Lecture 15. Psychedelics - The Dawning of a New Age in Psychiatry? Flashcards
What are psychedelic experiences characterised by?
A wide range of sensory, cognitive and emotional changes
What are the main three classes of psychedelic agents?
Lysergics
Entactogen
Dissociatives
What are examples of lysergic drugs?
Lysergic acid diethylamide (LSD)
Psilocybin
Mescaline
Dimethyltryptamine
What is an example of an entactogen drug?
MDMA (ecstacy)
What are example of dissociative drugs?
Ketamine (Special K)
Phencyclidine (Angel Dust)
What is the primary target for lysergic drugs?
5-HT₂ receptor agonists (especially 5-HT2A)
What is the primary target for entactogen drugs?
Monoamine releaser
What is the primary target for dissociative drugs?
NMDA receptors
What are the potential uses for lysergics?
Treating depression and addiction
What is the potential use for an entactogen?
PTSD treatment(?)
What is the potential use for ketamine?
Depression
What is the potential use for phencyclidine?
None
What molecule is LSD structurally similar to?
Serotonin
When was LSD first synthesised and by who?
1938, Albert Hofmann
How does LSD bind to the 5-HT2B receptor?
The extracellular loop 2 (EL2) lid traps LSD in the binding pocket of the 5-HT2B receptor
What effect does LSD and psilocybin have on the brain regions?
Higher brain region connectedness when compared to placebo
What do psychedelics cause the breakdown of?
Brain modular networks: ego dissolution (evaporation of self)
What conditions did early studies show LSD had an effect on?
Anxiety and depression disorders
Alcohol abuse
What is trait anxiety?
How anxious you would feel in a particular situation or in general
What is state anxiety?
How anxious you are feeling now
What symptoms does psilocybin alleviate?
Symptoms of depression in normal people and symptoms of anxiety and depression in cancer patients
Which disorder’s symptoms are reduced by MDMA?
PTSD
What effect does MDMA have on the brain?
Disrupts brain networks (like LSD and psilocybin)
Changes in ventromedial prefrontal cortex, hippocampal and amygdala resting state functional connectivity (RSFC)
What may the decrease in the posterior cingulate cortex’s RSFC lead to?
Less rumination/worrying and improve mood (also seen with psilocybin)
What may the decrease in the prefrontal cortex and hippocampal RSFC lead to?
Reduced anxiety and post-traumatic stress (possibly the basis of actions of MDMA in PTSD)
What may the increases in coupling between the hippocampus and amygdala lead to?
Improves ability to contextualise emotional information – reductions in coupling seen in PTSD
What effect does MDMA have on solitary octopus (O. bimaculoides)?
Makes them more sociable
What effects to ketamine and phencyclidine (PCP) have on humans?
Can induce positive, negative and cognitive psychotic symptoms (eg auditory hallucinations, thought disorders, emotional blunting and cognitive impairment)
What model are dissociative psychedelics involved in to induce effects of a mental illness?
Used as an animal model of schizophrenia (glutamate theory of schizophrenia), gives r
What can induce psychosis?
People who posses antibodies to NMDA receptor subunits (reduction in signalling)
What disruptions in signalling pathways occur in schizophrenia patients?
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)
What can benefit those living with schizophrenia?
Increasing co-agonist concentration (eg D-serine) can have benefits
When was ketamine introduced as an intravenous anaesthetic?
1970
What are the anaesthetic effects of ketamine?
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
What dangerous side effects can ketamine cause?
Kidney/bladder toxicity
What effect does ketamine have on depression?
Improvements in depressed mood, suicidality, helplessness, worthlessness (antidepressant)
What areas of the brain does ketamine reduce connectivity between?
Prefrontal cortex and posterior cingulate cortex (compare MDMA)
How might ketamine act as an antidepressant?
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
What stereoisomer of ketamine is FDA approved to treat depression?
Intranasal S-ketamine (Spravato)
What is the key to the success of psychedelic-based therapy?
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
