Psychoactive Drugs

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Psychoactive Drugs

• Dr. Kline
• Part I

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I.  How drugs are handled by the body?

• 1.     Absorption into the body.
•  2.     Distribution of the drug through the
  body, including the fetus, at time drug is taken.
•  
• 3.     Metabolism the detoxification of the
  drug by the body (liver). Most drugs are broken
  down into metabolites (by-products or waste) that
  no longer exert an effect.
•  
• 4.     Elimination of the drug, usually
  excreted through urine.
•  

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Six routes of drug entry into body

• 1.     Orally (tablets, capsules, liquid)
• 2.     Rectally (suppositories)
• 3.     Intravenous (injected in liquid form
  through a needle into the skin)
• 4.     Inhaled through the lungs (as gases,
  vapors, or particles)
• 5.     Through skin (patches on skin)
• 6.     Through mucous membranes (snorting or
  sniffing under tongue)
•  

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How drugs act on the system

• The pharmacological, physiological, or behavioral
  effects induced by a drug follow their
  interaction with receptors.
• This is called pharmacodynamics involves the
  mechanisms of drug action that occur at the
  molecular level.

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Drugs produce effects by

• binding to interacting with specialized
  receptors, located on the synapses of neurons.

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What are receptors?

• A receptor is a large molecule on the cells
  surface where endogenous compounds
  (neurotransmitters) induce their normal effects.
  
• Usually only 1-2 neurotransmitters is specific
  enough to fit or bind to a specific receptor.

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Binding to receptors

• 1.    A drug that binds to a receptor normally
  occupied by a given transmitter can initiate a
  cellular response similar or identical to that
  exerted by the transmitter.
• The drug mimics the action of the transmitter.
  Here, the drug is an agonist for that
  transmitter.  
• 2.  A drug that binds to a receptor blocks the
  neurotransmitter from stimulating the cell is
  called an antagonist.

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II. Dose-Response Relationships

• A dose-response curve may be plotted as
• the dose of a drug given as a function of the
  of people who show an effect at a given dosage.

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Drug Effectiveness

• The dose of a drug that produces the desired
  effect in 50 of subjects tested is called the
  ED50.
• The lethal dose for 50 of subjects (animals) is
  called the LD50.
• The ratio of the LD50 to the ED50 is used as an
  index of the relative safety of the drug is
  called the therapeutic index

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III. Drugs

• A. ALCOHOL (ethanol)
• Alcohol is found in different concentrations
  in liquid
• -12 in wine
• -3.5-5 in beer
• -40-50 in liquors
• It is most often expressed as proof which is
  twice the percent concentration (i.e., 80 proof
  40 ethanol).

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Alcohol absorption

• Alcohol readily diffuses across all biological
  membranes is completely absorbed by the entire
  GI tract.
• Alcohol usually takes 30-90 minutes to reach
  peak levels in the blood.
• About 20 of a single dose of alcohol is
  absorbed directly via the stomach.
• The remaining 80 is absorbed rapidly by the
  large intestine.

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Alcohol metabolism

• 85 by liver
• 5-by lungs (can be detected by breath)
• 15- broken down by stomach enzymes.
• A full stomach reduces a persons blood alcohol
  level, because the enzymes have longer time to
  metabolize the alcohol.

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Who has the higher blood alcohol level, men or
women?

• Women!!!
• 1.  Women --50 less gastric metabolism of
  alcohol, because they have lower levels of
  gastric enzymes.
• 2.  Since men have greater ratio of muscle to fat
  than do women, alcohol is more diluted in their
  blood (fat has little blood supply in contrast to
  muscle).
•  

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What are the effects of alcohol?

• 1. Physiological effects-
• Slows Respiration (CNS depressant)
• Sedative effects are additive when combined with
  other depressants (e.g., barbituates).
• Dilates blood vessels in skin (decreases body
  temp blushing).
• Lowers cholesterol (low doses) by lowering LDL
  increasing HDL.
• May cause heart damage (high doses-5 drinks per
  day).
• May cause liver damage (high doses over time)

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2. Psychological effects

• Behavioral disinhibition (low doses)
• Euphoria (low to moderate doses)
• Violent or irascible mood (moderate to high
  doses)
• Memory, concentration, insight are impaired
• Reaction time is impaired
• Motor system is impaired (cerebellum)
•  

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How does alcohol produce its effects?

• 1. Alcohol is a GABA agonist, it facilitates
  expression of GABA (inhibitory transmitter).
  Contributes to behavioral disinhibition, motor
  slowing.
• 2. Alcohol inhibits glutamate (excitatory
  system). Receptors, which may cause cognitive
  effects of alcohol intoxication, such as slurred
  speech memory loss.
• Alcohol increases levels of dopamine serotonin,
  likely providing both euphoric sedative
  effects.

