Biology 202
1998 Third Web Reports
On Serendip

Ecstasy

Rachel Mosher

Turning round I see, surprised,
a large, round, living temple.
I am here, part of it all,
I am part of it all.
I look at the world
and the world looks back at me.
I am not alone.
This is Ecstasy

Standing, I feel. So tender
and being held so tenderly.
My sadness is like a soft bud
velvet and moist,
my tear a dew drop
trembling on the tip of my nose,
I am so happy to feel.
This is Ecstasy

We sing, we laugh, we share
and most of all, we care.
We let each other see
the beauty inside
without shame or anxiety.
We're happy and free.
This is Ecstasy

--a professional Englishwoman after experiencing ecstasy for the first time

INTRODUCTION

The use of the designer drug named Ecstasy has intrigued me since I was introduced to it in Berkeley last summer. I was told of all its magical effects and had a hard time believing that a single pill could produce such a blissful state. I was also critical of the claim that the drug was completely non-toxic.

Now, I reflect on my summer experiences with students involved in the Rave (1) scene in Berkeley and I have new questions. If brain = behavior, what makes this group of people do drugs while another similar group (such as Haverfordians for example) would probably never dream of doing ecstasy? Also, why does one’s nervous system signal for outputs that can lead to an alteration of a person’s mental state? Is there a benefit to it, or is the brain just making bad decisions? By researching ecstasy I will attempt to understand why people use ecstasy and if its use is a mistake on the brain's part.

WHAT IS ECSTASY?

Ecstasy is a designer (2) drug that acts as both a stimulant and a hallucinogen. (3) Ecstasy is usually found as a 400 mg tablet, only 100 mg of which is its active ingredient 3,4 Methlenedioxy-methamphetamine or MDMA . (4) MDMA is a derivative of amphetamine found in its pure form as a white crystalline powder . (3) It is often used to provide a sense of well-being and unlimited energy. It is presently most widely used and distributed during raves- all night underground parties with techno music and extensive drug use frequented by teens and college students . (2) Despite its supposedly harmless effects, it is a schedule I illegal drug whose use and distribution is prohibited in most countries including the United States . (5)

THE EVOLUTION OF ECSTASY

Ecstasy use has changed dramatically over the past decades. This reflects both the changes in the social environment and the changes in people’s biological needs and cravings. By examining the usage trend of the drug, we can try to pinpoint the common reason why the different groups invited it into their lifestyles.

Ecstasy was first introduced as an appetite- suppressant in 1912 by the German Drug Company Merck. It faded away shortly after its introduction only reappearing once to be tested as a substance for psychological warfare in 1953 by the U.S. Army. It was finally reintroduced to the world in the sixties as a tool for psychotherapy by Alexander Shulgen, a biochemist at UC Berkeley who researched psychoactive drugs. For about ten or fifteen years, it was happily used for therapy and experimental purposes. Educated scientists and psychologists would manufacture it themselves in small laboratories, try it and recommend it to their friends as a way to improve their mental state and relationships with others. As the drug spread around the educated community, it began to seep into the public. By the late seventies, the demand for the drug grew faster than its supply. This lead to a rash of impure, fake ecstasy pills being produced and sold in the early 1980s. The drug was declared illegal in 1985 and classified as a schedule I drug following an outbreak of ecstasy-related health problems caused by these impure ecstasy pills. The government did not test the drug for toxicity before declaring it illegal nor did they allocate funds for future research into this area. After its prohibition, Ecstasy was imported into the United States by foreign countries and was bought mainly by experienced recreational drug users that were not willing to give up their favorite euphoric drug . (6)

In the period from the late eighties to the present ecstasy has had another wave of popularity. Teenagers became attracted to the drug when all night raves became popular. Raves are huge, secret parties with techno music and lasers. At raves, there are drug dealers who offer ecstasy which is the drug of choice. Most of these teenagers are not typical drug users. They only use ecstasy when they go to raves, which would be only on about two nights a month. It is usually the first drug that they have ever used.

