Cocaine &
Amphetamines
Cocaine – Background Info
From the leaves of Erythroxylan coca
 Ancient use in S. America
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Religious, Social, Euphoriant, and Medicinal
Active alkaloid 1st purified from the leaves
in 1860 – What we commonly know as
Cocaine.
Early Years
Proven to be one of the 1st local
anesthetics for surgery
 Sigmund Freud obtained and studied
cocaine’s psychological effects

Advocated its use and prescribed cocaine for
depression and chronic fatigue.
 Later he realized its adverse side effects

Early Years Cont.

Cocaine incorporated into numerous
medicines and beverages

Coca-Cola
Harrison Narcotic Act banned its use in
1914
 Recreational use increased dramatically in
the late 1960’s
 Inexpensive “crack” cocaine use spread in
the late 1970’s

Statistics
In 1985 – Estimated 5.7 million users
 In 1997 – Estimated 1.5 million users
 Use in high schools increasing

Forms of Cocaine
E. coca contains about 0.5-1.0% cocaine
 Leaves are soaked in kerosene and
gasoline and mashed
 Cocaine extracted in the form of coca
paste
 Paste approx 50-60% purity

Cocaine Hydrochloride
Paste is treated with numerous chemicals
to oxidize and purify the paste to form the
water soluble cocaine hydrochloride
powder.
 Can be close to 100% pure
 Can be injected, inhaled as powder, or
ingested orally
 Cannot be smoked

Freebase Form
A.k.a. Crack Cocaine
 Similar to the unpurified insoluble coca
paste.
 Made by reversing the oxidation process
 Cannot be inhaled (as powder) or injected
because it is not water soluble
 Forms a stable vapor when heated and
inhaled (smoked)

Pharmacokinetics

Absorption (Cocaine HCl)

Absorbed from all sites of application
 Mucous

membranes, lungs, stomach
Vasoconstrictor
 crosses
mucosal membrane poorly
Plasma levels peak 30-60 minutes
 Nasal Inhalation causes slow absorption
which allows for prolonged euphoric effect

Pharmacokinetics

IV injection
Bypasses all barriers to absorption
 Total dosage goes into blood stream and
eventually the brain


Smoking Cocaine Base
Absorption is rapid and complete at the lungs
 Effects onset in seconds, peaks in 5 minutes
and lasts about 30 minutes

Pharmacokinetics

Distribution
Penetrates brain rapidly
 Brain concentrations far exceed plasma levels
 Freely crosses the placental barrier

Pharmacokinetics

Metabolism & Excretion
Half-life 30-90 min.
 Metabolized by enzymes in both plasma and
liver
 Slowly removed from brain
 Positive urine tests for 12 hours
 Major metabolite is benzoylecognine

Use With Alcohol
In the presence of ethanol a different
metabolite is produced – cocaethylene
 Cocaethylene has the same physiological
effect on the brain as cocaine but more
toxic

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Euphoric effects last longer
Increases risk of dual dependency
Increases severity of withdrawal
Alcohol/Cocaine is the largest two drug
combination resulting in death
Mechanism of Action

Dopaminergic Actions
Potentiates the synaptic actions of dopamine,
norepinephrine and serotonin
 Cocaine attaches to and blocks presynaptic
dopamine reuptake transport proteins
 Dopamine stays in the synapse longer

Mechanism of Action

Behavior-reinforcing properties
Dopamine is the key NT for reinforcement
 Studies show cocaine increases sensitivity of
D3 dopamine receptors in nucleus
accumbens and other parts of the mesolimbic
system important for behavior reinforcment.

 Increased
density of D3 receptors in OD victims
 Responsible for craving
Effects of Short Term Use

Low dose, nontoxic physiological
responses include
Increased alertness
 Motor hyperactivity
 Tachycardia
 Pupillary dilation
 Increased glucose availability
 Shifts of blood flow from internal organs to
muscles

Effects of Short Term Use

Psychological Effects
Immediate euporia
 Giddiness
 Enhanced self-consciousness
 Forceful boastfulness


These last approx 30 min.
Effects of Short Term Use
Moderate euphoria lasts for 60-90 min
 A state of anxiety lasts for hours
 Thoughts race, rapid speech
 Sleep delayed
 Appetite suppressed
 A depressive state follows

Effects of Short Term Use

Effects in the CNS
Depletion of Oxygen
 Cerebral Atrophy
 Seizures
 Others


Numerous cardiovascular complications
can occur with prolonged or single use
Toxic and Psychotic Effects of
Long-Term, High Dose Use
Anxiety and sleep deprivation increase
 Hypervigilance
 Suspiciousness, paranoia, and
persecutory fears
 Toxic Paranoid Psychosis


Altered perception of reality that can result in
aggressive or homicidal actions as a
response to imagined persecution
Medical Complications

Many cardiovascular effects
Heart attacks
 Irregular heart rhythm

Respiratory failure
 Seizures

Tolerance and Sensitization
Tolerance to the “high” often occurs due to
downregulation
 Sensitization of the anesthetic and
convulsant effects occurs


Explains some deaths occurring after low
doses
Comorbidity
Chronic cocaine use produces virtually
every psychiatric syndrome
 300 abusers

