Hart13 ppt ch06

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Chapter 6Chapter 6

StimulantsStimulants



Stimulants are substances Stimulants are substances that keep a person going that keep a person going mentally and physicallymentally and physically

Cocaine and amphetamine Cocaine and amphetamine are restricted stimulantsare restricted stimulants

Caffeine and nicotine are Caffeine and nicotine are readily available stimulants readily available stimulants


History of CocaineHistory of Cocaine

Coca is a bush that grows in the Andes and Coca is a bush that grows in the Andes and produces cocaineproduces cocaine Coca has been harvested for thousands of years Coca has been harvested for thousands of years

and actively cultivated for over 800 yearsand actively cultivated for over 800 years



Natives of the Andes chewed Natives of the Andes chewed coca leaves to give them coca leaves to give them greater strength and greater strength and endurance endurance

The coca leaf was an The coca leaf was an important part of Inca cultureimportant part of Inca culture Used in religious ceremonies Used in religious ceremonies

and as currency and as currency

Coca leaf market



Coca wine:Coca wine: Angelo Mariani Angelo Mariani Used coca leaf extract in many Used coca leaf extract in many

products including lozenges, products including lozenges, tea, and, especially, winetea, and, especially, wine



Coca extract was later used in the United States in early Coca extract was later used in the United States in early versions of Coca-Cola and in many patent medicinesversions of Coca-Cola and in many patent medicines



Local anesthesia:Local anesthesia: Dr. W. S. Halsted Dr. W. S. Halsted Experimented with ability of cocaine to produce Experimented with ability of cocaine to produce

local anesthesialocal anesthesia Delivered via newly developed hypodermic syringeDelivered via newly developed hypodermic syringe

Cocaine was isolated Cocaine was isolated before 1860before 1860

Processing 500 kilograms Processing 500 kilograms of coca leaves yieldsof coca leaves yields1 kilogram of cocaine 1 kilogram of cocaine

Drying coca leaves



Early psychiatric uses:Early psychiatric uses:Sigmund Freud Sigmund Freud Studied use of cocaine as a treatment for Studied use of cocaine as a treatment for

depression and morphine dependencedepression and morphine dependence Later opposed use of the drug after nursing Later opposed use of the drug after nursing

a friend through cocaine psychosisa friend through cocaine psychosis


Early Legal ControlEarly Legal Control

46 states passed laws to regulate cocaine 46 states passed laws to regulate cocaine between 1887 and 1914between 1887 and 1914

Press and politicians made unsubstantiated Press and politicians made unsubstantiated claims about cocaine use among southern claims about cocaine use among southern blacks: blacks: Widespread Widespread Associated with increased violent crimeAssociated with increased violent crime

Negative publicity about cocaine influenced Negative publicity about cocaine influenced the passage of the 1914 Harrison Actthe passage of the 1914 Harrison Act


Forms of CocaineForms of Cocaine

Coca pasteCoca paste Crude extract created during the Crude extract created during the

manufacture of cocainemanufacture of cocaine Can be mixed with tobacco and Can be mixed with tobacco and

smoked smoked

Cocaine hydrochloride Cocaine hydrochloride Most common form of pure Most common form of pure

cocainecocaine Stable water-soluble salt Stable water-soluble salt


Forms of CocaineForms of Cocaine

FreebaseFreebase Prepared as a chemical Prepared as a chemical

base base Can be heated and the Can be heated and the

vapors inhaledvapors inhaled

Crack or rockCrack or rock Lumps of dried, Lumps of dried,

smokable cocainesmokable cocaine Prepared by mixing Prepared by mixing

cocaine with water and cocaine with water and baking sodabaking soda


Contemporary Legal Contemporary Legal Controls on CocaineControls on Cocaine

Cocaine use began to increase again at the end Cocaine use began to increase again at the end of the 1960sof the 1960s

Prior to 1985, the major form of the drug available Prior to 1985, the major form of the drug available was cocaine hydrochloride, which was snortedwas cocaine hydrochloride, which was snorted Cocaine was relatively expensive and its use was Cocaine was relatively expensive and its use was

associated with status, wealth, and fameassociated with status, wealth, and fame

Then an inexpensive ($5 to $10 a hit) form of Then an inexpensive ($5 to $10 a hit) form of smokable cocaine became available—crack smokable cocaine became available—crack Smoked cocaine has a greater abuse potential than Smoked cocaine has a greater abuse potential than

snorted cocaine snorted cocaine


Contemporary Legal Contemporary Legal Controls on CocaineControls on Cocaine

Media and politicians focused on crack use Media and politicians focused on crack use among urban blacksamong urban blacks Associated with violence and dependencyAssociated with violence and dependency

