BIOLOGICAL BASIS OF BEHAVIOR

Psychology 321                     	                   
Spring, 2005					HGH 225
Dr. John M. Morgan                 	MWF, 8am to 9:00                                                   


Chemistry/ Synaptic Transmitters Involved/ 
Part of the Neuron Affected
Kristy Gauthier

	MDMA, otherwise known as the designer drug ecstasy, X, XTC, 
Adam (MDMA), Eve (MDEA), E rolls and many others generic terms, 
is a street drug that most people associate with a feeling of 
physical stimulation. This drug has a normal dose of about 50 to 
300mg and can vary in color and shape depending on the maker. 
Most bootleg drug producers like to put a trademark stamp on the 
pill, which consists of many different designs. MDMA is 
administered orally and is absorbed through the gastrointestinal 
track where it travels up to the brain, which results in a high 
within about an hour. The high from one pill can last up to six 
hours. After administration of the drug is when the brain begins 
the release of the neurotransmitters serotonin and dopamine. A 
pill of ecstasy can also include other substances like 
amphetamine, ephedrine, caffeine, ketamine and sometimes 
substances that are unidentifiable to chemists. This can cause 
side effects that are beyond the scope of this research. What we 
do know is that MDMA is an organic molecule, which enables the 
molecules of MDMA to inhibit some of the neurotransmitters in 
the brain. Let us take a deeper look into that chemistry.
The chemistry of ecstasy, which we will refer to as MDMA, 
has been researched, by scientists, since the late sixties and 
what they have uncovered is very interesting. Scientists have 
found that, overall; MDMA begins with an organic root and ends 
up being a potentially dangerous drug, 3,4-methylenedioxy-n-
methylamphetamine. MDMA is based from an oil called safrole, 
which is derived from the sassafras root. Many pharmacologists 
and illegal manufacturers have used safrole as a starting 
material for many medicines and drugs because it is easily 
accessible and inexpensive.  Therefore, it is not surprising 
that this is the base for MDMA. As for most organic molecules 
MDMA consists of H (hydrogen), N (nitrogen), CH3 (a methyl 
group) and oxygen atoms, which ends up making C11H15NO2.  All of 
these molecules, including the base of the safrole, are organic 
which makes MDMA an organic molecule. When combined to make MDMA 
they act like an amphetamine (look almost identical to 
methamphetamine in there chemical brake down) to the body with 
its psychedelic reaction, which is why MDMA is usually 
classified as an amphetamine. When examining the MDMA molecules 
scientists found that the MDMA has two types of molecules that 
are exact mirror images of one another. It has been described as 
a right hand and a left hand, both being he same, but you would 
not be able to fit your right glove on your left hand. This is 
known as "optical isomers". 50% of the MDMA molecules are one 
type and 50% are the other type, (right and left) which is 
labeled as a racemic mixture of molecules. Scientists have found 
that one half of the molecules are (+) positively charged and 
the other half are (-) negatively charged. Both can be active in 
the cell at the same time. The two different types of molecules 
interact differently with the receptor cites in the different 
types of cells in the brain. The (-) molecules of MDA have been 
found to have long lasting effects that resembled LSD where the 
(+) of MDA have been found to have shorter lasting effect less 
like LSD. When the N-CH3 group is added on to make MDMA it 
looses its LSD like effect but the neurotransmitters released is 
still the same. Of the molecules one half of the them activate 
the brains serotonin receptors and the other half get taken up 
into the axons of the brains neurotransmitters and force these 
sites to released all of there stored up serotonin and dopamine 
into the synapse between cells, which will be explained in more 
depth later in the essay.  
	Serotonin and dopamine are both neurotransmitters in the 
brain and both of the neurotransmitters are effected buy the use 
of MDMA. What MDMA does to these neurotransmitters is provoke 
the release of both serotonin and dopamine and at the same time 
block the serotonin reuptake in the neurons.  MDMA also acts as 
a blockade to many other neurotransmitters (like an MAO 
inhibitor) but much less than it does these two. Most of the 
action provoked by MDMA takes place in the presynaptic cells and 
when taken up into the cells the MDMA affects the cell's axon. 
In the paragraphs that follow I will explain the actions that 
