Week 4 - Caffeine Flashcards
What is the family of drugs that caffeine belongs to?
methylxanthines (xanthine stimulants)
- occur naturally
- most widely used psychoactive drugs in the world
Commonly self-administered methylxanthines
- caffeine
- theophylline (tea)
- theobromine (chocolate)
less commonly self-administered methylxanthines
- Ilex plant (amazon; mate)
- guarana (south america)
- kola nuts (west africa)
what year was caffeine first isolated from coffee
1820
sources of caffeine
- coffee
- tea
- chocolate
- medication
- soft drinks & other foods
History of caffeine use
coffee
- Ethiopia (12th and 15th centuries)
- spread to europe
- 1st english coffeehouse opened in Oxford in 1650
History of caffeine use
tea
- china (780 A.D.)
- europe imports (1606)
History of caffeine use
cocoa
- mayas, aztecs, incas (pre-columbian)
- cortez introduced chocolate drink to spain in 1520
- 1728: 1st chocolate factory in england
Route of administration
- orally, i.m. or i.v.
- medically, given as salts rather than alkaloids - quickly absorbed
Caffeine content in food and drink
espresso - 145mg/50mL cup
energy drinks - 80mg/250mL can
instant - 80mg/ 250mL cup
tea - 50mg/220mL cup
coke - 36.4mg/375mL can
chocolate - 20mg/100g bar
no-doz - 100mg/tablet
absorption
- methylxanthines dissolve in tissue (are lipid soluble)
- absorbed from stomach & intestinal walls (little first-pass metabolism due to absorption from digestive system)
distribution
- caffeine cross BBB & placental barrier (reaches all organs)
- present in bodily fluids
- theophylline & theobromine less lipid soluble vs caffeine
when are peak caffeine levels reached?
45-75 minutes after oral administration
excretion
- half-life ~ 5 hours (dose dependent)
- ~1% excreted unchanged in adult urine - most caffeine converted to different metabolites
- caffeine does not accumulate over long periods of time, if not consumed >6pm
excretion
newborns
- ~85% of caffeine unchanged
- half life is 4 days
- remained excreted following different metabolic pathways than adults
Factors that mediate caffeine metabolism
- genetic differences - CYP1A2 gene: 1A = rapid, 1F = slow
- increased caffeine metabolism:
- > smoking
- > broccoli
- > hormone levels (in women)
- decreased caffeine metabolism:
- > alcohol
- > grapefruit juice
- > oral contraceptives
- > pregnancy
- > some antibiotics
Methylxanthines are antagonist to what?
adenosine receptors - esp. A1 & A2A subtypes, which interact with dopamine receptors
adenosine
inhibits the firing of neurons & blocks the release of many neurotransmitters
neurophysiological effects of caffeine at usual and high doses
usual: causes release of epinephrine & other catecholamines from brain tissues & adrenal glands - may contribute to stimulating effect (SNS)
high: blocks benzodiazephine receptors (may explain increased anxiety seen at high doses)
neurophysiological effects from chocolate
anandamide - endogenous substance that works at cannabinoid receptors - creating a ‘high’
physiological effects
nervous system
release of epinephrine - stimulation of sympathetic nervous system
physiological effects
spinal cord
- at high levels spinal reflexes more excitable
- higher doses - convulsions (possibly death)
physiological effects
medulla
regulatory centres stimulated - increased rate and depth of breathing (medications for newborns)
physiological effects
blood vessels
- various effects depending on part of the body
- constricts brain blood vessels, but dilates vessels in the rest of the body
- headaches & headache tablets
physiological effects
muscles
most effects outside the CNS are due to effect in muscles
- smooth muscles relax - theophylline & bronchi
- striated muscles strengthen - increased fatty acids and decrease fatigue in muscles; caffeine in sport
caffeine on behaviour
caffeine is thought to increase alertness, concentration, endurance, sensitivity but there are mixed results. Some accounts reflect expectancies rather than genuine caffeine effects
methodological considerations of caffeine research
- dose
- time of consumption
- nature of the task
- individual differences (personality, age, usual caffeine consumption, tolerance)
conditions for detecting positive effects
- low doses (20-200mg)
- non-habitual caffeine users
- if caffeine is a positive reinforcer for participants
caffeine on sleep
- methylxanthines can produce insomnia by increased time taken to fall asleep
- people wake easily as caffeine decreases acoustic arousal thresholds
- caffeine can counter the effects of pentobarbitual (sedative)
caffeine on weightloss
- correlation between amount of caffeine consumed and eating disorder patients
- hypothesised caffeine is a fat releaser, metabolism activator and appetite suppressant
caffeine on urination and defecation
