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PSYCHOPHARMACOLOGY

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Title: PSYCHOPHARMACOLOGY


1
PSYCHOPHARMACOLOGY
  • The scientific study of psychoactive drugs and
    their effects.

2
General Principles of Psychopharmacology
  • 1. Drug use in of itself is neither good nor
    badit just is.
  • Lets study the phenomena objectively, without
    preconceived moral judgment.
  • 2. All drugs have multiple effects
  • Therapeutic and side-effects may be context
    dependent..i.e. SSRIs may be used as a sleep aid,
    or drowsiness may be seen as a side effect.

3
General Principles of Psychopharmacology
  • 3. Drugs do not produce effects that are outside
    the organisms behavioral repertoire.
  • Instead they may magnify or diminish normal
    behaviors, or alter the probability or context of
    responses, etc..
  • 4. Drug effects are influenced by non-specific
    factors
  • In many cases the environmental context may alter
    a drugs effects. The physiological state and
    Psychological set of the individual may also
    have major influences.

4
Non-specific Factors
  • Set
  • The physiological and psychological state of the
    user.
  • Setting
  • The environment and social context in which the
    drug is taken

5
Cigarettes to get going or to chill out
6
Non-specific drug effects cont
The Placebo Effect Effects NOT based on
specific biological actions of the drug, but
instead are produced in some way by the
Expectations of the user.
7
Placebo Effect-
  • Placebo- Latin for "I shall please.
  • A placebo is an inert substance,..sugar
    pill..sham medication
  • Typically about 35 of subjects are responsive.
  • Has been effective in treating Pain, anxiety,
    depression, etc.
  • Some people may even experience placebo side
    effects/withdrawal

8
General Principles of Psychopharmacology
  • Drug Effects are influenced by Pharmacokinetics

9
Pharmacokinetics
  • the influences of route of drug administration,
    drug absorption, drug distribution, drug
    transformation, and drug elimination.
  • These factors influence how fast and how much of
    a drug gets to its sites of action, as well as
    the duration of a drugs effects.

10
General Principles of Psychopharmacology cont
  • Psychokinetic studies clearly indicate that drug
    effects are
  • 5. Dose-dependent
  • Consider the effects of mild coffee vs espresso!

11
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12
General Principles of Psychopharmacology
  • 6. Drug Effects are Time-Dependent
  • Consider early intoxication vs late

13
Early
Later
Way Late
14
Drug Effects are influenced by Pharmacodynamics
  • Drug effects on the target tissue
  • psychoactive drugs produce effects in the central
    nervous system (CNS)
  • Many psychoactive drugs bind to
    Neurotransmitter receptors
  • And alter the activity of brain cells ( neurons)
    and their functional relationships with other
    neurons
  • More on this later

15
General Principles of Psychopharmacology cont
  • Pharmacodynamic studies clearly indicate that
    drug effects are
  • 7. dependent on the type of drug and its site of
    action

16
DRUG SITES OF ACTION (more when we cover the
nervous system)
  • Different Psychoactive Drugs affect different
    Neurotransmitter Systems in the Brain that in
    turn have different consequences for behavior,
    thought and mood.

17
Classical Neurotransmitters
  • Acetylcholine
  • In the brain, it appears to be involved in
    learning/memory, attention as well as sleeping
    and dreaming.

18
Classical Neurotransmitters cont
  • Dopamine
  • implicated in movement control
  • Parkinsons Disease
  • Dopamine excess may be involved in Schizophrenia.
  • involved in the reward system of the brain.

19
Classical Neurotransmitters cont
  • Norepinephrine
  • primarily involved in control of
    alertness/vigilance.
  • Possible involvement in mood state

20
Classical Neurotransmitters cont
  • Serotonin
  • plays a role in the regulation of mood
  • It also has a role in the control of eating,
    sleep and arousal.

21
Classical Neurotransmitters cont
  • Endorphin/ Enkephalin
  • Modulates the experience of pain
  • Controls breathing and heart rate, cough reflex,
    nausea and vomiting
  • Modulates feelings of euphoria and reward

22
Classical Neurotransmitters cont
  • GABA
  • Most prevalent inhibitory neurotransmitter in the
    brain
  • GABA secreted by local interneurons all over
    the brain.
  • Implicated in relaxation/anti-anxiety

23
More on.Pharmacokinetics
  • Administration
  • Absorption
  • Distribution
  • Biotransformation
  • Excretion

24
DRUG ADMINISTERED

DRUG ABSORBED
DRUG DISTRIBUTED
DRUG METABOLIZED
DRUG ELIMINATED
25
Routes of Administration
  • Oral
  • Intramuscular (IM)
  • Intraperitoneal (IP)
  • Intravenous (IV)
  • Inhalation
  • Intracranial (IC)
  • Intracerebroventricular
  • Topical

