MDMA: (Ecstasy)
Chemistry, route of access and effects reported by
users.
By: Courtney E. Allen
Ecstasy is derived from Methamphetamine and Amphetamine.
Belonging to a class of drugs known as "designer drugs".
Designer drugs are created by changing the molecular
structure of an existing drug to create a new substance.
Methylenedioxymethanphetamine (Ecstasy) is a synthetic drug
that acts simultaneously as a stimulant and a hallucinogen.
The emperic formula for Ecstasy is C11 H15 NO2. In 1914
Merck was issued a patent for MDMA, but the toxicology of
this compound wasn't studied systematically until the early
1950's. In 1985 MDMA was classified as a schedule I drug. It
was suggested that MDMA, in a controlled, therapeutic
setting, promotes confidence and trust between patients and
therapists (1).
The production of this drug is fairly straightforward and
easy to concoct. Sarole, the active ingredient in nutmeg is
used to prepare the starting Ketone (3,4 Methylenedioxy
phenylopropane) by oxidizing with hydrogen peroxide in an
acid medium. The compound is then combined with Methylamine
in Alcohol. Alcohol powder treated with Mercuric chloride is
then added and boiled for many hours. The MDMA substance can
then be distilled off under pressure (2).
MDMA can be swallowed, smoked, injected or "snorted".
When Ecstasy is swallowed (usually in a capsule form) it has
three main routes of access. The first access is through the
gastrointestinal system. The second can be held under the
tongue where it is absorbed sublingually. Lastly it can
remain in the mouth where it is absorbed through the mucus
membrane. Once the drug has entered the body it must under
go extraction by the liver before it may feasibly reach the
circulation system. Once the drug reaches the systematic
circulation it is transmitted through the blood vessel wall,
to the brain, to the blood brain barrier. The blood brain
barrier is a semipermeable barrier produced by the cells in
the walls of the capillaries in the brain. After the initial
circulation of the drug into the blood brain barrier the drug
is then dispersed into other parts of the body where it has
no pharmacological activity (3).
Ecstasy is known to stimulate the Central Nervous System
and produce hallucinogenic effects. These effects are
usually characterized as a total consciousness and pure
connection with the universe. Ecstasy is the designer drug
of choice by most college students at present time because
the effects enable the user to stay awake with endless
amounts of energy for up to 8 hours (4).
Survivors of MDMA compare the feelings they experience
while under the influence of the drug with the feeling of
being in love. These feelings will usually be empathy,
openness, peace and caring. It has been reported to
transform personal relationships and boost self-esteem. It's
effects have been described as opening people up to their
intuition and feelings leading to expanded sense of self-
awareness and empathy for others. Many users as well as
survivors claim that their experience or "trip" with Ecstasy
had changed their life in profound ways (for the better). As
well as the positive effects experienced by users of Ecstasy
there are also the negative side effects. These side effects
range from psychiatric disturbances, including panic,
anxiety, depression and paranoid thinking. Survivors of
Ecstasy describe their feelings as, "Lost within one's own
mind, with no control over reality."
MDMA is also better known as the designer drug that
kills many people. It is not necessarily the drug itself
that kills, but the effect of the drug on the body. As
mentioned earlier Ecstasy is the choice drug of many college
students at raves, (all night dance parties) where users
dance straight for many hours. Many deaths associated with
MDMA are caused by dehydration. In conclusion it is very
important for users of Ecstasy to always drink plenty of
liquids while under the intoxication of the drug. After all
it is your own life you're dealing with.
REFERENCES:
1.Kinfe, Walker and Barnett. Cocaine, Marijuana, Designer
Drugs: Chemistry, Pharmacology, and Behavior. CRC press,
Florida. 1989. (2)
2.Snyder, Solomon H. Drugs and the Brain. W.H Freeman and
Company, New York. 1986.
3.Votava, Zdenek. Psychopharmacological Methods. The
Macmillan Company, New York. 1963. (3).
4.Mattews, Robert. JN: Pharmacology: Biochemistry &
Behavior;1989. Vol 33
5.Karch, Steven. The Pathology of Drug Abuse.CRS Press,
Inc,1993.(1)
6.Fischer, C.;Hatzidimitriou. Reorganizing of ascending 5HT
axon projections in animals previously exposed to
recreational drug 3,4 methelenedioxymetham phetamine
(MDMA,"Ecstasy"). Journal of Neuroscience. 15:5476 5485,
1995.
7.157 Seritonin Nuerotoxcity after MDMA: A Controlled Study
of Humans by George Ricaurte et al. 1994 Neuropsychology in
press.
