Ectasy

Question 1

Kollisch

Answer 1

synthesized MDMA molecule in 1912 at Merck

Question 2

Shulgin

Answer 2

published first testing in 1960 at DOW chemicals

Question 3

sources

Answer 3

extracted from cured plants:
- ocotea pretiosa
- sassafras albidum
- cinnamomum parthenocylon root bark

Question 4

sassafras

Answer 4

contains ~75-85% safrole - precursor

Question 5

ectasy

Answer 5

MDMA
hallucinogen

Question 6

MDMA

Answer 6

methylenedioxy-methamphetamine
contains methylenedioxy ring

Question 7

methylenedioxy ring

Answer 7

shifts stimulant effects toward mood and perceptions

Question 8

absorption

Answer 8

ingestion - tablet/capsule
insufflation - powder (molly)
75-100mg dose

Question 9

distribution

Answer 9

brain, lungs, liver, kidney, spleen
onset 30-45 min
TI = 14-16 (relatively safe)

Question 10

metabolism

Answer 10

liver
80% - CYP2D6
6 hr half life
2-3 hour high

Question 11

excretion

Answer 11

kidney
20% unchanged

Question 12

acute effects

Answer 12

empathogen - increased empathy
entactogen - lower guard
euphoria, energy, high self-esteem
sympathomimetic

Question 13

sympathomimetic effects

Answer 13

increased heart rate, hyperthermia, diaphoresis (increased sweating)

Question 14

cellular mechanisms

Answer 14

5HT (1B/2) agonist

reverses 5HT transporter → TAAR phosphorylation

blocks NE and DA transporters
(10x higher affinity for 5HT)

Question 15

5HT2B

Answer 15

Gq linked
agonist causes bruxism (jaw grinding), increased locomotion

Question 16

blocking 5HT 2B

Answer 16

blocks MDMA-induced 5HT release in NAc and VTA

prevents MDMA-induced DA release in NAc

use antagonist / genetic deletion

Question 17

physiological mechanisms

Answer 17

increases dopamine but not very reinforcing (limited self-administration) = lower break points

increases prolactin/oxytocin → due to 5HT (bonding/empathy)

increases cortisol by 800% → feelings of excitement and happiness, higher blood glucose

Question 18

shifts brain region activation

Answer 18

towards ventral striatum (thoughtfulness)
away from amygdala (fear, rage)

Question 19

cephalopods

Answer 19

express evolutionarily conserved 5HT transporter

MDMA affects behaviour → show pro-social effects (normally asocial octopuses interact)

Question 20

molecular drug targets

Answer 20

adrenergic receptors = sympathomimetic effects, hyperthermia

histamine type 1 receptors = ACh release, EPSPs

a7 nAChR → partial agonist, increases NT release

Question 21

tolerance

Answer 21

decrease in 5HT transporter activity (+DA, NE)
decreased transporter expression
depletion of NTs

Question 22

withdrawal

Answer 22

inability to thermoregulate
lethal → ‘suicide Tuesdays’ - symptoms peak 2-3 days after use

Question 23

dependence

Answer 23

more psychological than physical
biased agonism in 5HT (2C) receptor → low addiction risk

Question 24

dangers of acute use

Answer 24

bad trips - depression, anxiety, hallucinations, paranoia
serotonin syndrome

Question 25

serotonin syndrome

Answer 25

increased heart rate, bp muscle rigidity, hyper-diaphoresis, delirium, diarrhea, rhabdomyolysis → kidney failure, convulsion, death

Question 26

combination of MDMA + SSRIs

Answer 26

reduced effects of MDMA competition for 5HT transporters

Question 27

combination with MAO inhibitors

Answer 27

potentiate effects of MDMA increased NT availability

Question 28

hyperthermia

Answer 28

most common cause of overdose death cumulative effects from 5HT, DA, NE hyperactivity → dysregulation of temperature set points

Question 29

dysregulation of temp set points

Answer 29

D1 receptor in preoptic anterior hypothalamus augments temp set point in vivo MDMA increases DA release in AH

Question 30

hyponatremia

Answer 30

low Na+ in blood hyperthermia causes large water intake MDMA triggers ADH release → cerebral edema → vomiting, respiratory depression

Question 31

metabolites

Answer 31

certain metabolites cause cell death CYP enzyme metabolism differs greatly among individuals more or less susceptible to adverse effects, sudden death

Question 32

pharmacogenomics

Answer 32

random toxicity variability in enzyme profiles leads to particular toxic metabolite build up

Question 33

memory and attention deficits

Answer 33

induction of apoptosis in hippocampal neurons via caspase-3 pathway (rats)