Cocaine & Cocaine & AmphetaminesAmphetamines

Cocaine – Background InfoCocaine – Background Info

From the leaves of Erythroxylan cocaFrom the leaves of Erythroxylan cocaAncient use in S. AmericaAncient use in S. America

Religious, Social, Euphoriant, and MedicinalReligious, Social, Euphoriant, and MedicinalActive alkaloid 1Active alkaloid 1stst purified from the leaves purified from the leaves

in 1860 – What we commonly know as in 1860 – What we commonly know as Cocaine.Cocaine.

Early YearsEarly Years

Proven to be one of the 1Proven to be one of the 1stst local local anesthetics for surgeryanesthetics for surgery

Sigmund Freud obtained and studied Sigmund Freud obtained and studied cocaine’s psychological effectscocaine’s psychological effectsAdvocated its use and prescribed cocaine for Advocated its use and prescribed cocaine for

depression and chronic fatigue.depression and chronic fatigue.Later he realized its adverse side effectsLater he realized its adverse side effects

Early Years Cont.Early Years Cont.

Cocaine incorporated into numerous Cocaine incorporated into numerous medicines and beveragesmedicines and beveragesCoca-ColaCoca-Cola

Harrison Narcotic Act banned its use in Harrison Narcotic Act banned its use in 19141914

Recreational use increased dramatically in Recreational use increased dramatically in the late 1960’sthe late 1960’s

Inexpensive “crack” cocaine use spread in Inexpensive “crack” cocaine use spread in the late 1970’sthe late 1970’s

StatisticsStatistics

In 1985 – Estimated 5.7 million usersIn 1985 – Estimated 5.7 million users In 1997 – Estimated 1.5 million usersIn 1997 – Estimated 1.5 million usersUse in high schools increasingUse in high schools increasing

Forms of CocaineForms of Cocaine

E. coca contains about 0.5-1.0% cocaineE. coca contains about 0.5-1.0% cocaineLeaves are soaked in kerosene and Leaves are soaked in kerosene and

gasoline and mashedgasoline and mashedCocaine extracted in the form of coca Cocaine extracted in the form of coca

pastepastePaste approx 50-60% purityPaste approx 50-60% purity

Cocaine HydrochlorideCocaine Hydrochloride

Paste is treated with numerous chemicals Paste is treated with numerous chemicals to oxidize and purify the paste to form the to oxidize and purify the paste to form the water soluble cocaine hydrochloride water soluble cocaine hydrochloride powder.powder.

Can be close to 100% pureCan be close to 100% pureCan be injected, inhaled as powder, or Can be injected, inhaled as powder, or

ingested orallyingested orallyCannot be smokedCannot be smoked

Freebase FormFreebase Form

A.k.a. Crack CocaineA.k.a. Crack CocaineSimilar to the unpurified insoluble coca Similar to the unpurified insoluble coca

paste.paste.Made by reversing the oxidation processMade by reversing the oxidation processCannot be inhaled (as powder) or injected Cannot be inhaled (as powder) or injected

because it is not water solublebecause it is not water solubleForms a stable vapor when heated and Forms a stable vapor when heated and

inhaled (smoked)inhaled (smoked)

PharmacokineticsPharmacokinetics

Absorption (Cocaine HCl)Absorption (Cocaine HCl)Absorbed from all sites of applicationAbsorbed from all sites of application

Mucous membranes, lungs, stomachMucous membranes, lungs, stomach

VasoconstrictorVasoconstrictorcrosses mucosal membrane poorlycrosses mucosal membrane poorly

Plasma levels peak 30-60 minutesPlasma levels peak 30-60 minutesNasal Inhalation causes slow absorption Nasal Inhalation causes slow absorption

which allows for prolonged euphoric effectwhich allows for prolonged euphoric effect

PharmacokineticsPharmacokinetics

IV injectionIV injectionBypasses all barriers to absorptionBypasses all barriers to absorptionTotal dosage goes into blood stream and Total dosage goes into blood stream and

eventually the braineventually the brainSmoking Cocaine BaseSmoking Cocaine Base

Absorption is rapid and complete at the lungsAbsorption is rapid and complete at the lungsEffects onset in seconds, peaks in 5 minutes Effects onset in seconds, peaks in 5 minutes

and lasts about 30 minutesand lasts about 30 minutes

PharmacokineticsPharmacokinetics

DistributionDistributionPenetrates brain rapidlyPenetrates brain rapidlyBrain concentrations far exceed plasma levelsBrain concentrations far exceed plasma levelsFreely crosses the placental barrierFreely crosses the placental barrier