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B. MARIJUANA

• Dried crushed leaves flowering tops of the
  hemp plant, Cannabis sativa.
• Major ingredient-- delta-9-tetrahydrocannabinol
  (THC)
• Marijuana has 2-5 THC
• May be smoked, chewed, or eaten (in baked goods).
  

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What are effects of marijuana?

• 1. Physiological effects
• Produces analgesia
• Has antiemetic properties (decreases nausea
  vomiting)
• Increased HR blood pressure
• Dilated blood vessels in eyes (bloodshot eyes)
• Sedative effects

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2. Psychological effects

• Shifts in emotion
• Disrupted attention
• Impaired STM
• Altered sensory perception
• Time distortions (time moves more slowly)
• Motor activity impaired
• Hallucinations (with heavy doses)
• Panic (with heavy doses)

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How does marijuana produce its effects?

• We have cannabis receptors in the brain. These
  receptors are found in the
• 1. basal ganglia (fine motor system)
• 2. cerebellum
• 3. cortex (especially the frontal lobe)
• 4. hippocampus
• We dont have any cannabis receptors in the
  brainstem. THC does not affect basal body
  functions.

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Do we have a transmitter substance like THC in
our brains?

• Yes!!! We have anandamide which binds to
  cannabinoid receptors produces cannabinoid-like
  pharmacological effects.

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C. HALLUCINOGENS

• 1. LSD
• First synthesized in 1938, as a compound of ergot
  (a fungus that grows on rye) by Hoffman.
• Hoffman accidentally ingested the drug noticed
  its unusual effects.
• During 1950s, LSD was used as a model for
  examining treating psychosis was also used in
  therapy.

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LSD administration

• Is taken orally.
• ED50 is 25 micrograms to 300 micrograms.
• Usually is found on sugar cubes, stamps, candy
  dots
• Is absorbed within 1 hour peaks in 3 hours.
• Duration 6-8 hours.

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What are the effects of LSD?

• 1. Physiological Effects
• Slight increase in body temperature
• pupil dilation
• slightly increased HR blood pressure
• dizziness nausea

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2. Psychological Effects

• 1.     Altered perception, thinking, emotion,
  arousal
• 2.     time distortions (slowed)
• 3.     Intense visual auditory hallucinations
  (trasers)
• 4.     Cross-sensing (hearing colors seeing
  sounds)
• 5.     emotions shift rapidly (happiness to pit
  of despair)
• 6.     tension anxiety make lead to panic
• 7.     psychotic experience

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How does LSD produce its effects?

• LSD exerts its effects by interacting with
  serotonin receptors (5-HT receptors).
• Most researchers argue its a serotonin agonist.

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2. MESCALINE

• Comes from the crown or button of the peyote
  cactus.
• The crown is dried into a hard brown disk that
  softens when ingested.
• Is absorbed in 1-2 hours.
• Effects occur between 3.5 4 hours after
  ingestion. Vivid hallucinations most salient.
• --trip is long (10 hours)
• Right frontal activity seems to be high in people
  on mescaline. Agonistic for norepinephine
  serotonin.

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3. PSILOCYBIN

• Found in mushrooms (genera Psilocybe).
• Mushrooms are eaten raw.
• mushrooms grow through out world, including
  northwestern US.
• It peaks in about 2 hours, effects
• last 6-10 hours.

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How does it produce its effects?

• It appears to exert its effects as a serotonin
  agonist that stimulates 5-HT receptors especially
  in the frontal areas.

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4. MYRISTIN ELEMICIN

• Are agents found in nutmeg mace, two common
  household spices.
• ED50--1-2 teaspoonsusually brewed in tea
• Within 2-5 hours, you get symptoms similar to LSD
  (euphoria, visual hallucinations, psychosis,
  etc.)
• However, most people experience vomiting, nausea,
  tremors prior to the trip making it a one
  time event for many.

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D. STIMULANTS

• In general these drugs
• increase behavioral activity
• elevate mood
• increase alertness
• allay sleep
• increase brains metabolic neuronal activity.

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1. COCAINE

• Comes from the coca plant (Erythroxylon coca)
  found in South America.
• The active alkaloid in E. coca was isolated in
  1855, purified in 1860, named cocaine.
• In late 1800s, cocaine was used as an anesthetic
  (spinal, local), was added to medicines
  Coca-Cola.
• It was banned from use in medicines beverages
  in 1914 in the Harrison Narcotic Act.

