Exam 3: Hallucinogens Flashcards
3 broad categories of hallucinogens - what is in each (3)
serotonin like (LSD, Peyote, Psilocybin, DMT) belladonna alkaloids (acetylholine like, atropine, scopolamine) dissociative anesthetics (PCP, ketamine, salvia)
substances that produce distortions of perception and of one’s sense of reality
hallucinogens
properties of psychadelic (mind expanding) drugs
alter sensory perceptions in brain
perceptual disturbances
changes in thought processing (used in religious ceremonies)
what schedule drug are hallucinogens?
schedule 1
- no accepted medical uses, high abuse liability
most hallucinogens are ___
what are effects
alkaloids
antibacterial, anitmitotic, anti-inflammatory, analgesic, local anesthetic, hypnotic, psychotropic, antitumor activity
LSD
schedule 1
synthetic drug derived from ergot
ergot
LSD
toxic parasitic rye fungus
alkaloids in ergot contract smooth muscles of veins and arteries (restricts blood flow), uterus (early labor), changes in BP
poisoning led to gangrene (loss of blood flow to extremities, they die off) and death in the middle ages
accidental small dose ingestion led to hallucinogenic effects
Project MKUltra
manipulated people’s mental status by giving LSD forcefully to force spys to reveal secrets
pharmacology of LSD (ADME and route of admin)
route of admin: oral - so potent it is delivered by stamps/blotter paper
A: 30-60 min post-ingestion from GI tract
D: BBB and NO depot binding
M: SLOW in the liver into 2-oxo-3-hydroxy-LSD
E: half like ~5 hrs
peyote
schedule 1
peyote cactus - peyote button cut off and dried cactus crown
active ingredient - mescaline (alkaloid)
psychoactive effects like LSD, BUT LSD is way more potent
pharmacokinetics of peyote(mescaline)
route of admin: oral-peyote buttons - chewed raw or cooked and eaten
A: rapid from GI tract, onset within 30min highest effects ~2hrs post ingestion, effects last up to 8hrs
D: poor lipid solubility, not easily through BBB - so need higher dose to get effects
M: ~50% broken in liver - main metabolite= 3,4,5-trimethoxyphenylacetic acid
E: excreted in urine in 24-48 hrs - even though need high dose it is out quick, 50% unchanged in urine
psilocybin
schedule 1
many species of magic mushrooms have alkaloids with hallucinogenic properties
cave paintings depicted as early as 3500 BC
Timothy Leary
psilocybin project
- teach people to self administer drugs to free syches without reliance on doctors
typical dose of psilocybin
1-2g o dried/powdered mushrooms
- way less than peyote (10-25 mg)
psilocybin pharmacokinetics
route of admin: dried mushrooms eaten raw, boiled in water for tea, cooked with other foods to mask biter taste
A: broken down into psilocin - active component, only 50% absorbed, psilocin detected in blood plasma 30 min after ingestion
D: BBB, psychoactive effects 10-40min after ingestion, last 2-6hrs
M: psilocybin converted to psilocin which is broken down by MAO
E: excreted unchanged or as psilocin-glucuronide in urine (65%), 20% excreted in bile and feces
psilocin detected in urine up to 7 days - in system for long time
glucuronide
psilocybin
substance produced by linking glucoronic acid to another substance via special chemical bond, makes water soluble
body does this when it comes across toxins
DMT
schedule 1
naturally occuring compound in body - biological function unknwon
low levels in brain
inc in response to stress
packaged and stores in neurotransmitter vesicles - serotonin
Ayahuasca
Ayahuasca
DMT tea vine of the soul mix of 2 plants (one has DMT, other B-carbolines ) B-carbolines - inhibit MAO activity
what do you need to give DMT orally
MAO
what is DMT structurally similar to?
serotonin - share biosynthesis pathway
AADC converts tryptophan to tryptamine
tryptamine convets DMT to INMT
VMAT2 packages DMT into vesicles
pharmacokinetics of DMT
route of admin: smoked, snorted
A: DMT has no bioavailability taken orally - broken down by MAO, smoked or snorted produces short but very strong hallucinatory experiences
D: rapid to brain, active transport allows BBB, depot binding - small amount remains in brain for up to 7 days!!
