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Neuropharmacology > Lecture 15 > Flashcards

Lecture 15 Flashcards

1
Q

What are characteristics of a psychedelic experience?

A
  • increased sensory perception and illusionary changes - synaesthesia - enhanced mental imagery - ego dissolution - increased affectivity
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2
Q

What are the major classes of psychedelic agents?

A
  • lysergics - entactogen - dissociatives
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3
Q

What are examples of lysergics?

A
  • LSD - psilocybin - mescaline - dimethyltryptamine
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4
Q

What is an example of an entactogen?

A

MDMA

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5
Q

What are examples of a dissociative?

A
  • ketamine - phencyclidine
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6
Q

What are the primary targets of lysergics?

A

5-HT (especially 5-HT2A) agonists

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7
Q

What are the primary effects of entactogens?

A

Monoamine releasers

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8
Q

What are the primary targets of dissociatives?

A

NMDA receptors

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9
Q

What are the potential uses of lysergics?

A
  • depression - addiction
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10
Q

What are the potential uses of entactogens?

A

PTSD

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11
Q

What are the potential uses of dissociatives

A

Depression (only ketamine)

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12
Q

What structure do psychoactive monoamines mimic?

A

5-HT

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13
Q

How does 5-HT2R trap LSD?

A
  • 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
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14
Q

Which networks are active and disrupted by psychedelics?

A
  • somatosensory (sensations and movement) - control (decision making and judgement) - dorsal attention - default (when at rest) - salience (attention to obvious stimuli) - visual
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15
Q

How do lysergics affect brain region connectedness?

A
  • normal brain parcellation becomes disrupted - greater communication= brings in different sensory modalities or sensations
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16
Q

How do psychedelics affect ego dissolution?

A
  • increased ego dissolution compared to cocaine/alcohol - typical connectivity is local - psilocybin causes communication between previously unfamiliar regions
17
Q

What are some of the clinical applications of lysergics?

A
  • 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
18
Q

What might MDMA be used to clinically treat?

A

PTSD

19
Q

How does MDMA treat PTSD?

A
  • alleviates symptoms compared to placebos (e.g. reduces heightened arousal) - disrupts overactive networks e.g. rumination= for better contextualisation
20
Q

What brain networks have MDMA been shown to disrupt?

A
  • resting state functional connectivity - ventromedial prefrontal cortex (decreased) - hippocampus (decreased) - amygdala (increased)
21
Q

What does it mean if MDMA is an entactogen?

A
  • experience greater empathy for others AND ourselves - increases socialisation in previously solitary octopi
22
Q

How are dissociatives linked to the glutamate theory of schizophrenia?

A
  • induce positive, negative and cognitive symptoms of schizophrenia - NMDA antibodies= reduce signalling - disruption in glutamatergic signalling e.g. NR1 subunit
23
Q

How can the symptoms of schizophrenia be alleviated?

A

Increase co-agonist concentration e.g. D-serine

24
Q

What are the benefits of using ketamine as an anaesthetic?

A
  • rapid induction with wide safety margin - paediatric anaesthetic - bronchodilator - anti-inflammatory - neuroprotective - used in developing countries
25
Q

What are the potential downsides of ketamine as an anaesthetic?

A
  • misuse and addiction - kidney and bladder toxicity
26
Q

Could ketamine be used as an antidepressant?

A

Yes

27
Q

How symptoms of depression can ketamine treat?

A
  • depressed mood - suicidality - helplessness - worthlessness
28
Q

How networks does ketamine target?

A
  • reduces connectivity between prefrontal cortex and posterior cingulate cortex - default mode network - affective network
29
Q

What are mechanisms of action for ketamine as an antidepressant?

A
  • 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
30
Q

What are the principles of using psychedelics in psychiatry?

A
  • use the correct drug= acid ≠ LSD - correct dose - correct mindset= calm, relaxed, desire for change - correct setting= physical and social

Neuropharmacology (15 decks)

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