MDMA

Question 1

SOME IMPORTANT DATES IN
IT’S HISTORY

Answer 1

• 1912
  – Merck filed patent for an anti-bleeding medication
  for which MDMA was precursor
• 1953
  – Army Chemical Center in US funded secret testing
  of MDMA re: use as espionage or brainwashing
  agent
• 1978
  – First published human study (Shulgin) —> cross b/t alcohol (free) and psychedelic -> advocate for it in psycho therapy to help people open up (induced introspection) – got people talking
• becoame widely used in therapy

Question 2

HISTORY CONT’D

Answer 2

• From Late 1970s to Early 1980s
  – Use of MDMA advocated in psychotherapy
  – WAS not scheduled or illegal drug, recreational use
  began*****

Question 3

HISTORY CONT’D
* Between 1984 and 1986

Answer 3

– DEA used law (re: public safety) to “temporarily”
place drug in Schedule I category
– Hearings attended by scientists, psychiatrists,
psychotherapists, lawyers argued risks and benefits –> useful in therapy (problem was all anecdotal evidence) No control used** –> does it advance psychology at all??
- to keep at schedule 1: finding that this drug causes holes in brain (prions), also found brain damage (neuronal death) in rats (but not with MDMA but with MDA–> the amphetamine aspect AS WELL AS being injected into rats at much higher amounts than an oral dose)

Question 4

• Between 1986 and 1988

Answer 4

– Numerous trials and appeals conducted on
scheduling of drug
– End result: classified as a Schedule I *****
- but appeals to use MDMA in therapy occured

Question 5

Between 1985 and 1986

Answer 5

– Recommendation: classify drug as Schedule III
– Recommendation ignored

Question 6

Mid 1980s

Answer 6

– Rave movement began
– Reportedly raves can involve up to 30,000 people
-

Question 7

ADME

Answer 7

• Taken orally (tablet or capsule) or intravenously
• or absorbed through snorting
• or parachuting
• sublingually –> can avoid first pass metabolism

Question 8

ADME

Answer 8

• Taken orally (tablet or capsule) or intravenously (75-100mg)
• can take up to 3 doses (300mg)
• Effects realized within 30 to 60 minutes
• Effects last 3-6 hours
• Half life of 8 hours (40 hours to MDMA to leave the body)
• Metabolized by specific enzyme in liver that is deficient in small percentage of white and asian populations (effects can last much longer)
• problems with purchasing at rave (tablets will have more substances in it) up to 70 diff substance can be foudn in MDMA tablet –> 2004 TB talks about purity of MDMA is not as much of a concern as it used to be
• there are testing kits (Dance Safe)

Question 9

Pharmacological Actions

Answer 9

• Inhibits Serotonin Re-uptake
• Induces Release of Serotonin
• Induces Release of Dopamine
• Increases NE levels
  increase oxytocin uptake

Question 10

Basic Behavioral & Psychological Effects

Answer 10

• Increased Wakefulness — > elevated levels of NE
• Increased Endurance –> NE
• Heightened Sense of Emotional Closeness to Others –> from increases oxytocin hormone and reduction of fear response (love drug–> ironic cuz it is an SNS stimulant so you cant get an erection or orgasm)
• Heightened Self-Awareness –> discuss and explain their feelings (therapy)
• Feelings of Peace and Tranquility –> empathogen and enactogen as classification

Question 11

Some Adverse Psychological Effects

Answer 11

• Psychosis-Like States UNCOMMON –> hallucination (not common but can occur), paranoia and fear (someone is after you), disorganized thinking or speech (tangential),
• advocates of E –> have a genetic vulnerability to the drug (emotions exprerienced could be triggerd by other response ) –> trigger for preexisiting condition within them
• Pronounced Anxiety–> not paranoia but highly anxious
• Depersonalization and Derealization NOT COMMON –> depersonil (feel like they are separated from rest of world (glass separating them), detached form environment
• derealiz: enivormnent seems meaningless, people dont look real (cardboard)
• adovcates: say they occur spontaneously in the everyday world
• Depression (variable duration and intensity) –> come down
• can range in intensity or severity (low mood) –> loss of pleasure
• length of dep cna be variable (can be one day w/ low mood to showing clinical depression for 6 months)
• longer lasting depression = damage to serotinergic terminals (take 6 months for damage to be resolved)
• Cognitive Deficits? –> chronic use causes impaired attention, concentration and memory
• studies show mild mem deficits in delayed mem , some studies who NO deficit
• poly drug users can worse mems
• poor control in controlling for fatigue and premorbid attention problems
• Sleep Disturbances–> 3 days- months
  -longer lasting sleep problems is accompanied by excessive dreaming and scary nightmares

Question 12

Medical Risks Associated with MDMA Use
* Hyperthermia (increase in body temps)
– Factors contributing to hyperthermia (2)

Answer 12

• Prolonged exertion, warm environment
• Elevated levels of serotonin
• common cause of death from hyperthermia: disseminated intravascular coagulopathy******* (DIC) –> get blood clots forming throughout the body and they burst (internal bleeding!!!!)

study by Kalant (2001) et al: of 87 deaths 30 were due to hyperthermia
- most common cause of death of MDMA
- but if you get quick medical attention you will not die
- repetitive movement in club from NE, you can disregard the warning signals
- 9 were due to swelling of brain (hyponatremia)
- 4 were due to liver damage

