Download STIMULANTS

STIMULANTS
Allen Fowler
Mycheal Scott
Psyc 472
1
DEFINITION

Stimulants are a substance which tends to
increase behavioral activity when
administered
Elevate Mood
 Increase Motor Activity
 Increase Alertness
 Decrease need for Sleep
 Increase the brains metabolic and neuronal
activity

2
PROCESSES

While all stimulants increase behavioral
activity the component processes involved
differ.

Neurotransmitter or receptor processes
Increase neurotransmitters release
 Block reuptake


Inhibition of inhibitory neurotransmitters

disinhibition
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COMMONLY USED STIMULANTS
Caffeine
 Nicotine
 Amphetamine
 Cocaine
 Ephedrine
 Ritalin

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CAFFEINE AND NICOTINE
Allen Fowler
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CAFFEINE
(picture courtesy Erowid web site)
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CAFFEINE


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
Most commonly consumed psychoactive
drug in the world
Average intake per person per day is
between 80 to 400 milligrams
Consumption of caffeine is not considered
drug abuse
No regulation on sale or use
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CAFFEINE CONTENT
Item
Coffee (5 oz)
Tea (5oz)
Cocoa (5oz)
Chocolate (1oz)
Chocolate milk (1oz)
Cola drink (12oz)
OTC stimulants
OTC analgesics (aspirin)
OTC cold remedies
Average (mg)
100
50
5
25
5
100+
100+
35-65
30
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EFFECTS

Caffeine elicits positive effects such as

Enhanced mental alertness
 Sustained
intellectual effort
 No substantial disruption of coordinated intellectual
thought or motor activity
Increased energy
 A sense of well-being
 Faster and clearer flow of thought
 Reduced fatigue
 Need for sleep is delayed

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Effects

Caffeine may adversely effect tasks involving
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Heavy doses - 1.5 grams

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delicate muscle coordination
Accurate timing
Arithmetic skills
Agitation
Anxiety
Tremors
Rapid breathing
Insomnia
Lethal dose – 10 grams


100 cups of coffee
100 OTC stimulant capsules
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Effects

Caffeine causes a slight stimulant action
on the heart

Increases the workload
 cardiac


contractility
Increases cardiac output
Dilates coronary arteries

More oxygen to the heart
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Effects

Caffeine constricts cerebral blood vessels


Decreases blood flow by about 30%
Can relieve headaches

Bronchial relaxation

Increased secretion of gastric acid

Increased urine
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Effects

Chronic use associated with habituation
and tolerance

Quitting may cause withdrawal
Headaches
 Drowsiness
 Fatigue
 Negative mood

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Reproductive Effects

Freely crosses the placenta to the fetus

Consumed by estimated 75% of pregnant women

Breast milk contains levels equal or higher in concentration than mothers
plasma

Safety still unresolved

One study shows 300 mg relatively safe

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Another study shows 160 mg may cause growth retardation
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Higher doses increased intrauterine growth retardation
300mg intake even in the month before doubled the risk of spontaneous abortion
Recent study shows 6-10 cups per day is associated with increased risk of
spontaneous abortion

Moderate consumption does not increase the risk
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Therapeutic Uses

Asthma


Narcolepsy

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To help maintain daytime wakefulness
Migraine


Bronchial relaxation effects
Restricts blood flow in the cerebral cortex
Headache and other minor pain syndromes

In conjunction with aspirin
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Pharmacokinetics

Caffeine is rapidly and completely absorbed


Significant blood levels reached in 30-45 minutes
Levels peak in about 2 hours

Caffeine is freely and equally distributed through total
body water

Caffeine can be found in almost equal concentrations
throughout body and brain
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Pharmacokinetics

Caffeine has 3.5 to 5 hours half life

Extended half life for
 Elderly
 Pregnant

women
Up to ten hours
 Infants

Decreased half life for smokers
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Pharmacokinetics

Caffeine is metabolized in the liver by the
CYP1A2 subgroup of enzymes into three
metabolites

