Psychedelics Flashcards
classes of serotonin hallucinogens, derivatives, natural derivates (4)
- tryptamine
a. psilocybin and psilocyin -> magic mushrooms
b. DMT -> ayahuasca - lysergamine
a. LSD -> ergot - phenethylamine
a. mescaline -> peyote
current clinical trials associated with serotonin hallucinogens (4)
psilocybin and psilocyn -> MDD and AUD
DMT -> MDD
LSD -> GAD
mescaline -> ?
which receptor do most psychedelics mimic
5HT2A serotonin receptors (agonists)
which psychedelic is not a classical psychedelic (synthetic psychedelic)
MDMA or ecstasy
what effects are related to MDMA use + terms used to describe them (2)
pro-empathy effect -> empathogenic
socialising effect -> entactogenic
what causes decreased anxiety
one dose of LSD
what causes decreased percentage of heavy drinking days
psilocybin in combination with psychotherapy
which medication is comparable to psilocybin
escitalopram
psilocybin + psychotherapy vs escitalopram (3)
- similar results (not significantly different)
- BUT, psilocybin = 2 doses over 3 weeks and escitalopram = 1 dose every day
- psilocybin needs to be combined with psychotherapy
why does psilocybin need to be combined with psychotherapy
psilocybin can induce intense introspection and experiences (thinking about past and stuff) and can experience bad trips that a therapist can help guide through
advantages of psilocybin + psychotherapy in MDD compared to antidepressants (3)
- similar effects to classical SSRIs
- need to take it less often
- has been shown to treat people with MDD resistant to other antidepressants
which disorder can potentially be treated with MDMA + psychotherapy
PTSD (results were able to be reproduced)
receptors (a) psylocin (b) DMT (c) LSD have the most affinity for
(a) 5HT7, 5HT2B
(b) 5HT1D
(c) 5HT1A, 5HT2A, 5HT1B
effect of low and high doses of LSD in VTA and DRN + conclusions
VTA: low doses = no effect; high doses = decreased DA neurons
DRN: low doses = decreased 5HT neurons; high doses: none?
conclusion -> LSD in low doses only works on serotonin receptors, but at high doses also influences DA receptors (why at high doses get risk of psychosis)
neuroplastic effects of low doses of LSD
6 elements
- spinogenesis (more synapses, more connections)
- prevents loss of spines after stress
- regulation of receptor mediated endocytosis
- regulation of synaptic plasticity
- NT receptor internalization
- hyper- or hypomethylates different genes
genes + proteins methylated and expressed + transcription increased with low dose of LSD (4)
- Coro7
- Pef1
- Rps24
- Abhd6
general conclusions on LSD (3)
- LSD has anti-anxiety properties only in stressed animals
- LSD (similar to SSRIs), restores 5HT firing activity after stress through a 5HT1A autoreceptor desensitization
- LSD has neuroplastic effects mediated by methylation of genes corresponding to proteins implicated in neurogenesis and plasticity
psychedelics: low vs high doses effects (3)
low doses : social behavior, anxiety, antidepressants, AUD (via neuroplasticity and epigenetics)
high doses:
1. same as low doses
2. brain circuits, mind altering -> activation of circuits via 5HT2A
3. transcendental, thinking, meaning -> psychedelics-assisted therapy, reappraisal + integration
DA pathways (2)
VTA -> PFC, NAcc
substantia nigra -> striatum
5HT pathway
raphe nucleus -> hippocampus (related to DA pathways)
functions of 5HT pathways (4)
- mood
- memory processing
- sleep
- cognition
functions of DA pathways (5)
- reward (motivation)
- pleasure, euphoria
- motor function (fine tuning)
- compulsion
- perseveration
effect of repeated LSD in novelty suppressed feeding test
in home cage, latency doesn’t increase and LSD doesn’t have an effect
in novel environment, repeated LSD normalizes latency to feed which was increased after 15 days of chronic stress
effect of repeated LSD in open field test
prevents/ameliorates stress-induced anxiety
long term mechanism of action of SSRIs
blocks reuptake of 5HT into presynaptic neuron -> increases [5HT] in synaptic cleft -> high amount of 5HT will interact with 5HT1A autoreceptors and inhibit firing (acute effect of SSRIs) -> after couple weeks, downregulates 5HT1A autoreceptors (desensitization, increased firing, 5HT stays in synaptic cleft)
mechanism of action of LSD
same as SSRIs: desensitizes 5HT1A autoreceptors (long term, repeated microdoses) and increases/restores 5HT firing activity after stress
low vs high doses of LSD on head twitch response (hallucinogenic-like effect)
low doses -> minimal head twitch response
high doses -> larger head twitch response