26
Inhalation- a fast route
From lungs a direct shot to brain through carotid
artery
27
Absorption
  • Moving from the site of administration to the
    bloodstream
  • Drugs first travel in the bloodstream to get to
    sites of action
  • How fast do drugs leave the site of
    administration?
  • Route
  • Acidity/Alkalinity
  • Absorption relates to bioavailability
  • The amount of the drug that reaches the
    bloodstream and/or site of action

28
Distribution
  • Refers to factors influencing a drugs ability to
    get to its site of action after absorption
  • First Pass effect
  • Depends on route of administration
  • Protein Complexing

29
Role of the Liver in the First Pass Effect.
30
BRAIN
LUNGS
INHALATION
RIGHT SIDE OF HEART
LEFT SIDE OF HEART
INTRAVENOUS INJECTION
ORAL
LIVER
INTESTINE
INTRAMUSCULAR INJECTION
31
Protein complexing
Proteins in the bloodstream may bind to the drug
and slow or prevent its distribution
32
Distribution-Depot binding
Bone, Fat, Muscle, non-specific binding of drug
..affects distribution
33
Distribution-Blood-brain barrier limits drug
access to brain
34
Biotransformation/Metabolism
  • Drug Metabolization Enzymes break down the drug
    molecules to prepare them for ELIMINATION
  • Biotranformation occurs mainly in LIVER, but can
    occur in the nervous system, or in the blood
    stream as well
  • Enzymes break down drugs into metabolites
  • Metabolites can be active or inactive
  • Some drugs are not transformed at all..

35
Metabolism usually occurs at a characteristic
rate for a given drug
Drug Half-Lifes The amount of time
necessary for one half of the active
compound to be metabolized
Note most drugs obey the law of first order
Kinetics
36
Drug Elimination
  • Drugs are excreted in a variety of ways
  • Urine
  • Breath
  • Feces
  • Sweat
  • Can be excreted changed or unchanged (alcohol vs.
    psylocibin)

37
Trace Amounts may be detectable for long periods
of time
38
Hence Drug testing
39
Methods used by Psychopharmacologist
  • Dose-Response Curve
  • Plots the relation between the dose of the drug
    and the size of the effect

40
EFFECT
DOSE (DRUG AMOUNT PER UNIT OF BODY WEIGHT)
41
REACTION TIME
Seconds
DOSE ALCOHOL (g/kg)
42
DRC Characteristics
  • Slope
  • gradual versus steep

of Maximal Effect
Drug Dose
-Slope reflects sensitivity of effect to drug
dose
43
POTENCY THE DOSE OF A DRUG REQUIRED TO
PRODUCE A GIVEN EFFECT (LOWER VALUE MORE
POTENT) Maximum efficacy upper dose
where response levels out
44
Drug A is more Potent than Drug B
45
REMEMBER THAT ALL DRUGS HAVE MULTIPLE EFFECTS
  • SO DRCs can be developed for each effect..

46
NUMBER OF WORDS REMEMBERED
DOSE ALCOHOL (g/kg)
47
Aggressive Behavior
DOSE ALCOHOL (g/kg)
48
LOSS OF CONSCIOUSNESS
COMA
DEATH
REACTION TIME
OF INDIVIDUALS SHOWING EFFECT
DOSE ALCOHOL (g/kg)
49
  • ED50
  • NOT-THE DOSE OF A DRUG REQUIRED TO PRODUCE
    A 1/2 MAXIMAL EFFECT
  • ED50 IS- THE DOSE OF A DRUG REQUIRED TO
    PRODUCE A GIVEN EFFECT IN 50 OF THE
    INDIVIDUALS TESTED

50
  • LD50
  • THE DOSE OF A DRUG THAT WILL PRODUCE
    LETHALITY IN 50 OF THE INDIVIDUALS TESTED

51
LD50
NUMBER OF DEATHS
10.0
30.0
100.0
DOSE MORPHINE (mg/kg)
52
  • THERAPEUTIC INDEX
  • THE RATIO OF THE LD50 OF A DRUG AND THE
    ED50 OF A PARTICULAR EFFECT
  • LD50/ED50

53
Calculating the Therapeutic Index. MORPHINE
ANALGESIA
LETHALITY
ED50
LD50
DOSE (mg/kg)
54
Effective vs. Lethal Dose
  • Effective Dose (ED)
  • Dose level for chosen effect in of population
  • ED50, dose in which drug is effective for 50 of
    population
  • Lethal Dose (LD)
  • Dose level for death in of population
  • LD50 lethal dose for 50 of the population
  • Therapeutic Index
  • LD50/ED50 - Serves as margin of drugs safety
  • Higher ratio ? more safe/less toxic
  • 20 or more relatively safe, 100 preferred

