I just noticed the word is spelled “ecstasy” in the text of Cecil’s answer and in Slug’s illustration, but “ecstacy” in the headline for the page and on the homepage link.
:eek:
Cecil’s column is very thorough, and mentions all the mechanisms of fatal MDMA toxicity that I know of – everything from rhabdomyolysis to dilutive hyponatremia. It’s also refreshingly realistic in a world of shocking PSAs about people who died from taking a single tablet of pure MDMA. (This is incredibly rare, and there are probably far more cases of people who died from taking a single pill of acetaminophen.)
Temperature is a major factor in determining the risk of death via hyperpyrexia as well as neurotoxicity – it’s been shown that MDMA is far more neurotoxic at high temperatures, which is disturbing considering the environments it’s often used in. The first MDMA overdose to receive a lot of media attention here occurred at a hot, dusty, poorly-ventilated location (an industrial basement) without running water. Unfortunately, it’s hardly surprising that such an environment, combined with heavy drug use and strenuous physical activity (MDMA, being a stimulant, can allow people to dance for hours without stopping), can lead to severe harm or death.
Neurotoxicity is, I think, the primary reason not to take MDMA. There are not many drugs which have such severe neurotoxic effects – nothing recreational that I can think of, except methamphetamine. One of the few very neurotoxic drugs is MPTP, the product of a failed batch of synthetic heroin, induced advanced Parkinson’s disease in a group of addicts in the 1980s. MDMA isn’t really all that far behind, if the in vitro and animal studies are to be trusted.
Initial problems with animal studies have been mostly resolved – experiments have been made with doses similar to those taken by heavy MDMA users, and neurotoxicity does appear. (Initially, the doses were unrealistically high.) What remains to be seen is conclusive evidence that MDMA causes neurotoxicity in humans and that it has functional effects on them.
Several methods of decreasing the neurotoxicity are known (mostly because MDMA is a public health concern). SSRIs have been suggested for some time, but they also decrease the effect of the drug, which may lead people to take more of it. Vitamin C is an antioxidant which scavenges the free-radical metabolites of MDMA and dopamine (hydrogen peroxide is often mentioned), and supposedly reduces neurotoxicity. Other antioxidants, such as Vitamin E and alpha-lipoic acid, have also been suggested. Another concern is the depressed levels of serotonin following MDMA use; this can be partially rectified by taking SSRIs before MDMA. But MDMA is an irreversible inhibitor of tryptophan hydroxylase, one of the enzymes in the serotonin synthesis pathway, so the decreased serotonin levels are a product both of depletion during the MDMA high and of lowered production capacity lasting several weeks afterward.
I should note that ‘special K’ – ketamine, a veterinary anesthetic – has a very high threshold of safety. It’s very difficult to overdose on, but saying a person died “after taking MDMA and Special K” adds to the shock factor because they were taking horse tranquilizers. I’m not exactly sure how ketamine and MDMA interact with respect to body temperature, but there is likely to be some interaction. There are other drugs – an amphetamine analog called PMA, which is sometimes sold as MDMA, is the best known – which increase body temperature drastically and are very dangerous with MDMA. Methamphetamine, which is a tragically common party drug, is also in this category.
Now, neurotoxicity is the main reason why I don’t use MDMA, but not the only reason. MDMA users often don’t realize this, but those who are not under its influence can find them very annoying. =) MDMA use also leads to enjoyment of very bad music, and chronic MDMA users often become self-absorbed and arrogant. This seems strange given the effect of the drug itself, I know, but it happens – probably because MDMA users make a lot of shallow friendships with other users, and consider themselves very popular and important. MDMA users often befriend people they wouldn’t ordinarily like, or fall in love with people they aren’t compatible with; this is very bad socially.
If I recall correctly from my reading of The Case of the Frozen Addicts, by Langston William, the doctor who figured out the whole thing back in the 80’s, MPTP (methyl-phenyl-tetrahydropyridine) is structurally similar to meperidine (Demerol) but is different enough that it doesn’t bind to the mu opioid receptor, and hence has no use as a recreational drug. But its close relative, MPPP (methyl-phenyl-propionoxypiperidine), is a potent mu opioid receptor agonist, and thus is a highly desirable drug.