MDMA takes on the neurons and the effects that it has in the 
cells.
	Serotonin is found in the cytoplasm and the vesicles of the 
cell and it is released into the synapse when the cell becomes 
excited.  When it is released from the postsynaptic cell, 
serotonin can bind to serotonin receptors located both 
postsynaptically and presynaptically. After some time serotonin 
stops binding and is loose in the synapse again. At this point 
serotonin can either be recycled through a transporter in the 
presynaptic cell, it can be changed into something else by an 
MAO inhibitor or it can dissolve. When it is recycled the 
serotonin binds to the transporter and changes shape and 
transports the molecule into the cell where it is released into 
the cytoplasm.  The transport then reorganizes itself to enable 
it to accept another molecule. There are many drugs that block 
the reuptake if serotonin, which enables the cell to recycle any 
serotonin that has been released and makes the effect of the 
serotonin, which has already been released, longer. MDMA does 
not block the transport locations, since it is a similar size to 
serotonin. What is does is bind to the presynaptic transports 
and is taken up in the cell. After it undergoes the 
reconfiguration in the axon, similar to that of the serotonin, 
it is released into the cell. At this point the cell is able to 
bind the serotonin in the cytoplasm and move it back thought the 
transport into the synapse and this is when more MDMA can bind 
from the synapse. This is how the synapse becomes flooded with 
serotonin, because MDMA replaces it in the neurons. After a few 
hours of this all of the serotonin is dispersed and eventually 
is absorbed in the brain. Ironically MDMA inactivates the enzyme 
that synthesizes new serotonin; therefore the cells cannot make 
new serotonin. This results in low levels of serotonin in the 
body, which is associated with depression. After the drug wares 
off and the brain has time to regenerate the serotonin lost the 
levels are back to normal. This can take about 24 hours. The 
higher the dose and number of times MDMA is taken in a row the 
longer it takes the brain to regenerate the levels of serotonin. 
	Along with serotonin MDAM also causes the release of 
dopamine in the brain. Although it releases much less than 
serotonin this still has a major effect on the brain. This is 
done the same as serotonin by blocking the receptor sites and 
releasing dopamine from the postsynaptic cell into the synapse. 
Scientists have found that the release of dopamine is a reaction 
to the release of serotonin. Therefore when the serotonin is 
released into the synapse by the MDMA then the dopamine 
releasing cells are stimulated causing them to release the 
dopamine neurotransmitter into the synapse. (Nash and Brodkin 
1991). Scientists have proven this by giving MDMS to mice that 
do not have the serotonin transport. The result is MDMA has no 
effect on the hyperactivity of the mice, which is how scientists 
measure dopamine. When giving the drug to mice that have an 
increased level of serotonin transports, the result is a greater 
increase in dopamine released into the synapse. (Gudelsky and 
Nash 1996). 
	It is believed that dopamine is released through the 5-HT2 
receptor sites since when this site is activated with no MDMA 
present it results in increased dopamine levels in the brain. 
This site is also correlates with the psychedelic effects that 
most users of MDMA report. Another site that has been correlated 
with the use of MDMA is the 5-HT1B site. This site in the brain 
is where calmness is produced. There have been many studied done 
on rats and the what is found is that when this site is activated 
the rats produce increased locomotion. Scientists have also found 
that when rats become tolerant to the rug at the same does, the 
5-HT1b site does not respond. Scientists have also found that 
rats that are conditioned to press the button when MDMA is given 
to them cannon distinguish between MDMA and 
trifluromenthylphenylpiperazine (TFMPP), which is a drug that 
activates 5-HT1B. This shows the relationship between MDMA and 
the 5-HT1B site. What I have shown in this essay is the chemistry 
of MDMA, the route of access, and where it affects the cell to 
release serotonin into the synapse.
	MDMA is a drug that has been popular for many years. What 
scientists have found about the chemicals involved and the rout 
that this drug takes in the brain is profound. There are many 
other aspects that we will continue to discuss in this report 
that will help summarize all of the effects that can be derived 
from this drug. 
	