The typical ecstasy user has evolved from middle-aged scientists interested in improving relationships to inexperienced teenagers in their rebellious years. The drug itself has changed from a legal homemade compound with possible medical advantages to a schedule I illegal drug manufactured in a clandestine laboratory in another country. The pill itself has changed from pure MDMA (7) to a mixture of unidentified drugs, one of which is hopefully MDMA.

There are a few things that these user groups have in common that other groups do not that lead them to use ecstasy. The most obvious thing is environment. They are all in an environment where ecstasy use is accepted and promoted. The scientists users experimented with the drug as makeshift drug testings to find the medical benefits of MDMA. Their social group accepted the usage on the grounds that they were doing breakthrough drug tests. This group of people also did not have the stigma of the compound being an illegal drug at that point. The twenty-ish experienced recreational drug users were also in an environment where getting the MDMA was relatively easy and taking drugs was accepted. Their lifestyles revolved around using drugs on the weekends with their friends. If they did not use drugs, they would risk being an outcast to their group. The newest ecstasy user group also has the unique environment for ecstasy use. They are part of a culture that attends raves on the weekends. Not only do they have the drug available to them and friends their to support its usage, the rave setting is uniquely ecstasy . (8)

Besides being in similar ecstasy- accepting environments, the three groups probably also had psychological reasons for using ecstasy. These reasons will surface after examining the mental affects of the drug.

MENTAL EFFECTS OF ECSTASY

There is a lot of documented information on the mental effects of using ecstasy. The best way to capture the exact emotions of these effects is with a collection of comments and observations from people who have used the drug: "(Ecstasy) made me feel how all of us would like to feel we are anyway . . . smooth and open hearted, not soggy, sentimental or stupid . . ." , (9)

'The circuits of the brain which mediate alarm, fear, flight, lust and territorial paranoia are temporarily disconnected, you see everything with total clarity undistorted by animalistic urges You have reached a state which the ancients have called Nirvana, all-seeing bliss.' (10)

It is not a distortion of reality, you can if you have to- perform normal functions. But you don’t want to, who’d want to play tennis or drive a car when you are sitting on the mountain of blissful wisdom? (10)

Other users comment that they are able to relate to people more openly with less fear or defensiveness; women in particular report they become liberated and able to let go without fear of being taken advantage of by men, (9)

Men comment they have a much lowered feeling of sexual and physical aggression allowing them to increase emotional closeness and as one woman put it "bring out (their) feminine qualities," (9)

Other have commented that ecstasy opens the heart and allows love to flow to anyone they come in contact with this love feeling has been said to extend to the loving of oneself . (9)

One researcher was able to categorize these feelings into two distinct groups: Entactogenesis and Empathogenesis . (11) Entactogenesis is "a generalized feeling that all is right and good with the world . . . common things may seem to be abnormally beautiful or interesting." Empathogenesis is "a feeling of emotional closeness to others coupled with a breakdown of personal communication barriers . . . it's like a filter between what you want to express and what comes out of your mouth that you didn't even know existed is striped away." (11)

With information on the mental affects of Ecstasy, we can see that each of the groups had similar reasons to use the drug. They all craved a way to express themselves without being held back. The older therapist group used the drug as a psychiatric tool. Once they tested it themselves to become familiar with the effects, they offered it to their patients. These patients were having trouble enjoying their lives because of relationship or emotional problems. They even used it as a sort of hypnosis which would allow traumatic memories to emerge.

The twenty-ish recreational users had a slightly different reason for using ecstasy. These people were mainly students and yuppies who normally kept away from drugs. They probably used ecstasy because they craved some sort of change. Their lives were probably the same day after day- they worked/studied in the same place and with the same people and they didn’t have much to worry about. Their minds and bodies probably felt the need to break the monotony and have a new experience that would help them to see the world a little bit differently. They did not want to alter their lives in other ways like changing their job or friends because they did not want to commit to permanent changes that could turn out badly. Because ecstasy was available in their corner of the world, was accepted by their peers and only produced a temporary change, it did the job.

