Lecture 2: Intro To Psychopharmacology Flashcards
1
Q
What is psychopharmacology?
A
- the study of drugs effect on mood, perception, cognition, & behaviour
- pharmacology and psychology
- focuses on psychoactive drugs
2
Q
What are psychoactive drugs?
A
- Drugs that effect the CNS (brain and spinal cord)
- changes in the function and sometimes the structure of our brain
- PET scan: functional, show where molecules bind (give mildly radioactive substance, will bind in some places [radioactive cocaine, binds more weakly in long-term substance users.. isn’t directly binding to some areas
3
Q
Psychopharmacology
A
How drugs affect our mood/perception/behaviour/cognition; how they affect our CNS
4
Q
Behavioural pharmacology
A
From behaviourism
Starts out of how drugs affect behaviour
Often some aspect of operant/classical conditioning (Pavlov, animal models)
5
Q
Neuropsychopharmacology
A
The study of how drugs affect the nervous system and how these nervous system changes alter behaviour
6
Q
Why is psychopharmacology important?
A
- drug use is ubiquitous
- billion of ppl use psychoactive drugs daily; anti-depressants; coffee; alcohol
- field provides insight into human behaviour
- push the system in one way or another; make an inference on how healthy human/animal brain functions
- addiction is prevalent
- our solutions are currently unsatisfactory
- need better solutions to keep ppl safe
7
Q
What is a drug?
A
“An administered substance that affects physiological functioning.”
8
Q
Problem with drug definition
A
1) administered
2) affects physiological functioning
9
Q
“Administered”
A
Administered: some substance, if they are not administered, they are not a drug – testosterone in our bodies = not a drug, simply a hormone (pill/cream/injection = drug)
Many experiences are administered: walk in nature, will affect our physiological functioning
Dopamine: inside your body, is simply a neurotransmitter – outside your body, considered a drug
10
Q
“Affects physiological functioning”
A
Affects physiological functioning: does water do this? Yes
(food, vitamins, nutritional supplements – not considered drugs, yet they all affect physiological functioning)
11
Q
Exogenous
A
From outside the body
12
Q
Endogenous
A
From within the body
13
Q
Why are drugs used?
A
Instrumentally and recreationally
14
Q
Instrumentally
A
o Using the drug to accomplish some sort of specific purpose
In the morning, drink coffee to wake us up
Drinking alcohol to relieving stress
Taking drug to avoid withdrawal – instrumental
15
Q
Recreational drug use
A
o Using a drug for the sole purpose of experiencing the substances effects
Drinking alcohol in a recreational way to party and have fun
Xanax (prescription drug) used recreationally, to experience the effects
Historically have a problem with doing things fun; often a push to legalize cannabis – marketing shift towards medical marijuana – reframing for instrumental use, important part of legalization (advocating for instrumental drug use)
16
Q
Trade name
A
Often a marketing skew, not based on anything
- viagra (sounds vital)
17
Q
Generic names
A
Chemistry might be incorporated
- sildenafil
18
Q
Chemical names
A
Gives complete detail of the chemical structure of a drug
- 5-{2-(ethyloxy)-5-[4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
19
Q
Street name
A
Name used by those who take/sell the drug for the streets
- blue diamond
20
Q
Dose
A
o Higher dose = more of the drug, but how much for what person?
o Amount of drug, per body weight
o Milligram per kilogram / microgram per kilogram
o Drug study with rats: rats must be weighed before the drug is administered
21
Q
Dose-effect/dose-response curve
A
o Lower doses, we might not see the effect – want a higher effect
o Scatter plot; draw line of best fit through
o X axis
Increasing dose
o Y axis
Number of individuals responding to the drug
How strong the effect is felt
o Have to give the drug in different doses; multiple times over different sessions (commonly 3 different doses)
o Have to be based on experimental data; real world phenomenon
22
Q
ED 50
A
o Median effective dose
o The dose where 50% of the effect was observed or when the effect was observed in 50% of participants
o To find: need to draw it in, from the right
o Only experimentally derive; collecting data in the world
o Effect? Effect is arbitrary
Supposed to change our mood? How did the mood change? Can vary Sometimes there may be many effects; may separate these
23
Q
Potency
A
o Some drugs are more potent than others
o Potent = stronger
o If one drug is more potent than another, the more potent drug’s graph will be shifter to the left (take less dose); if a drug is less potent, the graph will be shifted to the right
24
Q
TD50
A
o Median toxic dose; typically far to the right
o Dose at which 50% of the subjects experience a toxic effects or when the toxic effects are experienced 50% of the time
o Studies done on animals
25
Therapeutic index
TD50/ED50
o Mathematical equation
o Doesn’t tell you a lot; if you have 3 different drugs – can compare
o Greater = margin of safety is larger
o Is not conservative
26
Certain safety index
o Mathematical calculation
o We want to know when anyone has a toxic effect – care about TD1 more, do not want anyone to feel the adverse effects if possible
Where 1% experience toxic effects
o Want everyone to have the benefits of the drugs, where 99% of the effect is there or 99% experience the effects
o More conservative – certain safety index
o Certain safety index larger (1 vs 7) = 7 is safer, ED is farther from TD
27
LD50
o Median lethal dose; where 50% of individual die at that dose
o To make sure the public is safe
28
Pharmacodynamics
o The physiological actions of the drugs; the actual mechanism
o Bind to glutamate receptor? What change does it cause?