INTERNET REFERENCES
8.http://www.drugfreeamerica.org/ectasyfaqs.html
9.http://www.medicaldevices.org/releases/Website.html
10.http:www,psykedelbok.se/ecstacy mdma.html
11.E is for Ecstasy by Nicholas
Saunders(nicholas@ecstasy.org) (4).
MDMA
Neuron and Neurotransmitters
By: Adrian Ramirez
This section of the group report will discuss three
aspects of MDMA: neurotransmitters involved, part of neuron
affected, and its potential changes. The neurotransmitter
that is primarily affected by MDMA is serotonin. But before
I get into that, let's take a look at what serotonin is and
what role it plays so that you can better understand where
MDMA comes into the picture.
Serotonin is a neurotransmitter that is found in the
brain (2%) and other places like blood platelets and the
gastrointestinal tract muscles (98%) (6). Like all other
neurotransmitters, serotonin carries messages between
neurons. In a presynaptic neuron an all or none impulse
activates and opens the calcium channels of a terminal bouton
to let calcium ions enter. This causes synaptic vesicles,
which contain the neurotransmitter, to fuse with the membrane
of the terminal bouton and release the neurotransmitter into
the synaptic cleft. As it diffuses across the synaptic cleft
a couple of things happen to serotonin: some of it binds to
the receptors of a post synaptic membrane, some of it is
destroyed, and some of it is sucked back into the neuron that
released it by a process called reuptake (1).
MDMA has been shown to inhibit the reuptake of
serotonin, which means that it remains in the synaptic cleft
and the message gets amplified (9). A reduction in the
density of serotonin uptake carriers is exhibited, and this
has shown to cause a loss of serotonin nerve terminals (8).
MDMA has also been found to cause an increase of serotonin to
be released by the terminal bouton into the synaptic cleft.
So not only would serotonin not be taken away from the
synaptic cleft, but there would be more of it being
released in the first place (9).
When a person is on MDMA serotonin levels are high
because neurons are working extremely harder than they
normally do. But even though serotonin levels are high
while on MDMA, the high is over a day or two later and there
is a significant decrease in serotonin levels. The neurons
are put to work for so such an extended amount of time that
naturally in the next couple of days the neurons of that
individual produce a low serotonin count. Regular users can
drop a third in the level of serotonin derived chemicals in
their spinal fluid (9). Furthermore, nonhuman primates have
shown to have a reduction (21%) in serotonin in the thalamus
and a reduction (16%) in the hypothalamus two weeks after
dosing on MDMA (10).
In another study, rats displayed progressive decreases
of tissue levels of serotonin and its metabolite 24 hours
after a single injection of a high dose (8). Studies on rats
have also shown that MDMA selectively destroys serotonin in
the brain stem, cortex, striatum, and hippocampus (3).
Serotonin levels in the brain reduced 73% to 94%, and 42% to
45% in the spinal cord in a study where 55 squirrel monkeys
were given MDMA (5mg/kg) twice daily for four days (8).
The other neurotransmitter shown to be significantly
affected by MDMA is dopamine. When there are low marked
serotonin levels, from the MDMA high being over, dopamine is
absorbed by the serotonal receptors. Since dopamine
shouldn't be here, a toxic metabolite created by an enzyme
breaks it down. This causes damage to the terminals of the
nerve cell. In one study, decreased levels of dopamine in
the striatum of rats emerged for a few hours after MDMA doses
were given (6). In another study, dopamine, serotonin, and
norepinephrine levels were measured in the striatum,
neocortex, hippocampus, and hypothalamus after
rats were given a dose of MDMA. Dopamine and norepinephrine
levels were reduced only from the highest doses, but
serotonin levels were reduced at a low dose in all regions.
In addition, it reduced serotonin uptake two weeks after
administration of MDMA (3).
As you can see from some of the effects that MDMA has on
neurotransmitters, the neurons involved in the activity of
those neurotransmitters are also very much affected. It has
been found that in doses known to evoke the MDMA
psychological syndrome in man, MDMA decreases the firing rate
of some serotonergic neurons in rats (5). In a series of
studies conducted with rats and nonhuman primates, doses
slightly higher than those taken by humans significantly
damaged serotonergic neurons. It was also reported that 12
to 18 months after the brains of squirrel monkeys had been
damaged by MDMA, nerve fibers that produce serotonin had
abnormally regrown in some areas of the brain and had failed
to regrow at all in others (2).
