Ecstacy

Question 0

What are some other names for ecstasy?

Answer 0

E, love drug, XTC, Adam, X

Question 1

What is ecstasy

Answer 1

 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

Question 2

Explain the administration of ecstasy

Answer 2

 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

Question 3

What are the effect on mood of ecstasy? (Psychological)

Answer 3

 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

Question 4

What are the physiological effects of ecstasy

Answer 4

 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

Question 5

How long does the high form ecstasy last?

Answer 5

 high lasts for 2 - 3 hours

Question 6

What is the mechanism of ecstasy in relation to amphetamine

Answer 6

 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

Question 7

Describe the mechanism of ecstasy

Answer 7

 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

Question 8

Explai ecstasy effect on dopamine and serotonin levels

Answer 8

 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)

Question 9

What are some other targets of ecstasy?

Answer 9

 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

Question 10

How is ecstasy metabolized

Answer 10

 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

Question 11

Explain tolerance with ecstasy

Answer 11

 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

Question 12

What are some damages caused by ecstasy

Answer 12

 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

Question 13

Describe serotonin syndrome

Answer 13

 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

Question 14

Describe hyperthermia and relation to ecstasy

Answer 14

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

Question 15

Describe hypo atresia and relation to ecstasy

Answer 15

 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)

Question 16

Describe ecstasy effect on neuronal death

Answer 16

 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

Question 17

Describe ecstasy effect on neuronal loss in humans

Answer 17

 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%

Question 18

Describe mechanism of toxicity with ecstasy

Answer 18

 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

Question 19

Describe deaths with ecstasy

Answer 19

 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

Question 20

What are the effects of ecstasy mixed with other substances

Answer 20

 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

Question 21

What is the significance of paramethoxyamphetamine?

Answer 21

 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

Question 22

What is legal ecstasy?

Answer 22

 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

Question 23

What is N benzylpiperazine

Answer 23

 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

Question 24

What is the mechanism of BZP

Answer 24

 levels of synap&c dopamine, noradrenaline and serotonin increase
 dopamine and serotonin are increased in the nucleus accumbens
 produces behaviours in animals that most closely resemble amphetamines

Question 25

What are he diners of BZP

Answer 25

 New Zealand emergency room study:
 19% of those admiZed due to BZP overdose had seizures, some not star&ng un&l 8 hrs a>er inges&on, 3 pa&ents were cri&cal
 some had cardiac events
 some had low blood sodium

Question 26

What is TFMPP

Answer 26

 TFMPP when added to BZP produces an effect that most closely mimics Ecstasy
TFMPP is an agonist at 5HT1 and 5HT2 receptors and seems to  study of transmiZers in rat brain shows this mixture produces

trigger serotonin efflux through the serotonin transporter
similar effects as ecstasy
 this study showed that several rats went into convulsions

Question 27

Explain the effects if BZP and TFMPP on dopamine and serotonin levels on the NA

Answer 27

BZP poor at increasing 5HT release
TFMPP better at increasing 5HT release
Together both produce synergistic effect