Question 13

Medical Risks Associated with MDMA Use
* Acute Hyponatremia

Answer 13

– Low plasma sodium level due to dilution of blood with water
– Occurs as a result of: (2)
* Excess water intake (repetitive behaviour from MDMA) –> overdo it
* MDMA caused secretion of anti-diuretic hormone (ADH) , which promotes water retention by kidneys

Question 14

Medical Risks Associated with MDMA Use

Answer 14

• Hepatitis (NOT COMMON) 50 reported cases all time –> damage and inflammation of liver

– Severity ranges (mild to severe)
– Repeat users may suffer from jaundice
- if liver damageis substantial –> can lead to death
- 4/87 from kalant

Question 15

Tolerance

Answer 15

• Tolerance develops to most of the positive
  effects in a few days
• Tolerance dissipates within a few days to a week
• With chronic use, amphetamine like effects are effects primarily seen –> increased endurance, alertness
• MDMA (mix of mescaline and amph) –> increased endurance, wakefulness

Question 16

Dependence

Answer 16

• Dependence issue “cloudy”***
  – Animal studies suggest dependency potential
  – animals will engage in task to get extasy and then Will self-stimulate/administer (Ratzenboek et al 2001, Schenk et al, 2003, Fanlegussi, 2007)
  – However, greater self-stimulation seen with other drugs than extasy (coke or nic vs MDMA)

– Few cases of “severe withdrawal symptoms” in humans
–> hav been cases that are consistent with dependance –> meets criteria for dependance disorder

– One of the first published studies (Janzen, 1999) reported three cases met the criteria for dep
1. 19y/o night club owner –> convulsions later still foudn it difficult to stop (aka dependance)
2. 30 y/o male poly drug user (not best study from doing more drugs) –> gained access to a large amount of M powder (intravenously admin 4x per day)
3. 38 y/o male w/ PTSD –> symptoms was emotional detachment (made him feel more connected with people ) –>
- collectively they all showed tolerance (increase in # of tablets)
- spent more time in using
- had more recover time (ex: night club owner would crash in the week days and then would feel better on weekends)
- relationships broke down
- lost jobs
more social isolated
- mild physilogical withdrawal symps
- fatigue
- weakness
- anadonia (loss of pleasure in normal pleasure activities)

– Tolerance, increased time using and recovering, neglected other activities , unsuccessful attempts to case use, mild physiological “withdrawal” symptoms

Question 17

Dependence

Answer 17

• Examples of studies showing users meeting
  criteria for lifetime Substance Dependence
  Disorder/Estascy Dependence Disorder

– Topp et al (1997) –> 64% of 185 “regular” ecstasy users were dependant
- symptoms showed
- compulsive use despite problems
- giving up important actiivtes
- couldnt withdraw

– Hansen and Luciana (2004) –> 53% of 26 US University students were dependant

– Parsons et al (2009)
– New York night club attendees–> 19% were dependant (more % met criteria for cocaine)
- 400 sample size

– Cottler et al (2008)
– 43% of 52 users were dependant

Question 18

Dependence

Answer 18

• Question re: withdrawal symptoms reflective
  of a true abstinence syndrome vs “come-
  down” effects

– Neuroadaption OR recovery phase
* e.g., Up or down regulation of receptors, damage to serontergic terminals vs “crash”

Question 19

If there is withdrawal, what does it
look like?

Answer 19

• autonomic hyperactivity (physical restlessness) , sweat, heart palps
• psychomotor agitation or retardation; insomnia or hypersomnia; (falling or staying asleep, long periods of time)
• fatigue; nausea, vomiting, or changes in
  appetite; (apatite very notable)
• transient visual, tactile, or auditory
  hallucinations or illusions; (canmeet criteral for HPPD)
• muscle aches;
• Anxiety; irritability, low mood, vivid, unpleasant dreams

Question 20

If there is psychological
dependence what does it look like?

Answer 20

might be biological predisposition to chronic use

Question 21

Dependence
When I start selling my stuff, my own apartment stuff, then that’s when I knew I got it out of control. And to this point now, I’m like
okay, I make enough money to buy it . . . I have enough in the bank right now to just sit there and it’s like I am a user, but I don’t think I am that bad of a user.

• She later said

Right now, I think it is still a little out of control, not as much out of control as me pawning and selling and prostituting myself for money, none of that. But, now that I sit back and actually think about it I am losing a little control. (Singer and Schensul, 2011)

= compulsive use of drug!!

Question 22

Dependence (excerpt from intreview)

Answer 22

• E: Have you ever tried quitting Ecstasy since
  you’ve really been on it?
• P: I’ll be saying I ain’t gonna take no more pills
  but I always end up taking back another pill
• E: Okay. Do you think it’s addictive to you?
• P: Yep
• E: Why do you think it’s addictive?
• P: Because I always be wanting to take an E pill
  (Singer and Schensul, 2011)

= compulsion

Question 23

Trajectory of Ecstasy Dependence

Answer 23

• Von Sydow et al (2002)
  – 93% decline in use 3 years later
• 50% no longer using drugs
• 43% still using but not as much
• not a long lasting dependin (93% decline in use 3 years after)
• reevaluated (53% stopped)
• 43 % still using but not as much

Question 24

combo of psychedelic (mescaline) with amphetamine