Silver staining techniques have also revealed evidence
of neuronal damage. Abnormal inclusions within the cell
bodies of dorsal raphe nucleus cells were found in rhesus
monkeys injected with MDMA (5mg/kg) twice daily for four
days. Fine fibre serotonergic axons, in both rats and
monkeys, seen through immunostaining were mostly swollen and
broken up in pieces. Another method, called
immunohistochemical staining, has shown that MDMA decreases
the number of serotonin antibody positive nerve fibers. Most
vulnerable to MDMA were the fine fibre type ascending axons
from the dorsal raphe nucleus (8).
In contrast to prior evidence, long term effects of MDMA
are less notable. Pictures of serotonergic neurons of a
brain cortex appear to show the normal amount of serotonin
staining one year after dosing MDMA. This suggests that there
is no decrease in the serotonin levels of this brain region
of the rat one year after exposure (11). Studies conducted
by the US Environmental Protection Agency (EPA) on rats and
mice have not observed any damage to serotonergic neurons due
to MDMA. Furthermore, senior researchers for the US EPA
express that prolonged decreases in brain serotonin cannot be
grounds to conclude that actual neuronal structures
themselves are destroyed. This means that MDMA can decrease
the levels of serotonin without destroying serotonergic
axons. Studies used to mark whether serotonergic axons are
still functioning after serotonin is drained have not yet
been conducted following MDMA exposure to rats or primates
(7).
There is no direct evidence confirming that MDMA
decreases serotonin in humans. Spinal taps, brain scans, and
injections of radioactive substances would have to be used in
studies to directly measure whether or not it causes
serotonin reductions. This is more dangerous than MDMA
itself. The best indirect evidence on humans is a study done
by Dr. McCann and Dr. Ricaurte in which the long term effects
of MDMA on experienced users was evaluated. They found that
a group of users, who used the drug an average of 95 times,
had about 32% less serotonin metabolite in their
spinal fluid on average than the control groups. Being that
the range of serotonin metabolites in spinal fluid is quite
large, 32% is relatively not a significant
difference (10). No differences were observed in a small
scale study where researchers compared cerebrospinal fluid
levels of five MDMA users to controls (8).
A couple of other factors to consider after reading this
section is that findings from nonhuman studies on MDMA are
being used to form hypothesis about it's effects on humans.
However, no definite conclusions are being made because there
are significant species dependent difference in response to
any drug. Rats, mice, and primates all respond differently
in some studies. So far primate studies
on MDMA aremost useful in assessing it's effects on humans,
but even these findings have to be validated by human
research (4).
REFERENCES:
1. Sabol, Karen. JN: Psychopharmocology; 1995 Sept. Vol 121
(1), pp. 57to65.
2. Fischer, C., Hatzidimitriou, G., Katz, J., Ricaurte, G.,
Wlos, J. JN: Journal of Neuroscience; 1995. Vol 15, pp.
5476to5485.
3. Glasgow. JN: Physiology and Behavior; 1995 Nov. Vol 58
(5). pp. 877to882.
4. Gold, Mark S. MD., Miller, Norman S. MD. March 1994. "LSD
and Ecstasy: Pharmacology, Phenomenology, and Treatment."
Psychiatric Annals, Vol 24 (3). pp. 131to133.
5. Lum, Janet T., Palmer, John R., Piercey, Montford F. JN:
Brain Research; 1990 Feb. Vol 526, pp. 203to206.
6. Sabol, Karen. JN: Psychopharmocology; 1995 Sept. Vol 121
(1), pp 57to65.
7. www.ecstasy.org/interviews.html, 9/22/98. "Interviews with
two foremost researchers into neurotoxity who hold opposing
views." pp. 1to8.
8. www.esctasy.org/leon.html, 9/22/98. "Toxicity of Ecstasy."
pp. 1to21. Leon van Aerts, Ph.D.
9.www.erowid.org/entheogens/x/x_media.shtml, 9/11/98. "X:
Media Coverage. Better Than Well." pp. 1to3.
10. www.maps.org/news-letters/v06n1/06108 neu.html, 9/22/98.
"MDMA Neurotoxicity: New Data, New Risk Analysis." pp. 1to9.
Rick Doblin.
11.www.maps.org/newsletters/v06n1/06113neu.html, 9/22/98.
"MDMA Neurotoxicity: Commentary on Article by Ricuarte and
Colleagues." pp. 1to2. James P. O'Callaghan, Ph.D..