55
Drug Interactions
  • Using multiple drugs increases the complexity of
    the experience
  • Antagonism One drug inhibits the effect of
    another drug
  • Cocaine and alcohol (Pharmacodynamic)
  • St. Johns Wort and Birth Control Pills
    (Pharmacokinetic)
  • Potentiation The two drugs together produced
    and enhanced effect
  • Alcohol and nicotine

56
Street dynamics
  • Reality is that with illicit drugs,
    pharmacodynamics is ignored
  • Most drugs are diluted
  • Changes ED
  • Most are cut with dangerous compounds
  • Changes LD
  • Sometimes dose is too high, leading to acute
    toxicity
  • Potentiation and Antagonism work here

57
OTHER FACTORS THAT INFLUENCE DRUG EFFECTU
  • Repeated use-
  • Tolerance, Sensitization ,Dependence and
    Withdrawal

58
Tolerance-Decreased response to drug /Shifting
DRC to the right
  • Metabolic
  • Liver enzymes
  • Cellular
  • Receptor down-regulation
  • Learned/behavioral
  • Context/cues

59
Tolerance cont
  • Acute vs. Protracted
  • Acute is within a single administration
  • Cross-tolerance
  • Tolerance to one drug leads to tolerance of other
    drugs in the same class.

60
Sensitization- Increased response to a drug with
repeated use/Shifting DRC to the left
  • Cocaine is a good example of a drug that induces
    tolerance (euphoria) and sensitization (movement)
  • Cocaine-induced sensitization can lead to,
    exaggerated stereotypical behaviors and seizures

61
Repeated Self-Administration
  • Mesolimbic dopamine system
  • Abused drugs all tend to activate this system
  • 3 stages
  • Pleasure
  • Associative learning through classical
    conditioning
  • Incentive salience
  • Craving (wanting)
  • Get DA release by cues/context alone

62
Animal Research Methods
  • Self-administration

63
Behavioral Pharmacology
  • Study of the relationship between the
    physiological actions of drugs and their effects
    on behavior and psychological function
  • Uses the principles of operant and classical
    conditioning to examine the effects of drugs as
    well as the differences and similarities between
    drugs
  • Self-administration studies
  • Discrimination studies
  • Conditioned place preference studies
  • Conflict paradigm studies

64
Self-administration
  • Train animal to press lever for drug
    administration
  • All drugs shown to be SA by animals are SA by
    humans
  • Alcohol
  • Cocaine
  • THC

65
Drug Discrimination
  • Drugs can serve as discriminative stimuli
  • Animals learn to respond in certain ways in the
    presence of a drug
  • Discrimination is related to interoceptive cue
  • Using these techniques, it appears that animals
    classify drugs just like humans
  • Amphetamine and cocaine alike, but different from
    morphine, while morphine is like heroin and other
    opiates
  • Method to ask animals about the interoceptive
    cues associated with different drugs
  • Press left lever if on morphine gt get food
    Right lever if given saline gt get food
  • Give new drug - is it like morphine?
  • Left lever - Yes
  • Right lever - No

66
Conditioned Place Preference
  • Pair drug administration with a place in the
    environment
  • Give animal a choice of where to hang out.
  • Measure where animal spends time

67
Conflict Paradigm
  • Train animal to associate both reinforcement and
    punishment with a certain behavior
  • Food and shock w/lever press
  • Administer a drug to test effects
  • Xanax

68
Drug Self Administration
69
Drug Development
  • Discovery of compound-in vitro tests
  • Animal studies--toxicity, efficacy, abuse
    potential , at least 2 species
  • Laboratory studies in humans
  • Clinical trials

70
Institutional Review Board
  • Must include physician and lawyer
  • Must review all protocols involving human
    participants
  • Evaluate Risks/Benefits
  • Voluntary, informed consent

71
Double-Blind- to control for placebo effects and
experimenter bias
Neither the subject nor the experimenter knows
which condition (drug or placebo) the subject is
in.
72
Drug Interactions
  • Antagonism
  • Additive Effects/Synergy

73
Drug Development
  • Discovery of compound-in vitro tests
  • Animal studies--toxicity, efficacy, abuse
    potential , at least 2 species

74
Institutional Animal Care Use Committee
  • Includes Veterinarian and Ethics expert
  • Evaluates all proposals
  • Weigh medical/scientific benefits against risk to
    animals
  • May refuse protocol or require changes
  • Unannounced site inspections (2/yr)

75
Drug Development
  • Discovery of compound-in vitro tests
  • Animal studies--toxicity, efficacy, abuse
    potential , at least 2 species
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