Ecstacy Flashcards
What are some other names for ecstasy?
E, love drug, XTC, Adam, X
What is ecstasy
ecstasy is an amphetamine even though it is o>en classified as a hallucinogen
also known as MDMA (3, 4 - methylenedioxymethamphetamine)
differs from methamphetamine by the presence of a methylenedioxy ring
modification of the aromatic ring tends to reduce stimulant effects, produces more serotonergic effects
ecstasy is MDMA - not caffeine or other drugs
Explain the administration of ecstasy
ecstasy is almost always taken in pill form
stacking - taking mul&ple doses simultaneously eg. triple
stack
depending on source, actual MDMA content/tablet ranges from 10mg - 150 mg - most feel most effects between 75 and 125 mg
most use occasionally, small percentage (10% or less) will use once per week - they may have trouble reducing use but seems to be more psychological dependence than physical
o>en used with alcohol, cannabis, amphetamines
What are the effect on mood of ecstasy? (Psychological)
positive mood change
drop in defence mechanisms, increased empathy for others - drugs that elicit these feeling called entactogens
increased self esteem
overall s&mulant effects
trials for use in post-trauma&c stress disorder
What are the physiological effects of ecstasy
as with other s&mulants, get rise in blood pressure, heart rate
hyperactivity
hyperthermia
jaw clenching, grinding of teeth (bruxism) due to excess serotonin release
How long does the high form ecstasy last?
high lasts for 2 - 3 hours
What is the mechanism of ecstasy in relation to amphetamine
ecstasy works essen&ally the same as amphetamine except its effects are predominately mediated through serotonergic nerve terminals
different profile due to the methylenedioxy ring
Describe the mechanism of ecstasy
blockade and reversal primarily of serotonin transporters
but also at dopamine and noradrenaline transporters
potency of block is 5HT > NA>DA
the affinity of MDMA for the 5HT transporter is 10 &mes higher than for the NA transporter
high serotonin levels may lead to release of oxytocin - hormone related to empathy
also leak of serotonin from vesicles into the nerve ending cytoplasm
par&al inhibi&on of monoamine oxidase
usually classified as a hallucinogen because of its agonist ac&ons at the serotonin (5HT) 2A receptor due to methylenedioxy ring
Explai ecstasy effect on dopamine and serotonin levels
in the nucleus accumbens of rats, see a moderate increase in dopamine (200 - 300%)
small compared to cocaine and amphetamines
with ecstasy, there is an larger effect on serotonin levels (1400%)
see this paZern in prefrontal cortex and other parts of reward pathway
not as reinforcing, don’t see as much addic&on, animals will self-administer but with breaking points (number of &mes animals respond to obtain drug) lower than drugs such as cocaine (one study with primates - cocaine 1913 vs MDMA 802)
What are some other targets of ecstasy?
