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Ecstasy: Neurotoxicity and How It Can Be Reduced

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Biology 202
2001 Second Web Report
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Ecstasy: Neurotoxicity and How It Can Be Reduced

Molly Flannagan

Ecstasy (MDMA) has become a drug of choice among 18-25 year olds (2), and its effects on behavior and neurotoxicity merit the attention of this class. Ecstasy use has become fairly widespread on college campuses and in rave and nightclub settings. This paper will look at the mechanism through which MDMA acts, its neurotoxicity, and how users can reduce risk involved with ecstasy use.

How does ecstasy work?

Ecstasy alters behavior by increasing serotonin levels in the brain. It accomplishes this by altering the neurotransmitter serotonin's reuptake process. (6) In the normal serotonin system, a serotonin neuron will receive a signal from a neighboring nerve cell to release vesicles of serotonin into the synaptic cleft. The post-synaptic cell (which has the appropriate receptors for serotonin) then picks up the molecule. When the serotonin binds to the receptor, it causes an electric signal to change the membrane permeability which causes changes in the body. When a vesicle of serotonin is released, most of the molecules are pulled back into the pre-synaptic cell. This process of drawing serotonin back into the original neuron for it to be reused is called reuptake. When MDMA is present in the system, however, it interferes with the natural process by preventing the serotonin from entering at the reuptake site. This causes an excess of serotonin in the system, which creates the feelings of euphoria associated with MDMA. (1)

Just how neurotoxic is ecstasy?

Users of MDMA are quick to praise the psychological effects of the drug, but the effects on their physical health can be detrimental. Studies show that heavy, prolonged use of MDMA can significantly reduce the number of serotonin transporters which are necessary to bring the neurotransmitter back to the neuron from which it was released. Studies supported by the National Institute on Drug Abuse (NIDA) showed that MDMA damages neurons that release serotonin, and that heavy MDMA users have lingering memory problems for at least two weeks after stopping the drug. In the first study, researchers used positron emission tomography (PET) to compare the brains of MDMA users who had abstained from all psychoactive drugs for three weeks and people who had never used MDMA. They found that the amount of MDMA used was directly linked to the number of serotonin transporters remaining. They also found that the degree of memory impairment is based on the amount of MDMA used. (3)

How can the neurotoxic effects of ecstasy be reduced?

Pre- and Post-loading can be used to lessen the harmful effects of MDMA. Pre-loading is taking supplements before rolling to help counteract the neurotoxic effects of ecstasy. A common pre- load consists of 200mg of 5-Hydroxytryptophan (5-HTP), up to 100mg of Vitamin B-6, up to 1000mg of Vitamin C, and 100mg of Magnesium. (3) Adding more serotonin to the system can counteract the mechanism through which MDMA damages nerve cells. 5-HTP is the direct precursor to serotonin, and can therefore combat the neurotoxicity of MDMA. Vitamin B-6 helps to convert 5-HTP into serotonin, thereby boosting its effect. Because MDMA is thought to be neurotoxic due to oxidized free radicals, the consumption of the anti-oxidant Vitamin C can also reduce the harmful effects of MDMA. Magnesium is used as a muscle relaxer to minimize involuntary jaw-clenching associated with ecstasy use. A post-load consists of the same supplements except that magnesium is unnecessary. (4) It is also beneficial to drink water during and after the use of ecstasy.

How does it all fit together?

Ecstasy has been proven to be neurotoxic when heavy doses are used frequently. However, it also appears that a moderate use of the drug, combined with harm-minimizing supplements can help to counter the negative effects associated with it. Ecstasy has become one of the most popular drugs among college-age students, and its popularity shows no sign of decreasing. As a result, it is critical for users to be informed of the risks involved and how they can reduce these risks. 