Inhibitory or Excitatory Potential Changes/ 
Affected Ion Channels
Julia Rose

	"MDMA affects the brain by increasing the activity of at 
least three neurotransmitters (the chemical messengers of brain 
cells): serotonin, dopamine, and nor epinephrine" (The Brain's 
Response to Hallucinogens). This increase in activity can be 
either excitatory or inhibitory in nature depending on the 
neurotransmitter involved and which part of the reaction to the 
drug is taking place. Every area of the brain containing 
serotonin, dopamine, and/or norepinephrine is affected by MDMA, 
but the serotonergic and dopaminergic pathways are principally 
affected. This includes the neocortex and much of the limbic 
system. Within the limbic system, the hypothalamus, basal 
ganglia, amygdala, and hippocampus are affected. In the reward 
center, the nucleus acumens, a place where dopamine neurons are 
prevalent, is affected (Hallucinogens). 
	In each part of the brain, action potentials or inhibitory 
responses to MDMA cause the side effects felt by users. The 
neocortex is responsible for memory and altered perceptions, 
while the limbic system influences changes in moods, emotions, 
and feelings of anxiety. The hippocampus is also responsible for 
memory, while the nucleus acumens is said to be responsible for 
feelings of pleasure or the reinforcing effects of MDMA. It is 
important to realize that all the pleasurable and not so 
pleasurable behavioral and physiological effects of MDMA are 
occurring because neurons within the cell bodies of our bodies 
are reacting to the foreign stimuli.    
	When MDMA crosses the blood brain barrier it begins to 
affect presynaptic neurons containing the neurotransmitters 
mentioned. It causes repeated EPSPs in addition to the 
spontaneous firing rate, which create an action potential 
releasing serotonin, dopamine, and norepinephrine from vesicles 
in the terminal boutons into the synapse (exocytosis). Once in 
the synapse, MDMA binds to receptors on the postsynaptic neuron 
and causes a decrease in its firing rate. The presence of so 
much serotonin as well as MDMA activates many receptors on the 
postsynaptic neuron
	There are approximately 15 different serotonin receptors, 
and the quantity of each type differs from person to person 
(Kalat 68). Because MDMA has an affinity for particular 
receptors and the quantity of those receptors can be so varied, 
the effects of MDMA are varied as well. This is why accounts 
from MDMA users change from person to person and from one use to 
the next. Whatever the quantity of receptors, MDMA binds to 
those it has an affinity for and causes the receptors to produce 
EPSP's. If enough EPSP's are sent to the cell body from the 
receptors then an electrical impulse will stimulate the release 
of more neurotransmitters into the synapse. It is the action at 
the serotonin synapses that are responsible for the 
hallucinogenic effects of MDMA. "…Ecstasy causes a sustained 
increase in the amount of serotonin in the synaptic space, 
leading to sustained activation of more serotonin receptors. 
This can produce an elevated mood (euphoria)" (Hallucinogens). 
	MDMA is a mixed agonist/ antagonist for serotonin. It 
mimics the characteristics of a monoamine in being nonacidic (no 
charge) in order to cross the blood- brain barrier and it 
increases the effects of serotonin by causing a flood of the 
neurotransmitters into the synapse. Problems arise when the 
abundance of serotonin has no where to go. Normally the 
neurotransmitter would bind to a transporter protein after 
detaching from the receptor that would carry it back into the 
neuron and either cause its breakdown to inactive chemicals 
through the enzyme MAO (monoamine oxidase) or recycle it. MDMA 
blocks the reuptake of serotonin by binding itself to the 
transporters. This stops the action of the transporter and is an 
inhibitory response to the stimuli of MDMA. 
	When MDMA blocks the reuptake of serotonin, it is depleting 
the body's supply. "Eventually, the serotonin neurons can't make 
serotonin fast enough to replace that which was lost, so once 
Ecstasy is gone from the body, less serotonin is released with 
each electrical impulse and fewer serotonin receptors are 
activated, producing depression-like feelings of anxiety" 
(Hallucinogens). In addition, there is some evidence that MDMA 
damages and even destroys serotonin neurons. "More detailed 
examination of this structural damage revealed that MDMA appears 
to prune, or reduce in number, serotonin axons and axon 
terminals" (Ecstasy 30). This theory of neurotoxicity caused by 
MDMA has had support from research involving animals. "Two weeks 
after receiving 20 mg./kg. of MDMA twice daily for four days, 
brain tissue taken from rat brains showed a substantial decrease 
in neurons containing serotonin; in fact, the axons of these 
