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PHAR 503 > 9. Psychedelics as Therapies > Flashcards

9. Psychedelics as Therapies Flashcards

1
Q

what do trypamines mimic? 3 examples?

A

trypamines mimic serotonin

Psilocin, DMT, LSD

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2
Q

what do phenethylamines mimic? 2 examples?

A

phenethylamines mimic dopamine

Mescaline, DOI

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3
Q

some positive effects of psychedelics

A
  • increased mood
  • increased creativity
  • sensory enhancement
  • visuals
  • spiritual experiences
  • personal revelation
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4
Q

some neutral effects of psychedelics

A
  • change in consciousness
  • pupil dilation
  • difficulty focusing
  • increased salivation and mucus
  • unusual body sensations
  • unusual thoughts and speech
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5
Q

some negative effects of psychedelics

A
  • anxiety
  • tension
  • increased perspiration
  • delusions
  • nausea, dizziness
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6
Q

why does ingestion of psychedelics give shorter trip?

A

broken down by MAO

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7
Q

among drugs of abuse, how harmful are LSD and psilocin?

A

LSD and psilocin have the lowest harm

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8
Q

how can we prevent drug-specific or drug-related impairment of mental functioning?

A

knowing drug function, what effects to expect, and effects in clinical setting, as well as giving the patient this knowledge

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9
Q

4 describe the use of psychedelics in relation to mental illness

A

people initially believed that psychedelics are an independent risk factor for mental health problems but psychedelics are actually associated with lower risk of mental health problems

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10
Q

describe the use of psychedelics in relation to suicide

A

reduced suicidal thinking, suicidal planning, and suicidal attempts

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11
Q

describe clinical trial with psilocybin vs niacin

A

reduced depression with psilocybin

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12
Q

describe clinical trial with psilocybin vs escitalopram

A

reduced depression with psilocybin

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13
Q

why is there no possibility of placebo with psychedelics?

A

because person will always know when they are tripping

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14
Q

how do psychedelics affect brain activity?

A

LSD causes higher brain activity

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15
Q

how do psychedelics affect brain connectivity?

A

Psilocybin causes higher brain connectivity –> activity spreads across the brain and parts of brain that don’t normally connect will connect

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16
Q

what is the hypothesis for psychedelic therapeutic action? explain

A

increase of brain entropy

consciousness balances between high and low entropy so psychedelics shift the balance towards the high entropy state

17
Q

what happens in low entropy state of the brain?

A

rigid brain, neuronal paths are very repetitive and rigid –> always the same areas activated in the same order

18
Q

what happens in the high entropy state of the brain?

A

when dreaming, near death experience, psychosis, etc. –> brain activity all over the place

19
Q

what is the explanation for the long-term effect of psychedelics? what does this indicate?

A

psychedelics promote the complexity of dendritic arborization –> indicates that there is a trip but also long-lasting effects from potentiation of neuroplasticity

20
Q

is the trip necessary for therapeutic action?

A

people who trip the most/on higher dose have more therapeutic activity

but other 5HTA agonists that are not psychedelics can also promote neuroplasticity and alleviate depressive symptoms

21
Q

radiolabeling assay at 5HT2A receptor

what can we conclude?

A

use radiolabeling assay to see how drugs displace radiolabeled ligand

LSD and many other psychedelics have higher binding and selectivity to 5HT2A –> we know these are psychedelic so psychedelic effect may depend on 5HT2A

22
Q

what type of receptor is 5HT2A? where is it found?

A

Gq coupled receptor

found pre and post-synaptically on membranes throughout neurons

23
Q

what type of agonists are psychedelics at 5HT2A?

A

full agonists or biased agonists

24
Q

what are biased agonists?

A

ligands have diff shapes which imprint diff conformations within the receptor to recruit specific partners and induce specific effects

25
Q

LSD vs 5HT

A

LSD is better recruiter of B-arrestin than 5HT to cause slow desensitization

26
Q

what allows LSD to give psychedelic effect? experimental proof?

A

LSD requires 5HT2A to give psychedelic effect

mice given LSD:
- in mice without 5HT2A there is no psychedelic effect
- in mice with 5HT2A there is psychedelic effect

27
Q

Describe the experiment looking at 5HT2A occupancy

A

use Cimbi-36 5HT2A agonist that is easily displaced by 5HT2A drugs
- Psilocybin fully displaced Cimbi-36 and therefore binds 5HT2A
- intensity of trip correlates to occupancy of 5HT2A receptor

28
Q

what is an example of a neuron type that 5HT2A activates?

A

activates cortical pyramidal neuron directly or indirectly

29
Q

general consequences of 5HT2A activation from psychedelics

A
  • perceptual/cognitive alterations
  • long-term behavioural change
  • neural plasticity
  • brain network changes

PHAR 503 (10 decks)

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