Psychopharmacology - intro Flashcards
what is Psychopharmacology
-the study of the effects of drugs on cognition, mood and behaviour (i.e their psychoactive properties)
drugs can only have psychoactive properties if..
if they interact with existing endogenous neurochemical
processes in the brain.
so they interfere with processes we already have
endogenous
generated from inside, already existing, drugs interfere with these processes
why study psychopharmacology/ types of psychopharmacological research
Drugs can be used as ‘probes’ to study functions of endogenous
neurotransmitter systems (NTs).
(understand systems better)
– Investigation of drug effects can also lead to development of
treatments for medical/psychological conditions (Alzheimer’s,
schizophrenia, depression, etc.).
two themes in psychopharm research
- Research is difficult!
– Evidence needs interpreting, critically. - We only know what we happen to have found
out so far.
– Methods aren’t perfect, and many discoveries come
about by chance.
what is important in the methodology for studying drug effects
-we need to know what a drugs effects actually are , so as with most science , we need to compare with the effects in a control condition
what is a confound
A confound is a potential alternative cause of what appears to
be a drug effect
in what cases can confounds be controlled in
Natural recovery.
(they could recover over time naturally?)
– Control by: comparison with no-treatment group.
- Expectation of drug effect.
– Control by: comparison with placebo condition (e.g., sugar pill)
and ensure “blinding” of conditions. - Expectation can still occur with placebo controls if side-
effects (or other drug effects) lead to correct guessing of
participant’s condition (“unblinding”).
– Control by: comparison with an active placebo condition (e.g.,
another drug with similar noticeable effects)
types of drug studies
-randomised controlled trials
-open label trials
-‘blinding’ of conditions, when can unblinding occur
Randomised controlled trials – RCTs:
* These trials involve a control condition (e.g. placebo, but could
be e.g. current best treatment) and random assignment of
participants to groups.
Open-label trials:
* Studies without blinding are referred to as being open-label.
(There may still be a comparison with a control group, e.g.
placebo).
“Blinding” of conditions:
– blind = participant unaware of group assignment;
– double-blind = participant and researcher unaware of group
assignment.
– N.B., “unblinding” can occur when effects are detectable.
types of drugs studies
between subjects
within subjects , crossover design, washout period
Between-subjects design:
* The comparison is between participants: drug group [participants 1,
3, 5…] versus control group [participants 2, 4, 6…]
Within-subjects designs:
* The comparison is between conditions for the same participants: drug
condition [participants 1, 2, 3… when receiving drug] versus control
condition [participants 1, 2, 3… when receiving e.g. placebo]
(at one point a participant will have a drug and at another point have a placebo)
- For instance, a crossover design. (E.g., “AB/BA” : drug-then-control
/ control-then-drug.
half participants have a drug first and few wakes later have a placebo , vice versa)
A “washout period” may occur between
treatments-taking the drug a few weeks later)
effects in drug vs placebo groups
khan et al study
-what does the change in placebo groups indicate?
-how do we conclude the effect of the drug treatment?
- N.B., % change in placebo group will include any natural time-course of condition
as well as expectancy effect of placebo. (No no-intervention group for comparison).
-The effect of drug treatment is difference between drug & placebo groups
measures of drug effects
-why be careful when using subjective measures?
Changes in subjective experience (‘phenomenology’) & mood (self-
report alertness, happiness, anxiety, etc.)
- Changes in physiological activity (fMRI, EEG, etc.)
- Changes in task performance (simple & choice RT tasks, vigilance
tasks, memory, problem solving, etc.) - Changes in behaviour (social co-operation, aggression, hyperactivity,
etc.)
─ N.B., subjective measures (e.g. ratings by self or researcher) can be
susceptible to bias or expectancy – hence double-blind technique.
what is a neurocognitive model
-what could the model be
a neurocognitive model aims to explain the relationship between specific neurotransmitter systems, cognitive processes and subjective experiences
The model could be of a type of drug effect
(stimulant, sedative, psychedelic, etc.)
- Or it could be of a neuropsychiatric conditions
(ADHD, depression, schizophrenia, etc.)
-3 way connection
examples of neurocognitive models
noradrenaline
components of the neuron and synapse
-dendrite
-cell body
-axon
enzymes and synthesis
synapse
- Dendrites receive chemical signals (neurotransmitters, NTs) from other neurons.
- The cell body (soma) includes the nucleus, which controls cell’s activity.
- The axon allows an electrical signal (action potential) to travel to axon terminal.