Unfortunately, a slight mistake when making MPPP will result in at least some MPTP being created. By itself, the MPTP is no big deal, but it is metabolized by monoamine oxidase type B into MPP+ (methyl-phenylpyridine). And unfortunately, MPP+ is not a good thing in the brains of primates, including humans – it is absorbed into the “substantia nigra,” a black-colored clump of cells in the brain that produces a lot of dopamine and is necessary in order to translate conscious thoughts into voluntary muscle movement. When enough MPP+ has accumulated that the substantia nigra is nearly destroyed, the person loses the ability to move voluntarily. This is essentially the same thing that happens with Parkinson’s.
Frankly, this is one of the more horrifying fates I can imagine – all the negative aspects of being paralyzed all over your body, but you can still feel pain and can itch and everything. And not just from the neck down like quadriplegia – this includes paralysis of the face, eyes, eyelids, etc. And of course you can’t speak either, so you can’t explain to people that you’re not actually comatose or catatonic, but fully conscious and feeling pain. People who have taken MPTP have fallen asleep from the opioid effects and woken up to find that they can’t move from the position they fell asleep in; one woman was in the same position for three days before she was found, by which time a nerve in her leg had been crushed for two of those days, causing unimaginable pain and fear.
Of course, since the problem is essentially a lack of dopamine in the region of the substantia nigra, MPTP-induced Parkinson’s (and anything similar, like the syndrome Oliver Sacks described in Awakenings, which was also a result of the destruction of the substantia nigra, but in those cases it was the result of some kind of illness rather than a result of drug use) can be treated by replacing the dopamine. But dopamine won’t fit through the blood-brain barrier, and injecting something directly into the brain is not usually viable long-term treatment option so you have to give patients levodopa (aka L-dopa), a dopamine precursor which does fit through the blood-brain barrier and which is quickly metabolized into dopamine. This will miraculously “unfreeze” the patient.
But of course there’s a problem – the dopamine that needs to be replaced is in a very specific location, and while treatment with levodopa will replace that missing dopamine, it does so by flooding the entire brain with dopamine. And flooding your whole brain with dopamine is undesirable, not only because dopamine is associated with the brain’s reward system and large doses of dopamine can be addictive, but also because the visual cortex and lymbic system and other parts of the brain can become hyperstimulated, causing wild hallucinations and extreme mood disturbances. People report seeing snakes and bugs everywhere, and they report powerful feelings of fear and anger. And then movements become exaggerated and uncontrollable, producing violent tremors and tics and the like. Eventually most patients have to stop levodopa therapy because the side effects have become intolerable.
The only therapy that I’m aware of that has reported slight long-term potential success is stem cell transplants onto the area of the substantia nigra, but since the stem cells are almost entirely derived from aborted fetal tissue, there are major political and ethical concerns associated with this treatment. But those who have tried it have reported at least slight success.
So the moral of the story is, if you’re going to take drugs, at least know precisely what it is you’re taking before you actually put it in your body – moral issues aside, it would be terrible to end up with instant permanent Parkinsonism just for a few minutes of euphoria.
I was wondering if you have a cite for this. I’m not denying it, I’m just interested to see what study/s this came from.
How silly of me not to mention this in my original post. The depleted serotonin levels can be overcome by post loading with 5-HTP (5 - Hydroxy Tryptophan).
Tryptophan (an amino acid) is a precursor to serotonin. Tryptophan is found naturally in turkey, bananas, meat, fish, poultry, nuts, soybeans, peanut butter, cooked dried beans, and dairy products. To produce serotonin, the body needs plenty of tryptophan, but unfortunately only about 1% of tryptophan makes it to brain in the form of 5-HT (serotonin), 98% is degraded and excreted through urine. The other 1% is used to make proteins and vitamin b3
The body converts Tryptophan to 5-HTP and then to 5-HT. The process of converting Tryptophan to 5-HTP is quite slow though (from memory several days) so eating foods high in Tryptophan is not going to replenish the lost serotonin quickly enough to have any effect in reducing neurotoxicity.
