ecstacy Flashcards
what class is ecstasy
an amphetamine even though it is often classified as a hallucinogen
what is the difference with methamphetamines and MDMA (structurally)
there is a methylenedioxy ring
what is the general effect of the methylenedioxyring compared to meth (2)
it reduces stimulant effects and produces more serotonergic effects
what is Molly
powder form of ecstasy
what is the precursor for ecstasy
safrole
what is safrole (where from)
an aromatic oil obtained from distillation of the root bark of sassafras
what have manufacturers started doing due to the scarcity of sassafras trees
started using different chemicals as a starting point
what is a risk when manufacturers use a different chemical as a starting point
increased risk of contamination with PMA
what is the administration with ecstasy
pill form
how can molly be administered and why
snorted because its a powder
what is the rate of onset for ecstasy and why
slow (up to 2 hours) because it is orally ingested
what is “stacking”
when you take multiple doses simultaneously
what can the dose range of MDMA pills be (content of actual ecstasy)
10-150mg
when do people feel the effects of ecstasy the most (what mg dose)
between 75-125mg
what % of people use ecstasy once per week
10%
is psychological or physical dependence more with ecstasy use
more psychological dependence
how long does the ecstasy high last
2-3 hours
what kind of mood changes with ecstasy
positive
what happens to defence mechanisms with ecstasy
less of them
what does entactogens mean
they are drugs that increase empathy for others
is ecstasy an entactogen
yes
what does ecstasy do to self esteem
increase
is ecstasy stimulant or depressant
stimulant
what kind of mental disease is ecstasy maybe good for
PTSD
how does ecstasy effect octapuses
increases their social interactions even though they are fairly solitary
what NT is most effected with ecstasy
serotonin
what does high levels of serotonin cause the release of
oxytocin
what is oxytocin
hormone that gives feeling of empathy and bonding
besides 5HT, what else does ecstasy cause the release of
cortisol
what is the % increase of cortisol with ecstasy
800% increase
when is peak cortisol released timed with ecstasy use (what symptoms correlated with)
excitement and happiness, lack of fatigue
why does cortisol cause a lack of fatigue
because cortisol can induce glucose release
what are 5 physiological effects of ecstasy
increase HR BP
hyperactivity
hyperthermia
bruxism -jaw clenching/grinding
what is bruxism
jaw clenching / grinding
what causes bruxism
excess 5HT release
what is the mechanism of action of ecstasy
blockade and reversal of serotonin transporters
but also DA and NE transporters
from NE DA 5HT block with ecstasy, name in order of potency of block
5HT > NA > DA
what is the affinity of ecstasy for 5HT transporter compared to the NA transporter
10X higher
does ecstasy bind to TAAR
yes
what happens once ecstasy binds to and effects TAAR
induces reversal of direction of transporters
what does ecstasy do to vesicles
leaks 5HT from vesicles into the nerve ending cytoplasm
what does ecstasy do to MAO
partial inhibition
why is ecstasy classified as a hallucinogen
because its an agonist at 5HT2A receptors
why is ecstasy an agonist at 5HT2A receptors
due to the methylenedioxy ring
what is the main hallucinogen receptor
5HT2A
what is the % increase of DA in rats NAc with ecstasy
200-300%
what is the % increase of 5Ht in rats NAc with ecstasy
1400%
where in the brain is there an increase in 5HT
in prefrontal cortex and NAc and other parts of he reward pathway
is ecstasy as reinforcing as cocaine or meth and why
not as much because less DA release comparatively
do you see much ecstasy addiction
not as much as like cocaine
besides 5HT DA NE
where does ecstasy also bind to (3)
adrenergic receptors
H1 (histamine)
nAChR type alpha 7
what happens when ecstasy binds to adrenergic receptors
cardiovascular effects and hyperthermia
what happens when ecstasy binds to histamine type 1 receptors
acetylcholine release –> excitation (think= anti-histamines make you sleepy, so this wakes you up)
what happens when ecstasy binds to alpha7 nAChR
partial agonist to increase NT release
which enzyme metabolizes ecstasy
CYP2D6
what % of ecstasy is metabolized by CYP2D6
80%
what % of ecstasy is excreted unchanged in urine
20%
how is ecstasy metabolized (what % is handled in what ways)
80% CYP2D6
20% excreted unchanged in urine
is ecstasy or amphetamine metabolism more complicated
ecstasy
how many metabolites of ecstasy are there
9
what do lots of the ecstasy metabolites cause
apoptosis
what is apoptosis
programmed cell death
what causes the random pattern of ecstasy toxicity
the wide range of CYP activity in humans - some more susceptible to production of harmful metabolites than others
how does ecstasy tolerance happen
decrease in transporter activity (5HT and also DAT and NAT)
what happens to transporters at neuronal membrane with ecstasy
decrease
what are 4 adverse effects following ingestion of ecstasy
depression, anxiety, hallucinations and paranoia
how severe is ecstasy withdrawal
it can be severe
what are 4 side effects of ecstasy withdrawal
lethargy, irritability, memory loss, panic
why can there be lots of depression after ecstasy use
exhausted the supply of NTs such as 5HT and DA
can ecstasy damage be lethal
yes
what causes serotonin syndrome
abnormally high levels of 5HT
what are 7 symptoms of serotonin syndrome
high BP HR, muscle rigidity, severe perspiration, delirium, diarrhea, hyperthermia, rhabdomyolysis
what are 4 ways you can die with serotonin syndrome
kidney failure, convulsions, shock, death
which drugs is ecstasy dangerous to take with
drugs that increase 5HT like psychiatric SSRIs
what is weird about SSRIs and ecstasy in animal models
they found that SSRIs can be protective
what is the leading cause of death for ecstasy
hyperthermia
what are 2 things that make ecstasy induced hyperthermia extra lethal
physical exertion and warm environment
how does excess 5HT from ecstasy cause hyperthermia
CNS dysregulation of body temperatures (the body doesnt know how to regulate heat anymore)
how does excess NE from ecstasy cause hyperthermia
adrenergic alpha1: vasoconstrict=retain heat
adrenergic beta3: mitochondria uncoupling=generate heat
how does NE on alpha1 cause hyperthermia
because it causes vasoconstriction and heat retention
how does NE on beta3 cause hyperthermia
mitochondrial uncoupling, generation of heat
how does excess DA from ecstasy cause hyperthermia
not sure but it does!!!!
