Exam 2: Hallucinogenics

Question 1

What are the characteristics of serotonin synapse?

Answer 1

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

Question 2

What are the origins and terminations of major serotonergic brain pathways?

Answer 2

Raphe Nuclei —> many areas

Question 3

What are the perceptual and cognitive effects characteristics of drug-induced altered state of conciousness?

Answer 3

lucid thinking, perspective,hallucination, syntesthesa, no stress, repress emotion, unity, transcendence

Question 4

What is the history behind the discovery and use of lysergic acid diethylamine (LSD)?

Answer 4

Discovered by Hoffman in 1938, synthesized LSD-25 by accident trying to stimulate respiration/circulation

Question 5

By what proposed mechanisms do serotonergic hallucinogens (psychedelics) exert their perceptual and cognitive effects?

Answer 5

5-HT2A Agonists

Tolerance = 5HT2A receptors decrease

5HT2A affinity predicts hallucinogenic potency

Disrupts cortical pyramidal neurons.

Question 6

What are the side-effects of administration of serotonergic hallucinogens?

Answer 6

Headache, nausea, vomiting, tremors, dizziness, muscle wekaness, increase risk behavior

Question 7

What are the risks of use, associated

with serotoninergic hallucinogens?

Answer 7

psychotic- fear, panic, confusion, delusion.

Question 8

What is Hallucinogenic Persisting Perception Disorder (HPPD)?

Answer 8

flashbacks, hallucinatons come long after LSD use.

Unpredicated, mechanisms unknown.

Question 9

Only serotonin ionotrophic

Answer 9

5-HT2A

Question 10

5-HT2A antagonists

Answer 10

Block perceptual effects of psilocybin

block serotonin syndrome

Question 11

LSD effective at

Answer 11

microgram doses, 1% reaches brain.

Question 12

LSD effects begin

Answer 12

30 minutes, persist 6-12 hours

Question 13

Most serotinergic admin

Answer 13

oral

Question 14

Hallucinogenic effects

Answer 14

lucid thinking, perspective,hallucination, syntesthesa, no stress, repress emotion, unity, transcendence

Question 15

What in brain accounts for hallucinations by serotinergic LSD?

Answer 15

Increased connectivity between different regions, decreased connectivity in others

rewire the brain.

Mediated by 5HT2A receptors

Question 16

LSD: tolerance vs. dependence

Answer 16

Rapid tolerance formation

No physical dependence (no withdrawal)

Weak reinforcing effects/psychology dependence (little chance of addiction)

Question 17

What is synthetic LSD?

Answer 17

Highly potent 5HT2A agonist

Associated with sublethal and lethal OD

Question 18

How do monoaminergic compounds exert both stimulant and hallucinogenic effects?

Answer 18

Have phenylethylamine structure for catecholamine receptors, but also have -O- for the serotonin recepetors?

Question 19

MDMA (ecstasy)

Answer 19

1914- Merck synthesized
STreet use in 60s
Schedule 1 due to neurotoxic potential

Question 20

MDMA (ecstasy)

Answer 20

1914- Merck synthesized
Street use in 60s
Schedule 1 due to neurotoxic potential

Question 21

Methylenedioxymethamphetamine:

1) Admin
2) onset
3) Physical dependence
4) Psychological dependence

Answer 21

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

Question 22

How do monoaminergic compounds exert both stimulant and hallucinogenic effects?

Answer 22

Have phenylethylamine structure for catecholamine receptors, but also have -O- for the serotonin receptors?

Question 23

By what synaptic mechanism is MDMA proposed to exert its effects?

Answer 23

Stimluates release of serontin.

1) enters via SERT
2) gets 5HT out vesicles
3) inhibits MAO
4) Reverses transport of 5HT into synapse

Question 24

What are the desired effects associated with use of MDMA?

Answer 24

Euphoria, empathy, sociability, sensations, altered perception, no anger/anxiety

Can also increase defensiveness/aggression

Question 25

What are the risk factors associated with the use of MDMA?

Answer 25

Sympathomimetic
Spasms, jaw clenching
Dehydration, hyperthermia, elevated heart rate, bp, kidney and liver failure, cardiac arrest, death sometimes

Question 26

What are the features of MDMA neurotoxicity to human use?

Answer 26

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.

Question 27

What are the potential therapeutic applications of MDMA?

Answer 27

Controversial, but MAPS is on the case

Question 28

By what mechanism do dissociative psychedelics, such as ketamine and phencyclidine affect glutamatergic neurotransmission?

Answer 28

Block channels of NMDA receptors

Question 29

Phencyclidine and Ketamine: Low dose

Answer 29

Intoxication, euphoria, psychedelic

Question 30

Phencyclidine and Ktmine: high dose

Answer 30

agitation or catalepsy, amnesia, analgesia, anesthesia, seizures, coma, death

Question 31

What are characteristics of glutamatergic synapses?

Answer 31

EAAT receptors

VGLUT vesicles

Question 32

Ketamine’s therapeutic uses

Answer 32

vet and pediatric, antidepressant

Question 33

Ketamine as predatory drug

Answer 33

sexual assault
blocks memory
allows movement/communication
colorless, odorless, tasteless

Question 34

LSD Neurochemical effects

Answer 34

5HT2 Agnoist

Question 35

Which has strong behavioral, tolerance, dependence, and toxicity/longterm effects. lethality?

Answer 35

Phencyclidine

Question 36

Phencylidine is a

Answer 36

NMDA channel blocker

Question 37

MDMA is a

Answer 37

5HT releaser

Question 38

Long term MDMA effects

Answer 38

5HT neurotoxin