1-hallucinogens Flashcards
what are the 4 types of hallucinogens
indole, catechol (amphetamine derivatives), anticholinergics, delirants
what are catechol hallucinogens (2 words)
amphetamine derivatives
what are the phantasticas
the indole and catechol hallucinogens
what are phantasticas
drugs altering perceptions
do you remain in communication with the outside world with phantasticas
yes
do you remain in communication with the outside world with deliriants
no
what are you aware of in phantasticas
both fantasy and reality simultaneously
is there physiological toxicity with phantasticas
very little - but some of the new ones are deadly
what is an example of indole hallucinogen
LSD
what kind of hallucinogen is LSD
indole hallucinogen
what is the backbone of serotonin
indole
what kind of backbone does LSD have
indole
what kind of backbone does psylocybin have
indole
what natural molecule is psylocybin like
serotonin
what natural molecule is LSD like
serotonin
where does bufotenin come from
toads
what kind of hallucinogen is bufotenin
indole
what kind of hallucinogen is the 2C drugs
catechol hallucinogens
what signalling molecule does indole hallucinogens similar to
serotonin
what signalling molecule does catechol hallucinogens similar to
dopamine and noradrenaline
what are 3 examples of catechol hallucinogens
- mescaline
- MDMA
- 2-C drugs
what are 4 examples of indole hallucinogens
- LSD
- psylocybin
- lysergic acid amide
- bufotenin
what kind of hallucinogen is lysergic acid amide
indole
what kind of hallucinogen is mescaline
catechol
what kind of hallucinogen is MDMA
catechol
what kind of hallucinogen is 2C drugs
catechol
what is ergot
a fungus that infects rye
what does ergot contain
lysergic acid and other complex ergot alkaloids
what is lysergic acid relative to LSD
its a precursor
what are 2 physiological effects of some ergot alkakoids
potent vasoconstrictors
uterine contractions
what is ergotamine used for and why
used for migraines because its a vasoconstrictor of cerebral blood vessels
what is the backbone of lots of ergot alkaloids (like ergotamine)
lysergic acid backbone
what were the two forms of the ergotism that had outbreaks
- one that severely constricted blood flow in limbs + made it feel like burning –> gangrene loss of limbs (vasoconstriction)
- some caused convulsions, delirium, hallucinations
what was Albert Hoffman doing when he made LSD
using ergot alkaloids as a starting point to synthesize new respiratory and circulatory stimulant
what was the compound that Albert Hoffman tested and felt strange (but not LSD yet)
lysergic acid diethylamide
what are 4 clinical uses that were used for LSD
- psychosis in animal model
- cluster headaches
- therapy (access subconscious, alcoholics)
- end of life anxiety
what kind of hallucinogen are the 2C drugs
catechol
what kind of hallucinogen are mandrake
anticholinergics
what kind of hallucinogen are the PCP
deliriants
why did timothy leary start using hallucinogenic mushrooms
as part of a legitimate research project
do animals self administer LSD or other hallucinogens
no, they will work hard to stop that task
is LSD or other hallucinogens reinforcing
no evidence (except with deliriants)
how do you administer LSD or other hallucinogens
mostly orally
what is the dose for LSD
10-300 micrograms
what is microdosing
taking sub threshold doses that are supposed to increase creativity
is LSD habit forming
no
what is the abuse potential of LSD
very low
what is very important to LSD especially when compared to other drugs
set (expectation of user) and setting (environment) can result in good or bad experience
what do effects start happening with LSD
30-90 mins
what % of the LSD gets into the brain
1%
where is LSD metabolized
in the liver
what is the half life of LSD
110 minutes
how long can LSD last for
5-12
why does LSD last longer than its half life
due to long association with 5HT2A receptors
what happens to visual experience on LSD
get hallucinations
what happens do your senses when on LSD
you get synesthesia (mingling of senses) and also visual hallucinations
what kind of emotions do you get when on LSD
intense
what 4 physiological effects of LSD and why
-increase BP
-vasoconstriction
-sweating
-dilated pupils
it is sympathomimetic causing autonomic response
why does -increase BP -vasoconstriction -sweating -dilated pupils happen with LSD
it is sympathomimetic so it causes autonomic responses
what is the mechanism of action of LSD
weak partial agonist at central 5HT2A, 5HT2B and 5HT2C receptors
what is the primary receptor target of LSD
5HT2A
where is there high levels of 5HT2A in the body
in the cortex
what does activation of the 5HT2A, 5HT2B and 5HT2C receptor cause
gene expression in those regions, even acutely
-Linked to neuroplasticity and glutamate signalling
what other kinds of receptors other than 5HT2A, 5HT2B and 5HT2C receptors play a role in LSD
dopamine receptors
why do some drugs that bind to the 5HT2A receptors cause hallucinations while others do not?