The conversion from 5-HTP to 5-HT though is quite quick (again from memory several hours), it is also quick to cross the blood/brain barrier, which means that serotonin can reach the brain in enough time to reduce neurotoxicity (obviously if there is serotonin in the synapse then dopamine will not be taken into the serotonin reuptake transporters, thus reducing neurotoxicity).
I like to pre load with 200mg of 5-HTP daily for 2 days before I take MDMA (this is to make sure I have plenty of serotonin in the brain to increase the effects of the MDMA). When I take the MDMA I take 1000mg of Vitamin C, and again another 1000mg of Vitamin C after 4 hours. I take another 200mg of 5-HTP (post loading) with food (I should state that you need to have food when taking 5-HTP as it is really quite harsh on the stomach) after the MDMA has worn off and before I go to sleep. The next day I will take another 200 mg with my first meal. This combination greatly reduces the come down, I don’t feel the slightest bit scattered the next day. I can vouch for this as I have also had MDMA without doing this and the next few days after you feel awful, you don’t feel like talking, your slightly moody, and its quite hard to concentrate.
It should be noted as well that taking methamphetamine/amphetamine in conjunction with MDMA greatly increases the neurotoxicity of these drugs.
I just plain disagree with a lot of this paragraph, but it’s your opinion and you’re entitled to it.
Have you ever tried MDMA before Roches?
[iSeveral methods of decreasing the neurotoxicity are known (mostly because MDMA is a public health concern). SSRIs have been suggested for some time, but they also decrease the effect of the drug, which may lead people to take more of it.*
The SSRI is to be consumed a couple of hours after taking Ecstasy.
I was under the impression that most (if not all) SSRI’s were only obtainable by prescription.
5-HTP and Vitamin C can be bought from chemists/health food shops without prescription, making it less of a hassle to get them.
Plus pre loading with 5-HTP will ensure your brain has plenty of serotonin for the MDMA experience (ie increase the effect of the drug instead of decreasing it, as with SSRI’s)
Where do you get 5-HTP supplements INSANE1? Are they available over the counter?
I remember the FDA banning tryptophan supplements back in the 80’s or early 90’s … wonder if that was 5-HTP or just actual tryptophan … do you live in the USA? Or elsewhere?
I live in Australia. I get my 5-HTP from www.clubnatural.com, the brand I get is here.
I should have clarified, I can’t buy 5-HTP in Australia (except in Queensland), though it is legal to order it from overseas.
I only mentioned you could get it in health food shops because I figured most of the people on this message board are American and the site I get 5-HTP from is American too.
There are other online shops where you can buy it from, but I have found ClubNatural to be the cheapest.
chorpler: If I remember correctly, MPTP is the result of a failed Demerol synthesis; I think it had something to do with an unforeseen E[sub]2[/sub] elimination reaction. About 5-HTP: it’s available in health-food stores in most areas (it’s used as a mild antidepressant/mood brightener). Tryptophan supplements (but not amino acid supplements containing tryptophan) were banned because of one contaminated batch. The ban hasn’t been lifted. (It’s theoretically possible to synthesize LSD and some other hallucinogens from tryptophan, so that might be why it’s still banned.)
INSANE1:
The low-dose oral study (which also introduces the idea of MDMA being toxic to dopaminergic neurons) is Ricaurte et al., Science 297, 2260-2263 (2002). An example of a study of functional effects potentially caused by MDMA neurotoxicity is *Br. J. Psych. *91, 181-188 (2000). One article that argues that the evidence for MDMA neurotoxicity is weak is *Pharmacol. Biochem. Behavior *71, 845-855 (2002). Note that the last article is written by a Canadian author, while Ricaurte is American.
I somewhat deliberately didn’t mention 5-HTP. There are a few issues with it; it’s not really all that good at crossing the blood-brain barrier, for one.* Also, pre-loading with 5-HTP may potentially increase the deleterious effects of MDMA and the risk of complications as well as increasing the positive effects. But, yeah, I know that 5-HTP is a possible way around the tryptophan hydroxylase inhibition issue. As I mentioned before, you should look into Vitamin E and alpha-lipoic acid in addition to Vitamin C. I’ve lost my reference for that.
