasedurinary output. again, caffeine hassome diuretic effects. in fact, a lot of diuretics aremade entirely from caffeine. and then, finally, youget bronchial relaxation.
in fact, some bronchialmedications contain caffeine. adverse effects ofcaffeine, for those who consume more than 12cups per day, or about a gram and a half of caffeineto 1,500 milligrams-- you can get agitation, anxiety,tremors, rapid breathing, and, of course, insomnia. a lethal dose is estimated atabout 10 grams taken orally, which is about 100cups of coffee. so you don't get this kindof overdose from coffee.
but death is usuallydue to convulsions, and then, respiratory collapse. there have been sixdeaths in humans from this kind of lethaldose in recent times. more recently, caffeine powdershave come on the market. and these products areessentially 100% caffeine. and a single teaspoonof pure caffeine is roughly equivalent to theamount in 28 cups of coffee. and so here's whereyou start to get
into the potential for overdose. so the 10 grams takenorally is-- a lethal dose is 50 vivarin tablets. but if you look atthe caffeine powder, we're talking about 4 teaspoons. and that's whereyou can get danger. and so, that's somethingto be very, very careful of and something to watch out for. caffeine has some other, whatwe call caffeinism effects.
at doses above 1,000milligrams a day, you start to get some seriouseffects-- delirium, excitement, ringing in the ear, flashesof light, low-grade fever, chilliness, flushing,insomnia, irregular heartbeat, loss of appetite. it looks a lot likeanxiety disorder, but does not respondto tranquilizers. the treatment, then, is justsimply to eliminate caffeine. and i do want to take a quicknote about pre-workouts.
most pre-workouts containpretty significant amounts so if that's somethingthat you're taking, you want to watch your caffeineintake when you take those. because you can get prettyjittery and get some anxiety. and i think it'ssomething that's well known in people who takethose kind of supplements. so follow this link,and you can take a look at some information abouthow much caffeine might be in your workout supplement.
so the most concerningadverse effects of caffeine is their effects on sleep. sleep is incrediblyimportant to us. and so disruption of sleepis incredibly unhealthy. it's bad for our health. it's bad for ourcognitive abilities. so it may impair the durationof quality of our sleep and cause repeated awakenings. and the other most concerningadverse effect of caffeine,
aside from keeping usawake, is that combination with energy drinks and alcohol,that i mentioned previously. people who are consumingalcohol and caffeine together increase theirsexually risky behaviors. they tend to getin more fights, are more likely to engagein prescription drug abuse, alcohol abuse,and cigarette smoking. so that combination reallyis something to be avoided. so how does caffeinedisrupt sleep?
well, caffeine actsprimarily by blocking all subtypes of the adenosinereceptors-- a1, 2a, 3, and 2b. adenosine levels usuallyincrease during the day and exert a sleep-inducingeffect in the brain. so as we get further into theday, we get closer to sleep. and as a result, by blockingthe adenosine receptors, caffeine promotes wakefulnessby blocking that effect. caffeine may producesome behavioral effects by removing the negativemodulatory effects of adenosine
from dopamine receptors, sothereby indirectly stimulating dopaminergic activity. so you do get some reinforcingeffects of caffeine because of that dopaminergicactivity-- i say, as i take anothersip of my coffee. so caffeine can befairly rewarding. it's certainly somethingthat can disrupt sleep. it does have some positivebehavioral effects. things to watch out forare caffeine tolerance
and dependence. the dsm-5, a diagnosticand statistical manual of mental disorders, haslisted some potential caffeine disorders or caffeinerelated disorders, which include caffeineintoxication, caffeine withdrawal, and othercaffeine-induced disorders. and the treatment forthese is, of course, simply stopping caffeine. people can becomeaddicted to caffeine
or physically addicted. individuals often becomedependent on caffeine. median daily intake ofabout 360 milligrams is what most people take. 40% of the population takesless than 300 milligrams. the withdrawal symptomsfrom caffeine dependence include headache, tiredness,lack of concentration, anxiety, irritability, increasedmuscle tension, depression, and evennausea and vomiting.
headache is probablythe number one complaint of caffeine withdrawal. and one of thethings that happens is caffeine has an effect onvasodilation in the brain. and, in fact, some headacheremedies, including excedrin, contain a prettyhigh dose of caffeine to try to treat headache. and so that's one of thethings that you watch out for, and then, of course,tiredness and lack
of concentration. this will resolveafter a few days once you get back to normal,if you don't consume any more caffeine. and, again, this isnot necessarily related to the quantity of caffeinethat one might use. it's to whatever doseyou're used to using, you can become dependent on. some effects of caffeine becometolerant in humans-- things
like increases in bloodpressure and heart rate, and increases inadrenaline and noradrenaline levels, anxiety,nervousness, extra energy. all those, we eventuallybecome tolerant to. and we don't actually getthat effect from the caffeine anymore. some effects that didnot show tolerance-- caffeine-induced alertness andwakefulness, cerebral energy metabolism.
that is, our brain increasesthe metabolic rate. it's one of thereasons why caffeine helps us think more clearly. caffeine has somereinforcing qualities. human subjects candiscriminate caffeine from placebo incoffee or capsules. so we can tell thedifference between coffee that contains decaf or not. doses of 300 milligrams or moreare most reliably detected.
but some people can detectcaffeine at much lower doses. caffeine is not apowerful reinforcer in animals self-administeringintravenously, but doesn't have thatkind of reinforcing property of cocaine. the reinforcementdoes vary with dose. intake is strongly relatedto avoiding withdrawal. caffeine releasesdopamine in the brain, but not in thatspecific pleasure site.
that is, it doesn'trelease dopamine in the nucleus accumbens. so it's not reinforcing,like cocaine is. but it does releasedopamine in the brain area related to movement inthe frontal cortex, which
is thought to be related toattention and concentration. so it is rewardingin some sense, but not directly rewarding byactivating that reward pathway. so that is our quick lecture.