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COCAINE (history)

• By 1930s, amphetamines replaced the popularity of
  cocaine.
• 1960s- cocaine makes a comeback when amphetamines
  become pricey.
• 70s-80s cocaine becomes chic with jetset.
• cheap crack cocaine becomes hit in poor
  areas.
•  

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Forms of cocaine

• Cocaine can be snorted, smoked, taken orally, or
  injected intravenously.
• Powdered cocaine (cocaine hydrochloride) 25 mg
  per line.
• Crack cocaine- (250 mg-1 gm) per smoke.

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Physical Effects

• Vasoconstrictor
• Increases norepinephrine dopamine
• Tachycardia
• Stroke, seizure, heart attack
• Increased blood pressure
• Local anesthetic

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Psychological Effects

• Euphoria
• Elevated mood
• Agitation
• Flight-of-ideas
• Grandiose thoughts

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How does it produce its effects?

• Cocaine blocks reuptake of dopamine,
  norepinephrine, serotonin, thereby increasing
  them in the CNS.
• Increasing dopamine levels in dopaminergic reward
  system results in euphoric/addictive effects of
  drug.

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2. AMPHETAMINES- Effects

• Vasoconstriction
• Hypertension
• Tachycardia
• Increased motor activity
• Loss of appetite
• Restlessness/tremors 
• hallucinations (amphetamine psychosis)
• Paranoid delusions

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Amphetamines-today

• 1.  Therapeutic use in the treatment of
  narcolepsy ADHD.
• 2.  To treat compulsive misuse of methamphetamine
  (amphetamine derivative).

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How do amphetamines cause their effects?

• They cause release of norepinephrine dopamine
  from presynaptic storage sites in nerve
  terminals.
• Peripheral NS activity --increased norepinephrine
   

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ICE- form of methamphetamine

• Was originally used to treat ADHD, not mostly a
  an illegal street drug.
• Street names of drug Speed, crystal, crank, go,
  ICE.
• Methamphetamine--orally, by IV injection,
  snorted. The base form (ICE) can be smoked.
• ICE-methamphetamine, crack-cocaine. Its the
  free-base, smokable form of the parent compound.

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NONAMPHETAMINE BEHAVIORAL STIMULANTS

• Does not have the same nucleus structure of
  amphetamines, but shares same action of
  increasing SNS activation.
• One of the most common of these is
• Methylphenidate (Ritalin)

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Methylphenidate (Ritalin)

• Has a short half life (2-4 hours).
• Concerta--A new sustained-release formulation of
  methylphenidate--taken in the early AM, it is
  good through the day.
• Is much more expensive than regular Ritalin.

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How does Ritalin exert its effects?

• Thought to increase norepinephrine dopamine, by
  blocking reuptake in the presynaptic neuron.
  Also stimulates the release dopamine.
• Once thought to exert its behavioral effects
  (calming) via increased dopamine, it is now
  thought that effects may be result of increased
  serotonin activity (or balance of both).

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3. CAFFEINE

• The most common psychoactive drug in world.
• Consumed -80 of adult population.
• 1 cup of coffee---50-150 mg of caffeine.
• Caffeine content of chocolate--25 milligrams per
  ounce.
• Average intake 3-5 cups of coffee every day.

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Absorption

• Significant blood levels of caffeine are reached
  in 30 to 45 min with complete absorption in 90
  min.
• Peaks in about 2 hrs decreases thereafter.
• The half-life is about 3.5 to 5 hours in most
  adults.

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Effects

•  
• tachycardia
• Increased Blood pressure
• Vasoconstriction
• Diurectic
• Increased mental activity alertness
• Increased wakefulness
• Agitation
• Tremors
• Anxiety
• Insomnia

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• HOW DOES CAFFEINE EXERT ITS EFFECTS?
• Caffeine exerts its effects by blocking adenosine
  receptors.
• Adenosine is a neuromodulator that influences the
  release of several neurotransmitters in the CNS.
• It appears to exert sedative, depressant,
  anticonsulsant actions. Thus, blocking adenosine
  causes anxiogenic effects.

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E. OPIATES

• A group of addictive sedatives that in
• moderate doses relieve pain induce sleep.
• The original principle opiate was opium, which is
  extracted from poppy seeds of the poppy plant
  (papaver somniferum).
• The psychoactive ingredient in opium is morphine,
  named for Morpheusthe Greek God of dreams.
• Two drugs are found in the exudate of the poppy
  morphine codeine.

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OPIATES-History

• Opium--has been used for thousands of years to
  produce euphoria, analgesia, sleep, relief from
  diarrhea cough.
• Ancient Greece Rome-- through the 16th-
  17th-centuries, opiums medicinal recreational
  uses were well established.
• A mixture of opium and alcohol, called laudanum,
  was used to treat practically every disease known
  during the 1800s.

