Chapter 10 - Psychomotor Stimulants (Cocaine & Amphetamine)

• Amphetamine


  Synthetic, chemically manufactured
• Amphetamines

  • Levoamphetamine (Benzedrine)
  • Dextroamphetamine (Dexedrine), more potent isomer, treat ADHD and narcolepsy
  • dl-amphetamine (Adderall), treat ADHD
  • Methamphetamine (Methedrine / Desoxyn), treat ADHD and obesity
• Amphetamines are the most abused drug
• Amphetamine street aliases (methamphetamine)

  • Uppers
  • Pep pills
  • Bennies
  • Whites
  • Dexies
  • Hearts
  • Speed
  • Meth
  • Crystal
  • Crank
  • Ice
• Cocaine


  White odorless crystalline powder derived from coca leaf paste, stabilized as salt using hydrochloric acid to produce cocaine hydrochloride
• Cocaine street aliases


  • Coke
  • C
  • Snow
  • Blow
  • Toot
  • Leaf
  • Flake
  • Freeze
  • Happy dust
  • Peruvian lady
  • White girl
• Weak bases


  Amphetamines have a pKa between 9 and 10
• Cocaine


  Weak base with pKa 8.6
• Amphetamine administration


  1. Oral administration (p.o.) used for medicinal purposes (decrease sleep or fatigue); easy to control blood levels

  2. More potent when administered by injection or inhalation compared to p.o.
• Cocaine administration


  1. Typically injected or inhaled (snorting)

  2. "Tooting": place cocaine HCl on foil; heat until it vaporizes, inhale vapor

  3. Oral: Chewing/sucking coca leaves (2% cocaine) by Adean Indians, used in social rituals and mild stimulation

  4. Snorting: Sniff Cocaine HCl into nostrils; absorbed into blood through nasal mucosa

  5. Intravenous: Produces intense initial rush of pleasure within 2 min that lasts about 10 min followed by a crash (lethargy)

  6. Freebasing: Convert Cocaine HCl into smokable, pure form called "base" or "free base", more potent due to an increase in lipid solubility

  7. Crack cocaine: Cocaine HCl mixed with baking soda solution; evaporate water, crystalline chunks; heated in pipe; inhale vapors
• Cocaine and amphetamines are one of the most addictive substances ever known
• Ranking of addictiveness


  • 1 - heroin
  • 2 - cocaine
  • 3 - nicotine
• Few minutes after high, user experiences "hangover"
• Amphetamine absorption


  1. Oral administration (p.o.) effects in 30 min, peak blood levels in 30 min – 4 hours

  2. Intravenous injection (i.v.) onset of effects in 5-10 min
• Cocaine absorption


  1. Intranasal – onset within 2 min, peak blood levels 10-20 min

  2. Freebasing and smoking crack – rapid absorption effects in 7-10 seconds
• Amphetamine and cocaine both readily cross blood-brain barrier
• Amphetamine metabolism and excretion

  1. Metabolized in liver, 50% excreted in unchanged form

  2. Excretion depends on urine pH (acidic excreted; basic reabsorbed)

  3. Amphetamine half-life (7-14 hours if urine acidic; 16-34 hours if urine is basic)
• Cocaine metabolism and excretion

  1. Metabolized by enzymes in blood and liver; half-life ~60 min

  2. Excretion via urine – contains metabolites (benzoylecgonine) 48-72 hours after use; urine testing

  3. Drug or metabolites also deposited in hair, hair testing can determine if using cocaine and how long ago within the last 90 days
• Cocaine


  Reuptake inhibitor, binds to transporter, prevents uptake
• Amphetamines


  • Substrate-type releasers: enter presynaptic neuron and get packaged in vesicles, alter vesicle pH, reverse vesicular monoamine transporters (VMAT), releases monoamines into cytoplasm, reverse MAT transporters in membrane to pump monoamines out into extracellular space
  • MAO inhibitors: prevent MAO from breaking down monoamines in cytoplasm
  • Block VMAT to prevent vesicular storage and cause release of monoamine (MA) into cytoplasm
• Peripheral nervous system effects (cocaine and amphetamine)

  • Excite epinephrine synapses
  • Sympathetic arousal (fight or flight): Increases heart rate, increases blood pressure, increases blood glucose, pupil dilation, relaxed bronchial muscles (increase respiration rate)
• Central nervous system effects (cocaine and amphetamine)

  • DA systems affected: Nigrostriatal (control of motor activity), Mesolimbic system (DA release in NAc)
• Local anesthesia (cocaine)


  • Cocaine blocks conduction of action potentials by blocking Na+ ion channels
  • Constricts blood vessels in local region where applied – retards absorption – localizes anesthetic effect
  • Numbs gums and nasal membranes of cocaine users
  • Procaine (Novacaine) – local anesthetic related to cocaine, but lacks the stimulant properties
• Body effects (amphetamine)


  • Sympathomimetic (mimics activation of sympathetic nervous system)
  • Methamphetamine (fewer PNS effects) preferred by drug users over d- or l-amphetamine
• Appetite effects (amphetamine)


  Appetite suppression: reduces food intake, no direct effect, missed food consumption is compensated by excessive eating
• Sleep effects (amphetamine)


  Prevents sleep, blocks fatigue, used by truck drivers, military pilots, soldiers on night missions, used as study aids by students, used to treat narcolepsy
• Subjective effects


