Guess what? It was the MDMA that killed her.

Nov 23 2009 Published by under MDMA

I am grateful to occasional reader and commenter Klem for putting me on the track of an older story. Klem was trying to argue that the authorities in Canada have long been issuing warning about non-MDMA content of "Ecstasy" and about the methamphetamine in particular. This is not news to me, of course. I am not unaware of the problem of non-MDMA psychoactive content of putative "Ecstasy" obtained on the illicit market. What I attempt to address, of course, is the seeming default assumption in the news reporting and subsequent reader comments that every case of Ecstasy fatality must have been caused by something (anything) other than 3,4-methylenedioxymethamphetamine.
Klem cites some 2005 reporting out of Vancouver and I was struck by this comment in the story.

A 13-year-old girl died in September when she took what she and friends believed was ecstasy they bought from a street dealer in Victoria.
Richard Stanwick, chief medical health officer for Vancouver Island, said an amphetamine overdose was suspected in Mercedes-Rae Clarke's death.

The tone is typical bait that is found irresistible by YHN. Statements that are more or less true in isolation adding up to a synthetic conclusion on the part of the reader that is just not justified at all. In my view, this type of report gives the reader the overwhelming impression that that bad scary drug they know as "Crystal Meth" (c'mon if it is in the common ecstasy preparation of a tablet or hydrochloride powder it is most assuredly not crystal) and not the totes safe and benign MDMA is at fault here.
Reporting on another incident a year later mentioned this case, again in the context of conveying the notion that methamphetamine in supposed "Ecstasy" was really at the root of medical emergency and death. Going to the Google, I find quite a number of followup re-postings of this essential story, including on what look to me like user forums. [You know, Duwayne, alleged harm reduction forums? Just sayin'..] Most of which follow this common thread of assuming or insinuating that if someone takes purported Ecstasy and goes into some sort of crisis it must be something other than MDMA.
As you know by now Dear Reader, I like to counter this impression.
The strongest way to do so is to point to available epidemiological evidence. Also, sometimes the Case Reports go out of their way to emphasize that all that was found was MDMA. Unfortunately this is far from universal. Some of the older Case Reports fail to cover much about the drug in question and, especially, fail to emphasize that they went looking for a host of other suspect compounds in addition to MDMA, if they even bothered to do so.
I like to point out, however, that in some of the deaths reported in the mainstream media, there will be followup stories confirming MDMA as the cause once the toxicity reporting comes out. Remember this story out of Edmonton? Well that area had another Ecstasy-related death last month and the story mentions the prior case without any inclusion of postmortem toxicity data which are surely available by now! Very regrettable that.
At any rate, the case of Mercedes-Rae Clarke from 2005 does have a followup which I found here.

She was with two girlfriends; one had tried ecstasy before and said it was fun. That girlfriend had bought three pills for about $10 each from a guy on the street in downtown Victoria.
When the three girls swallowed the little pink pills, Mercedes began almost immediately to vomit. Soon she complained of a terrible headache and that she couldn't see. Then her eyes rolled back into her head, and her body contorted in a seizure. One of the girls ran to the nearby house of a family friend to get help.
When [Mercedes' mother] arrived at the hospital about 90 minutes later, her child was unconscious, medical staff working around her. Mercedes never woke up again. Over the next 24 hours, she continued to have seizures, her blood pressure skyrocketed, her temperature soared, she had multiple heart attacks and resuscitations. She was placed on life-support on Sunday night. Everyone prayed a miracle would save her.
By late Monday night, Mercedes's brain scan showed no activity: The tiny pink pill had rendered her brain-dead.

Not atypical. The Case Reports often contain seizure or seizure-like symptoms as the first thing noticed and the trigger for someone calling emergency medical services in. This seems to be a universal for when toddlers are found to have accidentally ingested their parents' stash, btw. This story on Clarke is datelined in Sep 2006 so all subsequent news reporting which mentions this case should have considered the following. Right?

[Mercedes's mother] says the coroner's office told her a few weeks later that the drug was pure ecstasy--not laced with crystal meth, as rumour had it. Sherry also wants the world to know: "Ecstasy is seen as the fun drug, the one to take to a party and have a good time with, not nearly as bad as crystal meth. But ecstasy can kill, too."

Yes, yes it can.

