7 - MDMA/Ecstasy

Question 1

Merck

Answer 1

company that synthesized MDMA (Kollisch) in 1912

Question 2

DOW Chemicals

Answer 2

published the first testing in 1960

Question 3

sources

Answer 3

• Ocotea pretiosa
• Sassafras albidum
• Cinnamomum parthenoxylan
• Sassafras essential oil

Question 4

MDMA

Answer 4

• also known ecstasy

- methylenedioxy ring shifts stimulant effects towards mood and perception

Question 5

absorption

Answer 5

• ingestion or insufflation

- 75-100 mg per dose

Question 6

distribution

Answer 6

• on-set of 30-45 min
• brain, lungs, liver, kidney, spleen,
• therapeutic index of 14-16

Question 7

metabolism

Answer 7

• CYP2D6

- half-life of 6 hrs

Question 8

excretion

Answer 8

kidney

Question 9

acute effects

Answer 9

• empathy
• euphoria
• energetic
• higher self-esteem
• sympathomimetic

Question 10

physiological mechanisms

Answer 10

• 5-HT (1B/2) agonist, therefore it causes bruxism and increased locomotion
• reverses 5-HT transporters
• blocks DA and NE transporters
• switches to a higher affinity for 5-HT
• limited self-admin
• increases prolactin and oxytocin
• increases cortisol
• increases blood glucose
• activation of ventral striatum
• decreased activity in amygdala

Question 11

bruxism

Answer 11

jaw grinding

Question 12

5-HT2B blockers

Answer 12

• selective block inhibits 5-HT release

- deletion prevents 5-HT release

Question 13

other drug targets

Answer 13

• adrenergic receptors, resulting in sympathomimetic effects and hyperthermia
• histamine type 1 resulting in release of ACh and EPSPs
• alpha-7 nAChR resulting in release of NT

Question 14

tolerance

Answer 14

• decrease in 5-HT transporter activity

- depletion of neurotransmitters

Question 15

withdrawl

Answer 15

inability to thermoregulate

Question 16

“suicide Tuesdays”

Answer 16

withdrawl phase, usually on Tuesdays, after clubbing

Question 17

dependance

Answer 17

• more psychological than physical

- agonism may underlie low addiction risk

Question 18

dangers of acute use

Answer 18

• mindset can be amplified at time of drug use (depression, anxiety, hallucinations, paranoia)
• 5-HT syndrome
• combination with anti-depressants reduces effects
• combination with MAO inhibitors increases effects
• hyponatermia

Question 19

5-HT syndrome

Answer 19

• increased HR, BP
• muscle rigidity
• delirium
• diarrhea
• rhabdomyolysis

Question 20

D1 receptor

Answer 20

• MDMA increases DA release while D1 antagnists reduces it

- MDMA increases temp. set point while D1 antagonist prevents this

Question 21

hyperthermia

Answer 21

• cumulative effects from 5-HT, DA, and NE
• hyperactivity
• dysregulation of temperature set points

Question 22

hyponatermia

Answer 22

• low sodium in blood

Question 23

hyponatermia causes

Answer 23

• hyperthermia causes increase in water intake

- increase in anti-diuretic hormone

Question 24

hyponetermia effects

Answer 24

cerebral edema (swelling), therefore vomiting, and respiratory arrest

Question 25

CYP variation

Answer 25

enzymes differ from individuals, therefore a high trip is not guaranteed (some are more/less susceptible to adverse effects)

Question 26

long-term health effects

Answer 26

• memory and attention deficit

- apoptosis of hippocampal neurons from caspase-3 pathway

Question 27

caspase-3 (apoptosis pathway)

Answer 27

higher activation when MDMA is taken, therefore cells are more stressed out and undergo apoptosis