Anti-Drug Abuse Acts of 1986 and 1988Anti-Drug Abuse Acts of 1986 and 1988 Penalties for sale of crack cocaine significantly more Penalties for sale of crack cocaine significantly more

severe than penalties associated with powder cocainesevere than penalties associated with powder cocaine Tougher penalties for first-time users of crackTougher penalties for first-time users of crack

Concerns about federal cocaine sentencing policy Concerns about federal cocaine sentencing policy Does it overstate the seriousness of most crack Does it overstate the seriousness of most crack

cocaine offenses? cocaine offenses? Does it disproportionately affect the black community?Does it disproportionately affect the black community?


Mechanism of ActionMechanism of Action

Chemical structure does not tell us how or why cocaine Chemical structure does not tell us how or why cocaine affects the brainaffects the brain

Cocaine blocks reuptake of dopamine, serotonin, and Cocaine blocks reuptake of dopamine, serotonin, and norepinephrine norepinephrine


Cocaine AdministrationCocaine Administration

Chewing or sucking coca leavesChewing or sucking coca leaves Slow absorption and onset of effectsSlow absorption and onset of effects

““Snorting” through nasal mucous Snorting” through nasal mucous membranesmembranes Rapid absorption and onset of effectsRapid absorption and onset of effects

Injected intravenouslyInjected intravenously Rapid and brief effectsRapid and brief effects

SmokedSmoked Rapid and brief effectsRapid and brief effects


Cocaine EliminationCocaine Elimination

Cocaine is metabolized by enzymes in the Cocaine is metabolized by enzymes in the blood and liverblood and liver

Cocaine has a half-life of about one hourCocaine has a half-life of about one hour Major metabolites (detected by drug Major metabolites (detected by drug

screens) have a half-life of eight hoursscreens) have a half-life of eight hours


Potential Beneficial UsesPotential Beneficial Uses

Local anesthetic properties of cocaine were Local anesthetic properties of cocaine were discovered in 1860, but the drug was not discovered in 1860, but the drug was not used medically until 1884used medically until 1884

Synthesized drugs have largely replaced Synthesized drugs have largely replaced cocaine for medical usecocaine for medical use

Cocaine remains in use for surgery in the Cocaine remains in use for surgery in the nasal, laryngeal, and esophageal regionsnasal, laryngeal, and esophageal regions


Causes for Concern: Causes for Concern: Acute ToxicityAcute Toxicity

Acute cocaine toxicity causes profound CNS Acute cocaine toxicity causes profound CNS stimulation, which can lead to respiratory or stimulation, which can lead to respiratory or cardiac arrestcardiac arrest

Significant individual variation in the uptake and Significant individual variation in the uptake and metabolism of cocainemetabolism of cocaine Difficult to estimate the size of a lethal doseDifficult to estimate the size of a lethal dose

Rare, severe, and unpredictable reactions can Rare, severe, and unpredictable reactions can cause cardiac failure cause cardiac failure

Cocaine combined with alcohol can cause the Cocaine combined with alcohol can cause the formation of the toxic chemical cocaethyleneformation of the toxic chemical cocaethylene


Causes for Concern: Causes for Concern: Chronic ToxicityChronic Toxicity

Risks of regularly Risks of regularly snorting cocainesnorting cocaine Damage to the nasal Damage to the nasal

septumseptum Paranoid psychosisParanoid psychosis Damage to the heart Damage to the heart

musclemuscle


Causes for Concern: Causes for Concern: Chronic ToxicityChronic Toxicity

DependenceDependence occurs in some users occurs in some users Animal and human studies have shown that Animal and human studies have shown that

cocaine is a cocaine is a powerfully reinforcingpowerfully reinforcing drugdrug Some people experience Some people experience withdrawal withdrawal

symptoms symptoms


Causes for ConcernCauses for Concern

Cocaine use during Cocaine use during pregnancypregnancy Increased risk of Increased risk of

miscarriage and torn miscarriage and torn placentaplacenta

Long-term effects of Long-term effects of prenatal cocaine prenatal cocaine exposure still under exposure still under study study