19 responses so far

  • Jesse says:

    I'm not one of those who says or thinks MDMA is harmless, but what was (or what is a good working hypothesis) for the X-factor that allowed two of the three subjects (if we frame this as sort of an experiment) to survive with no ill effects?
    I mean, is it like certain drugs that are fine in some situations but you should never take with alcohol? (Like sleeping pills, to give a common example). Is it like the allergic reaction to penicillin?
    Most people who take MDMA don't die on a first go. So there is something that makes some people more prone to harm, it seems to me. Maybe an allergy, maybe some other issue?
    (Again, I am not endorsing it as a drug with no problems or ill effects, and god knows I am not saying anyone should take it willy-nilly).
    Most drugs I know that you OD on -- well, you need to OD. Heroin is not good for you but you can take it for quite some time before it really gets awful. Same with cocaine. I'm basing this on the fact that many doctors become addicted (more than people like to admit) and they are fine, with usually no outside indications of addiction until the dispensary checks its books. (In the US, this can take some time. I know at least one doc who was taking injectable cocaine for something like a year before the CDC called and asked if there was an epidemic of ENT problems. Thankfully he went to rehab).
    I think one reason that people are reluctant to believe many drugs do do harm is the absolute inability of many media outlets to get across the concept of differential harm. So they run a million 'reefer madness' stories. Think of all the urban legends surrounding LSD. This is especially true with drugs that a lot of people haven't taken. Nobody believes the reefer madness of reefer anymore, since something like 50% of adults have tried it at least once. Not many people have tried LSD so you can say any old thing about the effects and many will buy it.
    MDMA is in a middle stage, I think, as many teens and young adults have tried it, but not as many as marijuana. So the media outlets run all kinds of scare stories and the ones who have tried it don't believe it. (Understandably). The ones who haven't tried it sometimes eat this stuff up. And then they write another story that says MDMA will make you retarded or insane after one dose, and the cycle begins again.

  • Steve Clay says:

    I get the impression that DrugMonkey has no idea, he just wants us to know that we shouldn't rule out the possibility that pure MDMA (as would be available in the "legal and regulated" system some propose) may be all that's necessary to cause these kinds of incidents; that taking the drug could be akin to skydiving--almost completely safe, except when it kills you.

  • Shira says:

    If she vomited "almost immediately" after taking the pill, it's extremely unlikely that the undigested, now regurgitated pill caused the vomiting and other symptoms. She didn't snort it, she didn't smoke it, she didn't take it as a liquid tincture, so how could it cause immediate symptoms? Just because the symptoms started right after she took the pill, doesn't mean the pill caused them.

  • Ian Musgrave says:

    Jesse wrote

    but what was (or what is a good working hypothesis) for the X-factor that allowed two of the three subjects (if we frame this as sort of an experiment) to survive with no ill effects?

    It could be a) polymorphisms in either the drug metabolism enzymes or the receptors for the drugs or b) (less likely) drug-drug interactions.
    The body has a wide variety of enzymes that break down xenobiotics (literally anything from outside the body, including drugs). All of these enzymes have genetic variants, and different people have different combinations of these genetic variants. About one in 10 Caucasians do not get pain relief from codeine, because they have a poorly active variant of the enzyme which converts codeine to its active metabolite (morphine). That particular enzyme (cytochrome P4502D6) has around 80 variants, some of which have more activity, some of which have less or no activity, compared to the major variant.
    Similarly with the receptors that get activated by (indirectly) MDMA, these have a variety of genetic variants which might be involved an exaggerated response to MDMA. Not to mention variants of transporters, monoamine oxidases etc. etc.
    It is entirely possible that the lady in question had an enzyme variant which did not metabolise MDMA, possibly in conjunction with other variants, resulting in MDMA reaching toxic levels in her. Just as in the same way people with certain genetic variants can have toxic reactions from therapeutic levels of paracetamol.
    MDMA can by itself cause death or serious harm, and a big problem is that occurrence of the harm is unpredictable. To put this in perspective though, in the five years from 2001 MDMA was associated with 82 deaths in Australia. The number of MDMA users in Australia is not clear, but around 10% of 14-19 year olds and 6% of 20-29 year olds use the drug at least once a week (around 20% take it once a month). This gives a crude case fatality rate in the region of 0.01%, not dissimilar to that of the pain killer paracetamol (around 0.01% for UK and the US, can't get Australian figures).
    Both of these figures are distorted (multidrug use for MDMA and use in suicide for Paracetamol), but at least for acute ingestion, MDMA and the OTC analgesic paracetamol have similar toxic event incidences.
    Another way to look at it is that it has been estimated that roughly 100,000 MDMA containing pills are consumed each weekend. This means that (over 5 years, if the MDMA consumption figures are correct to within an order of magnitude) there is one death for every 320,000 pills consumed(or 1 in 390,000 if we only look at cases where we are sure that MDMA was directly involved), so while deaths are relatively rare, they occur at an appreciable rate per pill .
    Whether the risk/benefit ratio (feeling good with MDMA verses removal of pain with paracetamol) is similar is a matter of debate. But the bottom line is that MDMA can kill by itself, and while the risk is low it is very unpredictable.
    Educating people about these risks, given that people can wave away relatively high risks and yet run screaming from safe interventions like vaccines, is very problematical.

