Psychopharmacology & Psychopathology
Week 1 Lecture 1
Principles of psychopharmacology: Introduction
Drug categories:
1. Stimulants: feeling more awake, alert, confident or energetic (e.g., cocaine).
2. Opioids: sensation of pleasure and pain relieve (e.g., heroin).
3. Depressants: reduction of arousal and stimulation (e.g., alcohol).
4. Empathogens: increase in empathy, friendliness, and playfulness (e.g., MDMA).
5. Psychedelics: alteration of thinking, sense of time and emotions (e.g., LSD).
6. Cannabinoids: feeling of relaxation or euphoria (e.g., marijuana).
7. Dissociative: sensory alteration, dreamlike state and emotional detachment (e.g., ketamine).
Changing behavior and changing molecules in the brain: changing behavior can change molecules in the brain, also
the other way around, changing molecules in your brain can change behavior (e.g., serotonin transporter methylation
and response to cognitive behavior therapy in children with anxiety disorders).
▪ Aim: change behavior.
▪ Approach: change molecules.
LSD
Ergotamine, produced by fungi in rye. Ergotism (Saint Anthony’s fire).
Symptoms: convulsions, gangrene (but it is helpful to stop bleeding, vasoconstriction), and hallucinations.
History:
1. 1918: isolation of ergotamine.
2. 1938: synthesis of synthetic LSD-25 by Hoffmann.
3. April 16, 1943: first LSD trip.
4. 1962: LSD forbidden by law.
5. 1970 ‘s: Jan Bastiaans: controversial trauma treatment.
6. 1977: Herman van Praag: we need systematic LSD-research.
7. 2010: systematic research into psychodelects microdosing.
Mechanism: LSD is primarily a serotonin agonist. It locks the
receptor in its active state. It works on the serotonergic pathway.
Cannabis
Cannabis is considered as s a cure for psychiatric symptoms with
the aim to treat sleep and anxiety problems. The current treatment is via benzodiazepines (valium), but these have a lot
,of side-effects (e.g., drowsiness, addiction). They started experimenting with cannabis as a cure, they did not have any
positive or negative effects.
▪ If using cannabis chronically before 18th year of age > later have 8 IQ points lower compared to peers.
How does cannabis work?
▪ THC: targets CB1 and CB2 receptors, located throughout our body (incl. brain). This gives the ‘high’.
▪ CBD: targets many receptors but not CB1-R or CB2-R, located throughout out body (incl. brain). It is not
psycho active. Presumed pain relieving effects.
▪ Terpenes: causes the cannabis smell.
▪ Flavonoids (phenols): causes the cannabis taste.
CBD is claimed to help against fear, stress, pain, anxiety, eczema, sleeplessness, cancer. There is evidence that it helps
for Dravet Syndrome.
Levels of investigation
▪ We are interested in how molecules change our behavioral systems (e.g., Ritalin on the molecule level helps
you focus on behavioral level, and on the level of the synapse it blocks the dopamine transporters).
▪ There is a prototypical neuron with a basic structure (dendrites, soma, axons). If information flows from the
dendrites through the cell body, through the axon, to the synapse where information comes in. A threshold
will determine whether an action potential will be generated (neurotransmitters are then released).
▪ The functioning of the nervous system is an interaction between chemical activity and electrical activity of
neurons.
▪ Circuits can be local (within one gyrus), micro (neurons right next to each other), and interregional (long
neurons).
The degree to which are brain is interconnected, makes us human. You are born with the neurons you have; you do not
grow new brain cells. Learning is about who the neurons talk to (interconnections). As we grow older the connections
exploded hitting puberty, those connection prune aways as you grow older. Brains are highly plastic.
Classic neurotransmission:
Signals go from the pre-synaptic neuron to the post-
synaptic neuron. Synaptic vesicles transport the
neurotransmitters through the synaptic cleft, when the
threshold for an action potential is met. The vesicles
merge with the membrane at the end of the pre-
synaptic cleft and they release their neurotransmitters.
These neurotransmitters can than bind to receptors on
the post-synaptic neuron and have an effect there (i.e.,
excitatory or inhibitory).
,Free-floating membrane proteins:
The membrane of a neuron consists of lipids, and it is
mobile/plastic. Because of this, the receiving neuron can
respond for example when it wants to desensitize itself, it
then retracts the receptors back.
Types of synapses:
1. Axo-dendritic: axons that synapse on the dendrite.
2. Axo-somatic: axons that synapse on the cell body.
3. Axo-axonic: axons that synapse to other axons.
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.
Types of neurotransmissions:
1. Anterograde (classic): in the synapse the pre-
synaptic neuron releases neurotransmitters and
it binds to the post-synaptic neuron.
2. Anterograde (volume): the neurotransmitters
can diffuse through the rest of the brain, which
leads to neurotransmitters attaching to
receptors in other neurons.
3. Retrograde: neurotransmitters are released
from the post-synaptic synapse, and they travel
back to the pre-synaptic neuron.
Volume transmission (non-synaptic diffusion) is how most pharmaca work.
▪ Exceptions > dopaminergic drugs. Dopamine in the PFC diffuses away from the synaptic cleft, this is because
there are very few transporters for dopamine back in the pre-synaptic neuron.
, Auto-receptors are usually inhibitory, their function is to regulate neurotransmitter synthesis and/or release. When
neurotransmitters bind to auto-receptors a feedback mechanism is active that leads to less neurotransmitter synthesis
and/or release.
Retrograde neurotransmission:
▪ Endocannabinoid (endogenous marijuana): bind to presynaptic receptors and
inhibit synapse.
▪ Nitric oxide: to cGMP sensitive targets (2nd messenger system).
▪ Neurotrophic factors (e.g., NGF): all the way to the cell nucleus, modulating
gene expression.
6 key neurotransmitter system targeted by psychotropic drugs:
1. Serotonin (modulatory, either excitatory or inhibitory depending on receptor).
2. Norepinephrine (modulatory, either excitatory or inhibitory depending on receptor).
3. Dopamine (modulatory, either excitatory or inhibitory depending on receptor).
4. Acetylcholine.
5. Glutamate (primary excitatory).
6. GABA (primary inhibitory).
Serotonin, norepinephrine, and dopamine are mono-aminen, they can bind to each other’s receptors.
Neurons use chemicals to communicate, but these small molecules are not the key to understand the brain. The key is
to understand the receptors that they bind to.
The molecules are the same everywhere, yet ACh depletion in the brain leads to dementia and ACh depletion in the
muscles can lead to myasthenia gravis (i.e., autoimmune, neuromuscular disease that causes weakness in the skeletal
muscles, the bones that connect your bones and contract to allow body movement).
▪ GABA has > 160 receptor subtypes, they have different localizations and different effects.
▪ The neurotransmitter molecules are small and nonspecific, the receptors make the difference.
Major chemical classes of neurotransmitters: (1) small molecules, (2) peptides, (3) lipids, and (4) gases.
Psychopharmacology is not the same as neurotransmitters.
The neuron is a chemical factory:
▪ Many neuronal components.
▪ All with specific functions.