29
Pharmacokinetics
o How drugs are passing through our body
o Administered; stored; do they break down? Pass to the brain undisturbed? Metabolized the in the liver?
o How are they eliminated from the body? Exhaled? Through the urine?
30
Pharmacogenetics
o How differences in our genes, lead to differences in our biological makeup/pharmacodynamics and pharmacogenetics
o Some can tolerate drugs better, more/fewer of an enzyme
31
Psychoactive drug effects
- objective
| - subjective
32
Objective effects
o Drug effects that we are capable of directly measuring
o How does it change heart rate, salivary production, pupil dilation?
33
Subjective effects
o Drug effects that can’t be directly observed
o Affects our memory – have to study indirectly, memory test
34
How do we acquire info about the world
- authority
- intuition
- observation
- test
35
Authority
o Whose authority? Parents, school teachers, politicians, doctors
o Weakest form: only based on trust in that authority figure – is needed, valuable and useful, we cannot all be authority figures on everything
o Often exploited: humans built to listen to authority (social structure), often to susceptible to authority – to sell you things, generate a false authority, using terms with longstanding authority
o Often their authority does not extend farther than we usually believe it does (Dr. Spock)
36
Dr. Spock
Dr. Spock: child-rearing in the 1950s, they are humans with feelings they need be nurtured and cared for
Advice: to sleep your baby faced-down
Based on observation: they will not choke on the vomit
Not based on scientific data – reasonable inference based on science
Major danger! Sudden infant death syndrome, happened for years and years
At risks for respiration problems and SIDS
37
Problem with authority
o Often their authority does not extend farther than we usually believe it does (Dr. Spock)
o One problem with authority: bullshit
“One of the most salient features of our culture is that there is so much bullshit.” -Frankfurt, 1986
Differs from lies!
Lying: requires respect for reality
Bullshit: indifferent to reality, mix/dilute bits of truth with other thoughts – convincing others
Alternative facts???
Is not a new problem
Cf. Socrates and the sophists
Sophists who taught you how to win an argument no matter the subject – being right more important than being truthful
Tangible effects: lives lots due to the misrepresentation of facts
38
Intuition
(effortless knowledge, « gut feeling »)
o Commonly a starting point in science
o Draws from life (anecdotal) experience: so much information coming into your head is inaccurate – part of the intuition, so much going on in life cannot absorb all the information
o Sometimes correct
o Often wrong
39
Problems with intuition
Illusory correlation: no correlation between two sets of data, no relationship between these 2 variable – although the data could be misleading / astoundingly similar
Susceptible to bias
Overconfidence
40
Illusory correlation
no correlation between two sets of data, no relationship between these 2 variable – although the data could be misleading / astoundingly similar
See a statistical relationship, but not an actual one – not related
Humans are meaning-making machines: designed to sense patterns – often see sense/patterns where no pattern exists
Correlation does not equal causation
The number of ashtrays increasing in the house, probability of getting lung cancer increases… so it’s the ashtray? No, it’s the cigarettes
The 3rd variable problem; influencing both things we are observing
41
Susceptible to bias
Eugenics; « social philosophy » to take something as legitimate and good science, and extrapolate that ??? //
Natural selection extended unto humans – take those who have desirable traits and they should have lots of children, and those with undesirable traits should not procreate
Presume that there is desirable traits; and that they knew what they were
White dudes… biased
Women = meek, small, white, fair
Men = strong
Exterminating whole groups of people/sterilization (happened in Canada!)
Studying IQ based on race???
42
Overconfidence
The Dunning-Kruger effect
You are never more confident, than when you know basically nothing about an event – overconfident
Confidence quickly drops – realize all of the things you do not know
Mount Stupid in the Valley of Despair
The more experience, the less confidence you have… does bounce back eventually, but never again achieve the heights of mount stupid
43
Observation
o Critical to good science: empiricism (scientific, systematic, measurement)
o Works best with objective measures
o Still not enough to acquire the best information about the world…
Which ball will hit the ground first when dropped from the same height?