*: I think the carboxyl group would make 5-HTP too polar to cross the BBB, which excludes polar substances.
About my last paragraph: yes, it’s my opinion, but it’s based on experience. It works like this:
MDMA makes music sound better, so people on MDMA like music that they would not ordinarily like. =) (I think you know what I mean.)
MDMA makes people seem better and makes social interaction easier, so people on MDMA like people they would not ordinarily like (as much).
It also makes people think they’re really, really cool. They talk differently (yo, guy, lets spin this up). They do strange things. I guess the extreme examples are sitting in groups on floors, wearing plastic bracelets and furry things, dancing poorly, talking like kids, and SpEllInG wOrdZ liKe dIS!!!*
*: i.e. candy ravers, which apparently still exist. I should note that large groups of people doing MDMA together tend to have shared experiences, so the social effects of the drug can be quite different in non-club/rave settings.
All these things annoy me. Just me; I know it’s really enjoyable for them. I guess this is a personal thing; I just don’t like the way people on MDMA act. So, for me, a reason not to do MDMA is that I know it’ll make me act like those people.
I also get to like much better music this way. =) And, if Dr. Ricaurte is right, I get to keep my serotonin neurons, and I’m not going to become parkinsonic before I’m 30.
Bah. Stick to LSD like I do.
I fail to see why these are bad things.
Bullshit.
Aside from the SpEllInG (which is very annoying), I don’t see what’s so awful about any of this. Dancing is fun no matter how well you do it.
If I’m not mistaken the study you mentioned by Ricuarte (Science 297, 2260-2263 (2002)) was retracted after he found out that he had been mistakenly giving the animals methamphetamine instead of MDMA. Cites for this are here, here, here and here.
You will notice all the links come from the same site www.maps.org. This is a site advocating the use of MDMA for medical reasons. The only reason I copied the cites from there is because they keep links to articles of this nature and I was too lazy to google for the original links.
Also the study wasn’t oral doses (as far as I can see) of MDMA but rather the drug was intravenously administered, and I know of no one who shoots up MDMA (I have heard of it happening, but the effects seem to be too intense and aren’t enjoyable, no one seems to do it twice).
Ricuarte is also getting funding (in the tune of millions of dollars) from the National Institute on Drug Abuse and therefore working with an agenda to keep his funding. I wouldn’t trust a study run by this gentleman.
MDMA users often don’t realize this, but those who are not under its influence can find them very annoying. =) MDMA use also leads to enjoyment of very bad music, and chronic MDMA users often become self-absorbed and arrogant. This seems strange given the effect of the drug itself, I know, but it happens – probably because MDMA users make a lot of shallow friendships with other users, and consider themselves very popular and important. MDMA users often befriend people they wouldn’t ordinarily like, or fall in love with people they aren’t compatible with; this is very bad socially.
Sorry, I don´t know how to make the quote mark thingy but I have to say that this it the absolute opposite of all my experiences. I still hate bad music, become very concerned with everyone around me and and am pretty much just a happy camper. The same goes for almost everyone I know.
I´d say that what you talk about sounds more like cocaine users to me, it´s the reason I gave it up. You behave like an utter, utter idiot on that stuff…
Personally I never had any problems while on E but I eventually gave up on it since it seriously messes with your head and I grew tired of SSRI´s. I´ve only had a friend “OD” a couple of times and we took care of that with the standard cooling techniques. Mind you, none of those who had the problems had been dancing at all or doing anything physically exhausting (with the obvious excepton of eating E) before, so I don´t believe that the heat just comes from exertion.
so I don´t believe that the heat just comes from exertion
True, Ecstasy impairs your body’s regulation of temperature. But to cause huge rises, you need to either exert or take large doses. A regular single dose (anywhere between 60-120 mg) and relaxed behaviour does not induce fatal pyrexia.
Does this impairment of body temperature regulation also mean, perhaps, that MDMA will aid in weight loss? (What with more calories being burned to heat up your body, and stuff?)