The newest ecstasy users, the teenagers, have a slightly different reason for using the drug. They are in a stage of their lives where they are not yet comfortable with themselves and their personalities. Furthermore, their bodies will not let them express themselves because of possible dangerous consequences. They have received so much information from their parents and teachers telling them to stay away from strangers and dangerous etc. and internalized it. This build up of information about negative consequences of behaviors changes their action outputs. They are more defensive about how they act and what they say- they are very inhibited from being themselves. Inside, they are probably screaming for a way to show their true feelings and act with their real personalities. Using Ecstasy allows their bodies to bypass the action potentials that inhibit their actions. They are able to be their true selves. This is why their brain signals them to take the drug occasionally. Although each of the groups of Ecstasy users is different, the underlying cause of their use of the drug was to express themselves without being held back.

NEUROBIOLOGY

In order to understand what the nervous system is going through after Ecstasy is taken, we can examine what happens to MDMA inside the body. Ecstasy affects the same area of the brain as other common drugs such as Prozac, Cocaine, Phenfluramine, Dexfenfluramine and Zoloft . (3) They are all serotonergic drugs each found to affect a different part of the delicate serotonin system . It seems that the chemical MDMA, like amphetamines, is part of the class of drugs that are called SSRI or Selective Serotonin Re-uptake Inhibitors . (3) This means the MDMA molecule becomes entangled in the neurotransmitter serotonin's (5HT) reuptake process. With information on the serotonin systems and the known mental effects of the drug, it is possible to hypothesize about the direct relationship between the biological MDMA mechanism and the resulting mental effects.

Neurons, or communication cells living in the nervous system, are activated when the body needs to modulate something (which is all the time). The neurons communicate by releasing neurotransmitters which subsequently synapse with a receptor neuron, allowing the message to flow through . (11) Normally, in the serotonin system, a serotonin neuronal cell will get a message from another neuron to release one of its stored vesicles of serotonin (this is catalyzed by: Monoamine Exidase MAO, an increase in calcium levels and a change in polarity ). (11) Specific serotonin uptake cells which have serotonin receptors will pick up these molecules through a synapse. After the receptor binds to the serotonin, the electric change in the cell will modulate ion currents across the cell membrane. This can change membrane permeability to outside molecules and begin a cascade of molecule movement that results in changes in the body . (11) More specifically, serotonin neurotransmitters in the brain are found to regulate the mood, food intake (by stimulating GIT smooth muscles) and sleep . (12) In addition, serotonin is a precursor of the hormone Melatonin, stimulates the release of growth hormones (indirectly) and inhibits the release of Leutinizing hormone, Follicle stimulating hormone and Thyroid stimulating hormone (also indirectly) . (12) These alterations are different for each neuron, depending on its type and properties.

When MDMA enters the nervous system, it interferes with this precise neuronal communication system. Usually, after a vesicle of serotonin is released, more that half of the serotonin neurotransmitters are taken right back into the original nerve terminal where they are repackaged and reused. This is termed 'reuptake'. When MDMA is present, it interferes with this reuptake site, not allowing serotonin to reenter the original terminal . (13) This allows for a possible increase in serotonin synapses, temporary excess levels of serotonin in the blood and depleted serotonin nerve terminals. The serotonin concentration of the blood is restored to normal within twenty-four hours but serotonin tissue levels are found to decline for weeks- depending on dosage . (14) The receptor axons and neuron nerve terminals associated with the serotonin system are also found to degenerate- the nature and meaning of this is unclear . (14)