neurons appeared to be missing" (Ecstasy 30). 
	It is believed that the damage to serotonin neurons is 
caused by the production of free radicals. This is a 
metabotropic effect because it takes place not only while the 
drug is actively stimulating serotonin release, but well after, 
and is much slower than the positive effects reported by users. 
The free radicals are hydroxyls that the axons of serotonin 
neurons seem to be particularly susceptible to because of their 
mitochondria content. "The rich supply of mitochondria (which 
are a major source of oxygen radical formation) found in the 
terminals may cause the terminals to be especially sensitive to 
drugs like ecstasy" (Hallucinogens). When serotonin levels have 
been depleted from flooding the synapse and being metabolized, 
dopamine binds to the serotonin receptors and because it is 
toxic to serotonin neurons it causes them damage. MAO 
metabolizes the dopamine and breaks it down to hydrogen 
peroxide, which is also toxic to serotonin neurons. The hydrogen 
peroxide oxidizes areas of the cell that would not normally be, 
and this is the principal source of neurotoxicity (Brain on 
Ecstasy). This was found when researchers experimented with 
oxidation effects by observing what happened when they blocked 
Dopamine release or prevented MDMA from binding to the Serotonin 
transporters. The resulting absence of oxidation supported their 
hypothesis (Ecstasy 30).
	When the axons are no longer serviceable due to excessive 
damage, the brain compensates by building new connections in 
other areas. In a study involving squirrel monkeys researchers 
found that while certain areas of the brain had lost large 
amounts of serotonin axon terminals, ones such as the amygdala 
had increased amounts.  This points to the brain's propensity 
toward repairing damage by rebuilding further on (Ecstasy 30). 
Another complication caused by the production of free radicals 
is the destruction of tryptophan hydroxylase. "Indeed, 
investigators have found that MDMA-induced oxidation rapidly 
destroys tryptophan hydroxylase, which causes a long term 
depletion of serotonin in affected neurons and eventual cell 
death" (Ecstasy 30). To avoid damage, the serotonin receptors 
have a way of protecting themselves. They can down regulate 
themselves, in other words retreat back into the membrane of the 
dendrites. This essentially gives the receptor a chance to 
recuperate, and is likely to happen if large amounts of 
serotonin flood the synapse for extended periods of time 
(Ecstasy). The side effect of this phenomenon is that there are 
less receptors to bond to; the lowered serotonin levels in the 
user may cause depression (Brain on Ecstasy). Another way shown 
to prevent neurotoxicity is Prozac. Since Prozac is a selective 
serotonin reuptake inhibitor (SSRI), it binds to the serotonin 
receptors and blocks the dopamine from doing so (Brain on 
Ecstasy).
	The neurotransmitter Dopamine has not been found to have 
the same response to MDMA as serotonin with regard to damage to 
neurons. "…dopamine levels return to normal within hours after 
administration of either MDMA or met amphetamine" (Ecstasy 16). 
This could be because dopamine is replenished much faster than 
serotonin. Although Dopamine neurons do not appear to be damaged 
by sustained action potentials causing their release into the 
synapse, there are changes caused by MDMA. "Ecstasy can inhibit 
dopamine transporters and cause an increase in dopamine levels 
in the synaptic space" (Hallucinogens). Dopamine is an 
inhibitory transmitter because it causes a reduction in synaptic 
transmission. As MDMA stimulates the release of increased 
amounts of Dopamine into the synapse, it is decreasing activity 
in many other parts of the brain (Kalat 455). The effects of 
MDMA on Dopamine release are directly related to its effect on 
Serotonin because the two systems are connected (Ecstasy 16).  
For example, "serotonin neurons innervate dopamine neurons, that 
is, they make connections with dopamine neurons and send signals 
directly to these dopamine neurons" (Ecstasy 16). This means 
that serotonin can stimulate the release of Dopamine into the 
synapse and does so when MDMA creates an action potential that 
causes the release of serotonin.
	MDMA has an inhibitory affect on the neurotransmitter 
Norepinephrine as well. Norepinephrine terminals are involved 
with the uptake and removal of Dopamine from the synapse 
(Yamamoto 274). The Nucleus Acumens is affected when MDMA 
prevents the reuptake of Dopamine by the Norepinephrine 
terminals. Norepinephrine is found in the basal ganglia as well. 
The excitatory and inhibitory effects of MDMA on neurons and 
neurotransmitters are numerous. The important thing to remember 
is that axons of serotonin are far reaching and affect many 
areas of your brain and body that you might not have considered.
	 	 