PharmacokineticsPharmacokinetics

Metabolism & ExcretionMetabolism & ExcretionHalf-life 30-90 min.Half-life 30-90 min.Metabolized by enzymes in both plasma and Metabolized by enzymes in both plasma and

liverliverSlowly removed from brainSlowly removed from brainPositive urine tests for 12 hoursPositive urine tests for 12 hoursMajor metabolite is benzoylecognineMajor metabolite is benzoylecognine

Use With AlcoholUse With Alcohol

In the presence of ethanol a different In the presence of ethanol a different metabolite is produced – cocaethylenemetabolite is produced – cocaethylene

Cocaethylene has the same physiological Cocaethylene has the same physiological effect on the brain as cocaine but more toxiceffect on the brain as cocaine but more toxic Euphoric effects last longer Euphoric effects last longer Increases risk of dual dependencyIncreases risk of dual dependency Increases severity of withdrawalIncreases severity of withdrawal

Alcohol/Cocaine is the largest two drug Alcohol/Cocaine is the largest two drug combination resulting in deathcombination resulting in death

Mechanism of ActionMechanism of Action

Dopaminergic ActionsDopaminergic ActionsPotentiates the synaptic actions of dopamine, Potentiates the synaptic actions of dopamine,

norepinephrine and serotoninnorepinephrine and serotoninCocaine attaches to and blocks presynaptic Cocaine attaches to and blocks presynaptic

dopamine reuptake transport proteinsdopamine reuptake transport proteinsDopamine stays in the synapse longerDopamine stays in the synapse longer

Mechanism of ActionMechanism of Action

Behavior-reinforcing propertiesBehavior-reinforcing propertiesDopamine is the key NT for reinforcementDopamine is the key NT for reinforcementStudies show cocaine increases sensitivity of Studies show cocaine increases sensitivity of

D3 dopamine receptors in nucleus D3 dopamine receptors in nucleus accumbens and other parts of the mesolimbic accumbens and other parts of the mesolimbic system important for behavior reinforcment.system important for behavior reinforcment.Increased density of D3 receptors in OD victimsIncreased density of D3 receptors in OD victimsResponsible for cravingResponsible for craving

Effects of Short Term UseEffects of Short Term Use

Low dose, nontoxic physiological Low dose, nontoxic physiological responses includeresponses include Increased alertnessIncreased alertnessMotor hyperactivityMotor hyperactivityTachycardiaTachycardiaPupillary dilationPupillary dilation Increased glucose availabilityIncreased glucose availabilityShifts of blood flow from internal organs to Shifts of blood flow from internal organs to

musclesmuscles

Effects of Short Term UseEffects of Short Term Use

Psychological Effects Psychological Effects Immediate euporiaImmediate euporiaGiddinessGiddinessEnhanced self-consciousnessEnhanced self-consciousnessForceful boastfulnessForceful boastfulness

These last approx 30 min.These last approx 30 min.

Effects of Short Term UseEffects of Short Term Use

Moderate euphoria lasts for 60-90 minModerate euphoria lasts for 60-90 minA state of anxiety lasts for hoursA state of anxiety lasts for hoursThoughts race, rapid speechThoughts race, rapid speechSleep delayed Sleep delayed Appetite suppressedAppetite suppressedA depressive state followsA depressive state follows

Effects of Short Term UseEffects of Short Term Use

Effects in the CNSEffects in the CNSDepletion of OxygenDepletion of OxygenCerebral AtrophyCerebral AtrophySeizuresSeizuresOthersOthers

Numerous cardiovascular complications Numerous cardiovascular complications can occur with prolonged or single usecan occur with prolonged or single use

Toxic and Psychotic Effects of Toxic and Psychotic Effects of Long-Term, High Dose UseLong-Term, High Dose Use

Anxiety and sleep deprivation increaseAnxiety and sleep deprivation increaseHypervigilanceHypervigilanceSuspiciousness, paranoia, and Suspiciousness, paranoia, and

persecutory fears persecutory fears Toxic Paranoid PsychosisToxic Paranoid Psychosis

Altered perception of reality that can result in Altered perception of reality that can result in aggressive or homicidal actions as a aggressive or homicidal actions as a response to imagined persecutionresponse to imagined persecution

Medical ComplicationsMedical Complications

Many cardiovascular effectsMany cardiovascular effectsHeart attacksHeart attacks Irregular heart rhythmIrregular heart rhythm

Respiratory failureRespiratory failureSeizures Seizures

Tolerance and SensitizationTolerance and Sensitization

Tolerance to the “high” often occurs due to Tolerance to the “high” often occurs due to downregulationdownregulation

Sensitization of the anesthetic and Sensitization of the anesthetic and convulsant effects occursconvulsant effects occursExplains some deaths occurring after low Explains some deaths occurring after low

dosesdoses

ComorbidityComorbidity

Chronic cocaine use produces virtually Chronic cocaine use produces virtually every psychiatric syndromeevery psychiatric syndrome

