Hallucinogens Flashcards
what is a hallucinogen?
psychoactive agent that causes perception changes (hallucinations) - can change thoughts, emotions, and consciousness
what 2 NT systems do most hallucinogens alter?
monoaminergic or glutamatergic
what are 5 criteria for a drug to be classified a hallucinogen?
changes in thought/perception/mood, minimal intellectual/memory impairment, no major stupor/narcosis/excessive stimulation, minor ANS side effects, no addictive craving (not inherently rewarding)
what are 3 classical psychedelic drugs?
lysergic acid diethylamide (LSD, “acid”), psilocybin, and mescaline
what receptor do most psychedelics act on?
5HT2a
what produces ergot alkaloids? and what can they treat?
fungus on rye; migraine (vasoconstrictor)
how did Dr. Albert Hofmann accidentally discover LSD?
chemically manipulated pure ergot derivative to make it more stable
approx. how many targets does LSD have?
over 50 (including several 5-HT/monoamine)
action at what receptor gives hallucinogenic effects of LSD?
5HT2a
what is LSD?
high affinity partial 5HT2a agonist
how do we know 5HT2a is responsible for hallucinations?
transgenic 5HT2a knockout mice (lack receptor) do not show hallucinogenic behaviour to LSD (head bobs)
t/f: all 5HT2a agonists are hallucinogenic
false
what is a non-hallucinogenic 5HT2a agonist?
lisuride hydrogen maleate (LHM)
why aren’t all 5HT2a agonists hallucinogenic?
biased agonism
how does LSD show biased agonism to have hallucinogenic effects?
activates phospholipase A2 not PLC (like 5-HT) and regulates diff genes
what was measured to confirm LSD effects in humans?
oceanic boundlessness (spiritual experiences)
what blocked LSD effects in human study?
Ketanserin (5HT2a antagonist)
what are 3 ANS effects of LSD?
dilated pupils, incr HR and BP
what are 3 possible adverse effects of LSD?
anxiety, paranoia, and delusions
what is hallucinogen persisting perception disorder (HPPD)?
distressing visual hallucinations that appear after drug use
how much LSD can cause tolerance?
one dose (tolerance lasts for days)
what occurs w/ LSD tolerance?
downregulation of 5HT2a receptors (not other 5-HT receptors)
what is cross-tolerance w/ LSD?
tolerance of LSD w/ other hallucinogens at 5-HT receptors (psilocybin, DMT)
what does the structure of psilocybin contain? what is it similar to?
indole molecule (benzene fused to five-membered pyrrole ring) w/ an amine group; serotonin
what naturally contains psilocybin?
psilocybin mushrooms
when was psilocybin historically used?
in religious ceremonies (1000s of years)
what are effects of psilocybin?
euphoria, visual/mental hallucinations, distorted perception/sense of time, spiritual experiences
what are 2 adverse rxns to psilocybin?
nausea and panic attacks
t/f: psilocybin is a prodrug
true
what is psilocybin metabolized to in the body?
psilocin
what is psilocin?
partial 5HT agonist
what 5HT receptors does psilocin have high vs low affinity to?
high: 5HT-2b and 2c
low: 5HT2a
what causes hallucinogenic effects of psilocin?
binding to 5HT2a (like LSD)
what are dissociative hallucinogens?
drugs that distort perception of sight/sound and produce feelings of detachment from enviro/self
t/f: dissociative hallucinogens can lead to depersonalization and analgesia
true
what is phencyclidine? (2)
an NMDA receptor antagonist and dopamine transporter (DAT) antagonist (incr synaptic DA ~ ketamine)
t/f: phencyclidine is aka angel dust
true
t/f: phencyclidine does not have addiction liability
false, exception to most hallucinogens (is self-administered in animals and affect DA levels)
what was phencyclidine originally marketed as? what replaced it?
anesthetic medication; replaced by ketamine
what are 4 (possibly) adverse effects of phencyclidine?
changes in body image, paranoia, unpredictable mood, loss of ego boundaries
what is nitrous oxide aka?
laughing gas
what is N2O commonly used as?
dissociative anesthetic
what are 2 side effects of nitrous oxide?
euphoria and depersonalization
t/f: N2O is high potency and used alone for full anesthesia
false, low potency so usually mixed w/ another gas for full anesthesia
what are 3 targets of N2O in the brain?
non-competitive NMDA antagonist, stimulates endogenous opioid release, positive allosteric GABA-a modulator
what may cause analgesic effects of N2O?
release of dynorphin (endogenous opioid) and kappa opioid receptor activation
what do deliriant hallucinogens cause?
state of delirium (extreme confusion and inability to control one’s actions)
what is similar and different btwn deliriants and psychedelics?
both produce visual/auditory hallucinations but deliriants feel real and not drug-induced
what is low lucidity?
drugs users do not have the metacognition to identify their experience as a dream/fake/drug-induced (deliriants)
what receptors do deliriants block?
muscarinic ACh receptors (anticholinergic)
what is Datura stramonium?
widespread poisonous plant that has tropane alkaloids
what are 2 tropane alkaloids?
scopolamine and atropine (in Datura stramonium)
what are scopolamine and atropine?
competitive antagonists at muscarinic cholinergic receptors
what are 4 cognitive symptoms of Datura?
delirium, confusion, hallucinations, and unconsciousness
what are 4 systemic effects of Datura?
dry mouth, dilated pupils, muscle stiffness, tachycardia (lethal at high doses)
why can 1st gen antihistamines (like diphenhydramine) also produce deliriant hallucinations at high doses?
act on muscarinic receptors and have anticholinergic effects
