This Is Your Brain on Ecstasy!
August 16th 2010 04:23
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Serotonin is a neurotransmitter, and some brain cells have axons that contain only serotonin. These are called "serotonin neurons." Other brain cells produce and release different neurotransmitters, like dopamine or norepinephrine, and some produce and release more than one neurotransmitter. However, your serotonin cells only produce and release serotonin.
Ecstasy causes your serotonin neurons to release large amounts of serotonin , which are stored in the axon terminals. This massive serotonin release is responsible for the primary subjective effects of MDMA. MDMA also releases the neurotransmitters dopamine and norepinephrine.
When you take Ecstasy, the vesicles release enormous amounts of serotonin into the synapse. This significantly increases serotonin receptor binding (more serotonin in the synapse means a greater chance for some of them to bind to the receptors). This increased receptor activity leads to significant changes in the brain's electrical firing and is primarily responsible for the MDMA experience (i.e. empathy, happiness, increased sociableness, enhanced sensation of touch, etc.). Notice also that there is some dopamine in the synapse as well (the blue things). MDMA also causes dopamine release (from dopamine cells), but lets not discuss that yet. Keep it in the back of your mind (no pun intended) because it will come up later when we get into neurotoxicity. For now, just notice that the dopamine receptors have also been activated.
The effects of a normal dose of ecstasy last about four to six hours. We will be looking at what happens in the brain during the various stages of an ecstasy experience, as well as some changes that may occur in the brain after long-term, frequent use. But now let's take a look at the "reuptake transporters" (those yellow "H" looking things). To understand how ecstasy works over time in the brain, it is important to know what these things do.
Approximately three hours into your ecstasy experience your serotonin transporters have removed much of the serotonin from the synapse, but there is still plenty around to activate the receptors, so you still feel the desired effects of the drug. Pretty soon, however, the reuptake transporters will remove most of the serotonin from the synapse, and you will start coming down.
Depending on how much MDMA you took, you may end up depleting so much of your serotonin that fewer receptors are activated than before you took ecstasy, when you were in a normal brain state. This is what causes the "ate up" feeling that a lot of users experience when they come down. You can become very depressed at this point, feeling extremely non-social, tired and irritable.
Some people at this point are tempted to take more Ecstasy, because the contrast between how they were feeling an hour earlier and how they feel now is so extreme. But when they take more, it doesn't work. While it may give the user a little more energy (i.e increase the speediness), they won't recapture the empathy and other desirable MDMA effects. Remember, Ecstasy releases (and then depletes) the serotonin that you already have. It doesn't cause more serotonin to be created.
Your brain needs time in order to rebuild its serotonin levels. This could take up to two weeks. As expected, the larger the dose the greater the serotonin depletion and the longer it takes for your brain to replenish it.
One of the ways your brain adapts is through the up-and-down regulation of receptors. What this means is that if your serotonin receptors get hyper-activated by serotonin molecules, they may retreat into the membrane of the dendrite, essentially shutting themselves down for a while. One theory says they do this in order to avoid getting damaged from over-stimulation. Another theory says that it is just a way for your brain to maintain a balanced, normal state. Whichever one of these theories is true, it has been proven conclusively that serotonin receptors will down-regulate over time if bombarded with large amounts of serotonin.
This may lead to depression, even after your brain serotonin levels have been restored, because the serotonin cannot bind to downregulated receptors. Many ecstasy users we have interviewed have reported periods of depression lasting months or even a year or more following a period of heavy use. Keep in mind, however, that most evidence of MDMA-induced depression is anecdotal, based on reports by MDMA users. Since many people experience depression it is difficult to know for sure whether the depression experienced by MDMA users is really related to their MDMA use. While MDMA is known to reduce serotonin levels, serotonin levels varies greatly among healthy, non-depressed, non-MDMA users. Until more research is done, we cannot know for sure whether MDMA users actually have a greater risk of experiencing depression than non-users. (Of course, it is wise to be cautious, and so we have included a section on our health and safety page about ecstasy-related depression.)
Let's now turn to the issue of neurotoxicity . . .
The most current theory of how MDMA causes neurotoxic damage in laboratory animals goes like this:
After MDMA depletes serotonin, the reuptake transporters are left vacant and exposed. When this happens, dopamine enters the transporter and gets taken up into the serotonin axon, where it isn't supposed to be. Studies have shown that dopamine itself is toxic to serotonin cells. But if that weren't enough, MAO comes along and breaks it down into hydrogen peroxide, which is also toxic to the cell. (Yes, the same hydrogen peroxide they put in hair bleach!) The hydrogen peroxide then "oxidizes" certain parts of the cell which don't normally get oxidized ("oxidize," as used here, basically means to break down with oxygen). Researchers sometimes refer to this as oxidative stress, and a number of studies have looked at anti-oxidants like Vitamin-C as a possible agent to prevent MDMA's neurotoxicity (see our section about pre-loading on our neurotoxicity page for more info on this).
Once again . . .
To re-cap we have (1) serotonin depletion causing the uptake transporters to become empty. Then (2) dopamine, which exists in higher levels in the synapse now, enters the uptake transporter. (3) This dopamine is broken down by MAO into hydrogen peroxide. (4) The dopamine is toxic to the cell and so is the hydrogen peroxide, by producing oxidative stress.
How did they come up with this theory? And is there evidence for it?
The researchers who first devised this theory (Jon E. Sprague, Shannon L. Everman and David E. Nichols) called it an "integrated hypothesis." They looked at a decade worth of MDMA research and tried to put the pieces together. They came up with this theory in the summer of 1997 and it was published in 1998. To date, it is still the dominant theory of how MDMA causes axon damage in laboratory animals, and would most likely apply to humans as well, should neurotoxic damage in humans be proven conclusively.
What if you take Ecstasy while you're on Prozac?
Prozac has a greater affinity for the reuptake trasnporter than MDMA and serotonin both. Most people on Prozac don't feel much when they take ecstasy, because the ecstasy cannot get into the serotonin axon terminal in order to release the serotonin. The ecstasy does cause some dopamine release, as well as norepinephrine, so the user will feel a little something. But the primary effects will be largely inhibited.
Of course, this depends on how much Prozac the person is on, and how big of a dose of MDMA the person takes. Someone on a low dose of Prozac (10mg) will feel more effect than someone on a high dose (40mg). Someone who takes a low dose of MDMA (60mg) will feel less than someone who takes a high dose (150mg).
Interested? well if you are do use the link which will take you through a slideshow to show you what this ecstasy is all about.
Think twice, you fool, there's one born every minute.
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