Ecstasy Flashcards
What did Kollisch do?
Synthesized ecstasy in 1912 at Merck
What did Alexander Shulgin do?
Published first testing in 1960 at DOW chemicals
Where is MDMA sourced?
Extracted from cured Ocotea pretiosa, Sassafras albidum, or Cinnamomum parthenoxylon root bark
Sassafra essential oil contains 75-85% safrole
What type of drug classification does MDMA have?
It is chemically similar to both methamphetamine and mescaline
Both a stimulant and a hallucinogen
Where is MDMA distributed?
Brain
Lungs
Liver
Kidney Spleen
What is the onset of MDMA?
30-45 minutes
What is the therapeutic index of MDMA?
14-16
Relatively safe
How is MDMA absorbed?
Ingestion
Insufflation of powder from capsules
What is a typical MDMA dose?
75-100 mg
Where is MDMA metabolized?
In the liver
80% is degraded by CYP2D6
How is MDMA excreted?
By the kidneys
20% is unchanged
What are the acute effects of MDMA?
Empathogen - drop emotional guard, increase empathy
Euphoria, emotional empath, energy, enhanced self-esteem
Sympathomimetic
What are the physiological mechanisms of MDMA?
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
What does MDMA have a higher affinity for?
5HT transporters as opposed to NE transporters
What does blocking 5HT2B do?
Blocks MDMA-induced 5HT release in NAc and VTA
What does MDMA do to dopamine levels?
Increases dopamine but it is not very reinforcing
What does MDMA do to prolactin and oxytocin levels?
Increases their levels
Due to 5HT, involved in bonding, empathy
What does MDMA do to cortisol levels?
Increases cortisol by 800%
Correlates with feelings of excitement and happiness, increases blood glucose
How does MDMA change activation in the brain?
Shifts activation toward ventral striatum (thoughtfulness)
Decreases amygdala activity (fear, rage)
What do octopi high on MDMA exhibit?
Social behaviours even though octopi are asocial animals
What are the additional molecular targets of MDMA?
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
How is tolerance against MDMA developed?
Decrease in 5HT (DA and NE too) transporter activity
Transporter expression decreases
Depletion of neurotransmitters
What are the symptoms of MDMA withdrawal?
Inability to thermoregulate
Can be lethal, more likely to commit suicide after a bender
How does dependence on MDMA develop?
More psychological than physical
Biased agonism in 5HT2C receptor agonism may underlie low addiction risk
What are the dangers of acute MDMA use?
Bad trips involve depression, anxiety, hallucinations, paranoia
5HT syndrome
What is 5HT syndrome?
Increased heart rate and blood pressure
Muscle-rigidity
Hyper-diaphoresis
Delirium
Diarrhea
Rhabdomyolysis
What does rhabdomyolysis lead to?
Kidney failure, convulsion, and death
What happens when you combine MDMA with SSRIs?
The effects of MDMA are reduced due to competition for 5HT transporters
What happens when you combine MDMA with MAO inhibitors?
Can potentiate effects of MDMA due to increased NT
What is the relationship between MDMA and D1 receptor antagonists?
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
What is the most common cause of overdose death of MDMA?
Hyperthermia
Caused by cumulative effects from 5HT, DA, NE
Hyperactivity, dysregulation of temperature set points
What is hyponatremia and how does MDMA cause it?
Low Na in blood
Caused by large water intake due to hyperthermia
MDMA triggers anti-diuretic hormone release
Can result in cerebral edema
Why does MDMA cause random adverse effects in users?
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
What does variability in enzyme profiles lead to?
Particular toxic metabolite buildup
What are the long-term health effects of MDMA?
Memory and attention deficits
Induction of apoptosis in hippocampal neurons via caspase-3 pathway in rats