  • DrugMonkey says:

    IM, I touched on the poor metabolizing individual here at the end
    but did not yet get around to discussing the paper extensively. The de la Torre group seems to have concluded that individual differences in metabolism are less important than mechanism based inhibition of hepatic drug metabolism. Could be additive factor though?
    Shira, I suspect the imprecision of "almost immediately" covers a window sufficient for gastric absorption...
    Steve, it is blogging...a weakness is that I tend to take up limited topics in a given post, see above link for one avenue. I've talked a little about dose issues before too. I have not really talked about the environmental contributions nor, to my recollection, plasticity along the lines of sensitization. I may get to some of that eventually...

  • DuWayne says:

    Jesse -
    Ian actually provides a very good explanation, but I would like to make it considerably more concise - different people have different reactions to MDMA. This is true of all drugs, illicit or otherwise.
    Consider it from the perspective of general pharmaceuticals. Death is just one of the potential side effects of MDMA - not a statistically insignificant one. All drugs have potential side effects, it just happens that in this case one of those side effects happens to be rather more serious and direct than most.

  • Jesse says:

    Thanks, that helps a lot, all of you.
    I have to say I get skeptical too when I see a big screaming headline that says 'Ecstasy Killed My Daughter' or some such. Granted, it's my entirely non professional experience with the drugs involved, which always led me to believe that the bad drugs / drug taking (like heroin addiction) have effects that are much more prosaic -- and much sadder. And a lot of the legal drugs have, to my mind much worse and more immediate effects. See alcohol as exhibit A. But when you have been in close contact with a violent alcoholic it tends to bias you, you know?
    (In that case, hell, I would much rather the person had been taking ecstasy or smoking marijuana rather than drinking).
    But again, I am not one of those who thinks MDMA does no harm. It is an interesting drug, I will admit. (Though I don't seek it out anymore, as I did when I was a young 'un). I also think it could be used therapeutically -- there was some work on it as an anti-depressant for PTSD patients a while back (UNC I think?) but I don't know what they found, if anything.
    IM, noice comparison of toxic event instances, and I might add that the relative vriations in the quality of MDMA also play a role, whereas paracetemol (I can never get over that term 🙂 ) is more consistent.

  • Ian Musgrave says:

    DrugMonkey wrote:

    The de la Torre group seems to have concluded that individual differences in metabolism are less important than mechanism based inhibition of hepatic drug metabolism. Could be additive factor though?