WWW Sources


2) National Institute on Drug Abuse

3) NIDA-supported Research

4) Forum on Ecstasy

5) Rave Safe

6) Cannabis News



Comments made prior to 2007

After reading the article Ecstasy: Neurotoxicity and How It Can Be Reduced by Molly Flannagan I have one question. Is it suggested that a person using ecstasy take a pre-load as well as a post-load or is it suggesting to take supplements either before or after and not both times? If you did take supplements before AND after ecstasy use would you be overloading your system with vitamins? Would this be dangerous? ... Melody, 24 May 2006


Party Goer's picture

This article is inaccurate

Supplementation can definitely help with your roll and some of the stuff in this post is good, but there are some mistakes. I will not go through all of them here, but I recently read post that actually uses science and sources explaining all of the suggestions. check it out here

Serendip Visitor's picture


so anyone else notice the person who wrote this is named "Molly"?

Neuroscientist 's picture

Bad Article

Do not take 5-HTP before taking MDMA, you can increase your chance of experiencing serotonin syndrome and becoming very sick or needing a ride to the ER. Also, when you take 5-HTP serotonin will be synthesized and released by dopaminergic neurons. This could potentially cause problems. L-tryptophan is a more "natural" way of boosting serotonin because only serotoninergic neurons will have serotonin levels increased. However, in either case it may not be wise to take it the day of taking MDMA, perhaps taking it the day before is safer. That NIDA link is bogus.

Serendip Visitor's picture

Article is not correct

This article is full of mistakes, do not use this as a resource.
For example, Vitamin C is not protecting your brains from free radicals in the brain als it cannot pass the blood-brain barrier. You need an antioxidant like ALA for it (that is soluble in fat). It is suggested that Vitamin C recycles Vitamin E (which can protect you), though exact amounts are uncertain. Don't count to much on the effects.
Also, 5-HTP is not actually protecting your brain if taken with MDMA. Although this does not happen often, it can induce serotine syndrome if taken with MDMA. It might be true that 5-HTP as precursor to serotonine increases serotonine levels in the brain, and therefore reduces amount of free radicals but this is difficult to prove and 5-HTP has to be taken over a long time.

Serendip Visitor's picture

Everyone always talks about

Everyone always talks about seratonin when it comes to MDMA but norepinephrine and dopamine actually plays a huge role in its affects if MDMA only released seratonin than it would make you all relaxed and lazy and there would be no stimulation or excitement to it at all

Becky B's picture

Amount of Time to Replenish Serotonin Levels?

Hello, I stumbled onto this site and I was wondering if anyone can give me a webpage or some kind of factual based answer on how long it takes to replenish serotonin levels? I have a friend who rolled once last year, waited a year, and then rolled about a month ago. He also did a vitamin preloading/post-loading this last time he rolled. He wants to roll at a halloween event and is wondering if it's been a long enough amount of time to be safe.

Serendip Visitor's picture

Several studies have

Several studies have suggested that a minimum of 4 weeks should be waited inbetween each use of MDMA, but at least 6 weeks is suggested. To decrease the risks associated with MDMA use such as depleted serotonin levels, many users including myself take 5-htp which is avaliable in most supplement/drug stores and encourages and stimulates serotonin growth and can improve the roll/buzz dramatically although this should not be solely relied upon as there is no substitute to giving your body time to recover inbetween uses. I hope this has helped.

Anon25's picture

Amount of 5-HTP to pre-/post-load

This article mentions 200mg of 5-HTP as a pre-/post-load... The pills are sold in 50mg, and double-dose, 100mg capsules. 200mg is a bit much for a pre-load, ESPECIALLY if on a half-full stomach. An EMPTY stomach with 200mg will most definitely make you sick! I took 200mg once and quickly recalled a forum I read that explained to someone why people just don't take a lot of 5-HTP instead of X. The response was along the lines of, "Sure, if you don't mind all the vomiting and diarrhea". And sure enough.... So here's hoping I can save someone else the trouble; you MAY get away with 200mg on a FULL stomach, but I wouldn't risk it, stick to 100-150mg. Taking 200mg when you're about to go to bed after rolling, however, would be better, b/c you'll sleep through any "possible" nausea.

Serendip Visitor's picture


I work at GNC. You can get 5-htp in a 200mg time released tablet. it doesnt make me sick. even on an empty stomach

Anonymous's picture

MDMA is the main ingredient

MDMA is the main ingredient in XTC.. To see exactly what he took you would have to test a sample or if your lucky you can have a look here
you might just find it.