Primary Behavior Changes of MDMA
Kelsey Maffei

As an attempt to define the primary versus secondary (or 
side effect) behavior changes, I will first discuss the 
differences between the two.  One way to separate the two will 
be to refer to the primary behaviors as those that occur during 
the use of the drug.  This time span will include the behaviors 
that occur from the point of ingestion through the time when the 
effects of the drug wear off (approximately 4-6 hours after 
ingestion).  At this point I will go on to discuss the secondary 
effects on behavior and how they are a result of the primary 
effects.  With this distinction made, it will make the 
comparison easier to follow and understand.
	One of the first, and most commonly reported, behavior 
changes is that of a created sense of, or feeling of, empathy 
towards all individuals. In many this feeling is a dominating 
force that enables communication in an outwardly expressive 
manner, much different than is normally expressed if the 
participant were to be in a sober state.  As a result, MDMA was 
slated for use in the medical field by psychologists and 
psychiatrists who were interested in these qualities as an aid 
in therapy.  With lowered inhibitions and a willingness to 
express one's inner thoughts and feelings, many therapists were 
convinced that the drug would have very important therapeutic 
advantages.  These advantages would be clearly expressed in 
cases where months of therapy had little effect on creating an 
inviting space where patients could feel comfortable with 
sharing in the presence of a therapist.  Under close 
supervision, the therapeutic consequences could be priceless to 
the individual who potentially would be able to overcome a 
traumatic experience.  With this being only one of the primary 
behavior changes associated with the use of MDMA, it's easy to 
see how the complexity of such a drug can be easily 
underestimated.        
	When viewed from an outside perspective, someone in such a 
euphoric state would appear to be very outgoing and accepting of 
many types of people.  It's this sense of compassion towards all 
people that has created a phenomenon that expresses itself in 
the form of large dance parties, called raves.  People get 
together to enjoy music, dance, drugs, and most of all each 
other.  In a heightened state of awareness, participants are 
able to let go of their daily stresses and participate in an 
almost cathartic release of the tensions and inhibitions that 
hold them back on a routine basis.  Coupled with heightened 
levels of energy, a result of the stimulant effects of 
amphetamine, participants are able to maintain a high level of 
physical activity for long periods of time.  This quality is one 
that thrives on the rave culture experience in which the music, 
lights, and interactions with others creates a rich sensory 
experience for all to enjoy.  
In an effort to illustrate the effect that MDMA has on the 
body, Simon Reynolds (1998) suggests that, "Ecstasy turns the 
entire body surface into an ear, an ultrasensitized membrane 
that responds to certain frequencies."  Another behavior change 
that this implies is the idea that the body is hypersensitive to 
all forms of sensory stimuli.  With a strong likelihood to be 
associated with the aforementioned rave culture, participants 
are likely to seek situations that will fulfill their desire to 
experience everything around them.  Such experiences might 
include group affection with hugging and touching, or the 
auditory experience of shared inner thought processes.  Reynolds 
made sure to point out that the experience was "touchy feely, 
and amorphous sensuality, but it wasn't a sexuality."  The 
reason he made this distinction was that the euphoric feeling 
that ecstasy provided was often mistaken for an excuse to be 
overtly sexual in nature.  This, however, was not the case as 
many were led to believe.  It was merely a means through which 
people could express their inner most feelings without having to 
worry about being ostracized by the group.
Other behaviors that have been seen through the lens of 
laboratory experiments, as well as throughout the club scene, 
include involuntary teeth clenching, or biting of the inside of 
the cheek.  This is mainly a result of some of the chemicals 
that are used to cut the drug while it is being made, and can 
also be a result of other ingredients that are incorporated into 
the final product.  Due to the often painful consequences of 
such actions, many people that take the drug will often carry a 
pacifier or chewing gum to occupy the attention of their jaw 
should it become necessary.  It's this kind of behavior, 
expressed by adults sucking on a pacifier, which draws negative 
attention to the actions that are a result of the intoxication 
of ecstasy.  This negativity, one would think, would discourage 
people from participating in such acts; rather it seems to fuel 
the fire.  It's often viewed as a form of self expression and an 
acceptance of the culture that has become its following.   