Infant exposed to cocaine being monitored in ICU


Supply of Illicit CocaineSupply of Illicit Cocaine

Readily available in all Readily available in all major U.S. citiesmajor U.S. cities

Street cocaine averages Street cocaine averages about 50-75 percent pureabout 50-75 percent pure

Most illicit cocaine comes Most illicit cocaine comes from Peru, Bolivia, and from Peru, Bolivia, and ColumbiaColumbia

Seized cocaine


Cocaine: Current Use and Cocaine: Current Use and Future TrendsFuture Trends

2006 surveys indicate that about 2 percent 2006 surveys indicate that about 2 percent of adults currently use cocaineof adults currently use cocaine Down from a high of 7 to 9 percent in the 1980s Down from a high of 7 to 9 percent in the 1980s

Usage rates of cocaine and amphetamine Usage rates of cocaine and amphetamine tend to cycle in opposition to each othertend to cycle in opposition to each other


Amphetamines: Amphetamines: HistoryHistory

The Chinese used a The Chinese used a medicinal tea made from medicinal tea made from ma huang (Ephedra)ma huang (Ephedra) Active ingredient = ephedrine Active ingredient = ephedrine

Ephedrine is a Ephedrine is a sympathomimetic drugsympathomimetic drug Stimulates the sympathetic Stimulates the sympathetic

branch of the autonomic branch of the autonomic nervous systemnervous system


Amphetamines: Amphetamines: HistoryHistory

New synthesized chemical similar to ephedrine, New synthesized chemical similar to ephedrine, called amphetamine, was patented in 1932called amphetamine, was patented in 1932

Amphetamine was used medically Amphetamine was used medically Asthma Asthma NarcolepsyNarcolepsy Hyperactivity in childrenHyperactivity in children Appetite suppressant Appetite suppressant StimulantStimulant


Amphetamines:Amphetamines:HistoryHistory

Use by soldiers in World War II to fight fatigueUse by soldiers in World War II to fight fatigue 1960s1960s

Amphetamine + heroin injected together = speedball Amphetamine + heroin injected together = speedball Most street amphetamines came from prescriptionsMost street amphetamines came from prescriptions ““Speed scene” = a time and place in which people used Speed scene” = a time and place in which people used

and became dependent on intravenous amphetamine and became dependent on intravenous amphetamine

Amphetamines became more tightly controlledAmphetamines became more tightly controlled Many look-alikes appearedMany look-alikes appeared Some users switched back to cocaineSome users switched back to cocaine Illicit manufacture of methamphetamine grewIllicit manufacture of methamphetamine grew



Limited amphetamine Limited amphetamine availability increased availability increased the number of illicit the number of illicit laboratories making laboratories making methamphetaminemethamphetamine

Manufacture of Manufacture of methamphetamine is methamphetamine is dangerous and dangerous and associated with toxic associated with toxic fumes and residuefumes and residue Materials from a garage meth lab



Methamphetamine Methamphetamine hydrochloride crystals hydrochloride crystals Ice or crystal methIce or crystal meth SmokableSmokable

Methamphetamine abuse Methamphetamine abuse began in the western began in the western United States and then United States and then spread east; it is also now spread east; it is also now considered a “club drug”considered a “club drug”


AmphetamineAmphetaminePharmacologyPharmacology

Chemical structure of amphetamine is similar to Chemical structure of amphetamine is similar to the catecholamine neurotransmittersthe catecholamine neurotransmitters

The structure of methamphetamine allows it to The structure of methamphetamine allows it to more easily cross the blood-brain barriermore easily cross the blood-brain barrier Ephedrine and PPA are less able to cross the barrier Ephedrine and PPA are less able to cross the barrier

and so produce more peripheral than central nervous and so produce more peripheral than central nervous system effectssystem effects

Causes increased activity of monoamine Causes increased activity of monoamine neurotransmitters (dopamine, norepinephrine, neurotransmitters (dopamine, norepinephrine, serotonin) by stimulating their release serotonin) by stimulating their release