    That's important for multiple dosing. In the situation reported, where the subjects had only taken one pill with no prior ecstasy consumption (and as far as we can tell, no prior consumption of drugs that inhibit CYP2D6 like antidepressants), then CYP2D6 polymorphisms could play an important role, and mechanism-based inhibition no role.
    In the situation where people take a pill every day [1], and you get mechanism-based inhibition, then metabolite inhibition will make normal metabolisers have much higher MDMA concentrations, possibly enough for a toxic effect. Even so, in the de la Torre et al, 2005 study, after repeat dosing (metabolic inhibition) the MDMA AUC for the CYP*4/*4 poor metabolizer allele was still 2 times larger than the MDMA AUC of the CYP2D6 *1/*1 normal metabolizer, so I wouldn't like to say that mechanism-based inhibition was more important, especially if the subject had a phenotype more severe than *4/*4 (eg *5/*5 deletion). It certainly is an important factor to consider though.
    Mind you, with so many other possible polymorphisms in the metabolic pathways and transporters (eg the serotonin transporter which is important for MDMA's actions) and receptors (eg 5HT2B receptor polymorphisms) concentrating so much on the CYP2D6 might be a distraction, despite it being such an important pathway.
    Parenthetically de la Torre et al, 2005 used t-tests for data I know are non-normally distributed (AUC and Cmax), a bit slack. But the trick of using an outlier test to determine if their single CYP2D6*4/*4 subject was different from the CYP2D6*1/*1 was cute. I'll have to see if I can get that past the reviewers some time.
    [1] Or as more likely, go for the week without ecstasy, then pop a pill on Friday, and another couple on Saturday, then there is the potential for serious toxic levels to accumulate with the Saturday dose. First time users experiencing sever toxic reactions/death (assuming that friends/parents reports of subjects ecstasy use are accurate) will not have the metabolic-inhibition mechanism operating (unless they are on certain antidepressants or other drugs that inhibit CYP2D6).
    (disclaimer: I don't do research on the pharmacokinetics of MDMA, I try and kill pretend nerve cells with amyloid then rescue them with green tea extract. However, the folks two floors up are MDMA researchers, and I've been to enough presentations, poster sessions and marked enough of their theses to fake knowing something about the PK of MDMA)

  • DuWayne says:

    Jesse -
    You are making a false equivalence here, with this notion that there are other drugs that are far worse - on multiple levels.
    The first is in the baseline assumption that the effects of other drugs has anything to do with whether or not MDMA can cause the harm being claimed here. The harm being claimed here has been substantiated - people do in fact die of a normal dose of MDMA. That other drugs may or may not be more dangerous is completely irrelevant. That is not the question being discussed.
    The second is that in the case of MDMA, we are talking about an average single dose. Unless a person is severely allergic to either, a single dose of alcohol or heroin is quite unlikely to kill anyone or even make them seriously ill. The odds in those cases are considerably lower than the odds with MDMA.
    The third is that the immediate effects are not what you seem to make of them. The cases of MDMA death are very immediate. One does not, however, develop an acute dependence on heroin or alcohol immediately, based on a single dose. And honestly, people who have had a single drink aren't generally all that sad a sight and people on a single dose of heroin aren't either. With both it is the long term affects of abuse/addiction that are so unpleasant.
    Finally, yes, MDMA has been investigated as a potential treatment for PTSD. Not only has it been investigated, it has also shown a great deal of promise, in three studies that I am aware of. The problem that we end up coming back to, is that there are other treatments that show roughly the same level of efficacy, that are not as dangerous. Immediate death, via mechanisms we really don't understand is a hell of a something to put on the side effect profile - a pointless and unacceptable risk. This might be mitigated if we could work out why some people die from a single average dose - but without knowing what characteristic about a person would determine that, it would be irresponsible to prescribe it.

  • Jesse says:

    DuWayne -- I was just thinking that the sensational headlines often don't capture what really goes on, you know? Yes, people die of MDMA use. And people here posted great explanations of why it doesn't behave like the OD-able drugs I knew better.
    And you can OD and die from heroin (or booze, for that matter). When I said there were other drugs that could be worse I was thinking of how many kids injure themselves with booze - or even die. I understand they aren't taking a 'single dose' in the pharmaceutical sense.
    That's why I brought up the relative consistency of MDMA quality/manufacture, in light of the post about relative risks compared with tylenol/paracetemol. I was just thinking that one issue is that you never quite know what you are getting with MDMA.
    And thanks for the update on the PTSD research. I didn't expect that MDMA use would necessarily go anywhere, and frankly I thought the effects wouldn't necessarily help (unless you were able to rejigger it so it wasn't so extreme) and as you pointed out, the non-zero risk of dying isn't cool either.

  • Ian Musgrave says:

    DuWayne wrote:

    The second is that in the case of MDMA, we are talking about an average single dose. Unless a person is severely allergic to either, a single dose of alcohol or heroin is quite unlikely to kill anyone or even make them seriously ill.