Side Effect Behavior Changes of MDMA
Kelsey Maffei

The secondary effects on behavior are expressed in several 
ways that differ from one person to the next.  These effects can 
range from memory impairment and anxiety, to depression and mood 
swings.  They are a direct result of the chemical changes within 
the body that occur when someone uses ecstasy.  I will discuss 
the range of effects in more detail, with explanations that get 
to the root causes for each.
One of the major behavior changes, after the effects of the 
drug have worn off, is a symptom of the reduced levels of 
serotonin in the brain.  As ecstasy infiltrates the brain 
tissues, its effects cause the brain to produce copious amounts 
of serotonin.  Following such an extreme release of this 
neurotransmitter, the brain goes through of period of time in 
which it has a below normal level of serotonin.  This reduced 
level creates elevated levels of anxiety in users, and can often 
result in panic attacks that persist for several months 
following the use of the drug.  However, it is important to note 
that, according to a study from the European Journal of 
Pharmacology (Gurtman, et al, 2002); "whether such effects are a 
direct result of MDMA use… is, at present, uncertain."  This 
admission goes to show that correlation doesn't mean causation, 
and that until further research can be done we can only 
speculate about the relationship between the two.
Another side effect, that is reported to be affected by the 
levels of serotonin in the brain, is that of memory functioning.  
Several different areas of memory are included in this 
assertion, including cognitive capacity, recall over time, and 
planning ability.  It is suggested that heavy users, when 
compared to a control group, have a harder time with primary 
areas of brain functioning that relate to memory.  In a study 
conducted at the University of Cologne, in Germany (Gouzoulis-
Mayfrank, et. al, 2004), research indicates that, "findings of 
relatively low memory performance associated with heavy ecstasy 
use have been relatively consistent across different studies and 
user populations."  This assertion is fairly recent in the 
literature, which would suggest that the findings have taken 
note of the broad range of studies that came before it.  
With that said, it's hard to ignore the idea that a drug 
that induces such euphoric effects on the mindset of an 
individual, will have no ill effects on memory or other brain 
functioning.  When compared to the over the counter cold 
medicines or other pharmaceutical prescriptions for various 
symptoms, even those drugs have warnings about extended use and 
the potential side effects that are likely to occur.  It's easy 
to see the potential for hazardous effects of a drug that is 
made in home labs and cut with random chemicals, thus the lack 
of conclusive agreement about its effects make this drug 
particularly dangerous.   
As a result of the limited research, which may or may not 
be related to MDMA being classified in Schedule I by the DEA, 
these side effect symptoms are limited to the speculation of the 
research available.  The effect on the current research that the 
scheduling of MDMA has is that it limits the access of 
researchers to do new studies using experiments that are 
designed to test the effect of the drug.  As a result, the 
testing that is available involves finding people that are self 
reported users of ecstasy and are willing to participate in an 
experiment.  If the drug were scheduled in a way that it were 
accessible to research firms, overseen by the watchful eye of 
the Food and Drug Administration (FDA), a more accurate 
representation of MDMA's effects would be attainable.  A study 
could be designed in such a way as to eliminate such 
contaminating factors as a participant that while intoxicated by 
the MDMA also uses other drugs (i.e. alcohol, nicotine, 
marijuana, etc.), which is suggested to be quite common.  This 
factor is one of the major reasons that the findings of many 
research studies involving ecstasy users is correlational at 
best.  With so many other factors that go into deciding which 
effects are caused by which drug, and if the combination of two 
or more drugs is really the reason for the side effect behaviors 
is yet to be determined. 
Another area of behavior that seems to be affected by the 
interactions of the body and that of ecstasy is the relative 
mood changes that occur in the days or weeks following use of 
the drug.  Again a relation to the adjusted levels of serotonin 
and dopamine in the body, which is corroborated by self reports 
of the drugs effects, it's common for users to experience a lack 
of motivation and at times depression in the days following use.  
This can affect behavior by making a person more irritable in 
situations that normally do not induce this effect.  As a 
result, it can have negative effects on a user's social 
interactions with friends, family, and coworkers.  All the 
effects that have been mentioned are only a few of the possible 
effects on behavior that MDMA is reported to have. As further 
research continues, especially the longitudinal studies, we will 
continue to build upon this knowledge. 

