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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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