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The Neurobiology of Ecstasy (MDMA)



Contents:


1 through 7

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Cover: The Neurobiology of Ecstasy

Diagram of chemical structure of ecstasy 1: Introduction: long-term effects of ecstasy

An effective way of starting a presentation is to present something interesting or provocative. This first image shows sections taken from the neocortex of monkeys that were given ecstasy twice a day for 4 days (control monkeys were given saline). The section on the left, taken from the brain of a control monkey, shows the presence of a lot of serotonin. The middle section shows a section from a monkey two weeks after receiving ecstasy. Point out that most of the serotonin is gone. The section on the right shows a section from a monkey seven years after receiving ecstasy. Point out that although there has been some recovery of serotonin, the brain still has not returned to normal. Indicate that you will discuss this in your talk in more detail. Introduce the purpose of your presentation. Indicate that you will explain how ecstasy interacts with specific targets in the brain and what can happen after repeated or long-term use. Tell the students that you will review how neurons communicate with each other and how ecstasy alters this communication, resulting in changes in mood, behavior, and memory.


Diagram of chemical structure of ecstasy 2: Define ecstasy

ecstasy is a derivative of amphetamine (shown in purple on the image). Its chemical name is 3,4-methylenedioxymethamphetamine (MDMA) and it has a similar structure to methamphetamine. ecstasy has a variety of street names including, XTC, Adam, M & M, E, and essence. Explain to students that ecstasy is unlike other drugs of abuse, which are often derived from plants (e.g., cocaine, morphine, nicotine). In contrast, ecstasy is synthesized in clandestine laboratories--in fact, there are several "designer drugs" that are made (in clandestine laboratories) by altering the structure of the amphetamine molecule. Because ecstasy is synthesized in laboratories, its purity can vary substantially from lab to lab, and other compounds are easily combined into the same tablet (contaminants often include caffeine, ephedrine, ketamine - a mild hallucinogen and methamphetamine).


Pathways of absorption of ecstasy - see text 3: Ecstasy gets into the brain easily

The chemical structure of ecstasy allows it to reach the brain quickly after ingestion. Use the image to illustrate to the students the pathway that ecstasy follows from the mouth to the brain. First, the pill is ingested and it disintegrates quickly in the stomach contents. Once dissolved, some ecstasy molecules are absorbed from the stomach into the bloodstream, but most of the ecstasy molecules move from the stomach into the small intestine. There, they are absorbed into the bloodstream very easily.

The following explanation is optional and may be desirable for presentation to students who have had some chemistry: ecstasy is a weak base--this means that ecstasy is likely to "pick up" or accept a hydrogen ion (H+) from the surrounding medium (the gastric acid in the stomach is loaded with H+). After the ecstasy has accepted a H+, it has a charged (or polar) character, which makes it difficult to cross a biological membrane. Biological membranes have a nonpolar core, so compounds having a nonpolar nature are more likely to diffuse across the membrane (passive diffusion). Therefore, most of the ecstasy is not absorbed from the stomach into the bloodstream. Rather, the ecstasy molecules get emptied from the stomach into the small intestine. In the small intestine the more alkaline environment causes ecstasy to give up its H+, becoming more nonpolar. The large surface area and the more alkaline environment enable the ecstasy molecules to diffuse across the membrane into the blood capillaries very quickly.

Ecstasy molecules that have entered the bloodstream from the stomach and small intestines then travel to the liver (shown by the bottom blue arrows). In the liver, some of the ecstasy is metabolized to inactive compounds and the rest is carried through the veins to the heart (blue arrow). Once in the heart, the ecstasy is pumped to the lungs along with the blood, which becomes oxygenated and then returns to the heart (red arrow). Now, oxygenated blood carries the ecstasy from the heart to the brain (red arrow) and to other organs in body that have a high blood flow. Normally there is a barrier between the blood vessels in the brain and brain matter, which excludes many drugs from entering the brain. However, ecstasy is predominantly in its nonpolar form in blood and therefore it crosses the barrier into the brain very easily. It will take about 15 minutes for ecstasy to reach the brain if taken on an empty stomach.


See text 4: What we know azbout ecstasy

In recent years, there has been a lot of research carried out to understand how ecstasy affects the brain. Scientists have made a lot of progress in identifying how ecstasy changes mood and behavior. Indicate to students that ecstasy has short-term and long-term effects on the brain. The short-term effects of ecstasy include changes in brain chemistry and behavior. The long-term effects include changes in brain structure (based mainly on animal studies) and behavior. Tell them that you will try to illustrate how these changes take place. You could ask students if they have any knowledge of the short-term or long-term effects of ecstasy on the brain. If they volunteer some answers, list them on the board; indicate that you will discuss how some of these effects are produced.


Images of monkey, rat and human - how animal research is important 5: How do we know? Research in animals and humans

Bring up the importance of animals in research. Research in animals has provided us with a detailed understanding about the actions of ecstasy in the brain. In fact, many of the research findings obtained from animals, such as rats and monkeys, have now been replicated in humans. Indicate to the students that another important aspect of using animals in research is to understand mechanisms for toxicity produced by compounds. ecstasy is a classic example of a drug that produces toxicity (in the brain) and it would be impossible to study this in living humans. In the following set of images, the information highlighting how ecstasy works was obtained from research using animals.


See text - Illustration of brain 6: Brain areas sensitive to ecstasy

Before explaining how ecstasy works, it may be helpful to point out the areas of the brain that are sensitive to the effects of ecstasy. ecstasy affects cognition (thinking), mood, and memory. It also can cause anxiety and altered perceptions (similar to but not quite the same as hallucinations). The most desirable effect of ecstasy is its ability to provide feelings of warmth and empathy. Tell students that you will talk about the effects of ecstasy in more detail in a few minutes. There are several parts of the brain that are important in these actions of ecstasy. Point to the neocortex (in yellow), which is important in cognition, memory, and altered perceptions. Point to the several structures deep in the brain that make up the limbic system (e.g., the amygdala (red), hippocampus (blue), basal ganglia (purple), and hypothalamus (green), which is involved in changes in mood, emotions, and the production of anxiety (the hippocampus is also involved in memory). Scientists do not know yet which area of the brain is involved in the ability of ecstasy to generate feelings of empathy (you could ask students to suggest where they think ecstasy might do this - limbic areas are a good guess).


Illustration of neuronal anatomy - see text 7: Anatomy of a neuron

Now that the students know that there are specific regions of the brain affected by ecstasy, you will need to describe how it works. First, indicate that the different regions of the brain are connected by nerve cells or neurons via pathways. These pathways of neurons send and integrate information (electrical and chemical). Describe the neuron using the schematic in this image. The cell body, which contains the nucleus, is the center of activity. Dendrites receive chemical information from other neurons that is converted to electrical signals which travel toward the cell body. When the cell body receives enough electrical signals to excite it, a large electrical impulse is generated and it travels down the axon toward the terminal. In the terminal area, chemicals called neurotransmitters are released from the neuron in response to the arrival of an electrical signal. Tell the students that you will explain this in more detail, using the neurochemical serotonin as an example.

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