Psychadelics

Question 1

What are psychedelics

Answer 1

Psychadelics are substances that are change mood, alter perception and affect cognitive function.
They are known to induce experiences beyond ordinary consciousness.

Question 2

What psychedelic comes from ayuhasca

Answer 2

DMT- taken by long pipe or snorted
other plants containing with monoamine oxidase inhibiors. So DMT is not broken down the body so quickly

Question 3

What psychedelic comes from the peyota cactus

Answer 3

Mescaline

Question 4

What is LSD

Answer 4

LSD is a synthetic drug that was initially created in the lab for psychiatric experiments to induce psychosis.
1960s- popular recreationally - taken in tablet, liquid or small patches.
CLASS A drug

Question 5

Magic mushrooms

Answer 5

Magic mushrooms are the substcne pylocibin that is found in plants.

the prodrug Psylocybin is converted into the pharmacolgically active compund in the body- psilocin.

• widespread recreational drug of abuse
  -Class A drug

Question 6

Describe Psychedelic pharmacology

Answer 6

Psychedelics contain the groups catelocoamines, indoloamines and lysergamides

catecoloamines: benzene ring with 2 hydroxyl groups. structure is found in dopamine and mescaline

Indiloamines: benzene ring attached to 5 membered ring. Structure found in seratonin and DMT

lysergamides: most similar structure to indiloamines and found in LSD.

Question 7

Dopaminergic signalling: What type of receptors?, What are the receptor subtypes? How is dopamine metabolised?

Answer 7

Dopamine receptors are metabotropic GPCRs, with 7 transmembrane domains that upon binding result in the activation of G proteins.
- cysteine rich domain
- Venus fly trap domain

5 receptor subtypes:
G1&G5: couple to Gs —- Activate adenyl cyclase
G2, G3, G4: Gi/o—– inhibit adenyl cyclase

Metabolised by Monoamine oxidase

DAT: reuptake dopamine from the synaptic cleft

Question 8

What pathways do pschyadelics effect

Answer 8

Mesolimbic and mesocortical pathways

Question 9

Describe seratonin receptors, signalling types, metabolism and reuptake mechanism

Answer 9

The receptors for serotonin are the HT- receptors- GPCR - 7 transmembrane domains.

HT-1– Gi/0– inhibit adenyl cyclase
HT-2–Gq— activate DAG & IP3
HT-3– ligand gated ion channel
HT-4- Gs– activates adenyl cyclase

HT-5,6,7— Gs– activates adenyl cyclase

Metabolised by monoamine oxidase
Reuptake: SERT

Raphenuclei are the centre of the major projections of the serotonin neurones

Question 10

Describe seratonin receptors, signalling types, metabolism and reuptake mechanism

Answer 10

The receptors for serotonin are the HT- receptors- GPCR - 7 transmembrane domains.

HT-1– Gi/0– inhibit adenyl cyclase
HT-2–Gq— activate DAG & IP3
HT-3– ligand gated ion channel
HT-4- Gs– activates adenyl cyclase

HT-5,6,7— Gs– activates adenyl cyclase

Metabolised by monoamine oxidase
Reuptake: SERT

Raphenuclei are the centre of the major projections of the serotonin neurones

Question 11

What are the functions of seratonin

Answer 11

Serotonin has effects on various functions including mood, sleep, sensation, memory
processing, cognition and digestive functions – can lead to side effects of
psychedelics

Question 12

What are the functions of dopamine and serotonin

Answer 12

Dopamine and serotonin can modulate inhibitory and excitatory neurotransmission. Maintaining a balance between excitatory and inhibitory neurotransmission are important for brain function.

major inhibitory: GABA
major excitatory: GLUTAMATE

Question 13

How do psychedelics effect serotonin and dopamine

Answer 13

Psychedelics causes dopamine and serotonin receptor hyperactivity.

Dopamine like psychedelics (mescaline) : energetic, empathetic, sensual

5-HT like psychedelics: hallucination, disorientating and somatically heavy

Users of psychedelic substances often report experiences that fall into one of those
two categories

Question 14

What determines the effect of a psychadelic

Answer 14

receptor affinity: how strongly a psycadelic binds to its receptor

Receptor efficacy: the ability to activate the receptor

LSD and lisurade strongly bind to the 5-HT2a receptor. But only LSD has hallucinogenic effects- this suggests the affinity of a psycadelic doesnt always mean that it can exert an effect. Other factors such as the pharmakokinetics and the NEURONAL siganlling pathway are important.

• Molecular structure of the psychedelic drug will determine how quickly it is metabolised

Question 15

Mode of action of LSD

Answer 15

LSD binds to the 5-HT 2a receptors on the cortical pyramidal neurones
- LSD stabilises the 5-HT-2a neurones in an open conformation - coupled to a signalling pathway responsible for its psychedelic effects- the G protein - Gi/o and Src signalling pathway

Question 16

What are designer drugs?

Answer 16

Modify a pscyhadelic by adding complex tail - increases the duration of the trip

• slower metabolism
  -Reduced elimination

Question 17

What are designer drugs?

Answer 17

Modify a psychedelic by adding complex tail - increases the duration of the trip

• slower metabolism
  -Reduced elimination

Question 18

What is the physiology of psychedelics

Answer 18

Psychedelics act on different receptors not just Dopamine and serotonin receptors
it can bind to receptors expressed pre synaptically or post synaptically.
Thus they can cause excitation in some locations and inhibition in some locations.

Psychedelics can be partial and full agonists at different receptors.

This is why psychedelics have been understood to have modulatory signal interference.

Question 19

Effects of psychedelics of the 5-HT receptors

Answer 19

At the 5-HT receptor, psychedelics cause disinhibition and thus extreme excitation

—- can cause hallucinations – interferes with memory and mood
— expanded levels of consciousness.

Question 20

Effects of psychedelics of the 5-HT receptors

Answer 20

At the 5-HT receptor, psychedelics cause disinhibition and thus extreme excitation

—- can cause hallucinations – interferes with memory and mood
— expanded levels of consciousness.

LSD results in an increase in the overall connectivity between different brain regions.
This increases in connectivity is not uniform but occurs in regions that are more receptive to the effects of LSD - 5-HT receptors.

The increased connectivity compromises the modular organisation of the brain into functional regions
Blurs the perceptual boundary between self and the environment

Question 21

Describe how and where sensory info is processed

Answer 21

High density of 5-HT 2a receptors of level 5 dendrites ( receptors closest to the cell body on pyramidal neurons in the cerebral cortex)

• The high density of these receptors on the neurons enhance the brains sensory input and in creating an accurate top to bottom perception
• The timing and synchronisation of these circuits is important. L5 neurons process sensory information every 30-60 milliseconds.
• Breakdown of this circuit - leads to failure in processing of sensory input, it can lead to 2 things
• Feedback synesthesia: mixing up sensory modalities)
  -Perceptual overload : receive to much sensory information at once.

Question 22

What effects do psychedelics have on sensory processing

Answer 22

Subtle flickering or pulsing of light intensity
- Geometric grids and matrices
- Light halos/auras
- Loss of depth perception
- Sensory filling relies in precise temporal
aliasing (psychedelics disrupt this temporal
aliasing, producing optical illusions)

Question 23

What are the effects of psychedelics on the PNS

Answer 23

-5-HT-2a receptor agonism modulates smooth muscle contraction
- leads to vommiting
- reports of intense hallucination