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OPIATES-History

• During the civil war, opium addiction was a
  widespread problem.
• By 1914, the Harrison Narcotic Act was passed and
  the use of most opioid products was controlled.

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Opiates vs. Opioids

• Opiate-- is a drug that is extracted from the
  exudates of the poppy.
• E.g., morphine and codeine.
• An opioid is any exogenous drug (natural or
  synthetic) that binds to an opiate receptor
  produces agonist or morphine-like effects.
• E.g., heroin

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Endorpins (morphine-within)

•  Endorphins --any endogenous substance (naturally
  occurring in the body) that exhibits
  pharmacological properties of morphine.
• We have 3 families of endorphinsenkephalins,
  dynorphins, beta-endorphins.

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MORPHINE

• Is still the most potent pain reliever available
  (no other drug has its clinical effectiveness).
• Is administered orally, rectally, or by
  injection. Absorption is slow only 20 of the
  drug reaches the CNS.
• Is broken down by liver produces metabolites
  (morphine t-glucoronide) that are 10 to 20-fold
  more potent that morphine itself. These continue
  exerting analgesic effects.
• Morphines half-life 3 to 5 hours.

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MORPHINE-DRUG TESTING

• For 2 to 4 days following opiate use, urine
  screening tests can be used to detect codeine
  morphine as well as their metabolites.
• Heroin use can be tested for indirectly. Heroin
  is metabolized to morphine also often contains
  acetylcodeine (metabolized form of codeine).
• Although the tests cannot accurately determine
  which drug (heroin, codeine, morphine) was
  present.

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WHAT ARE EFFECTS OF MORPHINE?

• Analgesia
• Relaxation
• Euphoria
• Sedation
• Sense of transquility
• Reduced anxiety
• Respiratory depression
• Cough suppression

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HOW DOES MORPHINE EXERT ITS EFFECTS?

• Morphine, like other opiates opioids, exert its
  effects by stimulating opiate receptors widely
  distributed through the CNS (brain, brain stem,
  spinal cord).

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 CODEINE

• Is usually combined with aspirin or acetaminophen
  for the relief of mild to moderate pain.
• Half-life--3 to 4 hours.
• Codeine is metabolized by hepatic cytochrome
  CYP2D6 enzymes to morphine, many of its effects
  may be the result of morphine actions.
• Using serotonin-specific antidepressants can
  block the pain relief of codeine, because they
  block the conversion of codeine to morphine.

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HEROIN (diacetylmorphine)

• Is produced by a slight modification of the
  chemical structure of morphine.
• It cross the blood-brain barrier very rapidly,
  leading to an intense rush when it is either
  smoked or injected intravenously.
• It is metabolized to monoacetylmorphine
  morphine.
• Clinical use of heroin is legal in Great Britain
  Canada.

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F. ANTIDEPRESSANTS

• A broad class of drugs used to treat depression.
• What is depression???
• A state of great sadness characterized by
  feelings of despair, worthlessness, hopelessness,
  withdrawal from other.
• Its the common cold of psychopathologyweve
  all had symptoms at some point.

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Major depression DSM diagnosis made if

• Person has 5 of the following symptoms (next
  slide) for at least 2 weeks.
• Depressed mood or loss of interest pleasure in
  enjoyable activities (anhedonia) must be included
  in symptoms.

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Symptoms of major depression

• 1. Depressed mood.
• 2. Loss of interest and pleasure.
• 3. Significant weight loss or weight gain.
• 4. Difficulty in sleeping-Insomnia or
• hypersomnia.
• 5. Shift in activity level, psychomotor
  retardation, or agitated.
• 6. Fatigue or loss of energy.
• 7. Negative self-concept.
• 8. Difficulty concentrating.
• 9. Recurrent thoughts of death or suicide.

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1. Tricyclics

• E.g., imipramine (Tofranil) and amitriptyline
  (Elavil).
• These prevent reuptake of both norepinephrine
  serotonin by the presynaptic neuron.
• 2. Monoamine oxidase (MAO) inhibitors -
  tranylcypromine (Parnate)
• Keeps enzyme monoamine oxidase from
  deactivating neurotransmitters, thereby
  increasing the levels of both serotonin and
  norepinephrine.

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3. Selective serotonin reuptake inhibitors
(SSRIs) fluoxetine (Prozac) sertraline
(Zoloft). 

• Selectively blocks reuptake of serotonin.
• Efficacy of all three classes of drugs about the
  same (50-70 effective).
• Side effects fewer in SSRIs. Tricyclics can be
  dangerous.