Lecture 15 Flashcards
What are characteristics of a psychedelic experience?
- increased sensory perception and illusionary changes - synaesthesia - enhanced mental imagery - ego dissolution - increased affectivity
What are the major classes of psychedelic agents?
- lysergics - entactogen - dissociatives
What are examples of lysergics?
- LSD - psilocybin - mescaline - dimethyltryptamine
What is an example of an entactogen?
MDMA
What are examples of a dissociative?
- ketamine - phencyclidine
What are the primary targets of lysergics?
5-HT (especially 5-HT2A) agonists
What are the primary effects of entactogens?
Monoamine releasers
What are the primary targets of dissociatives?
NMDA receptors
What are the potential uses of lysergics?
- depression - addiction
What are the potential uses of entactogens?
PTSD
What are the potential uses of dissociatives
Depression (only ketamine)
What structure do psychoactive monoamines mimic?
5-HT
How does 5-HT2R trap LSD?
- binding is significantly prolonged - extracellular loop acts as a ‘lid’ which traps LSD molecule - mutant version of 5-HT2B receptor= increased lid movement frees LSD from receptor
Which networks are active and disrupted by psychedelics?
- somatosensory (sensations and movement) - control (decision making and judgement) - dorsal attention - default (when at rest) - salience (attention to obvious stimuli) - visual
How do lysergics affect brain region connectedness?
- normal brain parcellation becomes disrupted - greater communication= brings in different sensory modalities or sensations
How do psychedelics affect ego dissolution?
- increased ego dissolution compared to cocaine/alcohol - typical connectivity is local - psilocybin causes communication between previously unfamiliar regions
What are some of the clinical applications of lysergics?
- anxiety and depression disorders - alcohol abuse - reduced trait and state anxiety in terminally-ill patients - psilocybin= alleviates depressive systems in treatment-resistant patients and anxiety and depression in cancer patients
What might MDMA be used to clinically treat?
PTSD
How does MDMA treat PTSD?
- alleviates symptoms compared to placebos (e.g. reduces heightened arousal) - disrupts overactive networks e.g. rumination= for better contextualisation
What brain networks have MDMA been shown to disrupt?
- resting state functional connectivity - ventromedial prefrontal cortex (decreased) - hippocampus (decreased) - amygdala (increased)
What does it mean if MDMA is an entactogen?
- experience greater empathy for others AND ourselves - increases socialisation in previously solitary octopi
How are dissociatives linked to the glutamate theory of schizophrenia?
- induce positive, negative and cognitive symptoms of schizophrenia - NMDA antibodies= reduce signalling - disruption in glutamatergic signalling e.g. NR1 subunit
How can the symptoms of schizophrenia be alleviated?
Increase co-agonist concentration e.g. D-serine
What are the benefits of using ketamine as an anaesthetic?
- rapid induction with wide safety margin - paediatric anaesthetic - bronchodilator - anti-inflammatory - neuroprotective - used in developing countries
What are the potential downsides of ketamine as an anaesthetic?
- misuse and addiction - kidney and bladder toxicity
Could ketamine be used as an antidepressant?
Yes
How symptoms of depression can ketamine treat?
- depressed mood - suicidality - helplessness - worthlessness
How networks does ketamine target?
- reduces connectivity between prefrontal cortex and posterior cingulate cortex - default mode network - affective network
What are mechanisms of action for ketamine as an antidepressant?
- targets inhibitory NMDA receptors on inhibitory interneurons - less glutamatergic inhibition= increased glutamate - increased BDNF= alleviates depressive symptoms - i.e. use of intranasal ketamine as a stereoisomer
What are the principles of using psychedelics in psychiatry?
- use the correct drug= acid ≠ LSD - correct dose - correct mindset= calm, relaxed, desire for change - correct setting= physical and social
