Ecstasy/MDMA
Ecstasy/MDMA Overview
• MDMA = 3,4-methylene dioxy-Nmethyl amphetamine (Schedule 1)
• Shares properties of amphetamines
and hallucinogens
• Associated with electronic music
dance parties (“raves”)
• May have psychotherapeutic value
(entactogens, empathogens)
• Associated with 5-HT neurotoxicity
• “Ecstasy” often adulterated
(amphetamine, ketamine, PCP,
caffeine), may consist of 0 - 100%
MDMA
History
• Synthesized, patented by Merck (1912,
1914)
• Studied as appetite suppressant but never
marketed (50s and 60s)
• Researched by Army intelligence as potential
truth serum (50s)
• Limited recreational use (60s)
• Psychotherapeutic use (mid-late 70s): called
“penicillin for the soul”
• Use leaks out to expanding recreational useacquires name of Ecstasy (early 80s)
• DEA places MDMA in Schedule I (1985-88)
• Use spreads to Europe, becomes part of
raves, spreads back to U.S. (late 80s)
Hallucinogenic Psychotherapy Redux
“an easily controlled altered state of consciousness with emotional
and sensual overtones, and with little hallucinatory effect”
UC Berkeley biochemist/toxicologist Alexander
Shulgin, self-report after synthesizing and selfadministering 120mg MDMA, 1978
Combination of
• Stimulant effects
• Mild hallucinogen-like effects
• More unique emotional effects
MDMA Psychotherapy
• 1970s research appeared successful, but poorly controlled
• Advantages over hallucinogenic therapy:
–
–
–
–
–
–
shorter-acting
more introspection
greater intimacy/trust
reduced anxiety/depression
less altered perception
more stable body image and ego
• Current overseas research suggests decreased drug use,
other psychiatric improvements
Use of Ecstasy among 8th,10th and 12th graders
12
10
8
8th
10th
12th
6
4
2
0
95
96
97
98
99
'00
'02
'05
Perceived Harmfulness of
Obtaining Ecstasy
Reported by 12th Graders
80
70
60
50
% who
think
MDMA is
harmful
40
30
20
10
0
'00
'01
'02
'03
'04
'05
Methods of Ingestion
•
•
•
•
Orally
Snorted (Powder)
Smoked
Injected
• Effect lasts 3-6 hrs
• Average dose is 1-2
tablets (60-120 mg)
•
•
•
•
20 to 40 minutes
5 to 10 minutes
20 to 30 seconds
10 to 20 seconds
Acute Effects (cont)
 Mood (euphoria)
 Alertness (sympathomimetic)
 Heart rate, blood pressure,
body temperature
 Restlessness, locomotion
 Sensory intensity
 Fatigue, need for sleep
(insomnia)
 Appetite
 Empathy, communication,
talkativeness (empathogenesis)
 Feelings of sensuality, affection
(entactogenesis)
 Self-consciousness, fear,
embarrassment, defensiveness
 Nystagmus, jaw-clenching,
muscle tension (need for
pacifiers)
 Visual distortion, dizziness,
headache, nausea, vomiting
(more likely at higher doses)
Neurotoxicity
Raves
Raves
(GHB, Meth, K, Rohypnol, NO, LSD)
• Setting
– Club, Warehouse, Outdoors
– Psychedelic/Techno Décor
– Short notice
• “Tools”
– Pacifier/lollipops
– Masks
– Inhalants (e.g. Vicks)
– Glowsticks
Raves (cont)
• Music and Dance
– DJed electronica
– Usually fast (average 120
bpm) and high energy
• Philosophy
– “Technoshamanism” –
altering consciousness
through technology
– PLUR (Peace, Love, Unity,
and Respect)
Ecstasy experience
“The drug removes all your neuroses. It takes
away the fear of response. There is an
overwhelming sense of peace, you are at peace
with the world. You feel open, clear, tender. I
can’t imagine that anyone is angry under its
influence, or selfish or mean or defensive. You
have lots of insight into yourself, real insight,
which you hold on to after the experience is
gone”
Behavioral Effects
• Positive: mental stimulation, emotional warmth,
empathy towards others, general sense of wellbeing, decreased anxiety
• Negative/Undesirable: anxiety, agitation,
recklessness, nausea, chills, sweating, muscle
cramping, blurred vision, jaw clenching,
dehydration, high blood pressure, heart failure,
kidney failure, arrhythmia, loss of consciousness,
seizures, hyperthermia, hyponatremia (low
sodium levels)
Ecstasy-Viagra
• Clubgoers call a
combination of the two
drugs "sextasy" heightens sexual
experience.