Little information is available on how the MDMA interference with serotonin causes the specific mental ecstasy effects but I will hypothesize about how it might happen. It is known that serotonin synapses regulate the mood and the activation of certain hormones among other things. Perhaps when the serotonin neurotransmitter floods the system under the influence of MDMA some serotonin receptors are over stimulated by serotonin, and some serotonin receptors that were not supposed to pick up the signal did anyway. (These neurons might have been far away from the synapse). As a result, there could be an extreme increase or decrease in the level of the hormones regulated by serotonin. There could also be a significant mood swing. The shifts in the hormone levels could be responsible for the entactogenesis mental effects. For example, the emotional closeness felt could be directly caused by the overstimulation of a hormone 'C' that regulates the caring emotions each individual feels about their good friends. Instead of that hormone 'C' only being activated with good friends around, the hormone might be activated for everyone in sight allowing 'the love to flow...' The un-inhibited effect might be caused by the increased serotonin levels allowing the communication messages to bypass the past-experience area of the brain. It might do this by amplifying the signal so much (or perhaps increasing the velocity of the signal so much) that this specific area of the brain is overwhelmed and not able to process it. This would then allow the person to act in a situation with their initial response instead of having a defensive filter mechanism. The entactogenesis effects also seem explainable in terms of biology. For instance, an ecstasy user might feel unconditionally happy because the serotonin, normally used to alter the mood when specific events happen (for example, if you found a $100 bill in your desk, serotonin would make you feel happy), is able to synapse without needing an initiating external event when MDMA is around - hence unconditional happiness. The effect of lowered sexual and physical aggression could either be the indirect result of not having a reason to be aggressive because everything around is wonderful or it could be a direct result of decreased secretion of a hormone that signals the body to act aggressively.

This is just a brief hypothesis of the link between the neurobiology of MDMA and the mental effects of ecstasy. Even if different mechanisms are responsible, however, by guessing about the link, we can see that the MDMA enacts neurobiological changes that seem to fit well with the resulting mental effects.

NEUROTOXICITY

Why would the brain want a person to behave in a way that could be detrimental to itself? It would be doing this if Ecstasy was a toxic drug. The other alternative is that Ecstasy is harmless or that its toxic effects are so small they can be compensated by its benefits. By looking into the current research of the toxicity of Ecstasy, we can try to figure out if the brain is stupid to want the body to take ecstasy.

There are two trains of thought on the toxicity of ecstasy. Research on its affects have been conducted on animals, mainly rats, dogs and apes. Usually the animals are given specific doses of the drug and then killed. Their brains are subsequently sliced into sections and indirectly examined for damage because of the small size of the brain cells . (11) Based on these animal studies, the researchers agree on the basic biology of the system but have different interpretations of the damage incurred.

Researchers have found that MDMA has long term affects on the serotonin system which may or may not mean that it is toxic. The long term affects include:

1)Greatly reduced TPH activity (after repeated doses)

2)A reduced number of serotonin antibody positive nerve fibers

3)Degenerating axons and nerve terminals within the cell bodies of dorsal raphe nucleus cells. (15)

Although these effects have been documented, there are no corresponding lethality figures to go along with it. In fact, researchers are not sure if these three affects change the body's biological system at all and if the long-term affects are truly ‘long’ term. For instance, axons are regenerated and other important serotonin markers slowly make their way back to normal levels. It seems that regions closer to the brain stem are hyperinnervated with serotonergic fibres and the extent of the redistribution of the serotonin markers differs.

There are two opposing opinions on the consequences of this degeneration of parts of the serotonin system. One group assumes that the degregation of nerve endings is a mark of permanent brain damage. They think that even if regowth of these parts os possible, it will be abnormal and non-functional. believes that the neurotoxic effects of MDMA are very selective and because damage is limited to the axon and axon terminals, regrowth is possible but will be abnormal. In response to the lack of evidence of this brain damage, this group points out that it might not surface for awhile. They give the example of Parkinson’s Disease patients whose dopamine systems may be 90% degenerated before they get any of the symptoms of the disease . (14)

The opposing side offers a different interpretation of the research. They do not agree that total neurodegeneration has actually occurred. They point to the fact that this was determined indirectly through evidence that is not representative of the entire system. In fact, serotonin immunostaining data actually gives evidence of the opposite. Furthermore decreases in brain serotonin are not necessarily the same as the destruction of serotonergin axons. The evidence used by the other group to indicate the destruction is a measurement of the transmitter level in neurons. They do not ever look at the neuronal structures themselves. In other words, just because the serotonin level is decreased, it doesn’t necessarily mean the serotonergic axons were destroyed . (11)

The two different ideas of the neurotoxicity of Ecstasy show that there is a lot of controversy surrounding the toxicity of MDMA.

