Psychopharmacology and psychopathology (SOWPSB3BC16E)
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Radboud Universiteit Nijmegen (RU)
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Stahl\'s Essential Psychopharmacology
In this document you can find a summary of the lectures of the course Psychopharmacology and Psychopathology. As well as some Q&A questions given in the extra lectures with the correct answers. At the end there is partly a summary of some chapters in the book, but not all are covered. Chapter 1 til...
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Psychopharmacology
WEEK 1
Lecture 1 – Hanneke den Ouden - Introduction
Why is psychopharmacology so important for psychologists?
Psychopharmacology is about changing molecules to change behavior. This can be in every place of
the body or just a specific target. The aim is behavior change, and the approach is change of molecules.
These two (the aim and approach) interact with one another. This is why psychopharmacology is so
important. Psychologists are psychopharmacologists!
Example: Serotonin transporter methylation and response to cognitive behavior therapy in children
with anxiety disorders. Roberts et. al, 2014 Translational Psychiatry.
Should psychologists be allowed to prescribe drugs?
Yes and no. Psychologists know the most about behavior change, so you would say that psychologists
are the most competent to prescribe drugs. Psychotropic medications affect not only the developing
brain but all organ systems. This is why this topic is an ongoing debate, very controversial whether
psychologists must be able to prescribe drugs to patients. So at the moment it is not possible for
psychologists to do this. You must know everything about all organ systems as this is also affected by
psychotropic drugs and psychologists only know a lot about behavior change.
Most psychotropic drug prescriptions are written by general physicians who know very little about
either psychiatric mental health diagnosis or treatment.
Are drugs good or bad?
Ecstasy is safer than horse riding (professor David Nutt explains) → youtu.be/1BP367JdHro
• There are more people with brain damage from falling of a horse than from people using
ecstasy. By making it illegal people will think ecstasy is more dangerous than horse riding.
How can illegal drugs help our brains (David Nutt) → youtu.be/WOxSQHtJWlo
• Psilocybin can help people with anxiety/depression etc. So these drugs can have potentially
enormous opportunities for helping people deal with mental distress.
• Not only psychedelic drugs have these effects. Also non-psychedelic drugs have the same
effects:
o MDMA (ecstasy) helps people with PTSD and addiction.
o Cannabis helps people with pain, spasticity, cancer, epilepsy, inflammatory diseases,
and sleep disorders.
• Why don’t use these drugs?
o The WHL and the United Nations have said they are too dangerous. This is certainly
untrue. None of the patients died of it when the researchers were experimenting it
on the patients.
o A lot of people have closed minds about using these drugs for treatment.
A history of LySergic acid Diethylamide
LSD was originally the substance Ergotamine. Now we know it as a synthetically made drug. But it
wasn’t at first. This Ergotamine was produced by fungi that lived on the rye plant. In the middle ages
when people would eat bread that was made of rye that has this fungi on it they got the disease Saint
Anthony’s fire (Ergotism). People had the following symptoms. Convulsions – uncontrollable shaking
that is rapid and rhythmic, with the muscles contracting and relaxing repeatedly (seizures),
1
,vasoconstriction – their arteries and veins were tightened; this leaded to gangreen – legs were falling
off because there was no blood supply going there. And people would also get hallucinations – sensing
something that doesn’t exist.
Sidenote: In 1518 there was something called ‘The Dancing Plague of 1518’. People were dancing on
the streets for four to five days and people even died of exhaustion during this period. They think this
dancing has to do something with the Saint Antony’s fire disease, Ergotism.
This ergotamine turns out to be a precursor of lysergic acid which itself is a precursor of LSD. Does
that mean that this all is bad? Also in the middle ages these vasoconstrictive effects where helpful to
stop for example postpartum bleeding (a frequent cause of death for women after giving birth).
Timeline of history of LSD
1918: Ergotamine was isolated
1938: First synthesized synthetic LSD-25 by Hoffmann (it’s called LSD-25 because it was the 25th
molecule he tried) → Hoffmann’s book: LSD my problem child
1943: April 16 → first LSD trip. Hoffmann started working with it again after 5 years, and he had
some LSD on his gloves and he touched his mouth, so he got his first LSD trip because of that.
1962: LSD got forbidden by law because it was a very popular drug but ‘not good’ for people. The
fact that a synthetic drug is not forbidden, doesn’t mean that the drug isn’t dangerous. It’s
just that the authorities haven’t been able to evaluate it and deciding whether it should be
allowed or not. You always need to use your own minds for deciding to use it or not.
1970s: Jan Bastiaans (Dutch psychiatrist). He was using LSD to treat PTSD patients. With the idea that
they would open up. YouTube-link ‘2016: Andere tijden, LSD experiments in the Netherlands’:
https://www.youtube.com/watch?v=jzVMpVTsw-E&ab_channel=UnderdogHistory
1977: Herman van Praag argued that we needed systematic LSD research.
2010s: The start of systematic research into psychedelics. Especially focus on microdosing, low doses.
LSD: the mechanism
LSD is primarily a serotonin agonist. You can think about it like a key. LSD has the same key for opening
the lock just like serotonin. That’s why you can call it an agonist for serotonin, it works the same. The
lock is the receptor. LSD seems to work as well on the dopamine system and probably also on other
systems. The serotonin projection pathway, so serotonin is being produced there in the Raphé nuclei.