how long does how does ecstasys effect on thermoregulated last
long after the drug has left the body
what happens once rats are exposed to ecstasy over 3 to 4 days (body temp) then 4-6 weeks later are exposed to high ambient temperature
they have an impaired ability to thermoregulate
what is hyponatremia
low sodium in blood
what triggers excessive thirst
hyperthermia
what is water intoxication
huge water intake in short period of time, dilution of sodium in blood
why can ecstasy increase water retention
it can trigger excessive release of ADH
what are 2 ways that ecstasy can cause hyponatremia
1- hyperthermia can trigger excessive thirst
2- can trigger ADH release (water retention)
what are 4 ways that hyponatremia can kill you
cerebral edema (cells absorbing too much water)
vomiting
coma
respiratory arrest (compression of brain stem)
does ecstasy cause permanent neuronal loss
its controversial and contradictory
what happens to SERT in ecstasy users
there are less of them
where is most SERT lost in the brain in ecstasy users
occipital cortex and hippocampus
why is it not sure if ecstasy kills off neurons
you dont know if you have fewer neuron or just fewer SERT proteins
did they find volume loss (neuron loss) in ecstasy users
no not significant
what is produced as a byproduct of ecstasy metabolism by MAO
hydrogen peroxide
what does hydrogen peroxide form
hydroxyl radicals
what can hydroxyl radicals do
damage lipids and proteins
what does 5-HIAL do
reactive thing that damages proteins and lipids
what is 5-HIAL
a breakdown product of 5HT
what is the MAO reaction with 5HT
5HT –MAO–> H2O2 + 5-HIAL
what breaks down 5-HIAL
aldehyde dehydrogenase
what happens when you have ecstasy with alcohol
the byproduct 5-HIAL will compete with alcohol for aldehyde dehydrogenase and that will cause more damage
what does damage to mitochondria from 5-HIAL cause
damage to nerve terminals and eventual cell death (damaged mitochondria cause trigger apoptosis)
what can metabolism of ecstasy itself cause
quinones and semiquinones
what do quinones and semiquinones do
produce large amounts of ROS
what is the relationship between death and ecstasy dose
there isnt a clear relationship - sudden illness and death can occur even after small doses
what causes some users to have fatal reactions even to very small doses
rare combination of variability in genes for metabolic enzymes - may lead to increased production of toxic metabolites
what is PMA action timing compared to ecstasy
it has a more delayed reaction
how potent is PMA compared to ecstasy
it is more potent
what is a negative of PMA
it is neurotoxic
what is a mechanism of action of PMA
MAO inhibitor
what are 3 effects of PMA
hypoglycemia, hyperkalemia, hyperthermia
what is the difference of PMA and PMMA (structural)
PMMA has an extra methyl group, more similar to meth
is PMA or PMMA more toxic
likely equal
what is the methamphetamine version of PMA
PMMA
what is N-benzylpiperazine
synthetic compound from a family used in plastics, pesticides, resins (deworming cattle)
what is the mechanism of action of N-benzylpiperazine
increases mainly DA and NE release, minor 5HT release
what drug does N-benzylpiperazine mimic the most
amphetamines
what does N-benzylpiperazine lack in terms of trying to mimic MDMA
not a big 5HT impact, so not the big empathy experience
what does overdose of N-benzylpiperazine look like
seizures and cardiac distress hours after ingestion
what is the mechanism of action of 3-trifluoromethylphenylpiperazine (TFMPP)
serotonin efflux through serotonin transporter
what two drugs are often combined to mimic MDMA
3-trifluoromethylphenylpiperazine (TFMPP)
N-benzylpiperazine
what kind of NT release does 3-trifluoromethylphenylpiperazine (TFMPP) mimic to MDMA
it produces both the DA and 5HT level increase that MDMA does
what does 3-trifluoromethylphenylpiperazine (TFMPP) cause in animal models
rats going into convulsions
what is 3-trifluoromethylphenylpiperazine (TFMPP) often a main ingredient of
E or molly