 56%
met current criteria
 73% met lifetime criteria

Alcoholism and Heroin addiction extremely
high in cocaine users
Cocaine and Pregnancy

Many indirect effects from the
vasoconstriction of mothers blood vessels
Decreased blood flow and oxygen to Uterus
 Associated with

 Placental
detachment
 Preterm labor
 Stillbirth
 Low birth weight
 Others
Cocaine and Pregnancy

Direct effects from cocaine in the fetus

Neonatal neurological syndrome
 Abnormal

sleep patterns, tremors, seizures
Increased incidence of SIDS
Cocaine impaired children show difficulty
developing attachments, dealing with
multiple stimuli, aggression
 High incidence of ADHD

Treatment

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There is no consensus on a generally
accepted successful pharmacological
treatment.
Three problems that complicate therapy
1.
2.
3.
Intensity of the drug effect and reinforcing
action
Pronounced tendency toward relapse
Most addicts have a coexisting disorder
Treatment

Three areas of need for pharmacologic
intervention
1.
2.
3.
Antiwithdrawal agents to restore the
dopaminergic tone of the limbic system
Anticraving agents that block limbic
dopaminergic receptors
Treatment of coexisting disorders
Treatment

Psychosocial treatment offers the most
promise
Cocaine Anonymous
 Individual/Group counseling
 Cognitive behavioral therapy
 Psychodynamic therapy
 Behavior Reinforcement strategies

Amphetamines - Background

Used for over 60 years therapeutically for
numerous disorders
Schizophrenia
 Addictions (morphine and nicotine)
 Head Injury
 Hypotension
 Severe hiccups
 Others

Amphetamines - Background
Used in WW II to fight fatigue and
enhance performance
 Widespread abuse began in 1940’s with
students and truck drivers to stay awake
and increase alertness
 Were used as appetite suppressants

Mechanism of Action
All CNS effects caused by the release of
newly synthesized NE and dopamine from
presynaptic storage sites
 Behavioral stimulation and increased
motor activity result from stimulation of
dopamine receptors in the mesolimbic
system

Pharmacological Effects

Physiological Effects
Increased BP
 Decreased HR
 Increased alertness
 Psychomotor stimulant
 Loss of appetite

Pharmacological Effects

Psychological Effects
Euphoria
 Excitement
 Mood elevation
 Increased motor/speech activity
 Feeling of power

Pharmacological Effects

More effects
Task performance may improve
 Dexterity deteriorates

Pharmacological Effects

Metabolized in the liver
Excreted through the urine
 Detectable for up to 48 hours

Pharmacological Effects

At moderate doses
Respiratory stimulation
 Slight tremors
 Restlessness
 Greater increase in motor activity
 Insomnia
 Agitation

Pharmacological Effects

At high doses
Repetitive purposeless acts
 Sudden outbursts of aggression/violence
 Paranoid delusions
 Severe anorexia
 Overall psychosis and abnormal mental
conditions
 Amphetamine Psychosis: paranoid ideation

 Primarily
with meth users
Pharmacological Effects

In addition to the direct effects of the
drug….
Infections from neglected health care
 Poor eating habits
 Use of unsterile equipment
 Great deterioration in social, personal,
occupational affairs

Pharmacological Effects

Long Term evidence shows...
Psychometric deficits
 Poor academic performance
 Behavioral problems
 Cognitive slowing
 General maladjustment
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The effects on this list are permanent.
Dependence and Tolerance

Use becomes compulsive
Drug strongly effects areas of brain
associated with behavior reinforcement
 Physical dependence follows a classical
conditioning model
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Withdrawal occurs but not as dramatic as
with narcotics and barbiturates

Symptoms opposite of drugs effects
Dependence and Tolerance
Tolerance develops rapidly
 Necessitates the need for markedly higher
doses
 Tolerance to the euphoriant effects
develops which causes prolonged binging

ICE
Freebase form of methamphetamine
 Extremely potent
 High is intense and long lasting
 Chronic use can result in serious
psychiatric, cardiovascular, metabolic and
neuromuscular changes

ICE: Pharmacokinetics
Smoking causes immediate absorption
 Biological half-life around 11 hours
 60% metabolized in the liver after
distribution to the brain
 40% excreted unchanged

ICE: Effects and Toxicity
Effects similar to cocaine
 Potent psychomotor stimulants and
positive reinforcers
 Repeated high doses associated with
paranoid psychosis

ICE: Effects and Toxicity
Many permanent effects due to longlasting abnormal brain chemistries
 Can cause permanent alterations in…

Sleep functions
 Sexual functions
 Mood (permanent depression)
 Schizophrenia
 Movement disorders

ICE: Effects and Toxicity
Abnormal brain chemistries
 Studies show reduced neuronal density in
frontal lobe and basal ganglia in abstinent
meth users.

Other Behavioral Stimulants
Ephedrine
 Methylphenidate (Ritalin)

Ephedrine

In the news recently

Steve Bechler
Increases NE in the synapse
 Increases BP
 Weight Loss

Methylphenidate (Ritalin)
Mechanism similar to cocaine
 Also studies show it increases dopamine
like amphetamine
 Used for ADHD
 Can be taken IV with cocaine like rush
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