300 abusers300 abusers56% met current criteria56% met current criteria73% met lifetime criteria73% met lifetime criteria

Alcoholism and Heroin addiction extremely Alcoholism and Heroin addiction extremely high in cocaine usershigh in cocaine users

Cocaine and PregnancyCocaine and Pregnancy

Many indirect effects from the Many indirect effects from the vasoconstriction of mothers blood vesselsvasoconstriction of mothers blood vesselsDecreased blood flow and oxygen to UterusDecreased blood flow and oxygen to UterusAssociated withAssociated with

Placental detachmentPlacental detachmentPreterm laborPreterm laborStillbirthStillbirthLow birth weightLow birth weightOthersOthers

Cocaine and PregnancyCocaine and Pregnancy

Direct effects from cocaine in the fetusDirect effects from cocaine in the fetusNeonatal neurological syndromeNeonatal neurological syndrome

Abnormal sleep patterns, tremors, seizuresAbnormal sleep patterns, tremors, seizures

Increased incidence of SIDSIncreased incidence of SIDSCocaine impaired children show difficulty Cocaine impaired children show difficulty

developing attachments, dealing with developing attachments, dealing with multiple stimuli, aggressionmultiple stimuli, aggression

High incidence of ADHDHigh incidence of ADHD

TreatmentTreatment

There is no consensus on a generally There is no consensus on a generally accepted successful pharmacological accepted successful pharmacological treatment.treatment.

Three problems that complicate therapyThree problems that complicate therapy1.1. Intensity of the drug effect and reinforcing Intensity of the drug effect and reinforcing

actionaction

2.2. Pronounced tendency toward relapsePronounced tendency toward relapse

3.3. Most addicts have a coexisting disorderMost addicts have a coexisting disorder

TreatmentTreatment

Three areas of need for pharmacologic Three areas of need for pharmacologic interventionintervention

1.1. Antiwithdrawal agents to restore the Antiwithdrawal agents to restore the dopaminergic tone of the limbic systemdopaminergic tone of the limbic system

2.2. Anticraving agents that block limbic Anticraving agents that block limbic dopaminergic receptorsdopaminergic receptors

3.3. Treatment of coexisting disordersTreatment of coexisting disorders

TreatmentTreatment

Psychosocial treatment offers the most Psychosocial treatment offers the most promisepromiseCocaine Anonymous Cocaine Anonymous Individual/Group counselingIndividual/Group counselingCognitive behavioral therapyCognitive behavioral therapyPsychodynamic therapyPsychodynamic therapyBehavior Reinforcement strategiesBehavior Reinforcement strategies

Amphetamines - BackgroundAmphetamines - Background

Used for over 60 years therapeutically for Used for over 60 years therapeutically for numerous disordersnumerous disordersSchizophrenia Schizophrenia Addictions (morphine and nicotine)Addictions (morphine and nicotine)Head InjuryHead InjuryHypotensionHypotensionSevere hiccupsSevere hiccupsOthersOthers

Amphetamines - BackgroundAmphetamines - Background

Used in WW II to fight fatigue and Used in WW II to fight fatigue and enhance performanceenhance performance

Widespread abuse began in 1940’s with Widespread abuse began in 1940’s with students and truck drivers to stay awake students and truck drivers to stay awake and increase alertnessand increase alertness

Were used as appetite suppressantsWere used as appetite suppressants

Mechanism of ActionMechanism of Action

All CNS effects caused by the release of All CNS effects caused by the release of newly synthesized NE and dopamine from newly synthesized NE and dopamine from presynaptic storage sitespresynaptic storage sites

Behavioral stimulation and increased Behavioral stimulation and increased motor activity result from stimulation of motor activity result from stimulation of dopamine receptors in the mesolimbic dopamine receptors in the mesolimbic systemsystem

Pharmacological EffectsPharmacological Effects

Physiological EffectsPhysiological Effects Increased BPIncreased BPDecreased HRDecreased HR Increased alertnessIncreased alertnessPsychomotor stimulantPsychomotor stimulantLoss of appetiteLoss of appetite

Pharmacological EffectsPharmacological Effects

Psychological EffectsPsychological EffectsEuphoriaEuphoriaExcitementExcitementMood elevationMood elevation Increased motor/speech activityIncreased motor/speech activityFeeling of powerFeeling of power

Pharmacological EffectsPharmacological Effects

More effectsMore effectsTask performance may improveTask performance may improveDexterity deterioratesDexterity deteriorates

Pharmacological EffectsPharmacological Effects

Metabolized in the liverMetabolized in the liverExcreted through the urineExcreted through the urineDetectable for up to 48 hoursDetectable for up to 48 hours