effect of repeated low doses of LSD on social interaction
promotes prosocial effect; increased sociability and social novelty
effects of LSD (4)
- enhances empathy
- enhances social behavior
- togetherness
- used in the 60s for ASD
mPFC: (a) main role (b) implicated in which DSM-V disorder (c) high expression of which receptor
(a) social cognition
(b) ASD
(c) 5HT2A
repeated, low dose LSD (30ug/kg/day for 7 days) effects regarding sociability (4)
- increases social interaction
- increases preference for social stimulus
- increases preference for social novelty
- increases 5HT firing activity
effect of LSD when PFC is inhibited and conclusion
LSD can’t work if PFC is inhibited (fails to increases sociability) -> LSD activates PFC in social behavior
effect of repeated low dose LSD on AMPAr, NMDAr, 5HT2A and 5HT1A responses in PFC
AMPAr -> potentiated response
NMDAr -> no effect
5HT2A -> potentiated response
5HT1A -> no effect
what does LSD need to promote social behavior (4)
- 5HT2A receptor activation
- AMPAr activation
- intact mPFC glutamatergic neurons
- intact mTOR complex in excitatory neurons
effect of repeated LSD on mTOR phosphorylation in mPFC
increased phosphorylation of mTOR
intact mTOR complex is necessary for
three elements
- prosocial effect of LSD
- potentiation of 5HT2A receptor activation
- potentiation of AMPAr activation
what are psychedelics known for (4)
- increase well being
- decrease anxiety and depression
- expand self-awareness
- expand perception of inside and outside stimuli
which brain circuits do psychedelics alter (2)
- DMN (default mode network) -> collapse
- CSTC (cortico-striato-thalamo-cortical) -> activation
brain areas linked to DMN (3)
- mPFC
- PCC/precuneus
- angular gyrus
when is the DMN activated (3)
- thinking about the self
- thinking about others
- remembering the past and thinking about the future
what is the REBUS model
suggests that effects of psychedelics on cognition and perception may be due to relaxation of the precision weighting on beliefs
influence of psychedelics on processing information in the brain
brain becomes more flexible in processing sensory information and less constrained by preexisting beliefs or expectations
effect of psychedelics on DMN
reduce ability of DMN to control lower levels in brain, specifically subcortical structures (hippocampus, amygdala, thalamus)
(collapse of normally highly organized activity in DMN + decoupling between DMN and medial temporal lobes)
which state is the brain in when under the effects of psychedelics
entropic state -> can rewire how the brain thinks (high disorder, flexible states)
activity of LSD in (a) PFC (b) mediodorsal thalamus (c) reticular thalamus
(a) high activity
(b) high activity
(c) decreases high-firing neurons + increases low-firing neurons
brain area most activated by LSD
thalamus
psychedelic effects on thalamus (3)
- reduces thalamic filtering of interoceptive and exteroceptive stimuli
- decreases connectivity between association cortices and rest of the brain (decreased integrative processing)
- increases connectivity between sensory cortices and rest of the brain (increased sensory processing)
what are the models of how psychedelics reshape the brain (2)
- entropy model (general chaotic reshaping)
- circuits model (reshaping input-output and processing)
what is the cortico-thalamic circuit involved in
consciousness and integration of internal-external stimuli
effects of spiritual experience in treatment with psychedelics (2)
- patients described psilocybin experience as having substantial personal meaning and spiritual significance
- attributed to experience sustained positive changes in attitudes and behavior consistent with changes
significant differences in effects of non-responders vs responders to psilocybin/escitalopram
responders had higher scores of (a) spiritual experience (b) blissful state (c) insightfulness
effect of blocking 5HT2A with ketanserin on spiritual effects of LSD + conclusion
blocks experience of unity, blissful state, meaning, insightfulness -> spiritual effects mediated by 5HT2A receptor
feeling of connectedness in (a) responders vs non-responders and (b) escitalopram vs psilocybin
(a) responders showed more connectedness than non-responders
(b) psilocybin showed more connectedness than escitalopram
where do psychedelics act to open consciousness
thalamic nuclei
possible mechanism of psychedelics (5)
- 5HT2A activation
- 5HT firing activity of DRN (antidepressant effect)
- reticular thalamus
- thalamocortical pathways/DMN
- reappraisal of positive experience/spiritual awakening