- Enzymes control synthesis of neurotransmitters, which are stored in vesicles and
released from the axon terminal. - The signal is transmitted between neurons at the synapse
how is an action potential generated
-axon hillock
Multiple excitatory & inhibitory signals (‘post- synaptic potentials’;
PSPs) are integrated (combined) to determine whether an action potential is generated axon hillock: action potentials are triggered here if sufficient depolarisation (+ relative to -)
- Excitatory signals ________ the likelihood of receiving neuron
producing action potential
– Inhibitory signals ________ the likelihood of receiving neuron
producing action potential
Excitatory signals increase likelihood of receiving neuron
producing action potential
– Inhibitory signals decrease likelihood of receiving neuron
producing action potential
endogenous processes involving neurotransmitters
(1) synthesised by enzymes
& packaged in vesicles
(2) released,
then bind with
postsynaptic
receptors
(3) deactivated:
presynaptic reuptake or
broken down by
enzymes
the NT has to _______ to be able to produce an effect
fit the receptor (like a key in a lock)
what are the effects of the NTs at the post synaptic cell
NTs influence the opening and closing of post-synaptic ion channels. This
allows electrically charged ions to move in or out of the post-synaptic cell,
making it more or less likely to ‘fire’ (produce an action potential).
- Some NTs have less direct effects, e.g. modulating the effect of other NTs on
ion channels, or leading to other synaptic changes (e.g. for learning)
the effect of a neurotransmitter depends on _____
receptor type
NTs therefore have different
effects at different receptors (e.g. nicotinic and muscarinic ACh receptors)
explain NT deactivation
NT detaches from receptor &
is then:
* transported back into the pre-
synaptic neuron (reuptake)
or
- broken down by enzymes in
the synaptic cleft (products of
enzymatic breakdown may
then be recycled)
how do drugs work
-what can they influence
-agonists
-antagonists
Psychoactive drugs interact with NT systems.
- Drugs can influence NT synthesis, storage, release,
receptor interactions, and/or deactivation. - Drugs can have agonistic effects, where they mimic or enhance the effects of a NT.
- Drugs can have antagonistic effects, where they
block or reduce the effects of a NT.
what are some ways which drugs interfere with endogenous processes
synthesised by enzymes
& packaged in vesicles
(1)
synthesis (e.g. more precursor;
L-dopa – see Lecture 3)
(2) released,
then bind with
postsynaptic
receptors
binding (e.g. block
receptor; ketamine – see
Lecture 1)
(3) deactivated:
presynaptic reuptake or
broken down by
enzymes
deactivation (e.g.
block reuptake; SSRIs
– see Lecture 4)
two major neurotransmitters
glutamate and gaba
-glutamate and GABA work in opposition to each other to maintain the right balance between inhibition & excitation.
Both are found throughout the brain.
what are
glutamate
GABA
Glutamate (glutamic acid) is the main excitatory NT, released by ~ 50% of neurons.
It is a precursor for GABA.
- GABA (gamma-amino-butyric acid) is the main inhibitory NT, released by ~ 40% of neurons. It is synthesised from glutamate.
Gaba agonists
-what do they do
-examples, what are they commonly used for
Benzodiazepines (BZDs), barbiturates & alcohol
enhance the inhibitory effects of GABA and are:
– anxiolytic (reduce anxiety).
– sedative (reduce arousal / increase relaxation).
– hypnotic (promote sleep)
BZDs (diazepam, temazepam, lorazepam, etc.) are commonly
prescribed for anxiety and are also used as pre-anaesthetic
relaxants in surgery.
- Barbiturates are more potent GABA agonists – mainly
used as general anaesthetics, to induce coma (e.g. after
brain injury), & to treat epilepsy.
Gaba antagonists
what do they do and how
examples
-reduce the inhibitory effects of gaba (inhibit action of gaba)
flumazenil – blocks BZD site on GABA receptor; reverses BZD
sedation (e.g. after medical operation); antidote for BZD overdose
- picrotoxin – stimulant (increases arousal); convulsant (induces
epileptic seizures at high doses); antidote for barbiturate overdose
glutamate agonists
-what do they do
-example
-enhances glutamates excitatory effect
glutamate agonists (e.g. ibotenic acid, found in poisonous
mushrooms) are excitotoxic – i.e. can kill nerve cells through
over-excitation
glutamate antagonists
-what do they do
-examples
-blocks binding of glutamate so blocks excitatory effect of glutamate
-ketamine = NMDA receptor antagonist; blocks excitatory
effects of glutamate, used medically as sedative & anaesthetic.
glutamate has various receptor ____ ______.
-what is NMDA important for
-sub types
-is important in initiating the long-term synaptic changes necessary
for learning & memory.
– is also implicated in drug addiction, schizophrenia & epilepsy.