Pharmacological EffectsPharmacological Effects

At moderate dosesAt moderate dosesRespiratory stimulationRespiratory stimulationSlight tremorsSlight tremorsRestlessnessRestlessnessGreater increase in motor activityGreater increase in motor activity InsomniaInsomniaAgitationAgitation

Pharmacological EffectsPharmacological Effects

At high dosesAt high dosesRepetitive purposeless actsRepetitive purposeless actsSudden outbursts of aggression/violenceSudden outbursts of aggression/violenceParanoid delusionsParanoid delusionsSevere anorexiaSevere anorexiaOverall psychosis and abnormal mental Overall psychosis and abnormal mental

conditionsconditionsAmphetamine Psychosis: paranoid ideationAmphetamine Psychosis: paranoid ideation

Primarily with meth usersPrimarily with meth users

Pharmacological EffectsPharmacological Effects

In addition to the direct effects of the In addition to the direct effects of the drug….drug…. Infections from neglected health careInfections from neglected health carePoor eating habitsPoor eating habitsUse of unsterile equipmentUse of unsterile equipmentGreat deterioration in social, personal, Great deterioration in social, personal,

occupational affairsoccupational affairs

Pharmacological EffectsPharmacological Effects

Long Term evidence shows...Long Term evidence shows...Psychometric deficitsPsychometric deficitsPoor academic performancePoor academic performanceBehavioral problemsBehavioral problemsCognitive slowingCognitive slowingGeneral maladjustmentGeneral maladjustment

The effects on this list are permanent.The effects on this list are permanent.

Dependence and ToleranceDependence and Tolerance

Use becomes compulsiveUse becomes compulsiveDrug strongly effects areas of brain Drug strongly effects areas of brain

associated with behavior reinforcementassociated with behavior reinforcementPhysical dependence follows a classical Physical dependence follows a classical

conditioning modelconditioning modelWithdrawal occurs but not as dramatic as Withdrawal occurs but not as dramatic as

with narcotics and barbiturateswith narcotics and barbituratesSymptoms opposite of drugs effectsSymptoms opposite of drugs effects

Dependence and ToleranceDependence and Tolerance

Tolerance develops rapidlyTolerance develops rapidlyNecessitates the need for markedly higher Necessitates the need for markedly higher

dosesdosesTolerance to the euphoriant effects Tolerance to the euphoriant effects

develops which causes prolonged bingingdevelops which causes prolonged binging

ICEICE

Freebase form of methamphetamineFreebase form of methamphetamineExtremely potentExtremely potentHigh is intense and long lastingHigh is intense and long lastingChronic use can result in serious Chronic use can result in serious

psychiatric, cardiovascular, metabolic and psychiatric, cardiovascular, metabolic and neuromuscular changesneuromuscular changes

ICE: PharmacokineticsICE: Pharmacokinetics

Smoking causes immediate absorptionSmoking causes immediate absorptionBiological half-life around 11 hoursBiological half-life around 11 hours60% metabolized in the liver after 60% metabolized in the liver after

distribution to the braindistribution to the brain40% excreted unchanged40% excreted unchanged

ICE: Effects and ToxicityICE: Effects and Toxicity

Effects similar to cocaineEffects similar to cocainePotent psychomotor stimulants and Potent psychomotor stimulants and

positive reinforcerspositive reinforcersRepeated high doses associated with Repeated high doses associated with

paranoid psychosisparanoid psychosis

ICE: Effects and ToxicityICE: Effects and Toxicity

Many permanent effects due to long-Many permanent effects due to long-lasting abnormal brain chemistries lasting abnormal brain chemistries

Can cause permanent alterations in…Can cause permanent alterations in…Sleep functionsSleep functionsSexual functionsSexual functionsMood (permanent depression)Mood (permanent depression)SchizophreniaSchizophreniaMovement disordersMovement disorders

ICE: Effects and ToxicityICE: Effects and Toxicity

Abnormal brain chemistriesAbnormal brain chemistriesStudies show reduced neuronal density in Studies show reduced neuronal density in

frontal lobe and basal ganglia in abstinent frontal lobe and basal ganglia in abstinent meth users.meth users.

Other Behavioral StimulantsOther Behavioral Stimulants

EphedrineEphedrineMethylphenidate (Ritalin)Methylphenidate (Ritalin)

EphedrineEphedrine

In the news recentlyIn the news recentlySteve BechlerSteve Bechler

Increases NE in the synapseIncreases NE in the synapse Increases BPIncreases BPWeight LossWeight Loss

Methylphenidate (Ritalin)Methylphenidate (Ritalin)

Mechanism similar to cocaineMechanism similar to cocaineAlso studies show it increases dopamine Also studies show it increases dopamine

like amphetaminelike amphetamineUsed for ADHDUsed for ADHDCan be taken IV with cocaine like rushCan be taken IV with cocaine like rush