Ecstasy

Question 1

What did Kollisch do?

Answer 1

Synthesized ecstasy in 1912 at Merck

Question 2

What did Alexander Shulgin do?

Answer 2

Published first testing in 1960 at DOW chemicals

Question 3

Where is MDMA sourced?

Answer 3

Extracted from cured Ocotea pretiosa, Sassafras albidum, or Cinnamomum parthenoxylon root bark
Sassafra essential oil contains 75-85% safrole

Question 4

What type of drug classification does MDMA have?

Answer 4

It is chemically similar to both methamphetamine and mescaline
Both a stimulant and a hallucinogen

Question 5

Where is MDMA distributed?

Answer 5

Brain
Lungs
Liver
Kidney Spleen

Question 6

What is the onset of MDMA?

Answer 6

30-45 minutes

Question 7

What is the therapeutic index of MDMA?

Answer 7

14-16
Relatively safe

Question 8

How is MDMA absorbed?

Answer 8

Ingestion
Insufflation of powder from capsules

Question 9

What is a typical MDMA dose?

Answer 9

75-100 mg

Question 10

Where is MDMA metabolized?

Answer 10

In the liver
80% is degraded by CYP2D6

Question 11

How is MDMA excreted?

Answer 11

By the kidneys
20% is unchanged

Question 12

What are the acute effects of MDMA?

Answer 12

Empathogen - drop emotional guard, increase empathy
Euphoria, emotional empath, energy, enhanced self-esteem
Sympathomimetic

Question 13

What are the physiological mechanisms of MDMA?

Answer 13

5HT1B/2 agonist which caused bruxism (jaw-grinding) and increased locomotion
Reverses 5HT transporter involving TAAR-mediated phosphorylation of transporter
Also blocks NE and DA transporters

Question 14

What does MDMA have a higher affinity for?

Answer 14

5HT transporters as opposed to NE transporters

Question 15

What does blocking 5HT2B do?

Answer 15

Blocks MDMA-induced 5HT release in NAc and VTA

Question 16

What does MDMA do to dopamine levels?

Answer 16

Increases dopamine but it is not very reinforcing

Question 17

What does MDMA do to prolactin and oxytocin levels?

Answer 17

Increases their levels
Due to 5HT, involved in bonding, empathy

Question 18

What does MDMA do to cortisol levels?

Answer 18

Increases cortisol by 800%
Correlates with feelings of excitement and happiness, increases blood glucose

Question 19

How does MDMA change activation in the brain?

Answer 19

Shifts activation toward ventral striatum (thoughtfulness)
Decreases amygdala activity (fear, rage)

Question 20

What do octopi high on MDMA exhibit?

Answer 20

Social behaviours even though octopi are asocial animals

Question 21

What are the additional molecular targets of MDMA?

Answer 21

Adrenergic receptors which contributes to sympathomimetic effects and hyperthermia
Histamine type 1 receptors which causes ACh release and EPSPs
alpha7 nAChR which is a partial agonist and increases NT release

Question 22

How is tolerance against MDMA developed?

Answer 22

Decrease in 5HT (DA and NE too) transporter activity
Transporter expression decreases
Depletion of neurotransmitters

Question 23

What are the symptoms of MDMA withdrawal?

Answer 23

Inability to thermoregulate
Can be lethal, more likely to commit suicide after a bender

Question 24

How does dependence on MDMA develop?

Answer 24

More psychological than physical
Biased agonism in 5HT2C receptor agonism may underlie low addiction risk

Question 25

What are the dangers of acute MDMA use?

Answer 25

Bad trips involve depression, anxiety, hallucinations, paranoia 5HT syndrome

Question 26

What is 5HT syndrome?

Answer 26

Increased heart rate and blood pressure Muscle-rigidity Hyper-diaphoresis Delirium Diarrhea Rhabdomyolysis

Question 27

What does rhabdomyolysis lead to?

Answer 27

Kidney failure, convulsion, and death

Question 28

What happens when you combine MDMA with SSRIs?

Answer 28

The effects of MDMA are reduced due to competition for 5HT transporters

Question 29

What happens when you combine MDMA with MAO inhibitors?

Answer 29

Can potentiate effects of MDMA due to increased NT

Question 30

What is the relationship between MDMA and D1 receptor antagonists?

Answer 30

MDMA increases DA release in preoptic anterior hypothalamus and increases temperature set point D1 receptors antagonists reduces DA release and also abrogates increases in temperature

Question 31

What is the most common cause of overdose death of MDMA?

Answer 31

Hyperthermia Caused by cumulative effects from 5HT, DA, NE Hyperactivity, dysregulation of temperature set points

Question 32

What is hyponatremia and how does MDMA cause it?

Answer 32

Low Na in blood Caused by large water intake due to hyperthermia MDMA triggers anti-diuretic hormone release Can result in cerebral edema

Question 33

Why does MDMA cause random adverse effects in users?

Answer 33

CYP enzyme metabolism differs greatly among individuals Certain metabolites present in the drug breakdown cause cell death Some individuals are more or less susceptible to adverse effects and death

Question 34

What does variability in enzyme profiles lead to?

Answer 34

Particular toxic metabolite buildup

Question 35

What are the long-term health effects of MDMA?

Answer 35

Memory and attention deficits Induction of apoptosis in hippocampal neurons via caspase-3 pathway in rats