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Psychopharamcology lecture notesLecture 1: Basic principles
Why is psychopharmacology important for
psychologists?
Aim is to change behavior and the approach with
psychopharmacology is to change molecules. But this
works both ways. Psychologists are treating the
underlying neural component.
LSD
History
• Ergotaminem produced by fungi on rye. When you
ate the bread → ergotism (saint Anthony’s fire).
• Symptoms: convulsions (stuiptrekkingen), gangrene vasoconstriction (helpful to stop
postpartum bleeding), hallucinations.
• 1918: isolation of ergotamine → used in migraine for example.
• 1962: LSD forbidden by law. In 70’s dutch psychoatirisch: used LSD in trauma treatment, but
schrizopfrenic? Causes by the LSD? 1977: we need systematic LSD research! 2010s systematic
research intro psychedelics micro dosing.
Mechanism
• LSD is primarily a serotonin agonist = locks the
receptor in its active state
Cannabis
• Aim: treat sleep and anxiety problems
o In study no bad but also no positive effects, maybe higher doses.
• Current treatment benzodiazepines (valium) side effects like drowsiness and addiction so not
ideal.
• Psychological problems because of cannabis±
o Prospective study and control many factors: found that If using cannabis chronically before
18th year of age: later have 8 IQ points lower compared to peers.
o Also beginning evidence for risk for depression
How does cannabis work?
• THC
o targets CB1 and CB2 receptors
o located throughout our body (including brain)
o gives you the high
• CBD (cannabidol)
o Targets many receptors but not CB1-R or CB2-R
▪ Not psycho-active because of this
o Located throughout our body (including brain)
o Presumed pain relieving effects
, ▪ CBD oil at Kruidvat
o Claimed to help against fear, stress, pain, anxiety,. excema, sleeplessness, cancer etc….
▪ Evidence it helps for Dravet Syndrome (severe epilepsy in children). Double-blind study.
It works but why?
▪ Also studies that did not found effect, placebo maybe? CBD for chronic pain does not
work that well.
• Terpenes
o Smell
• Flavonoids (phenols)
o Taste
• Weed the plant is a mixture of many molecules that modulate each other. Together they make a
blend form of cannabis. This is really different from the synthetic THC like molecules that are
created in the lab. Synthetic is way more potent! Very careful with these! Kids went into coma!
o New synthetic drugs are legal. But only because the law lags behind the synthesis /
development. NOT because they are safe. Synthetic drugs are often very dangerous.
Multiple uses of chemicals
• One person´s cure is another person´s side effect
• Novichok: Acetyl-choline-esterase (AChE) inhibitor
o Block AChE (thus it blocks the enzyme that breaks down acetylcholine) → enhancing the
concetration of endogenous acetylcholine. binds to several places, irreversible. used in an
attempt to kill people.
o Also medical uses of these inhibitors!
▪ Alzheimer’s disease: because acetylcholine levels too low
▪ Myasthenia gravis (muscle): too low acetylcholine levels in
your muscles.
• Https://www.opcw.org/special-sections/eduction/multiple-uses-of-
chemicals/
Principles of psychopharmacology
(chapter 1-3 in the book)
Levels of investigation
Interested in how molecules change behavior. Levels in
between those many levels left that are often
overlooked. For example: Ritalin… helps you focus. But
Ritalin… blocks the dopamine transporters.. helps you
focus.
Neurons
• Many types of neurons. Overall they have the
same structure: dendrites, soma (cell body) and
axons.
• Neurotransmission (see graph)
o Information flows from the dendrites → cell
body → axons → synapses.
o Dendrites can pick up all kinds of stimulations
like light, drugs etc. integration of signals in
, the cell body.
o There is a threshold that determines whether there is an action potential propagated
through the axon.
o Axon releases neurotransmitter (e.g. dopamine) in the synapses. That combines to the next
neuron.
• Functioning nervous system is an interaction between chemical activity (how neurons talk to
each other, this we will learn in this course) and electrical activity (the action potentials, EEG) of
neurons.
