3. Psychadelics Flashcards
psychadelic history, 4 psychadelics
from greek for mind/manifest, named by humphrey osmond
johns hopkins cneter for psychadleic study
psychoactive substance that causes perceptual change/distortion/hallucination without toxic delirium (unlike amphets)
mescaline, psilocybin, lsd, ayahuasca/dmt
Mescaline
found in cacti in southwest/mexico
native american rituals
psilocybin
magic mushrooms
produce alkalouds with halluconigenic
it’s a prodrug, converted to psilocin that is the psychoactive agent
used in aztec/mayans rituals
timothy leary from harvard, made students do it
LSD
og resp. stimulant, neurosis/uncover feeling
psychedleic porps discovered in 1943
recreational use banned 1967
potent orally, dissolved water tabs
Ayahuasca DMT
orally active tryptamine hallucinogen
analogue of 5HT
potent MAO-A inhibitors (protecting DMT from degradation in gut)
structure of psychedelics
serotonin-like (indoleamines) = LSA/psilocybin/DMT and synthetic tryptamines
NE/AMPH-like (phenethylamines) = Mescaline
5HT2A Receptor and psychadelics
LSD binds high affintity with 5HT2A/B and phenethylamines
role in hallucinations, blocked by 5HT2A atnagonists
Psilocybin and plasticity
psilocybin desynchronizes DMN = plastiicty with 5HT2A receptors = dendritic/synpatic growth (antidepressant) treats MDD/treatment resistant depression
Animal models of psychadelics, abuse
head twitch response, but hard to sutdy
drug discirmiation - 5HT2A antags block discrimination
Not hugh abuse potential (no withdrawl/reinforcement)
rapid tolerance due to down regulation 5HT2AR
bad trip/hallucinogen persisting perception disorder/psychotic reaction
Clinical uses of psychedelics
LSD for cluster headaches, analgesia
Psilocybin for depression/anxiety lasted 4yrs
smoking cessation
microdosing prob placebo
PCP and Ketamine pharmacology
PCP - anesthetic, no resp depression, catatonic/rigidity upong waking so no longer, illegal in 1967 powder/pill
Ketamine - safer PCP, less potent anesthetic, veternarian (children safe), injectable liquid/powder half life 3hr
mechanism of PCP/ketamine
Noncomp antagonist of NMDAR
binding site inside channel (need Mg first)
blockade in hippo/cortex = cog deficits
Subjective effects PCP/ketamine
detached/numb/cog disorganization
Psychomimetic PCP = schizo symptoms
lightness/floating/itnrospection
Use of ketamine/PCP
reinforcing - high abuse
VTA/DA in NAcc
urological problems/memory deficits
frontal/temporal reduction in gray matter with ketamine
high doses cause apoptosis
Clinical uses PCP/ketamine
antidepressant, not euphoric, helps those with co-morbid anxiety
too high dose is anesthetic, not antidepressant
rapid reduction in depression, subanesthetic dose effects last week even though half life 3hrs
Disinhibition Hypothesis
3 neurons, Gaba onto Glutamate onto Postsyn
NMDAR on Gaba Ketamine/PCP inhibits, meaning less Gaba on Glut, more glut allows AMPARS/Ca influx releasing BDNF
dendritic growth and synaptogensis
Dextromethorphan
metabolized to dextrorphan (antitussive, cough suppresant)
hgih dose = NMDAR noncomp antag = similar effect to hallucinogen
