Exam 2: Hallucinogenics Flashcards
What are the characteristics of serotonin synapse?
Stored in vesicles, reserpine sensitive, release regulated by Ca2+ influx.
Reuptake by SERT
Degraded by MAO/Aldehyde dehydrogenase
Meta: 10 types
Ionotrophic: 1 subtype
Release regulated by 5HT1A autoreceptor
What are the origins and terminations of major serotonergic brain pathways?
Raphe Nuclei —> many areas
What are the perceptual and cognitive effects characteristics of drug-induced altered state of conciousness?
lucid thinking, perspective,hallucination, syntesthesa, no stress, repress emotion, unity, transcendence
What is the history behind the discovery and use of lysergic acid diethylamine (LSD)?
Discovered by Hoffman in 1938, synthesized LSD-25 by accident trying to stimulate respiration/circulation
By what proposed mechanisms do serotonergic hallucinogens (psychedelics) exert their perceptual and cognitive effects?
5-HT2A Agonists
Tolerance = 5HT2A receptors decrease
5HT2A affinity predicts hallucinogenic potency
Disrupts cortical pyramidal neurons.
What are the side-effects of administration of serotonergic hallucinogens?
Headache, nausea, vomiting, tremors, dizziness, muscle wekaness, increase risk behavior
What are the risks of use, associated
with serotoninergic hallucinogens?
psychotic- fear, panic, confusion, delusion.
What is Hallucinogenic Persisting Perception Disorder (HPPD)?
flashbacks, hallucinatons come long after LSD use.
Unpredicated, mechanisms unknown.
Only serotonin ionotrophic
5-HT2A
5-HT2A antagonists
Block perceptual effects of psilocybin
block serotonin syndrome
LSD effective at
microgram doses, 1% reaches brain.
LSD effects begin
30 minutes, persist 6-12 hours
Most serotinergic admin
oral
Hallucinogenic effects
lucid thinking, perspective,hallucination, syntesthesa, no stress, repress emotion, unity, transcendence
What in brain accounts for hallucinations by serotinergic LSD?
Increased connectivity between different regions, decreased connectivity in others
rewire the brain.
Mediated by 5HT2A receptors
LSD: tolerance vs. dependence
Rapid tolerance formation
No physical dependence (no withdrawal)
Weak reinforcing effects/psychology dependence (little chance of addiction)
What is synthetic LSD?
Highly potent 5HT2A agonist
Associated with sublethal and lethal OD
How do monoaminergic compounds exert both stimulant and hallucinogenic effects?
Have phenylethylamine structure for catecholamine receptors, but also have -O- for the serotonin recepetors?
MDMA (ecstasy)
1914- Merck synthesized
STreet use in 60s
Schedule 1 due to neurotoxic potential
MDMA (ecstasy)
1914- Merck synthesized
Street use in 60s
Schedule 1 due to neurotoxic potential
Methylenedioxymethamphetamine:
1) Admin
2) onset
3) Physical dependence
4) Psychological dependence
1) Oral, intranasal, intravenous
2) 30-60 min, duration 3-5 hours
3) withdrawal effects include fatigue, loss of appetite, inability to concentrate, dysphoria, depression, anxiety
4) craving, less than opioid/stimulant, more than other hallucinogens
How do monoaminergic compounds exert both stimulant and hallucinogenic effects?
Have phenylethylamine structure for catecholamine receptors, but also have -O- for the serotonin receptors?
By what synaptic mechanism is MDMA proposed to exert its effects?
Stimluates release of serontin.
1) enters via SERT
2) gets 5HT out vesicles
3) inhibits MAO
4) Reverses transport of 5HT into synapse
What are the desired effects associated with use of MDMA?
Euphoria, empathy, sociability, sensations, altered perception, no anger/anxiety
Can also increase defensiveness/aggression
What are the risk factors associated with the use of MDMA?
Sympathomimetic
Spasms, jaw clenching
Dehydration, hyperthermia, elevated heart rate, bp, kidney and liver failure, cardiac arrest, death sometimes
What are the features of MDMA neurotoxicity to human use?
1) Global/local reductions in SERT (not in striatum)
2) Low neurocognitive function
3) impaired mood/sleep/sex/immunity
4) impairments relate to dose/duration
Many confounding variables.
What are the potential therapeutic applications of MDMA?
Controversial, but MAPS is on the case
By what mechanism do dissociative psychedelics, such as ketamine and phencyclidine affect glutamatergic neurotransmission?
Block channels of NMDA receptors
Phencyclidine and Ketamine: Low dose
Intoxication, euphoria, psychedelic
Phencyclidine and Ktmine: high dose
agitation or catalepsy, amnesia, analgesia, anesthesia, seizures, coma, death
What are characteristics of glutamatergic synapses?
EAAT receptors
VGLUT vesicles
Ketamine’s therapeutic uses
vet and pediatric, antidepressant
Ketamine as predatory drug
sexual assault
blocks memory
allows movement/communication
colorless, odorless, tasteless
LSD Neurochemical effects
5HT2 Agnoist
Which has strong behavioral, tolerance, dependence, and toxicity/longterm effects. lethality?
Phencyclidine
Phencylidine is a
NMDA channel blocker
MDMA is a
5HT releaser
Long term MDMA effects
5HT neurotoxin