Physiological Effects of MDMA Use
Llew Richards

MDMA has significant cardiovascular effects. This is 
consistent with its norepinephrine releasing (Johnson et al. 
1991; Rothman et al. 2001) and £\_2 adrenergic agonist (Lavelle et 
al. 1999) properties. MDMA dose dependently produces robust 
increases in heart rate and blood pressure (de la Torre et al. 
2000a; de la Torre et al. 2000b; Grob et al.). Peak 
cardiovascular effects occur between 1 and 2 hours after MDMA 
administration and largely subside within 6 hours of drug 
administration.
A study suggested that the relationship between MDMA dose 
and cardiovascular effects was supralinear by de la Torre et al. 
(2000a) who reported unexpectedly high drug exposures (measured 
as AUCplasma for MDMA) and diastolic blood pressure increases in 
two volunteers given 150 mg MDMA. While pharmacokinetic data 
suggest MDMA has nonlinear kinetics, there is no clear evidence 
of supralinear relationships between dose and blood pressure or 
heart rate. In fact, there may be less increase in heart rate 
after higher doses. The tendency toward less heart rate increase 
with higher dose is consistent with a study using both conscious 
and anesthetized rats (O'Cain et al. 2000). In this rat study, 3 
mg/kg IV MDMA decreased heart rate, while lower doses tended to 
increase it or leave it unchanged.

Studies monitoring blood pressure found significant 
relationships between MDMA use and blood pressure. In one study, 
(Vollenweider et al. 1998) involving subjects without a history 
of MDMA use, one subject experienced hypertensive crisis from a 
dose typical of recreational use. The correlation of blood 
pressure is described, "A two way ANOVA for systolic blood 
pressure revealed a significant main effect of drug [F(1,2) = 
41.09; p < 02] and a significant drug x time interaction [F(3,6) 
= 11.31; p < 007]. Significant changes occurred in the 0 to 75 
minutes and 75 to 150 minutes interval (one way ANOVAs). Two way 
ANOVA for diastolic blood pressure was not significant, but one 
way ANOVAs showed significant changes in the 75 to 150 minutes 
and the 150 to 300 minutes interval. Increases were in the range 
of 10 to 30 mm Hg for systolic blood pressure and 5 to 10 mm Hg 
for diastolic blood pressure." (Vollenweider et al. 1998 
pp.245_246) This study shows a similarity in changes in systolic 
blood pressure, and a lesser similarity in changes in diastolic 
blood pressure. The occurrence of hypertensive crisis suggests 
caution in potential use and study.
Of the reported cases of acute toxicity following MDMA use, 
hyperthermia is often cited as a strong contributing factor. 
Research done by de la Torre and fellow researchers (de la Torre 
et al. 2000b) supports earlier research (Fitzgerald and Reid 
1994) examining this effect. The research shows an initial 
decrease in body temperature during an initial period of around 
an hour, followed by an increase of body temperature from the 
second to fourth hours. In explaining this phenomenon, 
Fitzgerald and Reid suggest that there is an increase in 
vasocongestion due to the stimulatory effects of MDMA. This 
increase in vasocongestion initially decreases circulation, 
resulting in lower temperatures. But as blood pressure increases 
and blood flow increases, this vasoconstriction traps heat in 
the circulatory system, resulting in higher body temperatures. 
In situations involving high levels of activity hyperthermia can 
become significantly more pronounced and more destructive. This 
hyperthermia is thought to be responsible for the high 
occurrences of dehydration among recreational users of MDMA.
Other behaviors are associated with MDMA use, but with less 
significant negative implications. A high occurrence of 
involuntary teeth grinding (bruxism) and jaw clenching has been 
reported with MDMA use. Users of MDMA often combat this effect 
by inserting something into their mouth (like a pacifier) which 
prevents tooth on tooth contact. (Cohen 1998) MDMA use is often 
characterized with a high frequency of pupil dilation. In one 
study, all of the subjects experienced increased pupil dilation 
except for a blind individual. Also, all individuals 
demonstrated normal light reflexes (Downing 1986). Another 
behavior reported by Downing is nystagmus, or involuntary eye 
movement. Typically, subjects who experienced nystagmus 
experienced it during the first or second hour following use. 
Rarely, subjects continued to experience nystagmoid movement 24 
hours after use.