• the two drugs are a
dangerous mix.
• can cause heart
problems and open the
door to sexually
transmitted diseases.
Pharmacokinetics
• Dose: ~ 80-160mg
(500mg – fatal)
• Route: Usually oral
(high bioavailability
from GI tract)
• Onset: 30-60 minutes
• Peak: ~1 hour
• Duration: 3-12 hours
Pharmacodynamics
• Indirect agonist for
– 5-HT
– DA and NE (less than 5-HT) – different from hallucinogens
• Mechanisms
– Block reuptake (5x amph)
– Reverse reuptake
– Others like AMPH?
Neurobiological Effects
1) MDMA increases oxytocin levels, which may strengthen
the therapeutic effects;
2) MDMA increases ventromedial prefrontal activity and
decreases amygdala activity, which may improve
emotional regulation and decrease avoidance, and
3) MDMA increases norepinephrine release and circulating
cortisol levels, which may facilitate emotional
engagement and enhance extinction of learned fear
associations.
DSM-IV Dependence Criteria by Pill Use
1-99 pills (n=387)
100-499 pills (n=178)
500+ pills (n=69)
100
p<.0001
p=.0014
p<.0001
80
p<.0001
p<.0001
60
p<.0001
40
p<.0001
20
0
Tolerance
Withdrawal
Takes substance in
larger amounts or
over longer period
Can't cut down
or control use
Much time spent
using/recovering
from use
Important
activities given
up for substance
Substance used
despite knowing it
caused physical or
psychological harm
rCBF differences between MDMA and placebo. Upper row: MDMA-induced increases in rCBF. a =
ventromedial frontal cortex (including orbitofrontal and ventral anterior cingulate cortex), b = cerebellum, c =
inferior temporal cortex, d = occipital cortex. Lower row: MDMA-induced decreases in rCBF. e = superior
temporal cortex, f = insula, g = Thalamus, h = pre-/paracentral cortex, k = left amygdala
Neurotoxicity
• Effect: destruction of 5-HT axons
• Suspected consequences
– Depression
– Personality changes (e.g. irritability)
– Cognitive impairment
• Verbal memory in particular
Neurotoxicity (cont)
• Possible mechanisms/factors
– Main candidate: Oxidative
stress
• Exhausted energy sources
• Free radical metabolites
– Cofactor: Body temperature
• Indices
– Tissue staining
– 5-HT and metabolite levels
– Reuptake transporter binding
THE END
5-HT Axons
Frontal
MDMA
MDMA
Methodological Issues
• Animal studies
– Route of administration
– Dose/Frequency
– Drug content
– Species differences
• Human studies
– Discussed in reader article
Use Statistics
• In 1998, 3.4 million Americans age 12+ (1.5%) had used
Ecstasy at least once
• Heaviest number users in ages 18 - 25 (1.4 million, i.e. 5%)
• From 1999 - 2000, use increased among 8th, 10th, and
12th graders but decreased from 2000-2005
• African-American students used less than white or
Hispanic students in 2000
Raves (cont)
• Ecstasy acute risks
–
–
–
–
Dehydration
Heat Stroke
Organ failure
Adulterants
• “Herbal Ecstasy”
– Natural stimulant (e.g. ephedrine)
– Similar acute risks
– Placebo psychoactive effects
Ecstasy “Hangover”
• Effects
– Depression
– Memory impairment
– Difficulty concentrating
• Possible causes
–
–
–
–
Neurotoxicity
Acute decrease in 5-HT levels
Concurrent drug use
Weekend contrast