M: metabolite= indole-3-acetic acid
E: rapid when taken WITHOUT MAO, excreted in urine in 24 hrs, 10% unchanged
if with MAO takes longer
ayahuasca pharmacokinetics
tea taken orally
B-carbolines block MAO and DMT breakdown in liver so DMT reaches brain
hallucnogenic effects start 30-60min post ingestion
peak 1-2hrs dissipate 4hrs - longer to kick in
effects of hallucinogens (8)
hallucinations altered perceptions profound effects on mood altered thinking processes altered physiological processes altered state of consciousness feeling of being separated from body psychosis
psychadelic effects time frame
begin 30-90min after ingestion
LSD trip can last 6-12 hrs
smoked DMT effects felt within seconds, peak over a few minutes, gone in an hour
flashbacks
re-experiencing hallucinations after chronic use, years later eventhough drug use stopped
unc;ear why
what determines if you will have a good or bad trip
dose, personality, previous drug experiences, context
4 phases of LSD trip
onset: 30min-hr after LSD
1st feel behavioral effects
plateau: 2 hrs in , time slows- perception it has been a long time
peak: 3 hrs in , synesthesia , most hallucinations
come-down: 5-6 hrs in
synesthesia
crossing of sensory modalities
ex: feeling sounds or hearing colors
smoking DMT effects over time
lungs burn, cough
loud sound in ears until feel yourself blow up and enter universe
break into another universe - heart beats faster
you have left body
visions fade out
euphora lats 30min ater visual trip
physiological effects of hallucinogens
sympathetic nervous system - pupil dilation inc HR BP T restlessness dizziness, vomiting, nausea - peyote and ahowasa
LSD, DMT, and psilocin are chemically similar to…
serotonin
mescaline is structurally similar to..
NE and amphetamine (metabolite p-hydroxymethamphetamine had hallucinogenic effects)
LSD binds with high affinity to at least ____ different serotonergic receptor subtypes
8
LSD, mescaline, DMT, and psilocin bind to what type of receptors and are what agonists
serotonin receptors
5-HT2A receptor agonists
hallucinogenic properties require the activation of what receptor subtype?
and… this alters levels of what neurotransmitter in cerebral cortex?
5-HT2A receptors
glutamate levels altered
why is LSD so potent?
why do its effects last so long?
LSD binding to 5-HT2A forms lid that locks LSD in place temporarily trapping it
lacks ability to unbind
sustained activation
where are 5HT2A receptors found
raphe, PFC, locus coeruleus
activation of 5HT2A receptors increases the release of what into the cerebral cortex to turn on PFC
glutamate
what do EEG studies show about hallucinogens
they disrupt the normal rhythmic oscillations in the cerebral cortex
- added extra stimuli for them to attend to that they would normally ignore
effect of hallucinogen on visual cortex
alters visual processes, including modal object completion
activation of occipital lobe
effect of hallucinogens on temporomedial cortex
inc activity - complex visual processing , integration area
some auditory hallucinations
effects of hallucinogens on cerebral cortex
inc sensory signals to PFC
effect of hallucinogens on locus coeruleus
dec spontaneous activity, sends normal suppressed sensory info to cerebral cortex
sleep states, dream like states
effects of hallucinogens on PFC
inc activity of PFC
central sensory integration area of cerebral cortex
serotonin receptor binding causing hallucinations: thalamus
involved in sensory routing and sleep (reticular patwhay - arousal) - hallucinations like dreams
activate your dreams while you are awake
sertonin receptor binding causing hallucinations in limbic pathway
emotional investment/context of meaning of hallucination vs dream
when ppl scared bc of a bad trip - see something scary in their environment like monsters chasing them
entorhinal cmpus and hippocampus for context
do hallucinogens produce depence and withdrawal symptoms
no
what hallucinogens produce rapid tolerance to repeated use through down regulation of 5HT2A receptors
most hallucinogens EXCEPT DMT
push to re-evaluate therapeutic uses for what 2 hallucinogens
psilocybin and LSD
why would hallucinogens improve mental health
when consume they have experience when they come off of it they get an afterglow period!!!
afterglow period
gives clarity, reduces negative affect (anxiety, fear, depression) in state of well being and calmness
it persists for days - longer time
used to treat long term chronic issues