    Not true for heroin. The response to heroin is also determined by receptor and metabolic enzyme polymorphisim. The majority of "average dose" deaths is due to acute respiratory depression. The "single dose" death rate is a bit hard to accurately reconstruct, but "single dose" death rates (somewhere around 17% of all heroin related deaths, counting only young first time or recreational users) are around 1 per 100,000 people for heroin, whereas for MDMA it is more like 1 per 1,000,000,000.

  • Ian Musgrave says:

    DuWayne wrote:

    The cases of MDMA death are very immediate. One does not, however, develop an acute dependence on heroin or alcohol immediately, based on a single dose.

    No, but you can drop dead more or less straight away from respiratory arrest with heroin.

  • DuWayne says:

    Ian -
    First, could you possibly provide a citation for the single dose death rate for heroin. I really don't have the time to spend trying to dig it up, but I hate spreading misinformation. It was my best understanding that a relative standard dose would be exceedingly unlikely to be fatal and that is where I come from when it is discussed (I occasionally get involved in peer discussions about drug use and abuse - something that is happening more and more often). I am not trying to play gotcha, nor do I assume you're lying or mistaken, I just don't feel comfortable making assertions without evidence to back them. I have evidence for the assertions I have made about heroin before, but they are based mostly on case studies, not statistical analysis.
    As far as the assertion I made about MDMA deaths being very immediate, that is relative to becoming dependent on heroin or alcohol. I did not intend that to be compared to death by heroin, which of course would be rather more immediate. Death from MDMA usually seems to happen within a matter of hours. When comparing that to the time it would take to see acute dependence, it is pretty damned immediate.

  • Ian Musgrave says:

    DuWayne wrote:

    It was my best understanding that a relative standard dose would be exceedingly unlikely to be fatal...

    1 in 100,000 isn't rare?
    I don't have those papers at this computer, but lets look at these figures for Australia. The death rate for heroin users per million population, (death rates for all opioids but primarily heroin, with some opium and morphine deaths) in the 15-24 age group - where the majority are first time users/recreational users not dependent users - is 13.3 per million population, the death rate for ALL age groups using ecstasy, including new, recreational and long time users is 0.8 per million population.$file/OPIOID+OVERDOSE+DEATHS+2004.pdf
    This really needs to be adjusted for the user base. In 2004 roughly 6 times more people tried ecstasy than heroin (and 6 times more people used ecstasy within 12 months than heroin). Even if we consider only 20% of the 15-24 age group deaths were first time/recreational deaths to heroin alone the result is still around 1 in 100,000 users. This will be an underestimate of all first time/recreation use.
    Why you want compare deaths with dependence I do not know, you have to be comparing apples with apples. You should be comparing death by MDMA to death by Heroin. Dependence to MDMA is a more tricky thing to evaluate.

  • Sketch says:

    Get educated moron she didn't die from using e she died from abusing it

  • DrugMonkey says:

    and the distinction here would be....?

  • Scientizzle says:

    The distinction?
    When *I* (and my friends) consume [insert drug here], we do it safely and there are incredibly unlikely to be any negative consequences to our actions.
    When negative consequences do occur, it is because those individuals weren't as careful/educated/healthy as we are. They weren't true mean intelligent recreational users. They were abusers.
    Think that's about right?

  • [...] If you've been following along my posts on the substituted cathinones you will recall that cathinone is beta-keto-amphetamine. And much like amphetamine, chemists can hang little bits off the core structure to create new and interesting drugs which may offer different subjective experiences. For people who are into that sort of thing. The compound termed "Methylone" is the cathinone cousin of 3,4-methylenedioxymethamphetamine or MDMA. Which we've discussed a time or two on this blog. As we've also discussed, MDMA can result in significant medical emergency and death. Yes, really, it is the MDMA. [...]

  • Best friend says:

    You all talk like its some experiment or your in a lab. I was her best friend and she did not abuse it , she used it once. ONE TIME. It wAs the MDMA that killed her. Everyone else survived. No matter what drug anyone takes they need to know that they chose to take a risk and they are willing to accept the end result. She wasn't a drug user or even a pot smoker. She was just a girl trying to figure out who she did it didn't want to be. And if sketch is who I believe he is ( the boy selling it). You chose to bring drugs into this world, and if not u someone else ? Yes! Let it be someone else because u would be able to sleep at night.

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