Molecular StructureMolecular Structure


Amphetamine Amphetamine Absorption and EliminationAbsorption and Elimination

Peak effects Peak effects 1.5 hours after oral ingestion1.5 hours after oral ingestion 5-20 minutes after intranasal administration 5-20 minutes after intranasal administration 5-10 minutes following intravenous injection or 5-10 minutes following intravenous injection or

smokingsmoking

Half-life Half-life 5-12 hours5-12 hours

Rapid tolerance (Rapid tolerance (tachyphylaxistachyphylaxis) can occur ) can occur after high dosesafter high doses


Beneficial UsesBeneficial Uses

Previous use for depressionPrevious use for depression to temporarily elevate to temporarily elevate moodmood Adjunctive therapy- a treatment used together with primary Adjunctive therapy- a treatment used together with primary

treatment. treatment. The benefit of amphetamines is that their effects occur rapidly The benefit of amphetamines is that their effects occur rapidly

compared with standard antidepressant medications. compared with standard antidepressant medications.



Weight controlWeight control Widely use to reduce food intake and body Widely use to reduce food intake and body

weight weight Effect is real but small Effect is real but small Combination of fenfluramine and phentermine Combination of fenfluramine and phentermine

was associated with heart valve damage and was associated with heart valve damage and lung disease in some people lung disease in some people



NarcolepsyNarcolepsy (uncontrolled daytime episodes (uncontrolled daytime episodes of muscular weakness and falling asleep)of muscular weakness and falling asleep) Stimulants used to keep patients awake during Stimulants used to keep patients awake during

the daythe day Newer drug modafinil (Provigil) promotes Newer drug modafinil (Provigil) promotes

wakefulness by increasing the activity of wakefulness by increasing the activity of norepinephrine and dopaminenorepinephrine and dopamine Low abuse potential Low abuse potential Doesn’t induce toleranceDoesn’t induce tolerance



Treatment of attention-deficit Treatment of attention-deficit hyperactivity disorder (ADHD)hyperactivity disorder (ADHD) Characterized by problems with Characterized by problems with

inattention, hyperactivity, and inattention, hyperactivity, and impulsivityimpulsivity

Stimulant medications can reverse Stimulant medications can reverse catecholamine-associated deficits catecholamine-associated deficits that may underlie ADHDthat may underlie ADHD

Due to side effects and concerns Due to side effects and concerns about the risk of abuse, other about the risk of abuse, other treatments for ADHD are being treatments for ADHD are being studied studied



““Smart pills”Smart pills” At a low level of arousal, may improve At a low level of arousal, may improve

performanceperformance At a high level of arousal, may decrease At a high level of arousal, may decrease

performance, especially on complex or difficult performance, especially on complex or difficult tasks that require concentration tasks that require concentration

AthleticsAthletics Under some circumstances, may produce slight Under some circumstances, may produce slight

improvements in athletic performance improvements in athletic performance


Effects of Stimulants on Effects of Stimulants on PerformancePerformance


Acute ToxicityAcute Toxicity

Acute behavioral toxicity Acute behavioral toxicity Increases in feelings of power, suspicion, Increases in feelings of power, suspicion,

paranoiaparanoia Potential risk of violent behaviorPotential risk of violent behavior

Very high doses may destroy Very high doses may destroy catecholamine neuronscatecholamine neurons

Contaminants formed during the Contaminants formed during the manufacture of illicit methamphetamine manufacture of illicit methamphetamine may have toxic effects on brain cellsmay have toxic effects on brain cells


Chronic Toxicity from Chronic Toxicity from High-Dose UseHigh-Dose Use

Paranoid psychosis Paranoid psychosis Two possible reasons for the psychosisTwo possible reasons for the psychosis

Heavy methamphetamine users have schizoid Heavy methamphetamine users have schizoid personalities. personalities.

Caused by sleep deprevation. Caused by sleep deprevation.

Higher risk among those who inject the drugHigher risk among those who inject the drug


Dependence Potential ofDependence Potential ofAmphetaminesAmphetamines

Often no obvious withdrawal symptomsOften no obvious withdrawal symptoms Produce psychological dependence Produce psychological dependence Capable of producing dependence as Capable of producing dependence as

defined by DSM criteriadefined by DSM criteria A potent reinforcerA potent reinforcer


Chapter 6Chapter 6


Hart13 ppt ch06

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