They land at the same time, although people think that the heavier one will hit the ground first
Naturalism: collection of old dead things, needed to observe and test those observations
44
Problems with observation
- bias/limited explanatory power
- frontal lobotomy
- vaccines and autism
45
Frontal lobotomy
Saw a report where a chimpanzee was no longer frustrated when aggravated, after frontal lobotomy – decided to test this on « disruptive humans »
Many non-consenting individuals received: children, psych patients, women more than men (consent could be given by husband or father)
Doctors office, drive needle in pupil, swish up the front of the brain
No therapeutic benefits
Tens of thousands of people
Dr.: shot by one of his patients, clearly still upset - paralyzed
46
Vaccines and autism
Andrew Wakefield
Study in small group of individuals, who got the mumps vaccine also had autism
100% of ASD individuals had the measles/mumps vaccine – everyone gets these vaccines
No control group
Developing a discrediting vaccine – trying to create a competing drug
Led to the movement against vaccines
47
Scientific skepticism
* Question authority and intuition
* Question your senses
* Question knowledge, beliefs
* Systematic doubt and continual testing
• BUT be careful of extreme skepticism/extreme postmodernity: these are the tools of obfuscation
o How can we ever really know anything?
Some senses, true
Pushing you away from asking the difficult/important questions
Our models of the world are amazingly accurate
48
The scientific method
Obersvation and testing
* Observation
* Idea
* Consult past research
* Hypothesis
* Design study to test hypothesis
* Ethical approval
* Collect data
* Analyze data
* Modify and repeat (if hypothesis is wrong), or…
* Consider implications of results, build theories
49
Good science (5)
- materialism
- universalism
- communality
- disinterestedness
- organized skepticism
50
Materialism
o Presumption that everything in the universe has a physical basis: matter or energy
o Can be measured directly or indirectly
o Everything corresponds to physical laws – love has a physical basis; addiction
51
Universalism
o When we observe the world, all of our observations are structured
o Objective, reliable, universally accepted way of doing something
52
Communality
o The methods and results of a scientific study, are open to all
o Allows for (1) replication, and (2) avoid manipulation of data/misrepresentation
o So many drug studies, just went missing, when they had bad results – never published
o Problem: no one wants to publish negative results
o Foundational growth
Studying flatworms, fish
Standard: worm researchers – because they shared all their data with each other, the field developed much faster
Other groups hiding the data
53
Disinterstedness
o A researcher shouldn’t have a stake in the outcome
| o Billions of dollars in drug development; more likely to skew/misrepresent the data
54
Organized skepticism
o Based on the scientific merit of the information; was this peer-reviewed, what are the methods?
55
Developing a theory
“Theory”
o Common use does not equal scientific use
o An idea, a concept, that connects many different aspects of our observations, to explain/describe a much larger thing
o Example: gravity (the moon, the sun, the waves, things dropping on the ground)
• Organize and explain a variety of facts/descriptions/observations
• Falsifiable
o Can be tested
• Generate new knowledge
• Parsimonious
o Two competing explanations; the simpler one is likely to be the best/right
56
Pseudoscience
* Often relies on authority
* Emphasis on scientific-sounding jargon
* Not falsifiable
* Poor/no methodology
* Poor/no/anecdotal evidence
* Not peer reviewed
* Ignores/conflicts with known/existing evidence
* Vague claims
• Often reinforces status quo or a worldview
o Testosterone = more masculine, do not lead to demonstrable changes in their behaviour
o Can travel really easily – strong effects
o In contact with children, a woman – aggressive, growing hair
• Does not facilitate further research
57
Science is NOT...
* A dogma (it’s simply a method)
* Scientists (its simply a method)
* Pharmaceutical companies (its simply a method)
* Doctors (its simply a method)
58
Science is as good as it currently gets...
* Science’s history is full of questionable characters, but the scientific method remains our best way of acquiring information about the world
* Scientific models of the world may be incomplete, but they’re certainly more accurate than any others
* Ignoring the best available evidence leads to tangible harm and misfortune
* Whether or not you believe in science, large institutions do and are using it (facebook, casinos)
59
Types of research
- basic
| - applied
60
Basic research
o Understanding the fundamental mechanisms; how they work; cause and effect; without thought in mind on how the science will be applied
61
Applied research
o Using basic research and applying it to real world problems
o Everyone wants applied research, but you cannot create applied research/solve the problem, without basic research
o Canadian funding, shifted towards applied science – about 10 years ago… need basic!!