Circuits
Neurons together make up circuits of neurons. These circuits can be local (in
one gryus of the brian), interregional (from one region to another) and micro
(very local, neurons next to each other). The degree to which our brain are
interconnected makes us special / humans. If you compare the
interconnection with other animals, makes us very different. What neurons
look like in species are similar but the connection is the big difference. As an
adult you don’t get any new braincells, but you can learn because of the new
connections. in puberty many connections. Brains are highly plastic.
Synapse
Synapse consists of two parts: pre-synaptic neuron
and the post-synaptic neuron and the signals go
usually from pre to post-synaptic neuron. Synaptic
vesicles are packages that are packed with the
neurotransmitter. When action potential: vesicles are
send to the snypatic cleft (not a empty space, see left
part of the picture) where they merge with the
membreme and release the neurotransmitters. These neurotransmitters can then bind with
receptors in the post synaptic neuron. This effect can be extititory (more activation) or inhibitiory
(less action).
Membrane consitis of lipids, oily layer. Extremly mobily, seals itself
again after touching, really plastic. Can fold in on itself so can swallow
the protein back in, reinsert himself. The receiving neuron can also
respond; when too much neurotransmitters and want to desentive
itself then it can contract the receptors in a way.
In reality: neurons branch into a douzend synapses. A lot of synapes
everywhere! Axons that synpases on to the dendrites = axo-dendritic. Axons that synapses the the
soma / cell body = axo-somatic. There are axons that connect to the initial part of other axons. Can
form thus between any part, can influence singalling on any stage along the process going from input
to whether there is an action potential and neurotransmitter release at the end of it.
Take home: brains are highly dynamic even though we don’t grow a lot of new neurons: who they
talk to changes all the time, and makes all the difference.
, Neurotransmission
Three main types of neurotransmission
• Anterograde: classic
o Pre-synaptic neuron releases
neurotransmitter and binds to the
post-synaptic neuron,
• Anterograde: volume = non synaptic
diffusion
o Neurotransmitter is not confined
(beperkt) to the synaptic cleft,
might attach to other receptors
while spreading.
o This is how most drugs work. Because it is spread to the whole brain. Can lead to side effects
because that gets everywhere.
o Volume neurotransmission: dopaminergic drugs. Defusing happens because of the very few
transporters that hover up the dopamine back into the pre-synaptic neuron so it gets the
chance to spread anywhere. Dopamine in prefrontal cortex is example of this.
o Autoreceptors are receptors on the dendrite that bind ligands that are released by the same
neuron. If the e.g. serotonin got all the way there, you probably have enough so the
autoreceptor can feedback to stop the process of serotonin release.
▪ Function: feedback mechanism to regulate neurotransmitter synthesis and/or release.
Usually inhibitory. (logic because if exhibitory: you depleted (uitputten) your neuron
very quickly, problematic).
• Retrograde
o Post synaptic neurons releasing in to response of the anterograde process, so it is talking
back.
o Examples:
▪ Endogenous marijunana, endocannabinoid are released by the post synaptic neuron.
▪ Nitric oxide: (laughing gas), actively transported back to the cell nucleus. Can change
things like gene expression, takes a long time.
Take home messages: in neurons the signals are electrical, between neurons: the signals are
chemical. Use chemicals to communicate.
Six key neurotransmitters
1. Serotonin → modulator neurotransmitter: can have both inhibitor or excitatory effects
depending on the receptor.
2. Norepinephrine / noradrenaline → modulator neurotransmitter
3. Dopamine → modulator neurotransmitter
4. Acetylcholine → modulator neurotransmitter
5. Glutamate → primary excitatory neurotransmitter, animo acids = building blocks of protein
6. GABA (y-aminobutyric acid) → primary inhibitory neurotransmitter, animo acids = building blocks
of protein
First 3 can bind to each other receptors. Most well-known are not necessarily the most important!
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