It goes all through the brain. More about serotonin you can find in lectures given by Gilles van
Luijtelaar and Judith Homberg. More about agonists and antagonists you can find in lectures 2 and 3.
2
,Cannabis: curse, cure or cause?
Cannabis is been kind of suggested as a cure for specific psychiatric problems, particularly anxiety and
sleeping problems. At the moment the current treatment is with benzodiazepines (Valium) what can
lead to drowsiness and addiction. The researchers didn’t find a lot of effects. While they used a really
high dose, it was well tolerated by the people with dementia (in the study) so they (the researchers)
can now start looking at higher doses. One of the components in Cannabis is THC:
Tetrahydrocannabinol.
• Link to the paper: ‘Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A
randomized controlled trial.’
Cannabis can also be thought of as a cause for psychological problems. When looking at thousands of
people there was found that using cannabis chronically before the age of 18 they later have 8 IQ points
lowered compared to peers. There is also an increased risk of depression when you use cannabis.
• Link to the paper: ‘Persistent cannabis users show neuropsychological decline from childhood
to midlife.’
People think that when drugs are legal it is safe to use, but this is not always the case!
How does cannabis work?
There are two main components of Cannabis of the weed you can grow: THC and THD
• THC targets the so called CB1 and SB2 receptors. These are located in the entire body including
the brain. They are very important for finetuning the whole immune homeostatic balance
within the host.
• CBD (Cannabidiol) is not psychoactive. It targets many receptors, but not CB1-R or CB2-R. It is
also located throughout our body. This is something you can actually buy at Kruidvat for
example in the form of an oil.
There are also terpenes and flavonoids (phenols) that cause (respectively) the smell and the taste.
Synthetic THC
These are new THC molecules that are being created just like the LSD, but they are synthetic. Again,
they are not illegal, because they are not evaluated yet by lawmakers. You have to be careful with
these! They are high-affinity, that means that they are attached and hang around for a long time. And
they are full agonists of the CB1 receptors. ‘Full’ means that act like a complete agonist, that they
really take over you cannabinoid system, they are super strong.
CBD – a panacea?
CBD is claimed to help against fear, pain, stress, anxiety, eczema, sleeplessness, cancer… But actually
there is not much evidence for these things. Panacea is a solution or remedy for all difficulties or
diseases. So, it is not right to say without (much) evidence that CBD is a panacea. There is only some
evidence that CBD’s help for the Dravet Syndrome (Devinsky et al., NEJM 2017). → Link:
https://pubmed.ncbi.nlm.nih.gov/28538134/ .
So cannabis might be a cure in some cases, but also a curse or a cause. In epilepsy, cannabis might be
able to cure the epilepsy. Maybe the cannabis works as well for people with chronic pain or in
dementia. Cannabis might be a curse or cause as well for different diseases. It can cause an IQ drop,
maybe even depression or a psychosis.
Questions about drug development (see lecture 7 of Barbara Biemans):
• Why aren’t antidepressants getting any better?
• Why are drugs so expensive?
3
, Levels of investigation
• Behavioral systems
o When you are investigating on another level than this one, you still have to take into
account the behavioral level.
o When someone is investigating on the level of molecules they have to go through all
the other levels as well (synapses, neurons, circuits) until they arrived to the
behavioral level. If someone is investigating at the level of circuits, than they don’t
necessarily need to pass the other levels below it.
• Circuits
o All these connections, of an axon synapsing on to a dendrite, releasing a
neurotransmitter to the receiving dendrites which can send an electrical signal to the
cell body which then integrates the information, send it on to the next axon which
sends it to the next dendrite, etc., are making circuits.
o These circuits can be local, within one gyrus in your brain.
o It can also be micro circuits, within a single cortical column.
o And they can be interregional, long distance connections, much more global.
• Neurons
o The functioning of the nervous system: is about the interaction between chemical
activity and electrical activity of assemblies of neurons (thousands of neurons at the
same time).
o Neurons exist of dendrites, the soma and axons (classic neurotransmission)
▪ Dendrites: the information comes in.
▪ Soma: all the information gets integrated in the soma, the cell body.
▪ Axon: the output of this information gets out via the axon to other dendrites.
• Synapses
o Axo-dendritic: classic neurotransmission: axons synaps on to a dendrite.
o Axo-somatic: axons can also synaps on the cell body, then there is no spines.
o Axo-axonic: they can even synaps to the initial segment of the axon itself.
• Molecules, ions → neurons use chemicals to communicate!
Ritalin helps you focus, we phrase what the molecules are doing in
terms of the behavior that they’re affecting. But actually what
Ritalin is doing: is blocking the dopamine transporter (at a molecular
level), and somehow that means that at all the other levels
(synapses, neurons, circuits) there is also an effect going on what
ultimately leads to help you focus (behavioral level).
Anatomical infrastructure mediates the effects of chemical
neurotransmission on behavior. The anatomical infrastructure
exists of the circuits, neurons and synapses.
It’s not the building blocks that make us special among other
mammals. But it is the many connections that make us special!
The shape of a neuron is telling something about it’s function. If you
have for example a very large dendritic tree, you get lots of input
integrated from many neurons from many regions of the brain, but
you may have a single output. But if you have a neuron that has not
so many input, it can still transfer a lot of information to many parts
of the brain: for example serotonin and dopamine neurons can
reach a lot of parts in the brain, but do not need many input.
4
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