Psychopharmacology
The effects of drugs and medication on human brain and behavior
-L. Kenemans- second edition –
1. What are psychotropic drugs?
Psychotropic drugs: Substances that influence behavior through an effect on the central nervous
system, primarily the brain. They interact with neurons and influence their signals. Through the
nervous system they influence patterns of muscle activity- behavior.
- Recreational: To have fun or as reward
- Medicinal: To reduce, change or otherwise control problematic behavior
Drugs also can block connection and have temporal paralyzing effects (that mostly don’t go through
the blood-brain barrier. Example. Tubocurarine & Atropine
1.1 Intake
The most common way to consume psychotropic drugs is food. The amino acids are converted into
neurotransmitters (incl. dopamine and serotonin). Also common is pills where the uptake is slow and
some of the effective substance breaks down. The quickest way for effect is to inject, snorting
(insufflation) or smoking the drug. A considerable slower way is substances composed of hormones.
The slowest way is intake through the skin.
Extended-release formula: A way of packaging pills that the uptake is slower and ensures a more
constant blood level throughout the day. Another advantage is that is has to be taken at the start of
the day so parents can control the intake. Example. ADHD medication
1.2 Dosing
To indicate a good dose, it’s important to make a dose-response curve. Its important to look at the
lowest effective dose and the highest dose without too much side effects.
1.3 Side effects and therapeutic window
It’s important to keep the desired effect in mind when a dosage is chosen. The
therapeutic window is determined on the one hand by the lowest dose that
forms an average lower limit for observing any desirable effect. The upper limit
is the highest average dose that results in an unacceptable level of undesirable
side effect. The larger the therapeutic window, the more suitable the substance
is for treating a symptom or syndrome.
1.4 Titration and tolerance
Titration: The act of determining the optimal dose.
Titration is a process of weeks and in 20-40% of cased the acceptable result is not found. Sometimes
in the process Tolerance (reduces desirable or undesirable effects die to the chronic administration of
the substance) develops. One possible method to compensate for the reduced efficacy is to increase
the dose, but that also has disadvantages as addiction.
1.5 Research into how psychotropic drugs work
The goal is to explain phenomena and to make them predictable. The first phase is the pre-clinical
explanatory research phase about the components and how the drug works. The most drugs that are
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, found are from observing effects. The goal in the last phase is often to determine whether the drug
has the desired effect in a specific group of patients, without explaining why. This is to predict if it will
work in a unknow patient.
1.6 Placebo control
Research starts with an open label study where patients get the medication and they observe the
effects. To control for spontaneously effect a placebo (a pill without working effects) is giving to
patients who think they (might) have working medication (double blind). An active placebo can also
be used if people could notice that they are on the placebo group. This is a pill with similar effects but
not the same therapeutic effect.
1.7 Random tests and statistics
A double-blind placebo study can still me influences by outside parameters. To control for this
random samples, need to be drawn on basis of age, education, gender, nationality, ethnic
background, severity of symptoms and other relevant parameters. To see the effect a baseline
measurement is taken to score the patients before the treatment. Side effects must be quantified
and analyzed in terms of probability. A second consideration involves the seriousness of the side
effect.
1.8 Pre-clinical and clinical research
Pre-clinical research
Animal testing which involves manipulating the genes, brains of simply the behavior of animals in
such a way they replicate human pathological condition. They use rodents (rats and mice) because
they are more similar to human, especially in anxiety (startle reflex).
Clinical research
Phase 1: A small group of healthy volunteers to see the tolerable doses (Titration)
Phase 2: Research the therapeutic effect in people with the condition (double blind, placebo)
Phase 3: Large group of double-blind, placebo-controlled studies (at least two)
This phase takes around 3-4 years and costs are around 30 million
Phase 4: Research about the side effects
2. The structure of the nervous system
2.1 Research methods
Magnetic Resonance Imaging (MRI): Subatomic particles, such as hydrogen protons, are briefly
pushed out of balance. When the particles return to their original position, they emit energy, when
an MRI scanner can pick up as a signal. The scan produces an image from this.
2.2 The exterior of the brain
Gyri: The cortex is characterized by the sausage-like windings.
Sulci/fissures: Gyri are flanked by shark clefts.
Grey matter: The cortical tissue that makes up al these windings and folds. Grey
matter is unique in that it’s largely composed of tightly packed neuronal cell bodies,
called somas. This is made up out of the short extensions that receive signals.
White matter: The longer extensions of a soma that transmit signals.
Glial cells: Cells that play an essential role in the development and maintenance of
the structure of the neurons, but also the signals that the neurons exchange with
one another.
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, Medial longitudinal fissure: Divides the brain in the left and right hemisphere. The bottom is
composed of white matter called the corpus collosum and connects the two hemispheres.
Sylvian fissure: A lateral sulcus
which separates the outer sides of
the cortex from the parts closer to
the middle.
2.3 Connections to the
exterior of the brain
Nerve cells in a specific area of the
body are mostly connected to a
specific part of the brain. There is
like a map of specific places in the
brain connected to a specific little
place in the brain. Another place
gives meaning to that piece of information.
2.4 The bottom of the brain
The cerebellum has a lot more neurons relative to the cortex. It is related to
the motor cortex, everything that is related to time, timing and learning from
timed events. Its located right next to the spinal cord which sends information
to the body which is surrounded by the vertebrae. All of the spinal cord
sections in the brain are grey matter. They do not form a pleated blanket, but
are rather collected into clumps or globules. In the medulla, pons and midbrain, the
white matter is formed by nerve pathways that form the connection between the cortex
and the spinal cord, between the cortex and the areas themselves, and between these
areas and the spinal cord. The pons and the midbrain contain certain nuclei that play an
important role in the effect of psychotropic drugs. One of these is the locus coeruleus in
the pons. It contains a fan of nerve pathways that form connections with practically
every part of the cerebral cortex and signals. This mean that a
substance that affect processes here will easily have major impact
on our behavior. The Ventral Tegmental Area (VTA) also plays an
important role in maintaining behavior through the reward center. The
Substantia nigra plays also a crucial role in regulating motor activity. In
Parkinson disease there is neuron death in this area that causes tremors.
Dorsal: On the side of the back (top of the brain looking at animals), motor
cortex (superior)
Ventral: Side of the stomach (bottom of the brain), thalamus & corpus
callosum (inferior)
Rostral = anterior (front), prefrontal cortex
Caudal = posterior (back), occipital cortex
Lateral= (outside), Medial= (Inside)
2.5 The interior of the brain
Thalamus: A collection of densely packed nuclei, such as the lateral geniculate nucleus (LGN). All
nuclei have a different connection with a brain part, example LGN -> occipital. The thalamus is part of
the basal ganglia. The basal ganglia are constantly in connection with the substantia nigra in the
midbrain for motor control.
Nucleus accumbens: Part of the basal ganglia is part of the connection in the brain’s reward system.
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