7 - MDMA/Ecstasy Flashcards
Merck
company that synthesized MDMA (Kollisch) in 1912
DOW Chemicals
published the first testing in 1960
sources
- Ocotea pretiosa
- Sassafras albidum
- Cinnamomum parthenoxylan
- Sassafras essential oil
MDMA
- also known ecstasy
- methylenedioxy ring shifts stimulant effects towards mood and perception
absorption
- ingestion or insufflation
- 75-100 mg per dose
distribution
- on-set of 30-45 min
- brain, lungs, liver, kidney, spleen,
- therapeutic index of 14-16
metabolism
- CYP2D6
- half-life of 6 hrs
excretion
kidney
acute effects
- empathy
- euphoria
- energetic
- higher self-esteem
- sympathomimetic
physiological mechanisms
- 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
bruxism
jaw grinding
5-HT2B blockers
- selective block inhibits 5-HT release
- deletion prevents 5-HT release
other drug targets
- 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
tolerance
- decrease in 5-HT transporter activity
- depletion of neurotransmitters
withdrawl
inability to thermoregulate
“suicide Tuesdays”
withdrawl phase, usually on Tuesdays, after clubbing
dependance
- more psychological than physical
- agonism may underlie low addiction risk
dangers of acute use
- 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
5-HT syndrome
- increased HR, BP
- muscle rigidity
- delirium
- diarrhea
- rhabdomyolysis
D1 receptor
- MDMA increases DA release while D1 antagnists reduces it
- MDMA increases temp. set point while D1 antagonist prevents this
hyperthermia
- cumulative effects from 5-HT, DA, and NE
- hyperactivity
- dysregulation of temperature set points
hyponatermia
- low sodium in blood
hyponatermia causes
- hyperthermia causes increase in water intake
- increase in anti-diuretic hormone
hyponetermia effects
cerebral edema (swelling), therefore vomiting, and respiratory arrest
CYP variation
enzymes differ from individuals, therefore a high trip is not guaranteed (some are more/less susceptible to adverse effects)
long-term health effects
- memory and attention deficit
- apoptosis of hippocampal neurons from caspase-3 pathway
caspase-3 (apoptosis pathway)
higher activation when MDMA is taken, therefore cells are more stressed out and undergo apoptosis