Complete Physiological and Side effect changes
By: Joseph Segal
The average dose of "ecstasy" ranges from 100 to 150
milligrams (1). There are two major effects of MDMA the
mental effects and the amphetamine effects. The mental
effects are emotional closeness, insight, improved
communication, and empathy. Users of MDMA may be attracted to
the drug because they feel that it has the ability to
increase empathy and self insight. Advantages of MDMA over
traditional psychedelics are less distortion of sensory
perception and fewer unpleasant emotional reactions (2). Many
individuals describe strong euphoric and sensual effects
associated with MDMA. Most users describe a dramatic drop in
defense mechanisms and increased empathy towards others.
Combined with the amphetamine effects this may heighten or
intensify intimate communication. Another desired effect of
MDMA is that clarity of thought and concentration is believed
to be increased. This may be due to the high level of
serotonin that the drug increases. Because nerve endings may
become numb as a result of the drug, the feeling of enhanced
sensuality may be because all things touched may feel softer
than normal, but of course when nerve endings are numb
tactile senses actually desensitize (7).
With increased use of MDMA the desired mental effects
tend to decrease because the serotonin has been overused.
Therefore, less serotonin exists in the terminal for MDMA to
take advantage. Since serotonin is being overworked and its
functions are involved with pleasure, a person may feel
pleasure in nearly every way possible for example: dancing,
touching, communicating and thinking (4).
Of course there are negative and undesired mental
effects. These effects are psychiatric disturbances, which
include panic, anxiety, depression and paranoia.
The physiological effects tend to appear within 20-60 minutes
after ingestion. The user generally experiences a "rush" of
energy caused by increased heart rate. This is described as
mild but can give a sense of well being. After this surge in
energy, the high begins to level off which lasts 2-3 hours,
the user gradually begins coming down, and this results in a
feeling of fatigue. The feeling of fatigue or as some would
say "relaxed" causes users to be unaware of the stimulant
side effects (7). Another physiological effect of people who
over abuse MDMA seem to experience a lower sexual drive. The
other undesirable physiological effects are caused by the
amphetamine part of the drug. These effects are high blood
pressure, insomnia, high pulse rate, dilated pupils, and
rapid oscillation of the eyeballs (nystagmus) (5). If dosage
is increased the undesired effects increase, but the desired
euphoric effects decrease with higher dosage. The amphetamine
effects remain potent and the mental effects drop off with
repeated use. Other undesired physiological effects of MDMA
may include respiratory distress, edema, hypothermia, and
temporary kidney stoppage (oliguria). Many users also claim
to be severely dehydrated while using MDMA. This may be due
to the oliguria. The more common physiological effects are
muscle tension, sleep problems, sweating, chills, blurred
vision, fainting, nausea, hallucinations, tremors, and
increased pulse (8).
Side effects while using this drug are quite common
especially with the amphetamine compound of MDMA. These side
effects are dilated pupils, tension in the jaw, grinding of
the teeth, and dry mouth. Many users claim headaches while
under the influence of this drug, with another common side
effect being aching muscles (3). Because of the over
productivity of serotonin, the days after will show a
depletion of serotonin. Low serotonin may result in
depression. MDMA stimulates the central nervous system and
produces hallucinations. Unfortunately, there may be more
severe side effects. For example, studies with rats and
monkeys have shown that the use of MDMA may reduce the level
of serotonin in the brain by as much as 90% for at least two
weeks (2). Serotonin effects thinking, mood, sexual function,
sensitivity to pain and eating habits. So continued abuse of
this drug may cause dysfunction in either one or all of these
areas (8).
In conclusion, MDMA otherwise known as Ecstasy is a
designer drug, which plays many psychological and
physiological effects on the body and mind. Evidence has
shown various results which display what the drug can do,
specifically inside the brain. Keep in note that further
evidence has to be found in order to make any further
conclusions.
References:
1. Glasgow, JN: Physiology and Behavior; 1995 Nov. vol. 58(5)
pp877-882
2. Knife, Redda. Cocaine, Marijuana, Designer drugs... CRC
Press; Ann Arbor, Michigan, 1990.
3. Sabol, Karen. JN: Psychopharmacology; 1995 Sept. Vol
121(1) pp57 65
4. Smith, Reynard. Textbook of Pharmacology. W.B. Saunders
co. Philidelphia, PA. 1992.
5. Palfai, Tibor. Drugs and Human Behavior. Brown and
benchmark. Madison, WI. 1996.
6. Internet. www.flashback.se/archive/mdma.report
7. Internet. www.drugfreeamerica.org/ecstasy_faqs.html
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Copyright © 1995, Dr. John M. Morgan, All rights reserved -
This page last edited October 7, 1998
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