Ecstasy Flashcards
1
Q
Ecstasy
A
- AMPH even though it is often classified as a hallucinogen
- MDMA-differs from methamphetamine by the presence of a methylenedioxy ring (leads to reduced stimulant effects and more serotinergic effects
2
Q
MDMA precursor
A
- sassafras trees are aromatic trees
- safrole is an aromatic oil that is obtained form the distillation of the root bark
- safrole precursor for MDMA
- safrole is structurally almost there
3
Q
Administration
A
- pill
- stacking, taking multiple doses simultaneously (tables range from 10mg - 150 mg), feel effects at 75 mg - 150mg
- most use occasionally, small percentage once per week (psychological dependence rather than physical)
4
Q
Psychological effects
A
- high lasts for 2-3 hours
- positive mood change
- drop in defence mechanisms, increased empathy (entactogen), increased self esteem, overall stimulant effects
- trails for use in PTSD
5
Q
Physiological effects
A
- get rise in HR and BP
- hyperactivity
- hyperthermia (dancing increases core temp=dangerous)
- jaw clenching, grinding of teeth due to serotonin release
6
Q
Mechanism
A
- essentially same as AMPH but effects predominately mediated through serotonergic nerve terminals (different profile b/c methylenedioxy ring
- blockage and reversal of 5HT transporters (also DA and NA) 5HT>NA>DA
- affinity of MDMA for the 5HT transports 10 times higher than for NA
- high 5HT may lead to release of oxytocin
- also leak of 5HT from vesicles into nerve ending cytoplasm and partial inhibition of MAO
- usually classified as hallucinogen b/c agonist actions at 5HT 2A receptor due to methylenedioxy ring binding to it
7
Q
Ecstasy effects on dopamine and serotonin levels
A
- NACs see moderate increase in DA (200-300%) small compared to AMPH and cocaine
- large effect on serotonin levels (1400%)
- see this pattern in prefrontal cortex and other part of reward pathway
- not as reinforcing don’t see as much addiction (animals SA but breaking points)
8
Q
Other receptor targets
A
- adrenergic alpha 2 receptors: may be responsible for some cardiovascular effects (receptors control NT release, too much NT release in heart muscles)
- histamine type 1 receptors: stimulation can lead to acetylcholine release
- nicotinic alpha 7 receptors: also implicated in some nicotine effects
9
Q
Metabolism
A
- mainly in liver (80%), 20% excreted unchanged in urine
- more complicated than AMPH
- as many as 9 metabolites of MDMA have been found to induce programmed cell death in neurons
10
Q
Tolerance
A
- decrease transport activity (like methamphetamine)
- primarily 5HT transport but also DA and NA
- also results in loss of transporter at the neuronal membrane
11
Q
Damage
A
- depression, anxiety, hallucinations and paranoia (use up supply of NTs)
- withdrawal or rebound can be severe
- “suicide Tuesday”
- lethargy, irritability, memory loss, panic
12
Q
Serotonin syndrome
A
- from abnormal high levels of serotonin
- rapid onset: increased hr and bp, muscle rigidity, severe perspiration, delirium, diarrhea, hyperthermia, rhabdoyolysis
- can lead to kidney failure, convulsions, shock, death
- ecstasy very dangerous is taking psychiatric drugs that work by increasing serotonin levels
13
Q
hyperthermia
A
- increase body temp to 43 degrees (fetal)
- issues are: warm environment, physical activity, peripheral vasoconstriction (retention of core body temp)
- loss of thermoregulatory mechanism in CNs
- loss of body signals such as thirst, exhaustion (some drink some don’t feel thirsty)
- increased muscle tone
- heat production
14
Q
Hyponatremia
A
- state of low sodium in blood
- sometimes excessive thirst triggered by hyperthermia, water intoxication leads to dilution of sodium in blood
- also MDMA can trigger excess release of ADH which leads to water retention
- leads to cerebral edema (brain swelling), vomitting, coma, respiratory arrest (from compression of brain stem
15
Q
Neuronal death
A
- animal studies show serotonergic neurons tend to die when exposed to MDMA
- less transporters in humans or drug not binding to them (can’t say whether it is neuronal death or other mechanisms)
- more in notes
16
Q
Mechanism of toxicity
A
- in process of 5Ht metabolism by MAO hydrogen peroxide is generated can form hydroxyl radicals which can damage lipids and proteins (leads to death of neurons)
- 5-HIAL is reactive and can also damage proteins and lipids
- linked with alcohol (ADH busy metabolizing ETOH so can’t metabolize 5HIAL to 5HIAA
- damage to mitochondria results in damage to nerve terminals and eventually cel death
- metabolism of MDMA itself can produce quinones and semiquinones that produce large amounts of ROS
17
Q
Deaths from MDMA
A
- sudden illness and death can occur even after small doses and sometimes first time
- no clear relationship between dose and death
- most deaths from hyperthermia (more reasons in notes)
18
Q
Other substances mixed in pills
A
- ecstasy often mixed with other drugs or contains no MDMA at all
- AMPH methAMPH, caffeine, ibuprofen, ketamin
- sometimes deliberately taken with other drugs (viagra, sextasy, viagra may be neuroprotective) or LSD (candy flip
19
Q
Other substances
1) PMA
2) PMMA
A
1) PMA (paramethoxyamphetamine)
- delayed reaction but more potent and neurotoxic, also MAO inhibitor
- increases 5HT and DA
- street name death: hypoglycemia, hyperkalemia and hyperthermia
- sometimes sold as ecstasy or mixed in
2) PMMA (methamphetamine version of this
- just as toxic
20
Q
N-benzylpiperazine
A
- BZP predominant ingredient in pills
- not natural, synthetic from a family used in pesticides, plastics, resins
- liquid free-base form or pills
- levels of DA, NA and 5HT increase
- in NACs (DA and 5HT)
- produces behaviour that most resemble AMPHs
- cardiac events, low blood sodium (late onset drugs)
21
Q
3-trifluoromethylphenylpiperazine
A
- TFMPP when added to BZP produces an effect most closely mimics ecstasy
- TFMPP agonist at 5HT 1 and 5HT2 receptors, seems to trigger serotonin efflux through transporter
- BZP itself equivalent levels of DA and 5HT (300-400%)
- TFMPP large 5HT increase (600%), only 100% for DA
- together: large increase in both DA and 5HT (1286% and 872%) sinergy occuring