Subjective Reports of MDMA Use
Llew Richards

In reading several reports of individuals who have 
experimented with MDMA several common experiences can be found, 
but no experiences can be thought of as universal.
One of the most commonly reported experiences is a feeling of 
peace. Some users categorize this experience as a feeling of 
intense calm. They simply cannot imagine hostile or aggressive 
feelings towards any other person. This feeling objectively can 
be observed in the relative sedation of those experiencing a 
'high'. In one person's experience, once the MDMA had begun to 
affect their body in earnest, they felt no desire to move or do 
anything other then remain sitting where they were. They didn't 
report so much an inability to move as much as an inability to 
imagine a situation better then their current situation. As 
evidenced by the number of dance clubs in which MDMA is used 
frequently, MDMA clearly does not block physical activity. Some 
experienced users report that they have a brief window of 
opportunity after ingesting MDMA to engage in an active behavior 
(such as dance). After this window is over, they become too 
entranced in their experience to change anything. I! f they 
manage to become active during this time, they feel very 
energized and report the calm as being a more external feeling.
This externally manifested calm can be described be such 
terms as love, oneness, peace, happiness, trust and other such 
broad positive terms. MDMA users who have experience MDMA use at 
clubs or dances often comment on groups of users who group 
together. Reports from users involved in these groups express a 
synergistic effect of being around others who are using MDMA. 
Many users who came to social situations alone reported their 
attempts in finding other users with which to socialize. One 
user described the "cuddle puddles" in which several users would 
sit together. These areas would have pillows and water available 
for the users. The user reported that they would sit, talk and 
describe their sensations to each other. One of the primary 
sensations shared was their tactile sensations.
A very commonly described effect of MDMA is an increased 
enjoyment of sensation. All sensations are described as being 
more interesting, or intense. One common sight described at 
several raves (underground dance parties) is the surgical mask 
smeared with mentholated petroleum. Often, users will crush MDMA 
and dust the inside of the mask with it, or will take MDMA 
orally and simply smell the menthol. Users often describe the 
effect as giving them awareness of their own breathing. Because 
sensation of any kind is often described as pleasant, and the 
mentholated mask adds sensation, this is a very common 
occurrence. Another sensation which is frequently explored is 
that of sight. Many users describe that colors become more vivid 
and patterns develop profound meaning. Raves often have a wide 
variety of lighting effects which are reported to enhance and 
stimulate an experience with MDMA. Some frequently reported 
occurrences are strobe lights, spotlights, colored lights and 
any moving light which causes unpredictable results. Many users 
use phosphorescent sticks or rings which are reported to create 
'trails' in the air when waved, especially in the dark.
Rather than experiencing a sense of calmness, some users 
develop anxiety either during or after the use of MDMA. The 
pleasant feeling described above often occurs simultaneously 
with feelings of energy and excitement. This excitement, when 
taken to extremes, often leads to paranoia and 'jitters'. One 
report described taking MDMA at a dance club. The growing energy 
and anxiety felt too intense for the individual, and they became 
concerned about pains in their chest. An experienced user with 
them suggested that they dance, as it tended to help with such 
experiences. The user reporting began to dance, and after a 
while the feelings of anxiety began to recede.
Related to the feelings of too much energy are nervous 
physical habits that are reported by many users. Several reports 
describe occurrences of bruxism. Some times the user experiences 
increased levels of anxiety because of this uncontrolled 
behavior. Other times the behaviors go unnoticed until pointed 
out by a bystander, or the results of the behavior become clear 
when the drug wears off. One report describes the 'loose teeth' 
that the user had the next day from apparently grinding their 
jaw. The user planned on bringing a pacifier to combat this 
problem the next time they were to experiment with MDMA.
Another common behavior to report is of lower back pain. 
Several users described their first experience with MDMA to be 
very pleasurable except for intense pain in their back either 
during or after the use of the drug. Some frequent users develop 
aforementioned back pain after subsequent uses of MDMA, while 
some users experience (as mentioned above) during their first 
use. This pain ranges from a mild tolerable pain to debilitating 
pain which precludes all activities until the drug wears off.
Because of the often pleasant effects mentioned earlier, MDMA 
has a strong association with sensuality and sexuality. Most 
users describe intimate feelings with people around, but not all 
equate those feelings with sexuality. Those who do engage in 
sexual activity often find the experience to be engaging but not 
fulfilling. As impotence is a common side effect of MDMA use, 
this experience is not surprising.
While most users experience some or all of the above 
experiences, some users report little or no effects from MDMA. A 
small number of reports available describe little more than a 
headache or discomfort while using MDMA. Some of these 'non-
experiences' could be attributed to the impurities often found 
in street MDMA. 























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http://www.erowid.org/chemicals/mdma/mdma.shtml

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