WEEk 4 - caffeine Flashcards
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
Caffeine Withdrawl
- 600mg/day can cause physical dependence >6-14 days; smaller doses over alonger period of time
- Withdrawal symptoms may start <12-28 hours of abstinence, peak ~20-50 hrs, & can last up to a week
- 27-57% of coffee drinkers who abstain for 24 hours report withdrawal symptoms
- Withdrawal could explain: headaches, irritability & those people who are best avoided until they have
their morning cup of coffee - ‘weekend headaches’ & feelings of illness on holidays/weekends
Self-administration in animals
In animals:
* Caffeine is not a robust reinforcer
* Self-administration is variable & inconsistent; with no tendency to increase dose over time
Self-administration in humans
In humans:
* Reinforcing properties vary considerably btwn individuals
* Preference may be determined by level of dependence (i.e., withdrawal symptoms)
But in general:
* Caffeine s.a. related to state of physical dependence
* High doses less reinforcing than lower doses
* Preference may be context dependent
Caffeine-other drug interactions
- Common belief that caffeine can counteract the effects of sedative– hypnotic type drugs
- empirical evidence is equivocal
- Caffeine shows interesting interactions with another drug with which it is commonly used - nicotine
- caffeine may enhance reinforcing & subjective stimulant qualities of nicotine in humans
- smokers metabolise caffeine quicker than nonsmokers
- Smoking cessation → caffeine consumption ↑caffeine levels by >200%
- implications for smoking cessation programs
Harmful effects of caffeine
- Chromosomal damage at v. high doses
- ↑chromosomal damage caused by other agents (e.g., radiation)
- 200mg dose ↓placental blood flow by 25%
- Slows growth in the fetus & birthweight, esp. 1st trimester
- ↑ risk of miscarriage? (19% ↑ risk/150mg caffeine intake, Li et al., 2015)
- Potentiates effect of smoking
- Rate of metabolism slows with pregnancy – so baby gets higher & higher doses of caffeine
- Methylxanthines in breast milk can reach toxic levels (v.slow metabolism in newborns)
Caffeine and Cardiac disease
↑ blood pressure
* Heart disease/attacks???
* CYP1A2 gene (1F form: slow metabolisers): Campos (2006)
* Boiled coffee may ↑ cholesterol
Caffeine and cancer
- Animal studies do not support association
- May ↑ effect of other agents which cause cancer
Caffeine and Abnormal Behaviour
Caffeinism: results at 5-10 cups per day
- Sensory disturbance, delirium, fever, insomnia, irritability, irregularheartbeat, psychomotor agitation
- DSM-V: “caffeine intoxication” & “caffeine withdrawal”
- Panic attacks & ↑ anxiety
- From caffeine blocking benzodiazepine receptors
- Caffeine may also decrease effectiveness of some antipsychotics (e.g., chlorpromazine)
Caffeine and bone density
- Accelerated loss of bone density in postmenopausal women who consume less than recommended calcium dose
Caffeine and lethality
- Lethal dose ~150–200 mg/kg of body weight (Hodgman, 1998); other reports of 30- 80 cups of coffee (3-8 grams of caffeine) taken orally
- Death results from respiratory collapse & convulsions
- Australia has banned caffeine powders & highly concentrated caffeine solid and semi-solid products for this reason:
Caffeine use & psychopathology
- High caffeine intake:
- may be misdiagnosed as an anxiety disorder
- can cause agitation & hyposomnia which can lead to diagnosis of bipolar disorder
- reported to exacerbate psychosis
- Caffeine may be a complicating factor in anorexia nervosa
- Caffeine may interact with psychotropic medications incl. antidepressants (tricyclics & SSRIs)
