Lecture 6/10: psychedelics and treatment Flashcards
(39 cards)
what are the different serotonin hallucinogens?
- psilocybin/psilocyn (magic mushroom)
- DMT
- LSD
- mescaline
which psychedelic have clinical trials for major depression?
- psilocybin/psilocyn (magic mushroom)
- DMT
which psychedelic have clinical trials for AUD?
psilocybin/psilocyn which has been shown to produced robust decreases in percentage
of heavy drinking days
which psychedelics have clinical trials for generalized anxiety?
LSD which has been shown to produce long-lasting effects
serotonin hallucinogens are _______ agonists
5-HT2A
The terms _______
and ___________
have been coined to describe the pro-empathy and socializing effects of MDMA
empathogenic; entactogenic
how does psilocybin compare to escitalopram for major depression?
is it similar but, only two 25 mg doses (3 weeks apart) of psilocybin was given where escitalopram was given daily
how do different doses of psilocybin compare for major depression (1mg vs 25 mg)?
25 mg better than 1 mg
MDMA (+ psychotherapy) was shown to be helpful for which disorder?
PTSD
what are the 3 levels of targets/effects of psychedelics as a therapeutic?
- neurons (receptors that it targets, neuroplasticity/epigenetic effects)
- brain circuits/mind-altering effects (activation of circuits)
- transcendental thinking, meaning
general path of 5-HT in the brain
- produced in the dorsal raphe
- goes to the limbic system/prefrontal cortex
which receptors does psilocin target?
SERT, 5-HTs, and a-adrenergic
which receptors does DMT target?
5-HTs
which receptors does LSD target?
5-HT, a-adrenergic, Dopamine, beta, and histamine
what is the effect of repeated low-dose LSD treatment? (general neurobiology)
enhances 5-HT firing activity (like SSRIs) and desensitizes 5-HT1A autoreceptors (which causes the increase of firing - disinhibition)
how does low vs high dose LSD compare? (general neurobiology)
in low dose and high dose we see a decrease in 5-HT neurons of the dorsal raphe nucleus, but we only see a decrease of DA neurons in the VTA in high doses, which should mean that low doses are less addictive
effect of repeated, low dose LSD on stress?
reduced stress-induced anxiety in open field test and in novelty suppressed feeding test
did low dose LSD show hallucinogenic-like effect in mice?
no, minimal difference in head twitch response
how does low-dose LSD affect neuroplasticity/epigenetics?
- induces spinogenesis,
- engages epigenetic
mechanisms involved with plasticity (increased methylation of DNA in CpG islands) - prevents the loss of spines after stress
how does low-dose LSD affect social behaviour in mice?
- Increases social interaction
- Increases preference for a social stimulus
- Increases preference for social novelty
- Increases 5-HT firing activity
what is the neural basis for the pro-social behaviour induced by LSD?
- potentiates AMPA and 5-HT2A response but not NMDA and 5-HT1A in the mPFC
- this AMPA/5-HT2A activation along with a intact mPFC glutaminergic neurons are required
- increases Akt and mTOR phosphorylation in mPFC
- an intact mTOR complex in excitatory neurons are required for the prosocial effect + the potentiation of 5-HT2A and AMPARs
which brain circuits are affected by high dose LSD? what effect does this have?
cortico-thalamic circuit, which is the circuit most involved in consciousness and integration of internal-external stimuli, in other words, it filters reality into something rational
what is the default-mode network (DMN)?
includes the mPFC, posterior cingulate cortex, and the angular gyrus,
what does the DMN control/mediate?
- neurological basis for the self (autobiographical information, self-reference, emotional perception of one’s self)
- thinking of others (emotions, moral reasoning, social evaluations)
- remembering the past/future
