Caffeine

neurophysiological effects of caffeine

antagonist of adenosine (inhibitory neuromodulator) = stimulation

typical doses of caffeine lead to

release of epinephrine from brain tissues and adrenal glands = stimulating

high doses of caffeine lead to

blocking benzodiazepine receptors = anxiety

absorption of caffeine

lipid soluble, low pKa = absorption directly from digestive system with little first pass metabolism 

distribution of caffeine

crosses BBB and placental barriers 

peak levels 45-75 min after oral admin 

excretion of caffeine

<2% excreted unchanged, half life around 5 hours but dose dependent, does not accumulate

metabolism in humans is unique

factors increasing metabolism

smoking, broccoli

factors slowing metabolism

alcohol, grapefruit juice, antibiotics, oral contraceptives, oestrogen (pregnancy)

NS effects

epinephrine release - sympathetic NS activation 

spinal cord effects

reflexes more excitable

medulla effects

regulation centres stimulated - increased rate and depth of breathing

blood vessels effects

constricts brain BV, dilates in rest of body = headache relief

muscles effects

smooth muscles relax, striated muscles strengthen 

positive reinforcer

non habitual caffeine users experience positive effects in low doses - caffeine is a positive reinforcer

effects on animals

short term, increases SMA

long term, decreases SMA

death from convulsions, automutilation

conditioned responses in humans 

increases responses to negative stimuli and avoidance responding 

discriminative properties

rats can discriminate, partial generalisation to cocaine and amphetamines, humans can discriminate at low doses 

Turkey drugs

substances which mimic effects of caffeine can mimic effects of cocaine

chronic caffeine admin

upregulation (more) adenosine receptors

caffeine withdrawal

starts 12-28 hours after abstinence, peaks 20-50 hours, lasts up to a week

600mg/day causes physical dependence

withdrawal in animals

decreases locomotor activity

caffeineism

sensory disturbance, delirium

self administration in animals

caffeine is not a robust reinforcer - variable and inconsistent

self administration in humans

reinforcing properties vary due to level of dependence, context

high doses less reinforcing than low

other drug interactions

enhances nicotine qualities, possibly can counter sedative drugs