And jordan prescription medicines are PROVEN to be just as dangerous as mdma. i beg to differ on the "everyday average person" because the "everyday average person" could not make mdma even if they tried. Grow up.

Anon25's picture

Thank You

I hate to see uneducated statements like Jordan's... MDMA's chemical structure is closest to that of Adderall, but MDMA is its own drug, it *IS* ecstasy! X is often cut with other amphetamines, which is why all users are encouraged to purchase test kits!

ed's picture

Ecstasy, MDMA and MAOIs

My first question is about the exact chemical difference between MDMA and ecstasy and how this changes its physical effects on the body?

My second question is about MAOIs and ecstasy. Reports have stated that mixing MAOIs with ecstasy MDMA or cocaine is very dangerous to he point of proving fatal. A friend of mine who is on a prescribed dose of 5mg/day of Selegiline (I-deprynl), a selective MAO-B inhibitor was recently spiked with ecstasy. He forcibly puked out what he had swallowed on feeling these symptoms which I believe considerably reduced the damage that intake could have done. He has stopped taking his selegiline since the next day and the only after effects have been a lot of sleep and back pain in the following two days. There is no way of knowing how much ecstasy he consumed aside from the description of 'moderately raised levels of pleasure and excitement'. What are the possible dangers he faces, considering the drug was obviously absorbed by his system given the symptoms he experienced?

Jordan's picture


To answer RE: ecstasy VS SSRIs is; Prescribed medication such as Zoloft and Prozac contain the same sort of chemicals if you will but are less harmful because the people who make them are scientists with university degrees and ecstasy is made by an everyday average person but with different chemicals which are sort of the same but not exactly the same. Also some chemicals found in ecstasy completely different to those in Zoloft or Prozac. They people who make these drugs are supplementing chemicals for others because they want it to be stronger or they cannot get the same chemicals.

Serendip Visitor's picture

Jordan Ecstasy (MDMA) is an SSRI

And is exatcly what it was PRESCRIBED for... In HOSPITALS... In the EIGHTIES!! It was made by scientists in labs just as it is now. The labs may be clandestine but regardless they are equally as integrated with the technique of making XTC if not more creative. Jordan my friend you don't know a damn thing about what you are talking about. Thats all I'm saying.

Anonymous's picture

How long before taking X

How long before taking X should I pre-load the suggested supplements?

Anonymous's picture

About 1.5 - 2 hours before

About 1.5 - 2 hours before if you can... The sooner, the better. I've chased a pill of X with 5-HTP and my pill didn't seem to kick in as good as I knew it could. However, I felt subtle effects of the X longer than I normally would have.

Anonymous's picture

Ecstasy Vs. SSRIs (i.e. Prozac)

It sounds like ecstasy is a seretonin reuptake and why does it differ from medicinal SSRIs (Selective Seretonin Reputake Inhibitors) such as Prozac and Zoloft?

Serendip Visitor's picture

Big difference

SSRI means Selective Serotonin Reuptake inhibitor. They just block the transporters in the brain which re-uptake serotonin from the synapse.

MDMA is is an SNDRI (Serotonin-Norepinephrine-Dopamine Reuptake inhibitor) not just an SSRI. It also a poten SNDRA(Serotonin-Norepinephrine-Dopamine Releasing Agent.)

It releases and blocks the re-uptake of 3 neurotransmitters. It works 10times more on Serotonin than on Dopamine/Norepinephrine, so the effects are mostly Serotonergic(Empathy,Loved up, etc)

Anonymous's picture

RE: Ecstasy Vs. SSRIs (i.e. Prozac)

I have heard that besides inhibiting the functions of the seratonin reuptake systems, it also causes seratonin vessicles to dump much more seratonin into the synapses than normal, whereas SSRIs do the former but not the latter. So not only is less being removed from the synapses, but ontop of it much more seratonin is being dumped in. Making X basically an "extreme SSRI". This could be totally false though.