Lecture 15. Psychedelics - The Dawning of a New Age in Psychiatry?

Question 1

What are psychedelic experiences characterised by?

Answer 1

A wide range of sensory, cognitive and emotional changes

Question 2

What are the main three classes of psychedelic agents?

Answer 2

Lysergics
Entactogen
Dissociatives

Question 3

What are examples of lysergic drugs?

Answer 3

Lysergic acid diethylamide (LSD)
Psilocybin
Mescaline
Dimethyltryptamine

Question 4

What is an example of an entactogen drug?

Answer 4

MDMA (ecstacy)

Question 5

What are example of dissociative drugs?

Answer 5

Ketamine (Special K)
Phencyclidine (Angel Dust)

Question 6

What is the primary target for lysergic drugs?

Answer 6

5-HT₂ receptor agonists (especially 5-HT2A)

Question 7

What is the primary target for entactogen drugs?

Answer 7

Monoamine releaser

Question 8

What is the primary target for dissociative drugs?

Answer 8

NMDA receptors

Question 9

What are the potential uses for lysergics?

Answer 9

Treating depression and addiction

Question 10

What is the potential use for an entactogen?

Answer 10

PTSD treatment(?)

Question 11

What is the potential use for ketamine?

Answer 11

Depression

Question 12

What is the potential use for phencyclidine?

Answer 12

None

Question 13

What molecule is LSD structurally similar to?

Answer 13

Serotonin

Question 14

When was LSD first synthesised and by who?

Answer 14

1938, Albert Hofmann

Question 15

How does LSD bind to the 5-HT2B receptor?

Answer 15

The extracellular loop 2 (EL2) lid traps LSD in the binding pocket of the 5-HT2B receptor

Question 16

What effect does LSD and psilocybin have on the brain regions?

Answer 16

Higher brain region connectedness when compared to placebo

Question 17

What do psychedelics cause the breakdown of?

Answer 17

Brain modular networks: ego dissolution (evaporation of self)

Question 18

What conditions did early studies show LSD had an effect on?

Answer 18

Anxiety and depression disorders
Alcohol abuse

Question 19

What is trait anxiety?

Answer 19

How anxious you would feel in a particular situation or in general

Question 20

What is state anxiety?

Answer 20

How anxious you are feeling now

Question 21

What symptoms does psilocybin alleviate?

Answer 21

Symptoms of depression in normal people and symptoms of anxiety and depression in cancer patients

Question 22

Which disorder’s symptoms are reduced by MDMA?

Answer 22

PTSD

Question 23

What effect does MDMA have on the brain?

Answer 23

Disrupts brain networks (like LSD and psilocybin)
Changes in ventromedial prefrontal cortex, hippocampal and amygdala resting state functional connectivity (RSFC)

Question 24

What may the decrease in the posterior cingulate cortex’s RSFC lead to?

Answer 24

Less rumination/worrying and improve mood (also seen with psilocybin)

Question 25

What may the decrease in the prefrontal cortex and hippocampal RSFC lead to?

Answer 25

Reduced anxiety and post-traumatic stress (possibly the basis of actions of MDMA in PTSD)

Question 26

What may the increases in coupling between the hippocampus and amygdala lead to?

Answer 26

Improves ability to contextualise emotional information – reductions in coupling seen in PTSD

Question 27

What effect does MDMA have on solitary octopus (O. bimaculoides)?

Answer 27

Makes them more sociable

Question 28

What effects to ketamine and phencyclidine (PCP) have on humans?

Answer 28

Can induce positive, negative and cognitive psychotic symptoms (eg auditory hallucinations, thought disorders, emotional blunting and cognitive impairment)

Question 29

What model are dissociative psychedelics involved in to induce effects of a mental illness?

Answer 29

Used as an animal model of schizophrenia (glutamate theory of schizophrenia), gives r

Question 30

What can induce psychosis?

Answer 30

People who posses antibodies to NMDA receptor subunits (reduction in signalling)

Question 31

What disruptions in signalling pathways occur in schizophrenia patients?

Answer 31

Disruption has been seen of glutamatergic transmission in people with schizophrenia (eg NR1) Genetic studies show disruption of NMDAR-associated signalling pathways (eg NR2A subunit)

Question 32

What can benefit those living with schizophrenia?

Answer 32

Increasing co-agonist concentration (eg D-serine) can have benefits

Question 33

When was ketamine introduced as an intravenous anaesthetic?

Answer 33

1970

Question 34

What are the anaesthetic effects of ketamine?

Answer 34

Dissociative anaesthetic – patient appears awake but detached from surroundings Rapid induction, wide safety margin Pre-hospital/Battlefield anaesthetic/analgesic of choice Paediatric anaesthetic Bronchodilator (keeps airways clear) Anti-inflammatory Neuroprotective Primary anaesthetic in developing countries Also used in veterinary medicine

Question 35

What dangerous side effects can ketamine cause?

Answer 35

Kidney/bladder toxicity

Question 36

What effect does ketamine have on depression?

Answer 36

Improvements in depressed mood, suicidality, helplessness, worthlessness (antidepressant)

Question 37

What areas of the brain does ketamine reduce connectivity between?

Answer 37

Prefrontal cortex and posterior cingulate cortex (compare MDMA)

Question 38

How might ketamine act as an antidepressant?

Answer 38

Ketamine acts as an NMDA antagonist and targets NMDA receptors on inhibitory neurone, increasing glutamate release, more excitation is networks Rearranging existing synaptic networks to alleviate symptoms of depression

Question 39

What stereoisomer of ketamine is FDA approved to treat depression?

Answer 39

Intranasal S-ketamine (Spravato)

Question 40

What is the key to the success of psychedelic-based therapy?

Answer 40

Correct set and setting in which the patient comes with the correct mindset, and is supported through the session by qualified and supportive councillors and given correct dosages