62
Researching the effects of psychoactive drugs
Conceptual variable
Operational variable
63
Operational variable
Our measured variable, represents the conceptional variable
| Ex. Score on memory test
64
Conceptual variable
Psychological concepts, cannot be directly measured
| Ex. Love, memory, attention
65
4 general categories of variable
- independent
- dependent
- situational
- participant
66
Independent varibale
a) Independent variables: what the researcher manipulates (drug study, the dosage of the drug – compared to a placebo group)
67
Dependent variable
b) Dependent variables (response variables): the response to the independent variables (score on the memory test; the reaction time/accuracy)
68
Situational variable
c) Situational variables: aspects of the testing environment; what time of day; the lab space; the temperature
Need to be held constant; held in relation to what we are testing
69
Participant variable
d) Participant variables: how old; man/woman; socioeconomic status
70
Relationships between variables
• Non-experimental method: correlation research
o No true independent variable: unethical (testing addiction)
o Main problem: not directly controlling variable, might have the…
• Issue with correlation: the 3rd variable problem
• Experimental method
71
Causality
- covariation of cause and effect
- temporal precedence
- no more plausible alternative explanation
72
Covariation of cause and effect
o If the cause is there the effect happens, the cause isn’t there the effect does not happen
o Injection epinephrine = increase heart rate (what if you are excited? – not always true)
73
Temporal precedence
o You do not know what is going on in that persons life at that time
o Creatures of time: show ideally that cause happened first, then the effect happens afterwards
74
No more plausible alternative explanation
o Often comparing competing ideas against each other; to insure you have found the right one
o Parsimony – the most plausible explanation
75
Clinical drug studies
- independent variable - dosage of drugs
- placebo as control
- treatment arms
- blinded procedures
76
Placebo as control
o Exception: if treatment already exists
o Animal trials: « vehicle » - no drug in the solution/drug…
o Creating a new drug – testing is it better than the best available medication on the market?
77
Treatment arms
o Different levels/amounts of the independent variables, what dose
o Low dose; high dose; medium dose; placebo group
78
Blinded procedures
Single blind
Double blind
Open label
79
Single blind
participant doesn’t know which treatment arm they are in – human are susceptible to expectations – participants keen to help the research
80
Double blind
both the participant and the researcher does not know who are in which treatment arm – administrator will be looking for a specific responses, removing information to avoid biases
81
Open label
blind experiments sometimes unethical; experimental methods/cancer treatments, potentially dangerous, needs to be clear to the participant what dosage they are receiving, keeping them away of the risks – necessary in some drug studies (placebo group, but they know they are not receiving the drug!)
82
Animals for model research
• Animals are used for psychopharmacological research: (extended human lifespan by about 10 years)
o Understand basic mechanisms, genetics, etc.
(Fruit fly is great model for genetics; rat brains are similar to human brains)
o Bc there are no viable alternatives
Giving heroin to undergraduates
o Bc they have high predictive value
o Have a number of protections in place (e.g. CCAC, ACC): federal, provincial, institutional levels
83
Human research - ethics
• Ethical considerations must be made
o Federally mandated committees review human research proposals
o Informed consent: warned of potential risks, right to back out at anytime without penalty
84
Therapeutic drug development
1 Identify disorder to treat
-Decisions include feasibility and profitability concerns
2 Drug synthesis* (first sometimes)
-Chemists synthesize experimental compounds
3 Biological experimentation -High-throughput screening methods provide basic biological information about compounds. Results are sent to chemists and guide synthesis of further compounds.
4 Focused screening methods - Focused testing occurs with most promising compounds identified during Stage 3
5 Safety pharmacology
-Tests identify adverse effects and toxic doses
6 Clinical trials
- Most effective and safest compounds tested from previous stages are tested in humans. Regularly approval sought after positive clinical findings.
85
Clinical trials
Phase 1 - Determine a drug’s most likely and frequent adverse effects to occur during treatment; No toxic, lethal effects - Low dose of the drug given short term -Normally healthy volunteers if feasible
Phase 2 - Determination of therapeutic effectiveness; experimental drug may be compared to standard medical treatment; adverse effects continue to be monitored
Where most drugs fail; no beneficial effects - May be higher dose of drug, but still given short term -Participants with disorder to be treated
Phase 3 - Further determination of therapeutic effectiveness; experimental drug may be compared to standard medical treatment; adverse effects continue to be monitored
-Doses selected based on Phase 2 results, but likely given long term -Participants with disorder to be treated, but more inclusive for other populations and those with coexisting conditions
Phase 4 - Occurs after FDA approves a drug for the market; might address remaining questions or concerns about the drug; goal is to further determine features of a drug’s therapeutic effectiveness and adverse effects - Dose selected on Phase 3 results, but likely given long term -Participants with disorder to be treated, might focus on unique effects in different populations or certain other medical conditions; choice of participants may come from results of Phase 3
