9. Psychedelics as Therapies Flashcards
what do trypamines mimic? 3 examples?
trypamines mimic serotonin
Psilocin, DMT, LSD
what do phenethylamines mimic? 2 examples?
phenethylamines mimic dopamine
Mescaline, DOI
some positive effects of psychedelics
- increased mood
- increased creativity
- sensory enhancement
- visuals
- spiritual experiences
- personal revelation
some neutral effects of psychedelics
- change in consciousness
- pupil dilation
- difficulty focusing
- increased salivation and mucus
- unusual body sensations
- unusual thoughts and speech
some negative effects of psychedelics
- anxiety
- tension
- increased perspiration
- delusions
- nausea, dizziness
why does ingestion of psychedelics give shorter trip?
broken down by MAO
among drugs of abuse, how harmful are LSD and psilocin?
LSD and psilocin have the lowest harm
how can we prevent drug-specific or drug-related impairment of mental functioning?
knowing drug function, what effects to expect, and effects in clinical setting, as well as giving the patient this knowledge
4 describe the use of psychedelics in relation to mental illness
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
describe the use of psychedelics in relation to suicide
reduced suicidal thinking, suicidal planning, and suicidal attempts
describe clinical trial with psilocybin vs niacin
reduced depression with psilocybin
describe clinical trial with psilocybin vs escitalopram
reduced depression with psilocybin
why is there no possibility of placebo with psychedelics?
because person will always know when they are tripping
how do psychedelics affect brain activity?
LSD causes higher brain activity
how do psychedelics affect brain connectivity?
Psilocybin causes higher brain connectivity –> activity spreads across the brain and parts of brain that don’t normally connect will connect
what is the hypothesis for psychedelic therapeutic action? explain
increase of brain entropy
consciousness balances between high and low entropy so psychedelics shift the balance towards the high entropy state
what happens in low entropy state of the brain?
rigid brain, neuronal paths are very repetitive and rigid –> always the same areas activated in the same order
what happens in the high entropy state of the brain?
when dreaming, near death experience, psychosis, etc. –> brain activity all over the place
what is the explanation for the long-term effect of psychedelics? what does this indicate?
psychedelics promote the complexity of dendritic arborization –> indicates that there is a trip but also long-lasting effects from potentiation of neuroplasticity
is the trip necessary for therapeutic action?
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
radiolabeling assay at 5HT2A receptor
what can we conclude?
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
what type of receptor is 5HT2A? where is it found?
Gq coupled receptor
found pre and post-synaptically on membranes throughout neurons
what type of agonists are psychedelics at 5HT2A?
full agonists or biased agonists
what are biased agonists?
ligands have diff shapes which imprint diff conformations within the receptor to recruit specific partners and induce specific effects
LSD vs 5HT
LSD is better recruiter of B-arrestin than 5HT to cause slow desensitization
what allows LSD to give psychedelic effect? experimental proof?
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
Describe the experiment looking at 5HT2A occupancy
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
what is an example of a neuron type that 5HT2A activates?
activates cortical pyramidal neuron directly or indirectly
general consequences of 5HT2A activation from psychedelics
- perceptual/cognitive alterations
- long-term behavioural change
- neural plasticity
- brain network changes
