Biology 103
2002 First Paper
On Serendip

MDMA (3, 4-Methylenedioxymethamphetamine), or ecstacy, belongs to a category of
substances called "enactogens" which literally means "touching within." "It is a Schedule I synthetic, psychoactive drug possessing stimulant and hallucinogenic properties." (6) It is composed of chemical variations of the stimulant amphetamine or methamphetamine and a hallucinogen, usually mescaline.

An slide show of the chemical process that occurs when MDMA is introduced to the body
can be found on the website www.dancesafe.org. (2) Basically, the group of brain cells that are affected by ecstacy is the serotonin neurons. Each one of these cells has multiple axon terminals which release serotonin to the rest of the brain. The exchange of serotonin from cell to cell occurs in the gap between the axon terminal of the serotonin neuron and the dendrites of the next neuron. This region is called the synapse. Serotonin is critical to many brain functions, including the regulation of mood, heart-rate, sleep, appetite, pain, and many others. As a result, it is extremely important that the neurons release the proper amount at the right time.

After the serotonin is released into the synapse, it comes in contact with receptors on the dendrite of another cell. When a molecule attaches to one of these receptors, it sends a chemical signal to the cell body. Based on information from all the receptors put together, the cell body decides whether or not to fire an electrical impulse down its own axon. If a certain amount of receptor binding occurs, the axon will fire, causing the release of neurotransmitters into the synapses of other cells. This is how brain cells communicate and regulate the amount of neurotransmitters present at any given time. Research has shown that the amount of serotonin receptor binding influences your mood. When more receptors are active, you are happier.

Along with the receptors on the dendrite, serotonin molecules also bond with "reuptake transporters" on the axon's membrane. The transporters are responsible for reducing the amount of serotonin in the synapse if the cell body decides that there is enough receptor binding. One way to look at the system is to think of a revolving door. The serotonin enters on one side and the transporters spin around and deposit it on the other. Molecules can only move from the synapse to the axon.

When MDMA is present in the brain, enormous amounts of serotonin is released into the synapse. This increases serotonin receptor binding which causes changes in the electrical impulses sent throughout the brain. MDMA also causes serotonin that has been removed from the synapse by the reputake transporters to be re-released from the axon. In a sense, the revolving doors are frozen in the open position and the cell body becomes overwhelmed with serotonin. It flows freely into the receptors and is recycled over and over again. This alteration in normal brain function produces the effects associated with ecstacy. These include euphoria, an enhanced sense of pleasure and self-confidence, peacefulness, and empathy. It is fairly common for a pill of ecstacy to be laced with other drugs and this can alter the experience. If speed is present, for example, teeth-clenching, depressed appetite, and insomnia are present in addition to the effects of MDMA. Ecstacy begins to work on the brain after 20 to 40 minutes, with the peak effects after the first hour.

After a few more hours, the MDMA begins being broken down by the body and reputake
transporters resume normal functioning. They usually remove much of the serotonin from the synapse after approximately three hours, although there is still enough present to maintain the feeling of the full effects. However, most of the serotonin will be gone by the end of the fourth hour. An enzyme called "monoamine oxidase" (MAO) is also present in the brain and aids in the breakdown of serotonin.

The state of the brain where serotonin levels begin to return to normal after being under the influence of MDMA is called "coming down." There are fewer activated receptors because so much serotonin has been released in the past few hours that most of the supply in the brain has been used up. At this point, there might be even less serotonin circulating than before the MDMA was introduced. Some people choose to take more MDMA at this point to make coming down easier, but eventually the drug will have no effect at all because there is no serotonin left in the entire brain. Serotonin levels might remain depleted for up to two weeks while the brain rebuilds its supply.

One negative side effect of ecstacy results from this period of recovery after taking a pill. Perpetually lowered serotonin levels have been proven to cause depression. If MDMA is present in the brain on a regular basis, serotonin is never fully replenished before it is released all at once again. Normally, it takes a long time for the brain to produce new serotonin because it involves a complicated series of metabolic reactions. The process does not normally need to be accelerated because the brain would never release such large quantities of serotonin without the influence of MDMA. As a result, when levels are depleted so rapidly, the brain needs time to recover. This is when people experience depression.(2)

The long-term effects of ecstacy use are still relatively unknown. One current theory is that ecstacy is a neurotoxin, meaning it causes permanent brain damage and psychiatric disorders later in life. Much of the current press on this issue is exaggerated, but studies have shown that MDMA degenerates the serotonin axons of lab animals. So far, studies of frequent human users (75 times or more) have shown reduced brain serotonin levels and reduced serotonin uptake. No signs of cognitive or psychological problems were noted. Evidence regarding the memory loss associated with ecstacy use is inconclusive. It is still unknown whether this is due to neurotoxicity or temporary changes in brain chemistry that correct themselves with time.(2)

Ecstacy is not a new drug. It was first synthesized in 1914 by a German pharmaceutical company that believed it had uses as an appetite suppressant. The drug first appeared in America sometime around 1970 and was legal until 1985. Although the most common instances of ecstacy use today are recreational, it was first utilized by a small group of psychotherapists as a tool to treat Post Traumatic Stress Disorder. However, its effectiveness was outweighed by its unknown and unpredictable side effects. Shortly after its use in psychotherapy was discontinued, a new market for MDMA emerged. Ecstacy was initiated into the illicit drug culture around 1980. It was not widely accepted until it was picked up in the club scene and began appearing at raves.(6)

The popularity of ecstacy has continued to increase in recent years. A study done by
Harvard University of 14,000 college students from 119 U.S. four-year colleges revealed that the prevalence of ecstacy use increased 69% between 1997 and 1999. A smaller sample of ten colleges showed that this trend remained consistent in 2000.(1) The conclusion of the study stated that "ecstacy use is a high risk behavior among college students which has increased rapidly in the past decade.".

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