at doses taken recrea&onally, it will also bind to
adrenergic alpha 2 receptors - may be responsible for
some cardiovascular effects
histamine type 1 receptors - s&mula&on can lead to acetylcholine release
nico&nic alpha 7 receptors - also implicated in some nico&ne effects
How is ecstasy metabolized
mainly in the liver - 80% metabolism, 20% excreted unchanged in urine
much more complicated than amphetamine metabolism
as many as nine metabolites of MDMA have been found to induce programmed cell death (apoptosis) in neurons
Explain tolerance with ecstasy
just as with methamphetamine, ecstasy results in a decrease in transporter ac&vity
primarily the serotonin transporter but dopamine and noradrenaline also
also results in a loss of transporters at the neuronal membrane
What are some damages caused by ecstasy
adverse effects following inges&on can include depression, anxiety, hallucina&ons and paranoia
withdrawal and/or rebound can be severe
“suicide Tuesdays” following a weekend of clubbing
lethargy, irritability, memory loss, panic
the supply of neurotransmiZers such as serotonin and dopamine is exhausted
Describe serotonin syndrome
from abnormally high levels of serotonin
rapid onset - increased heart rate and blood pressure, muscle rigidity (esp. in lower limbs), severe perspira&on, delirium, diarrhea, hyperthermia, rhabdomyolysis (muscle breakdown)
can lead to kidney failure, convulsions, shock, death
ecstasy is very dangerous if taking psychiatric drugs that work by increasing serotonin levels - eg Prozac, a serotonin specific re-uptake inhibitor for depression
Describe hyperthermia and relation to ecstasy
reports show it can increase body temperature to 43oC (fatal)
issues are
warm environment
repe&&ve physical ac&vity
peripheral vasoconstric&on
loss of thermoregulatory mechanism in CNS
loss of body signals such as thirst, exhaus&on
increased muscle tone
heat produc&on
Describe hypo atresia and relation to ecstasy
hyponatremia is a state of low sodium in the blood
some&mes excessive thirst is triggered by
hyperthermia
water intoxica&on - huge water intake in short period leads to dilu&on of sodium in blood
also MDMA can trigger excessive release of an&diure&c hormone (ADH) which leads to water reten&on
leads to cerebral edema (brain swelling from cells absorbing too much water), vomi&ng, coma, respiratory arrest (from compression of brain stem)
Describe ecstasy effect on neuronal death
animal studies have shown that serotonergic neurons tend to die when exposed to MDMA
Hatzidimitriou et al (1999) showed neuronal loss in squirrel monkeys a>er MDMA twice/day for four days
7 yrs later, some regenera&on
s&ll controversial in humans - issue of polydrug use, adulterants in the pills such as PMA
Describe ecstasy effect on neuronal loss in humans
this study compared recrea&onal users to non-users
used on average 96 &mes over three years
used a radioac&ve drug that binds to serotonin transporter to see levels in the brain
marked deficits in several brain areas, some as high as 50%
Describe mechanism of toxicity with ecstasy
in the process of 5-HT metabolism by monoamine oxidase, hydrogen peroxide is generated
this can form hydroxyl radicals which can damage lipids and proteins
5-HIAL is reac&ve and can also damage proteins and lipids
damage to mitochondria results in damage to nerve terminals and eventual cell death
metabolism of MDMA itself can produce quinones and semiquinones that produce large amounts of reac&ve oxygen species
Describe deaths with ecstasy
sudden illness and death can occur even a>er small doses some&mes the first &me
no clear rela&onship between dose and death
of 87 ecstasy related deaths- 8 from heart/circula&on, 4 liver damage, 9 cerebral edema, 30 hyperthermia, fourteen suicide/accident, 22 unknown
What are the effects of ecstasy mixed with other substances
ecstasy is o>en mixed with other drugs or contains no MDMA at all
amphetamine, methamphetamine, caffeine, ibuprofen, ketamine o>en found in pills
some&mes taken deliberately with other drugs - Viagra (sextasy), LSD (candy flip)
Strangely, there is some evidence that Viagra may be neuroprotec&ve with respect to MDMA-induced neurotoxicity
European sources tend to have higher MDMA content than North American
What is the significance of paramethoxyamphetamine?
PMA - paramethoxyamphetamine - delayed reac&on but more potent and neurotoxic, also MAO inhibitor - causes increase in serotonin, dopamine
earned street name “death” and is linked to fatali&es in several countries
hypoglycemia, hyperkalemia (excess potassium in blood – can lead to heart stoppage) and hyperthermia
some&mes sold as ecstasy or mixed in
PMMA is the methamphetamine version of this and can be
just as toxic
What is legal ecstasy?
esp. in the UK, purchase of “legal” or “natural” ecstasy on streets, even from internet
what is it?
is it really legal? Now a schedule III drug in Canada
What is N benzylpiperazine
BZP is the predominant ingredient in these pills
it is not natural - synthe&c compound from a family used in plas&cs, pes&cides (deworming caZle), resins
liquid free-base form or pill