the diethylamine group of LSD induces or locks the receptor into a specific shape that results in activation or a specific signalling pathway
-biased agonism
what is biased agonism with LSD
LSD preferentially activates a specific signal transduction pathway via the 5HT2A receptor
does lysergic acid cause hallucinations and why
weak effects because its too small for the receptor
does ergotamine cause hallucinations and why
no because its too big
does LSD cause hallucinations and why
yes strong because the size is just right
is lysergic acid too big or too small to cause hallucinations
too small
is ergotamine too big or too small to cause hallucinations
too big
what part of LSD causes it do have the perfect shape for receptor interactions
diethylamide
what pathway is 5HT2A usually coupled to
G protein receptors
what G protein is activated with 5HT2A and what does that cause
Gq and phospholipase C activation and increased Ca++ and PKC
what pathway is activated when LSD binds to 5HT2A
beta arrestin (G protein independent)
what do arrestins cause
proteins that promote internalization of G protein coupled receptors and desensitize those that remain on cell surface
(desensitization and internalization)
what pathway do non-hallucinogen compounds activate on 5HT2A
Gq
what pathway do hallucinogen compounds activate on 5HT2A
beta arrestin
what receptor conformation does LSD cause to 5HT2A and what does this cause
binds so that a “lid” closes over it so it increases binding time (Decreases ability to leave receptor)
what contributed further towards the beta arrestin signalling pathway
the fact that LSD binds so a “lid” closes over it
what kind of neurotransmitters does LSD increase the release of and where
glutamate from glutamatergic neurons in the cortex
where are 5HT2 receptors in the brain region with glutamatergic neurons
presynaptic
what does activation of presynaptic 5HT2 receptors in the cortex cause the release of
increase glutamate release
where is there the most 5HT2 glutamate release
in the medial prefrontal cortex which is important for perception and information processing
what does the medial prefrontal cortex do
interface between cognitive and emotional systems, where emotions and meanings of things is experienced
what NT in the cortex is thought to be one of the major contributors to the hallucinogenic effects
glutamate
what happens in chronic LSD animal studies
dramatic increase in GABA A receptor levels
what is the locus coeruleus
a part of the fear centre, detects novelty in the environment
what part of the brain is part of the fear centre and detects novelty in the environment
locus coeruleus
how does LSD make the ordinary seem extremely novel
via 5HT2A receptors that increase input to the locus coeruleus
what does LSD do to dopamine receptors and which one
high affinity agonist to D2 receptors
where does LSD bind to D2
in the human striatum
what can over stimulation of the DA receptors cause
hallucinations - but no reward
has there been a reported death from LSD overdose
no
is LSD physiologically safe
yes
why can LSD be dangerous
if you do unsafe things while under the influence
what is hallucinogen persisting perception disorder
when you get sudden and unexpected return to the drugged state
how long do hallucinogen persisting perception disorder flashbacks last and what senses are involved
short, visual
what may cause hallucinogen persisting perception disorder
release from body fat many
when does hallucinogen persisting perception disorder happen the most
when taking other drugs or under stress, even years after last taking the drug
does tolerance happen with LSD how fast
yes very quick
if taken repeatedly, how many days does complete tolerance take to develop
2-3 days
what characterizes LSD tolerance
5HT2 receptors rapidly dissapear
how long does it take for LSD sensitivity to return
within a week
can you become cross tolerant with LSD and mescaline and psylocybin
yes
what are the LSD withdrawal symptoms like
none
what are the LSD addiction symptoms like
none
