Lecture 21 - Hallucinogens Flashcards
a psychoactive agent that causes changes in perception
hallucinogen
most hallucinogen drugs alter function of the:
monoaminergic or glutamatergic neurotransmitter systems
what are the four classes of hallucinogens?
1) classical psychedelics
2) dissociative agents
3) deliriants
4) oneirogens
what distinguishes the classes of hallucinogens?
mechanism of action and effects
includes drugs with perception-altering psychedelic effects, and have a common mechanism of action at the 5HT2a receptor
classical psychedelics
lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT) are all examples of:
classical psychedelics
LSD was discovered accidentally by:
Dr. Albert Hofmann
compounds that are produced by a fungus that grows on rye
ergot alkaloids
ergot alkaloids are known to be good:
vasoconstrictors (why they were originally studied to treat cardiovascular disease and migraines)
when Dr. Hofmann tried to chemically manipulate ergot alkaloids, he ended up making:
lysergic acid diethylamide (LSD)
how many targets does LSD have?
50 known targets (including several serotonin receptors)
LSD has a very high affinity for:
the 5HT2a receptor
the hallucinogenic effects of LSD are mediated by:
5HT2a receptors
LSD is a:
high affinity partial agonist at the 5HT2a receptor (and other 5HT receptors)
how do we know 5HT2a activation is responsible for hallucinations?
transgenic mouse models lacking these receptors (knockout) do not show hallucinogenic like behaviour (head bobs) to LSD
true or false: all 5HT2a agonists are hallucinogenic
false
why is it that not all 5HT2a agonists are hallucinogenic?
biased agonism
at the 5HT2a receptor, LSD activates:
the phospholipase C signalling pathway
non-hallucinogenic 5HT2a agonists activate:
the beta-arrestin signalling pathway
it was found that pretreatment with the 5HT2a receptor antagonist _______ blocked the effects of LSD
ketanserin
what are the effects of LSD due to activity at the 5HT1 receptor?
dilated pupils, increases heart rate, and increases blood pressure
what are the effects of LSD due to activity at the 5HT2b receptor?
valvopathies are possible with chronic use (even in microdoses)
what type of hallucinations are caused by LSD?
distortion of sensory perception, range from simple colour patterns to more complex scenes, sometimes come with feelings of enlightenment
what are the potential adverse psychiatric effects of using LSD?
anxiety, paranoia, and delusions
distressing visual hallucinations that appear following drug use
hallucinogenic persisting perception disorder (HPPD)
how is LSD tolerated in the body?
a single dose of LSD can lead to profound tolerance that lasts for several days
tolerance of LSD is accompanied by:
downregulation of 5HT (but no other receptors)
is cross tolerance of LSD with other hallucinogens acting at serotonin receptors possible?
yes
classical psychedelic which contains an indole ring with an amine group (structurally similar to serotonin)
psilocybin
what are the effects of using psilocybin?
euphoria, visual and mental hallucinations, changes in perception and a distorted sense of time, spiritual experiences
what are the adverse effects of using psilocybin?
nausea and panic attacks
true or false: psilocybin is a prodrug
true
psilocybin is rapidly dephosphorylated into ______ when ingested orally
psilocin
psilocin is a:
partial agonist at 5HT receptors
psilocin has a high affinity for the _____ and _____ receptors, and slightly lower affinity for the _____ receptor
5HT2b, 5HT2c, and 5HT2a
what causes the hallucinogenic effects of psilocin?
activity at the 5HT2a receptor
type of hallucinogens which distort perceptions of sight and sound, and produce feelings of detachment from the environment or self
dissociative hallucinogens
the use of dissociative hallucinogens is often associated with _____, and can lead to _____
analgesia, depersonalization (out of body experiences)
phencyclidine (aka angel dust) is an:
NMDA recpetor antagonist, and an inhibitor at the dopamine transporter (DAT)
the use of phencylidine (PCP) leads to:
increased synaptic levels of dopamine (increases release and blocks reuptake)
why has phencyclidine (PCP) been largely replaced by ketamine as an anesthetic?
for its highly addictive effects
dissociative hallucinogen which produces changes in body image, loss of ego boundaries, paranoia, and depersonalization
phyencyclidine (PCP)
type of hallucinogen that induces a state of delirium characterized by extreme confusion and an inability to control ones actions
deliriant hallucinations
both _____ and _____ can produce visual and auditory hallucinations
deliriant hallucinogens, psychedelics
type of hallucination where imagery is often perceived as real and users may not be aware they are in a state of drug-altered consciousness (low lucidity)
deliriant hallucinations
deliriant hallucinogens tend to block:
muscarinic acetylcholine receptors (anticholinergic)
a widespread poisonous plant that contains tropane alkaloids such as scopolamine and atropine
datura stramonium
atropine and scopolamine are:
competitive antagonists at the muscarinic cholinergic receptors
symptoms of datura stramonium use include:
delirium, confusion, hallucinations, and loss of consciousness
hallucinogen associated with systemic effects like dry mouth, dilated pupils, muscle stiffness, tachycardia, etc.
datura stramonium
is the use of datura stramonium lethal?
yes (at high doses)
true or false: at very high doses, first generation antihistamines can produce deliriant hallucinations (related to their anticholinergic effects)
true
why are fist generation antihistamines a potentially inappropriate medication for older adults?
older adults are more susceptible to the delirium effects of first generation antihistamines
a substance that produces a dreamlike state of consciousness
oneirogen
salvinorin A is an:
agonist at the kappa opioid receptor
salvinorin A is derived from:
the plant salvia divinorum
produces very short acting hallucinations (~5 minutes); includes featues of classical psychedelics, dissociative hallucinogens, and anticholinergic deliriants; and is characterized by an immersive dream state similar to REM sleep
salvinorin A