stimulates due to antagonistic effects on adenosine receptors found in the kidneys and colon
animal studies on caffeine
- caffeine & theophylline increase spontaneous motor activity (dose dependent - max 20-40mg/kg), long term treatment decreases spontaneous motor activity
- LD50 for rats and mice = 250mg/kg when administered intraperitoneal
- death may results from convulsions, long term treatment decrease seizure sensitivity
- auto-mutilation can cause death in animals exposed to caffeine at larger doses (185mg/kg for 14 days)
conditioned responses
- Pavlov - caffeine increases responses to negative stimuli, therefore interrupting conditioning experiments
- caffeine increases avoidance responding
- response profile of caffeine on operant conditioning is similar to those of amphetamine for some behaviours
discriminative properties
- rats can discriminate caffeine & saline at 32mg/kg
- generalisation at lower doses of caffeine & higher doses of theophylline but not to nicotine
- partial generalisation to cocaine & amphetamines if trained to discriminate low doses
- Turkey drugs: caffeine based amphetamine look alike drugs can mimic discriminative stimulus effects of cocaine
- humans can also discrimiate caffeine at low doses, but this may not generalise to theobromine
Tolerance
- chronic caffeine administration causes increased upregulation in adenosine receptors
- many studies have shown that caffeine has less effect on heavy coffee drinkers
tolerance at different rates
cardiovascular: 2-5 days
increased urine output: never
sleep: 7 days
subjective effects: 4 days
withdrawal
in humans
- most common, headache
- fatigue
- drowsiness
- lethargy
- decreased motivation
- irritability
- deceased self-confidence
- flu-like symptoms
withdrawal
in animals
caffeine withdrawal effects can be demonstrated
- decreased locomotor activity; disruption of ongoing operant responding
how many mgs and days can cause physical dependence
600mg for >6-14 days; smaller doses over a longer period of time
when do withdrawal symptoms start
<12-28 hours of abstinence, peak ~20-50 hrs, can last up to a week
what percentage of coffee drinkers report withdrawal symptoms
27-57% who abstain for 24 hours
what can withdrawal explain?
- headaches, irritability
- weekend headaches & feelings of illness on holidays/weekends
Self-administration in animals
- caffeine is not a robust reinforcer
- variable and inconsistent; with no tendency to increase dose over time
- does potentiate reinforcing effects of cocaine and will act as a primer for cocaine
self-administration in humans
- reinforcing properties vary considerably between individuals
- preference may be determined by level of dependence
generally: - self-administration related to state of physical dependence
- high doses less reinforcing than lower doses
- preference may be context dependent
caffeine interaction with sedative-hypnotic drugs
evidence is equivocal on whether caffeine can counteract effects of sedative hypnotic
caffeine interaction with nicotine
- may enhance reinforcing & subjective stimulant qualities of nicotine in humans
- smokers metabolise caffeine quicker than nonsmokers (smoking cessation increases caffeine levels when consumed)
harmful effects
reproduction
- chromosomal damage at very high doses
- increased chromosomal damage caused by other agents
- 200mg dose decreases placental blood flow by 25%
- slows growth in the fetus & decreases birthweight (esp 1st trimester)
- increases risk of miscarriage
- potentiates effect of smoking
- rate of metabolism slows with pregnancy
- mathylxanthines in breast milk can reach toxic levels
harmful effects
cardiac disease
- increased blood pressure
- heart disease
- boiled coffee may increase cholesterol
harmful effects
cancer
- animal studies do not support association
- may increase effect of other agents which cause cancer
abnormal behaviour: caffeinism
results at 5-10 cups a day
sensory disturbance, delirium, fever, insomnia, irritability, irregular heartbeat, psychomotor agitation
abnormal behaviour: panic attacks and anxiety
- from caffeine blocking benzodiazepine receptors
- caffeine may also decrease effectiveness of some antipsychotics
harmful effects
Bone density
accelerated loss of bone density in postmenopausal women who consume less than recommended calcium dose
harmful effects
lethality
- lethal dose ~150-200mg/kg of body weight (30-80 cups of coffee taken orally
- death results ffrom respiratory collapse and convulsions
- australia has banned caffeine powders and highly concentrated caffeine products
Psychopathology of caffeine use
- High caffeine intake can be misdiagnosed as an anxiety disorder, can cause agitation and hyposomnia leading to diagnosis of bipolar disorder, can exacerbate psychosis
- complicating factor in anorexia nervosa
- interacts with psychotropic medications
