What is caffeine?
*Belongs to a family of drugs known as methylxanthines (Xanthine stimulants)
- Occur naturally
- Most widely used psychoactive drugs in the world
- Commonly self-administered methylxanthines:
- Caffeine
- Theophylline
- Theobromine
What are the sources of caffeine?
- 1st isolated from coffee in 1820
- Coffee – fruit of the Coffea tree; coffee berry contains seeds which are removed & roasted
- Tea – leaves of the Camellia sinensis; leaves are usually dried & crushed
- Chocolate – seeds from Theobroma cacao; seeds are fermented, dried, roasted & crushed
- Medication – analgesics, diet pills, allergy relief, stimulants, cold & flu remedies
- Soft drinks & other foods (e.g., viking bars; baked goods; energy drinks)
Route of caffeine Administration
- Normally taken orally, but can be i.m. or i.v.
- When given for medical reasons methylxanthines given as salts rather than alkaloids – more readily/quickly absorbed (e.g., Aminophylline as bronchodilator for asthma)
Absorption of coffee
- Methylxanthines readily dissolve in any tissue & are quite lipid-soluble
- Typically absorbed from stomach & through intestinal walls; absorption occurs directly from digestive system with little first-pass metabolism
Distribution of caffeine
- caffeine crosses the blood-brain barrier & placental barriers (thus reaches all organs in the body)
- present in all bodily fluids
- Theophylline & theobromine less lipid soluble vs. caffeine
- Peak caffeine levels reached 45-75 minutes after oral admin.
- many factors can affect absorption time (e.g., coffee ~45mins; chocolate ~1.5- 2hrs)
Excretion of caffeine
- Metabolism of caffeine in humans is unique
- Half-life ~ 5 hours, but may be dose-dependent
- ~ 1% excreted unchanged in urine in adults*; most caffeine is converted to different metabolites
- Caffeine does not accumulate over long periods of time, if not consumed >6pm
- *Newborns (<7-9 months)
- excrete ~ 85% of caffeine unchanged -> half-life of caffeine is ~ 4 days
- remainder excreted following different metabolic pathways than adults
Factors that mediate caffeine metabolism
- Genetic differences – e.g., CYP1A2 gene (P450 enzyme): 1A ~rapid, 1F ~slow metabolisers
- Factors that increases caffeine metabolism:
- Smoking
- Broccoli (brassica family)
- Hormone levels (in women)
factors that decrease caffeine metabolism
- Alcohol
- Grapefruit juice
- Oral contraceptives
- Pregnancy
- Some antibiotics
Neurophysiological effects of caffeine
At usual doses:
- Methylxanthines primarily act as antagonist (blockers) of adenosine receptors – esp. A1 & A2A subtypes, which interact with dopamine (DA) receptors
- Adenosine: inhibits the firing of neurons; & blocks the release of many NTs (e.g.,bAch, NE, DA, GABA, 5-HT)
- causes release of epinephrine & other catecholamines frombrain tissues & adrenal glands → may contribute to stimulating effect (SNS)
at high doses:
*blocks benzodiazepine receptors (may explain ↑anxiety seen at high doses)
How do you explain the high you get from chocolate
Chocolate also contains substances that resemble anandamide (endogenous substance that works at cannabinoid receptors)
- Other compounds in chocolate block its metabolism
Could this explain the popularity of chocolate beyond the effects predicted by the presence of caffeine?
How does caffeine affect the Nervous System
Release of epinephrine→ stimulation of sympathetic NS
How does caffeine affect the spinal cord
- At high levels spinal reflexes more excitable
- Higher doses → convulsions (possibly death)
How does caffeine affect the Medulla?
- Regulatory centres stimulated → increased rate & depth of breathing
How does caffeine affect the 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
How does caffeine affect the muscles?
- Most effects outside the CNS are due to effect in muscles
- Smooth muscles relax – theophylline & bronchi
- Striated muscles strengthen – increase fatty acids & decrease fatigue in muscles; caffeine in sport
Effects of caffeine on behaviour: Making the genius quicker
At low-moderate doses:
- caffeine usually thought to ↑ alertness, concentration, endurance, sensory sensitivity etc. (subjective perception)
- mixed research results (?due to methodological problems/ poor experimentaldesign)
- Goldstein, Kaizer & Warren (1965): subjective ratings did not match performance on attention or coordination tasks
- Some subjective accounts may reflect expectancies rather than genuine caffeine
effects (?)
What are some of the methodological considerations of caffeine research
- Dose
- Time of consumption
- Nature of the task
- Individual differences
- Personality
- Age
- Usual caffeine consumption
- Tolerance etc.
Conditions for detecting positive effects
- Low doses (20-200mg)
- Non-habitual caffeine users (effects in such users suggest not due to alleviation of withdrawal symptoms)
- If caffeine is a positive reinforcer for participants
Effects of caffeine on sleep
*Methylxanthines can produce insomnia by ↑time taken to fall asleep & decreasing total sleep time
- People also wake more easily, as caffeine decreases acoustic arousal thresholds
- Caffeine can counter the effects of pentobarbita
affeine effects on other behaviours:
the dieter’s friend?
- Caffeine, weight loss, & diet pills
- A mechanism for accounting for subjective weight loss effects:
- fat releaser?
- metabolism activator?
- appetite suppressant?
- Eating disorders & caffeine
Caffeine effects on other behaviours:
prompting nature’s call
- stimulation of urination & defecation
- Kidneys & colon: adenosine receptors
Conditioned responses to caffiene
- Pavlov (1927): caffeine ↑ responses to negative stimuli, therefore interrupting conditioning experiments
- Caffeine appears to ↑ avoidance responding
- Response profile of caffeine on operant conditioning is similar to those of amphetamine for some behaviours, but very different for others
Discriminative properties
- Rats can discriminate caffeine & saline at 32 mg/kg
- Generalisation @ 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 discriminate caffeine at low doses, but this may notgeneralise to theobromine
What is tolerance
Tolerance & withdrawal
Tolerance
* Chronic caffeine administration causes ↑(upregulation) in adenosine receptors
* Many studies have shown that caffeine has less effect on heavy coffee drinkers
* Different effects of caffeine show tolerance at different rates
* Cardiovascular: 2-5 days
* Increased urine output: never?
* Sleep: 7 days
* Subjective effects: 4 days
What is withdrawls?
In humans:
* Most common symptom of withdrawal is headache
* Also: fatigue, drowsiness, lethargy, decreased motivation, irritability, decreasedself-confidence, flu-like symptoms (eg nausea, vomiting, or muscle pain & stiffness)
* Symptoms closely related to dose
In Animals: caffeine withdrawal effects can be demonstrated
decreased locomotor activity; disruption of ongoing operant responding