Theophylline
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Bronchial relaxation
Paraxanthine
Theobromine
Theophylline and Paraxanthine act similar to caffeine
About 10% is excreted unchanged
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Mechanism of Action
Major site of action
– Adenosine receptors
– Most potent at adenosine A1 and A2A
Caffeine works as an antagonism agent
– Blocks the adenosine receptor
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Mechanism of Action
– Adenosine is a neuromodulator
Modulatory effect increasing or decreasing the rate at which
neurons fire
Works in conjunction with the G protein processes
– Adenosine appears to exert sedative, depressant, and anticonvulsant
actions
Works to slow down the system
Important to sleeping
– Adenosinergic neurons form a diffuse system
No exclusively adenosinergic pathways
Adenosine stimulates GABAA inhibitory neurons
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Mechanism of Action
– Adenosine is created from the process by
which the body breaks down ATP for energy
ATP is used throughout the body for energy
Used for high energy bursts such as exercising
and running
Phosphates form a high energy bond
Cells break the phosphate bond to extrapolate the
energy
When the phosphates are pulled off the adenosine
is now free to have an effect in the body
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Mechanism of Action
A1 receptors inhibit excitatory neurons
–
–
–
–
Dopamine, glutamate, and ACh
secreting neurons
Reduces production of cAMP
Slows the activity of the kinase
Reduces occurrence of the action
potential
A2A receptors stimulate inhibitory
neurons
–
–
–
–
GABAA neurons
Stimulates production of cAMP
Increases activity of the kinase
Increases occurrence of the action
potential
picture courtesy “The Brain a Neuroscience Primer
”
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Mechanism of Action
Adenosine A receptors
1
– Inhibit the release of dopamine and glutamate
– Limit the release of acetylcholine
Blockade of A receptors
1
– Modest reward
– Increased vigilance and mental acuity
– Creates arousal effect
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Mechanism of Action
Adenosine A2A receptors
– Stimulate GABAA neurons of inhibitory
pathways
– Inhibit dopamine activity
Blockade of A2A receptors
– Increases the potency of endogenous
dopamine
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Mechanism of Action
Caffeine facilitates a disinhibition process
at adenosine receptor sites
Caffeine removes the negative effects of
adenosine from dopamine receptors
increasing dopamine activity
– Caffeine does not stimulate dopamine release
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NICOTINE
(picture courtesy Erowid web site)
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NICOTINE


Primary active ingredient in tobacco
One of the three most widely used
psychoactive drugs

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Caffeine
Alcohol
Few or no therapeutic applications
Important because of widespread use and
toxicity
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Background Information

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Indigenous to the Americas
1492 Columbus beaches in West Indies
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Natives offer them tobacco as gift
1556 first plants taken to Europe
1571 believed to have curing properties for
36 different ailments
1575-1600 becomes “duty” of every man of
fashion – worth its weight in silver
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Background Information

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1881 Cigarette rolling machine invented
1889 2.4 billion cigarettes produced annually in
U.S.
1904 3 billion cigarettes sold in U.S.
1912 13 billion cigarettes sold in U.S.
WWII through mid-1960’s smoking considered
cool
Now beginning to be shunned as unhealthy and
unwise
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Background Information

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Responsible for the deaths of 1100 Americans
every day
Each day
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6000 American teenagers try their first cigarette
3000 children become regular smokers
1000 of these will die from smoking related disease
9 in 10 smokers become addicted before age 21
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Background Information
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½ of all people who have smoked have quit
% American adults who smoke has fallen
from 50 in 1965 to 25 in 1998
Smoking identified as the major
preventable cause death and disability
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As far as 30 years ago
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Background Information
o
Nicotine is only one of about 4000
compounds released by burning tobacco
o
Adverse cardiovascular, pulmonary, and
carcinogenic effects are from the other
compounds
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Effects

Nicotine exerts powerful effects on
Brain
 Spinal cord
 Peripheral nervous system
 Heart
 Various other body structures
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Effects

Stimulation of the vomit center in the brain
stem and sensory receptors in the
stomach
Nausea in early stages of smoking
 Tolerance develops rapidly

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Reduces weight gain

probably by suppressing appetite
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Effects

Stimulates release of ADH (antidiuretic hormone)
causing fluid retention
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Reduces activity of afferent nerve fibers from muscles
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Higher doses
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Reduction in muscle tone
May be partially involved with relaxation effect
Can induce nervousness and tremors
Seizures in toxic overdose
Smoking associated with increased occurrence of panic
attacks and panic disorders
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Effects

In the CNS nicotine increases
Psychomotor activity
 Cognitive functioning
 Sensorimotor performance
 Attention
 Memory consolidation

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Effect

Nicotine can improve performance on
vigilance and rapid information processing

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Effects are greater for working memory rather
than long term memory
Nicotine exerts an antidepressant effect

High smoking rates among depressed
individuals may be an attempt at self
medication
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Effects

Nicotine exerts a potent reinforcing action
Indirect activation of midbrain dopamine
neurons
 Greatest in early phases
 Diminishes over time
 Smoking is continued to avoid withdrawal
symptoms

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Reproductive Effects
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Smoking during pregnancy increases rates
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spontaneous abortion
Stillbirth
Early postpartum death
Preterm deliveries

Intrauterine growth retardation is increased 40%

2000 infant deaths per year attributed to
smoking
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Reproductive Effects

Smoking reduces oxygen delivery to the
fetus resulting in varying degree of fetal
hypoxia
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Fetus does not receive as much oxygen
Smoking may result in irreversible
intellectual and physical deficiencies
Increased prevalence of ADHD
 Lower IQ scores
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Tolerance

Nicotine does not appear induce a pronounced
degree of biological tolerance
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Increased use in early stages which usually levels off
as smoking is continued
Smokers adjust nicotine intake to maintain 20 to 40
nanograms per milliliter of plasma
Does induce physiological and psychological
dependence