BRAIN = SMART

There are two pieces of evidence that lead to the idea that the brain knows what it is doing by taking the drug. First of all, there has yet to be documented proof of adverse affects to Ecstasy users. Studies done on heavy MDMA users did not show any proof of depression or senile dementia- the characteristics of the brain damage that Ecstasy supposedly caused. In fact, the long term MDMA users actually scored better than non-users being 'less impulsive, more harm-avoidant, and with decreased indirect hostility.' (11) Secondly, Ecstasy is not an addictive drug. In fact, it has security from frequent regular use because it produces tolerance quickly. The pleasant effects decrease and actually disappear completely within a week's daily dose . This makes frequent use practically unknown. Because the only research that shows Ecstasy to be dangerous was that done with heavy, repeated Ecstasy dosages it does not seem probable that the research would apply to the usual occasional use of Ecstasy. It seems definite that this type of short-term occasional use does not cause damage because there would many more reports of Ecstasy-related medical problems then there are now. Therefore, even if there are dangers when Ecstasy degenerates 90% of the serotonergic system, the brain knows this will never happen. It must think that the benefits from the drug are worth the little degeneration that it causes. It might also be possible that this little degeneration leads to less inhibition and is good for the brain!

CONCLUSION

Ecstasy is a unique drug. It is used for its ability to change the nervous system in such a way to facilitate personal expression. This expression frees people to be themselves and feel happy about their lives. It is able to do this by changing the regulation of the serotonin system for a brief period of time. This alteration may or may not cause permanent brain damage with heavy usage. Human studies do not back up the brain damage claim- even in heavy users. In the usual occasional user, brain damage seems highly unlikely- especially since MDMA is not addictive and as soon as users experience negative effects, they can stop usage. The brain seems to know that the benefits outweigh the negative effects because it makes the decision to let the body take it.

Further human studies on the inhibition level of past Ecstasy users would be useful. If it is true that using the drug just a few times allows a person to positively change their attitudes toward relationships and toward themselves permanently, this might be a result of the slight degeneration of the serotonin system. Maybe it is overly regulated in these users before they took the drug and that is why their brain wanted them to take Ecstasy in the first place.

REFERENCES

1. The subculture that I am referring to is one of going to 'raves' each weekend and taking drugs such as ecstasy, mushrooms and marijuana on a regular basis.

2. Drug Free Resource - Designer Drugs are created by changing the molecular structure of an existing drug to created a new substance. They are often made in clandestine laboratories.

3. Dosage and Effects

4. What Ecstasy is and where it comes from

5. http://ecstasy.org/e4x

6. History of Ecstas

7. What Ecstasy is and where it comes from

8. What Ecstasy does and how it works
'Ecstasy ofternconsists of various other drugs such as mixtures of LSD and amphetamine or caffeine . . . only half the samples were pure MDMA, with nearly half the remainder being MDA or MDEA while the rest was either another drug altogether or fakes.' When MDMA is experienced at raves, it lacks some of the subtle effects experienced in quiet surroundings, but has an extra quality not seen when the drug is taken in private. The combination of the drug with music and dancing together produces an exhilarating trance-like state, perhaps similar to that experienced in tribal rituals or religious ceremonies."

9. What Ecstasy does and How it Works

Psychiatric Effects)

10. Experiences

11. Serotonergic Drugs

12. Toxicity of Ecstasy- Neurobiology

13. http://ecstasyandprozac.html

14. Toxicity of Ecstasy by Leon van Aerts, PhD. (under "articles on toxicity and risk")

15. MDMA Selectively Damages Central Sertonergic Neurons in Nonhuman Primates


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