  • Improves mood, feel good (vigor, elation); decrease in fatigue, increase in energy, and increase in motivation to work
  • Amphetamine: rush (intense feelings of euphoria with i.v. or inhalation)
  • Cocaine when snorted produces numbing sensation ("freeze"), followed by exhilaration and well being (20-30 min), followed by mild depression called "comedown" or "crash"
  • Rush is universally described in sexual terms ("orgasm"), but shows rapid tolerance
• High dose effects


  • Stereotyped behaviour: Punding (repetitive performance of behaviour over extended period of time)
  • Psychosis: High doses of amphetamine produce auditory and visual hallucinations, delusions of persecution / grandeur; hostility and violence triggered by paranoid belief, Formication (tactile hallucination that bugs are crawling under the skin)
  • Meth mouth: black, stained, rotting teeth
• Effects on performance


  • Increases endurance, decreases fatigue, improves reaction time, performance on digit span, improves attention and vigilance, but produces tunnel vision, impairs performance on task that requires flexibility and changing strategies
  • Improves athletic performance (competitive swimming, running), banned by national sports federations
  • 2.3 times more likely to be killed in auto accident under the influence of amphetamine, erratic driving, weaving and drifting out of lane
• Tolerance


  • Acute tolerance: Continuous use of cocaine decreases ability to cause rushes / improve mood ("Coke-out"), dissipates in 24 hours if stop taking it, develops to euphoric effects, but not to effects on blood pressure and heart rate
  • Chronic tolerance: Appetite-suppressant effects disappear within 2 weeks, Cardiovascular effects diminish, Lethal effects develop tolerance – enables extremely high doses
  • Sensitization: Punding and psychosis more likely to be experiences with repeated doses
• Amphetamine


  • Improves attention in ADHD children (deficit in monoamine (MA) functioning in prefrontal cortex)
  • Improves athletic performance (competitive swimming, running)
  • 1% improvement in swimming time
  • Banned by national sports federations
• Amphetamine use


  2.3 times more likely to be killed in auto accident
• Amphetamine use


  Erratic driving, weaving and drifting out of lane
• Acute tolerance


  Continuous use of cocaine decreases ability to cause rushes / improve mood ("Coke-out"), dissipates in 24 hours if stop taking it
• Chronic tolerance


  • Appetite-suppressant effects disappear within 2 weeks
  • Cardiovascular effects diminish
  • Lethal effects develop tolerance – enables extremely high doses (15,000 mg amphetamine in 24 hours)
• Sensitization


  Punding and psychosis more likely to be experiences with repeated doses
• Withdrawal


  • "Comedown" after single dose (depression and lethargy) is the withdrawal syndrome
  • Depression is the most common symptom
  • Severity of depression varies with dose and duration of intake
  • Other symptoms: fatigue, vivid dreams, insomnia or hypersomnia, increase in appetite, psychomotor agitation or retardation
• Cocaine use patterns


  • Binge (run-abstinence), not continuous use
  • Speedball: cocaine or amphetamine plus heroin, heroin decreases jitteriness from sympathetic stimulation, cocaine decreases the nod (sleepiness)
• Amphetamine use patterns


  • Also run-abstinence
  • Speed freak: injects every 2 hours for days, do not sleep, eat little, show psychosis, then crash sleep for 24-48 hours
• Methamphetamine


  • Cheaper than cocaine (¼ g can cost $25)
  • A single high can keep someone high for 6-12 hours
  • Easy to make – anyone can do it
  • 3.5 times more powerful of cocaine
  • 12 million Americans said that they tried meth once
  • Estimated that 26 million people used meth
  • 70,000 meth addicts in Australia
  • People that use meth commonly commit crimes (commit ~85% of property crimes in Oregon)
  • 1 in 4 inmates test positive for meth when first arrested
  • Causes people to be hyper, paranoid, delusional, violent
  • Coby describes meth as having "super powers" (set a new record in track and field, racked up dozens of arrests over the years, survived his meth addiction without physical damage)
  • Makes users feel like they are very brave and can do anything
  • Side effects: crawling sensations (pick at their skin and creates open sores), losing teeth ("meth-mouth"), affects judgement, users feel overheated, bursts of energy
  • At first, meth can make users feel euphoric
  • 1 in 20 college students said that they have tried meth
  • 100 years ago, meth was designed by the Japanese (used by soldiers in WWII to keep them awake and suppress hunger)
  • Most common in Asia (especially Thailand, known as Yaba)
  • In Asia, meth comes in pill form laced with caffeine (common in working people – helps keep them awake and make more money, many employers hand out these pills to workers, these workers become addicted)
  • Thailand had many violent cases due to meth
  • In 2003, in 3 months, many drug dealers were killed by the police, which caused fear among users
  • Meth forces more dopamine out of neurons
  • Mice on meth would frequently press a bar to receive the rewarding effects, and when the meth was removed, stressful situations made the mice go back to find the meth
  • Studies reveal that meth can permanently damage the brain (brain shuts the overload neurons down, making less dopamine available)
  • Meth can be made from common cold medicine (ephedrine, lithium from batteries, ether from spray cans, cold medicine, and farm feed)
  • Many explosions occur in meth labs
  • Meth can be made under 1 hour
  • The man-made molecule is very similar to dopamine molecules
  • Montana Meth Project targets young people to prevent youth from trying it
  • Mexican meth suppliers took over mom-and-pop shops in the US (becoming more potent and more dangerous)
  • Methamphetamine is the most addictive drug (92% of users relapse after treatment)