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Habituation
Rebound effect
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Withdrawal Symptoms
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Intense nicotine craving
Irritability
Anxiety
Anger
Difficulty concentrating
Restlessness
Impatience
Increased appetite
Weight gain
Insomnia
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Therapy

Nicotine replacement therapy doubles
successful quit rates
Skin patches
 Gum
 Nicotine nasal spray

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The use of Zyban has also been shown to
increase successful quit rates
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Pharmacokinetics
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Easily absorbed in the body
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Lungs
Buccal and nasal mucosa
Skin
Gastrointestinal tract
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Nicotine is suspended in the minute particles (tars) in
smoke

Orally administered blood levels of nicotine are
comparable to smoking
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Pharmacokinetics

Only about 20% of the nicotine in a cigarette is inhaled
and absorbed into the bloodstream
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Nicotine which is not immediately absorbed is rapidly
metabolized by the hepatic enzyme CYP2A6
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Inhalation allows controllability of dose
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Frequency of breaths
Depth of breaths
Time in lungs
Number of cigarettes
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Pharmacokinetics
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Nicotine is thoroughly distributed in the body
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The liver metabolizes 80 to 90% before excretion to the
kidneys
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No barriers to nicotine distribution
Rapid brain penetration
Crosses placental barrier
Appears in all bodily fluids
Primary metabolite is cotinine
The elimination half life in chronic users is about 2 hrs
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Mechanism of Action
Nicotine activates specific acetylcholine
(ACh) receptors known as nicotinic
receptors
Nicotinic receptors are located throughout
the body
– Skeletal muscle
– Sympathetic and parasympathetic neurons
– CNS
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Mechanism of Action
ACh is released, broken down, and
reabsorbed very quickly (microsecond)
allowing the receptor to respond to new
Ach
ACh receptors work as a fast first
messenger system
– Attached directly to ion channels
– Binding has an immediate response
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Mechanism of Action
picture courtesy pharyngula.org
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Nicotine replaces ACh at nicotinic receptor
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Beats out the ACh at the binding site
Works as an agonist
Opens ion channel allowing depolarization to occur
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Peripheral Nervous System

Activation of nicotinic receptors in the PNS
Increases blood pressure and heart rate
 Causes the release of epinephrine from the adrenal
glands
 Increases the tone, secretions, and activity of the
gastrointestinal tract
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Central Nervous System
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Nicotinic receptors are widely distributed and may be
present at the presynaptic terminals of neurons which
secrete
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Dopamine
Acetylcholine
Glutamine
Activation by nicotine facilitates the release and
increases the action in the brain of these
neurotransmitters
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Central Nervous System

Dopamine levels are increased in the
Ventral tegmentum
 Nucleus accumbens
 Forebrain
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Stimulation of these areas account for the
behavioral reinforcement, stimulant,
antidepressant, and addictive properties of
nicotine
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Central Nervous System

Increases in acetylcholine contribute to the
cognitive potentiation and memory facilitation
properties of nicotine
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Facilitation of glutaminergic neurotransmissions
contribute to the improvement in memory
functioning
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Smoking Diseases
Smoking accelerates the
depositing of fat in the arteries



Increased risk of heart attack and
stroke
Smoking weakens the immune
system
Smoking irritates the lining in the
lungs impairing respiration


Smokers cough
Emphysema
picture courtesy quantumclinic.com
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Smoking Diseases
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Lung cancer
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90-95% of male
deaths
70-75% of female
deaths
Cancer of the mouth
and throat

Chewing tobacco
Picture courtesy quantumclinic.com
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Smoking Diseases
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Cardiovascular disease
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Carbon monoxide decreases amount of oxygen
delivered to the heart while nicotine increases the
workload
Carbon monoxide and nicotine increase narrowing
(atherosclerosis) and clotting (thrombosis) in the
coronary arteries
Increased risk of coronary heart disease
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Smoking Diseases
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About 4000 Americans per year die from
lung cancer caused by second-hand
smoke
37000 deaths per year from heart disease
caused by second hand smoke
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Sources
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Julien, Robert M. (2001). A Primer of Drug Action (ninth ed.).
Caffeine and Nicotine (pp 220-248). NY, New York: Worth
Publishers.
Tompson, Richard M. (2000). The Brain: A Neuroscience Primer
(third ed.). NY, New York: Worth Publishers.
http://www.erowid.org/psychoactives/psychoactives.shtml
http://home.howstuffworks.com/caffeine.htm
http://www.nida.nih.gov
http://pharyngula.org/~pzmyers/neuro/synapse/index.php?print
http://www.quantumclinic.com/quitsmoking/quit-smoking-stopaddiction-cigarettes-nicotine-lung-cancer-photos.htm
http://www.ccc.nottingham.ac.uk/~mqzwww/adenosine.html
http://www.pbs.org/wgbh/nova/cigarette/nicotine.html
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